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Kapila Katherine W.L. Vig Greg J. Huang Associate Editor Kristin Y. De Koster Volume 53 Craniofacial Growth Series Department of Orthodontics and Pediatric Dentistry School of Dentistry; and Center for Human Growth and Development The University of Michigan Ann Arbor, Michigan ©2017 by the Department of Orthodontics and Pediatric Dentistry, School of Dentistry and Center for Human Growth and Development The University of Michigan, Ann Arbor, MI 48109 Publisher's Cataloguing in Publication Data Department of Orthodontics and Pediatric Dentistry and Center for Human Growth and Development Craniofacial Growth Series Anecdote, Expertise and Evidence: Applying New Knowledge to Everyday Orthodontics Volume 53 ISSN 0162 7279 ISBN 0-929921-00-3 ISBN 0-929921–49–6 No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form by any means, electronic, mechanical, photocopying, re- cording, or otherwise, without the prior written permission of the Editor-in-Chief of the Craniofacial Growth Series or designate. EDITOR ADDRESSES Sunil D. Kapila Professor and Eugene E. West Endowed Chair University of California San Francisco 513 Parnassus Ave, Box 0422 San Francisco, CA 94143 Katherine W.L. Vig Division of Orthodontics Department of Developmental Biology Harvard School of Dental Medicine 188 Longwood Ave Boston, MA 02115 Greg J. Huang Professor and Chair Department of Orthodontics D569 Health Sciences Bldg 1959 NE Pacific St University of Washington Seattle, WA 98195 CONTRIBUTORS JEREMY ABDUL, Dental Student, School of Dental Medicine, State Uni- versity of New York at Buffalo, Buffalo, NY. SERCAN AKYALCIN, Associate Professor, Postgraduate Program Director, School of Dental Medicine, Department of Orthodontics, Tufts University, Boston, MA. AYMAN AL DAYEH, Assistant Professor, College of Dentistry, Department of Orthodontics, University of Tennessee Health Science Center, Mem- phis, TN. THIKRIAT S. AL-JEWAIR, Clinical Assistant Professor and Interim Program Director, Department of Orthodontics, State University of New York at Buffalo, Buffalo, NY. IGNACIO BLASI JR., private practice, Tysons Corner, VA. S. JAY BOWMAN, Adjunct Associate Professor, Center for Advanced Den- tal Education, Saint Louis University, Saint Louis, MO; instructor, The University of Michigan, Ann Arbor, MI; Assistant Clinical Professor, Case Western Reserve University, Cleveland, OH; Visiting Clinical Lecturer, Se- ton Hill University, Greensburg, PA; Milton Sims Visiting Professor, Univer- sity of Adelaide, Adelaide, Australia; private practice, Portage, Ml. EDWIN CHANG, Oral Radiologist, private practice, Toronto, Ontario, Can- ada. DoBIN CHOI, Orthodontic Graduate Student, School of Dentistry, Depart- ment of Orthodontics, West Virginia University, Morgantown, WV. MARTYN T. COBOURNE, Professor of Orthodontics, Department of Or- thodontics, King's College London Dental Institute, London, England. R. SCOTT CONLEY, LB Badgero Professor, Associate Professor and Chair, Department of Orthodontics, State University of New York at Buffalo, Buf- falo, NY. ANDREW T. DiBIASE, Consultant in Orthodontics, Department of Ortho- dontics, William Harvey Hospital, Ashford, England. ROBERT DURAND, Associate Professor, Faculty of Dentistry, Université de Montréal, Montréal, OC, Canada. SYLVIAA. FRAZIER-BOWERS, Associate Professor, School of Dentistry, De- partment of Orthodontics, University of North Carolina, Chapel Hill, NC. GREG.J. HUANG, Professor and Chair, Department of Orthodontics, Uni- versity of Washington, Seattle, WA. PRIYANKA KAPOOR, Associate Professor, Department of Orthodontics and Dentofacial Orthopedics, Faculty of Dentistry, Jamia Millia Islamia, New Delhi, India; Professor, Department of Biochemistry, All India Insti- tute of Medical Sciences, New Delhi, India. O.P. KHARBANDA, Professor and Head, Centre for Dental Education and Research, Division of Orthodontics and Dentofacial Deformities, All India Institute of Medical Sciences, New Delhi, India. STEVEN J. LINDAUER, Professor and Department Chair, School of Den- tistry, Department of Orthodontics, Virginia Commonwealth University, Richmond, VA. NICK MADDUX, private practice, Virginia Beach, VA. MOHAMED I. MASOUD, Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA. RAJESWARI R. MOGANTY, Professor, Department of Biochemistry, All In- dia Institute of Medical Sciences, New Delhi, India. PETER NGAN, Branson-Maddrell Endowed Professor and Chair, Depart- ment of Orthodontics, West Virginia University, Morgantown, WV. TUNG NGUYEN, Associate Professor, Department of Orthodontics, Uni- versity of North Carolina, Chapel Hill, NC. CLARICE NISHIO, Assistant Professor, Faculty of Dentistry, Université de Montréal, Montréal, OC, Canada. KEVIN O'BRIEN, Professor of Orthodontics, School of Dentistry, Univer- sity of Manchester, Manchester, England. SPYRIDON N. PAPAGEORGIOU, Postdoctoral Fellow and Orthodontic Resident, University of Bonn, Bonn, Germany. GLENN T. SAMESHIMA, Chair and Program Director, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA. GABRIEL SENTIES-RAMIREZ, private practice, San Antonio, TX. vi KELTON T. STEWART, Associate Professor & Graduate Program Director, School of Dentistry, Department of Orthodontics & Oral Facial Genetics, Indiana University, Bloomington, IN. JULIEN STRIPPOLI, Orthodontics Resident, Faculty of Dentistry, Université de Montréal, Montréal, OC, Canada. SAWSAN TABBAA, Clinical Assistant Professor and Research Director, De- partment of Orthodontics, State University of New York at Buffalo, Buf- falo, NY. TIMOTHY TREMONT, Associate Professor, School of Dentistry, Depart- ment of Orthodontics, West Virginia University, Morgantown, WV. ESERTÜFEKCI, Associate Professor, School of Dentistry, Department of Orthodontics, Virginia Commonwealth University, Richmond, VA. ROBERT L. VANARSDALL JR. (deceased), Professor and Chair Emeritus, Director Postdoctoral Periodontic/Orthodontic Program, School of Medi- cine, University of Pennsylvania, Philadelphia, PA. KATHERINE W.L. VIG, Department of Developmental Biology, Orthodon- tic Section, Harvard School of Dental Medicine, Boston, MA. NEIL R. WOODHOUSE, Specialist Registrar in Orthodontics, Department of Orthodontics, King's College London Dental Institute and Royal Alexan- der Children's Hospital, Brighton, England. Vii PREFACE New diagnostic and therapeutic approaches to Orthodontics range from novel methods to expedite tooth movement to contempo- rary appliance designs and advanced technologies, including 3D imaging. These protocols offer unprecedented opportunities such as individu- alization of treatments, improved diagnostics, efficient and efficacious therapy, and enhanced outcomes. On the other hand, these new devices and approaches pose challenges to the discerning clinician and patient who want to know whether a specific new technique offers diagnostic or therapeutic advantages over currently accepted methods. Furthermore, the integration of proven new approaches into everyday practice often can be burdensome. Finally, decisions on the use of such new methods add to the already existing lack of consensus concerning several tradition- ally difficult questions such as open bite correction, root resorption and obstructive sleep apnea. This proceeding of the 43rd Annual Moyers Symposium and 41st Annual International Conference on Craniofacial Research (the Presym- posium) contains reports, original research and review articles written by international experts on the evidence—or lack thereof—for traditional, new and emerging approaches in orthodontics. An improved understand- ing of the currently available evidence for these diagnostic and treatment modalities will provide strong rationale and justify their application to everyday patient care. As in the past, the Symposium honored the late Dr. Robert E. Moy- ers, Professor Emeritus of Dentistry, and Fellow Emeritus and Founding Director of the Center for Human Growth and Development. The meeting was co-sponsored by the Department of Orthodontics and Pediatric Den- tistry and Center for Human Growth and Development at the University of Michigan, for whose support we truly are grateful. We wish to thank Michelle Jones of the Office of Continuing Den- tal Education for coordinating and efficiently running the Presymposium and Symposium, Kris De Koster for her invaluable help in editing this vol- ume and Katherine Ribbens for her technical assistance in generating this monograph. Finally, we thank all the speakers and participants of the Sym- posium and Presymposium, as well as those who purchase the volumes of the Craniofacial Growth Series (CGS). Because the series spans more than 40 years, several of the volumes now no longer are available in print. Efforts are being made to reproduce out-of-print monographs so the wealth of information in them can continue to be accessed. All CGS volumes are sold through Needham Press; orders can be placed online (www.needhampress.com) or by phone (734.668.6666). Sunil D. Kapila December, 2016 TABLE OF CONTENTS Editor Addresses Contributors Preface Making Rational Decisions in an Era of Evidence-based Orthodontics Katherine W.L. Vig and Kevin O'Brien Harvard School of Dental Medicine, University of Manchester Anterior Openbite: Crib Therapy in Children and Newer Strategies for Adults Greg J. Huang University of Washington Treatment of Class III Malocclusions with TSADs: Is It Worth the Burden? - Peter Ngan, Nick Maddux, DoBin Choi, Timothy Tremont West Virginia University, private practice Sutural Loading During Bone-anchored Maxillary Protraction Ayman Al Dayeh University of Tennessee Peri-miniscrew Biomarkers as Indicators for Miniscrew Stability or Failure O.P. Kharbanda, Priyanka Kapoor, Rajeswari R. Moganty All India Institute of Medical Sciences Myths and Legends: Unraveling the Complex Associations Between Vibrational Force, Tooth Movement and Pain During Initial Alignment with Fixed Appliances Martyn T. Cobourne, Andrew T. DiBiase, Neil R. Woodhouse, Spyridon N. Papageorgiou King's College London, William Harvey Hospital, University of Bonn 17 27 41 69 93 Xi A View from the Clinical Trenches: Vibration and Tooth Movement S. Jay Bowman Saint Louis University, Case Western Reserve University, The University of Michigan Piezo-corticision-assisted Orthodontics: Truth and Myths Clarice Nishio, Julien Strippoli, Robert Durand Université de Montréal Applying New Knowledge to the Correction of the Transverse Dimension Robert L. Vanarsdall Jr. and Ignacio Blasi Jr. Private practice, University of Pennsylvahia Extraction Versus Non-extraction: Long-term Research Findings on Arch Width and Buccal Corridors Sercan Akyalçin Tufts University Orthodontic Applications of Computer-aided Design and Computer-aided Manufacturing (CAD/CAM) Tung Nguyen University of North Carolina Evidence for Utilizing Three-dimensional Technology in Orthognathic Surgery and Sleep Apnea Care R. Scott Conley State University of New York at Buffalo Upper Airway Dimensions and Hyoid Bone Position in Skeletal Class II Adolescents Treated with Functional Appliances: What is the CBCT. Evidence? Thikriat S. Al-Jewair, Jeremy Abdul, Sawsan Tabbaa, Edwin Chang State University of New York at Buffalo, private practice Anecdote, Expertise and Evidence: Applying New Knowledge to Everyday Orthodontics: Can 3D Photogrammetry Replace Cephalometrics? Mohamed I. Masoud Harvard School of Dental Medicine 119 147 167 195 207 219 239 263 xii Orthodontic Root Resorption: Theory and Practice Glenn T. Sameshima University of Southern California Diagnosis of Tooth Eruption Disorders: Is Dental Ankylosis a Distinct Eruption Disorder? Gabriel Senties-Ramirez and Sylvia A. Frazier-Bowers Private practice, University of North Carolina The Truth About White Spot Lesions: Etiology, Prevention and Management Eser Tüfekçi and Steven J. Lindauer Virginia Commonwealth University Vicarious Learning in Orthodontics: Value or Valueless? Kelton T. Stewart Indiana University 287 297 315 329 xiii MAKING RATIONAL DECISIONS IN AN ERA OF EVIDENCE-BASED ORTHODONTICS Katherine W.L. Vig and Kevin O'Brien ABSTRACT This chapter is based on the 20th Annual Robert E. Moyers Memorial Lecture entitled Making Rational Decisions in an Era of Evidence-based Orthodontics, which was the keynote address at the 43rd Annual Moyers Symposium on the theme of Anecdote, Expertise and Evidence: Applying New Knowledge to Every- day Orthodontics. It is intended to overview how an evidence-based approach has evolved in dentistry and specifically in orthodontics. The medical model em- braced clinimetrics and developed the methodology in designing clinical trials and randomized controlled trials (RCTs). There is now an accumulating wealth of scientific literature, but how this will translate into clinical practice still is evolv- ing and translated by clinicians into everyday practice. The clinician should be aware of alternative treatment interventions and their risk, costs and benefits when discussing treatment options with patients and parents/caregivers during the informed consent process, which currently is the standard of care. Obtaining an evidence-based model requires critical thinking, especially in areas of contro- versy. The impact of marketing on both practitioners and consumers has esca- lated and unsubstantiated claims for treatments have become comfortable, con- venient and appealing. Therefore, the need to access high-quality evidence and understand that there are several components of an evidence-based approach— which include the patients' preferences and the clinician's expertise—that need to be taken into account during the decision-making approach to healthcare in dentistry and orthodontics. KEY WORDS: quality of evidence, clinical practice, marketing In areas of Uncertainty, areas not yet conquered by logic or science, we are open to persuasion by all sorts of methods, some remote from logic and science. (Caplan, 2016) Making Rational Decisions INTRODUCTION Dr. Robert E. Moyers was an educator and leader in orthodontics at a time when the digital age was waiting to be discovered, slides were carried in carousels, manuscripts written on typewriters and professional letters dictated and transcribed into shorthand by professional secretar- ies. Dr. Moyers was a visionary and his leadership paved the way to the digital age and our contemporary approach to evidence-based orthodon- tics. His distinguished career in orthodontics included serving his country with distinction during World War II. Details of his career as a war hero and as the most highly decorated dentist in the U.S. Army are available (Vig et al., 2007; McNamara, 2014, 2015). The purpose of this chapter is to consider how an evidence-based approach in orthodontics and dentistry has evolved and how it is being evaluated and applied to clinical practice. As not all levels of evidence are equal, a pyramidal hierarchical approach has been established to provide and critically appraise the strength of the evidence. This inevitably has led to the critical clinician evaluating what we “really know” about our treat- ments. It also is clear that in order to provide a level of informed consent, we advise our patients of alternative treatment interventions and the prior probability estimate of alternative treatments, but this information can be established only with data and a decision analysis approach. Past experience has improved the design of future prospective clinical trials as they are being developed, reviewed and funded. The role of bias has been recognized and uncertainty created in assessing the level of risks, costs and benefits of alternative treatment interventions. This inevitably has resulted in clinicians realizing uncertainty exists, which impacts their confidence in the choice of decisions. There is a level of discomfort in un- certainty when making decisions without the prior probability estimate of the anticipated outcome. Recognizing the consequences of alternative treatment interventions and discussing the outcomes and possible ad- verse events with parents and patients before starting treatment is man- dated as a standard of care and is the clinician's responsibility. Vig and O’Brien MAKING RATIONAL DECISIONS Can We Practice Evidence-based Orthodontics When Making Clinical Decisions? Practicing clinicians make many treatment decisions on a daily basis which are influenced by their clinical experience. Decisions typically are made by experienced clinicians using their expertise and intuitive approach, combined with the current available evidence without being 100% certain. If someone is 100% certain about all her/his decisions, per- haps s/he should examine her/his critical evaluative skills. Therefore, it behooves us to reduce uncertainty, which may be done by analyzing the available scientific literature and research so that we base our treatment decisions on the highest quality of information available. If this informa- tion is not available, then we need to disclose this to our patients. Likewise, if innovative treatments have not been tested yet in clinical trials, in spite of unsubstantiated claims for their effectiveness, our patients should be informed. The evidence from well-designed, high- quality, quantitative and qualitative research studies reduces bias, am- biguity and uncertainty. Holding to this higher level of certainty requires diligence and constant updating. It is easier to find and absorb lower lev- els of evidence (e.g., case reports, expert opinion and persuasive market- ing of advertised products) without evaluating the supporting evidence critically. All aspects of our lives are influenced by uncertainty and this is particularly true for the clinical decisions that we make. The aim of scien- tific investigation is to try to reduce this uncertainty as much as possible. Conversely, clinical uncertainty is increased by claims for treatments that are not based upon research evidence. We would all like to practice evidence-based dentistry and ortho- dontics; as a result, reducing uncertainty is integral to this aim. When we consider the nature of evidence that should reduce uncertainty, a good place to start is the well-established pyramid of clinical evidence (Fig. 1). This ranks the type of research study design in terms of the strength of Making Rational Decisions Systematic Review / RCT Prospective cohort Case control (retrospective) Z Case series Z Case report Figure 1. Pyramid of clinical evidence. the evidence that it provides. While this emphasis is commendable, we should not forget that the optimum practice of evidence-based care is not influenced solely by research. For example, Sackett and colleagues (1996) pointed out that we should consider that there are three compo- nents that contribute to evidence-based care: clinical research, clinical experience and patient opinion (Fig. 2). The proportion of each component that influences a final clinical decision is its relative strengths. Importantly, all evidence that is based on clinical experience and research should be explained fully to our patients/ parents so that they can make an informed decision on their choice of treatment. Paradoxically, there also is a resistance to accepting the results of clinical research and the commonly-cited arguments for challenging the pyramid may be put together as a pyramid of denial (Fig. 3). Coping with Uncertainty Can we provide information to our patients confidently when we are uncertain? As an example, one may consider information identified from two Cochrane systematic reviews, the more recently completed of which focused on Orthodontic treatment for prominent teeth and aimed to assess the effect of early orthodontic treatment for Class || malocclu- sion (Harrison et al., 2007; Thiruvenkatachari et al., 2015). This treatment Vig and O'Brien clinical / Clinical Experience | Research EBC | Patient | opinion | Figure 2. Three components that contribute to evidence-based care. My patients are different Not individualised / You did it wrong A. You should have asked us / Z We know better A know best Figure 3. Pyramid of denial. has been provided in two phases: the first is a course of early treatment When the child is approximately eight years old; this is followed by a sec- ond phase when s/he is in early adolescence. Three large randomized tri- als were identified which are well known in orthodontic research (Tulloch et al., 2004, Dolce et al., 2007; O'Brien et al., 2009). For most of the orth- odontic effects of treatment, there was no advantage to treat children Making Rational Decisions early. Nevertheless, there was some evidence that early intervention re- sulted in a 9% reduction in the incidence of trauma. While this finding may be important clinically, there was a moderate degree of uncertainty in these findings. The provision of evidence-based care clearly has an important role in providing information as part of informed consent. In both the U.S. and the U.K., this is regulated as a standard of care by the profession (D’Cruz and Kaney, 2015). The doctor/dentist and patient should have a partnership based on trust and openness. Importantly, our patients/ parents/caregivers should be informed well in their choice of treatment concerning significant risks and reasonable alternative treatments. We, therefore, need to be able to provide more information to our patients about our care with an informed explanation on the benefits of treatment and the probabilities of risks. While this seems possible in an era of evidenced-based doctrine, there still lingers the concept that orthodontics has been practiced successfully for over a century, albeit with what we in the 21st century would consider poor quality evidence. This lack of strong evidence, with convincing rhetoric, has fueled the controversies for over 100 years including the classic extraction/non- extraction debate. While medicine was gaining momentum in the late 20th century with clinical trials and well-designed randomized clinical tri- als (RCTs), dentistry was lagging behind. Until the 1990s, orthodontics, as the oldest specialty in dentistry, had few RCTs. The steep learning curve of an evidence-based approach had profound implications in education since our knowledge previously was based largely on clinical experience. The appeal of marketing strategies was a comfortable way of introducing innovative appliances and techniques, which all seemed to work without the need for any supporting evidence. The harms in dentistry tend to be relegated to white spots on the enamel and root resorption, but rarely involve considerations of life and death, unlike in medicine. Contemporary Issues in an Era of Evidence-based Orthodontics When we consider the changes in orthodontic research over the past 20 years, two notable milestones coincide with an acknowledgment that all was not well. The most well-known quote is that of David Sackett (1986), an American-based medical researcher and a doyen of the “evi- dence-based care” movement. When asked to review the quality of or- Vig and O’Brien thodontic research at the Moyers Symposium that year, he stated that “orthodontics is reliant on an evidence base that is on a par with po- diatry, dianetics and scientology.” In his opinion, arguments were won or lost on the basis of rhetoric rather than science. No RCTs had been done in orthodontics in 1985 and it was behind treatment modalities such as acupuncture, hypnosis and homeopathy. This soon was followed by the conclusions of a review into the functional appliance literature by Tulloch and associates (1990). They concluded that “the literature was so weak, in terms of reliance on poorly controlled, retrospective studies, poor sample size calculations and inap- propriate use of statistical tests, that it was not possible at that time to support or dismiss the growth modifying effects of functional appliances.” In 1995, Sackett returned to the Moyers Symposium fearing it would be a repeat of 1985. In his presentation to the Moyers Symposium that year, he indicated that he was as positive about our prospects as a specialty as he was negative ten years before (Sackett, 1995). At the 1994 Moyers Symposium, the outcome of the Class || RCT results were being reported. Since then, many important studies have been published about a variety of treatments including early Class Il treatment, bracket types, retainer regimens, management of displaced canines and extra-oral headgear (Tulloch et al., 2004; Dolce et al., 2007; Baccetti et al., 2009; O'Brien et al., 2009; Silvola et al., 2009; Shawesh et al., 2010). These ar- ticles should have changed not only the orthodontic practice of more enlightened clinicians, but also should change the clinical practice of all orthodontists. For the next generation of practitioners, this information should be updated annually and included in the educational programs of all orthodontic residency programs. Although the advantages of RCTs are undeniable, the findings of orthodontic trials are not always accepted universally because they tend to challenge long-held beliefs that often are ingrained into our treatment approaches. This has meant that orthodontics often is unwilling to ac- cept the results of well-conducted, scientifically valid trials of common treatment methods, but enthusiastically embraces treatment methods that have not been tested clinically to a level of evidence that withstands scientific scrutiny, but perhaps are described and illustrated beautifully in marketing brochures. Making Rational Decisions The Effect of Marketing Strategies in Orthodontic Practice This leads us to consider that there is a risk that advertising claims counteract research evidence, thereby leading to increased uncertainty about an intervention. Current examples of this include the promotion and widespread adoption of non-compliance Class Il correctors and new methods that attempt to increase the speed of tooth movement. Howev- er, the best example of this was the wholesale acceptance of self-ligating brackets, often accompanied by a new treatment philosophy (Damon, 1998). The theoretical advantage of this design was that friction was re- duced and, thus, tooth movement was faster. This also was incorporated into a “new philosophy” that promoted treatment without dental extrac- tions and the stimulation of bone growth. The main source of informa- tion that underpinned this change was the marketing literature available both directly from the manufacturing companies and indirectly from or- thodontists' websites. Interestingly, this advertising was directed not only to the profession, but also often to our patients and their parents. The advertising material quoted research that was at a low scien- tific level and published in journals that were not refereed; some of these were produced by the manufacturers. Paradoxically, several RCTs and now systematic reviews that were published in the refereed literature showed that self-ligating brackets do not have any of the claimed advan- tages over conventional brackets with regard to the speed of initial align- ment, increased comfort for the patient or total treatment time (Miles, 2007; Pandis et al., 2007; Scott et al., 2008; Fleming et al., 2009a,b,c, Fleming and Johal, 2010; Marshall et al., 2010). It could be assumed that having experienced the situation with self-ligating brackets, the orthodontic profession would have learned from this experience. Unfortunately, this is not the case and there now is widespread adoption and selling of devices that apply vibration to the teeth with the aim of decreasing treatment time. The studies that have supported this new technology are characterized by small numbers and questionable methodology (Pavlin et al., 2015). Other studies designed to a higher standard are providing information suggesting that these de- vices are not effective (Woodhouse et al., 2015). It is clear that over the last 20 years, orthodontics has begun to develop a strong scientific basis to support some of our treatment modalities. Unfortunately, there is a tendency for our specialty to forget its research base when new and bet- Vig and O’Brien ter treatments are developed. Currently, we seem to be ignoring our sci- entific knowledge with the increasing pressure to provide treatment that is faster, better and more comfortable. Practicing and Believing in Evidence-based Orthodontics Because it is difficult to do irreversible serious harm in ortho- dontics with white spots on the crowns of teeth and root resorption, perhaps we should consider if orthodontists need to practice evidence- based care. The counter argument is that we need to practice ethically by ensuring our treatment is based on the available evidence and not on beliefs reminiscent of alchemy or convincing, but unsubstantiated rheto- ric. We also need to inform patients of all the potential risks and benefits of alternative treatment interventions. It is incumbent on us as clinicians to be careful, therefore, not to make statements based on poor research evidence (e.g., the indiscriminant benefits of non-extraction treatment, methods of speeding up treatment and orthodontics to reduce sleep- disordered breathing in children and sleep apnea in adults). The nasal airway has intrigued orthodontists for a century including our beliefs about the consequences of enlarged tonsils and adenoids, which result in mouth breathing and distortion of facial growth in children (Vig, 1998). We need to assess carefully the quality of the scientific literature based on all clinical trials and systematic reviews beyond the one paragraph conclusions of the study. There is a need to justify our clinical experience in the absence of research and inform our patients of studies that do not show benefits of our proposed treatment. In comparison to medicine, dentistry and orthodontics have been slow to embrace evidence-based care founded on a combination of research evidence, patient opinion and preferences and the clinical knowledge and expertise of the providers. In making clinical decisions based on clinical experience, it is easi- er to remember the cases that worked well, but failures should have equal importance. Sources available for contemporary information include social media, listening to advocates for certain treatments and interventions, but one should be cautious as this information may be biased toward success- fully treated cases. Another source is the easily assimilated information from marketing where critical skills are important to discriminate between those with high quality supporting evidence and those lower down on the pyramid (Fig. 1); not all evidence is of equal merit. Making Rational Decisions Ideally, we should base our treatment decisions on evidence and when it is not available or is absent, accept that our decisions are based on clinical experience. This should be disclosed to the patient and parent/ caregiver during the consent process. When we follow this caveat, we are practicing evidence-based orthodontic care for our patients (Fig.2). HAS AN EVIDENCE-BASED APPROACH PROVED SUCCESSFUL IN MEDICINEP Medicine is well ahead of orthodontics in clinical trials, evi- dence and guidelines. However, in a recent publication by Greenhalgh and colleagues (2014), the authors consider the right balance between evidence-based care and the characteristics and values of individual pa- tients as a top priority. The application to evidence-based orthodontics requires synthesis of research evidence that is relevant to the individual patient and explains this to her/him in terms that s/he can understand. In other words, we should not be so rigid that we simply apply the re- sults of the most recent relevant systematic review to the patient's con- dition. For example, we have good evidence from trials and reviews on the most effective methods and optimum timing for the treatment of a child with prominent teeth. Nevertheless, we should not treat every child with prominent teeth with a functional appliance—we must go back to basic diagnosis and identify the etiology of the problem. To suggest treatment for all these patients in order to reduce the chances of incisal trauma requires a discussion with the patient/parent of the relative risk and numbers needed to treat. A recommendation to screen children at a young age to detect and intercept developing malocclusion is laudable, but currently there is no strong evidence on the effectiveness of inter- ceptive treatment or how many children we need to screen to intercept one orthodontic problem. As a result, we need to appraise the evidence for routine screening of all children by age seven. There also is a need to be more critical of guidelines and their sources of evidence and not necessarily take them at face value. Recommendations that removal of a primary canine encourages eruption of the permanent canine requires a RCT to assess the full effectiveness of this clinical intervention and means we do not know if this intervention is effective. 10 Vig and O’Brien Asking the Right Ouestions of Research We all need to learn to interpret research. Publications con- cerned with data reported as means of only a few millimeters or degrees do not consider the effect size and confidence intervals. Most high quality medical journals make the reporting of confidence intervals a require- ment of publication. In orthodontics, we tend to take the numbers at face value without an assessment of the small differences that excite only us, along with an evaluation of the level of uncertainty. We are not practic- ing evidence-based care if we do not take these small differences into account. We are interested in a small, but important, part of the human body, but we have many journals reporting Studies of mixed quality and doubtful relevance. This adds to the confusion of evidence-based ortho- dontics. More imaginative research is needed to move away from our values, which mean very little to anyone but orthodontists. The role of qualitative research and Health Related Ouality of Life (HROol) outcomes that are relevant to patients have been ignored until recently and then tend to be associated with those patients who have medical collabora- tions associated with orthognathic surgery or craniofacial anomalies with orofacial clefts. The medical concerns of Greenhalgh and associates (2014) apply equally to dentistry and specifically orthodontics. Our cur- rent involvement in espousing evidence-based healthcare requires in- terpreting the limited high quality literature in evidence-based dentistry carefully to avoid the mindset of treating our patients as a set of teeth characterized by features that we place into categories and treat accord- ingly. To achieve this aim, there is a steep learning curve by the profes- sion to become skilled in interpreting the literature. We need to question critically and continuously the recommendations of both professors and industry-sponsored advocates espousing the concept of “evidence.” As in medicine, our journals ideally need to raise their quality of accepting manuscripts for publication. This would increase their impact factor and value while our researchers should be encouraged to be more imaginative. In an open access publication by Prasad and lonnidis (2014), the authors raise the question whether we should continue with established healthcare practices that do not have an evidence-based approach. They considered three main types of healthcare intervention: 11 Making Rational Decisions 1. Those that are known not to work when RCTS have been carried out; 2. Those for which the evidence base is uncertain; and 3. Those that are in development. This concerns treatment where the best evidence shows no efficacy or the harms outweigh the benefits. One of the best orthodontic examples is our attempt to achieve orthopedic or skeletal change. The evidence that we now have Strongly suggests that we cannot change skeletal pat- tern by modifying and redirecting growth with functional appliances or headgear—yet we continue to attempt this change. High-quality evi- dence from RCTs indicates that functional appliances tip teeth effectively and good results are achieved in those patients whose skeletal discrepan- cy is not severe. However, in the child with a severe skeletal discrepancy, should, we still provide treatment with functional appliances or should we provide surgery, more effectively, when s/he is older? Where is the harm in reducing the severity of the discrepancy and possibly enhanc- ing the child's self-esteem in the case of teasing and bullying? This early intervention is potentially an unnecessary course of treatment that in- troduces additional dental compensation which then needs correcting if and when orthognathic surgery is considered. Likewise, there is no evi- dence to support the concept that headgear causes Skeletal change and the potential harms may outweigh any possible benefits. However, this is directed at skeletal change as the primary outcome, not the quality of life, for the child who is enduring taunting and teasing at school concern- ing his/her teeth. Therefore, the authors suggest that de-implementing practices reflects a recommitment to evidence-based healthcare. This directive in medicine should be considered seriously in our approach to evidence-based dentistry and orthodontics. CONCLUSIONS We have considered that orthodontics has developed rapidly into a specialty that has begun to operate on an improving evidence base. As a result, the uncertainty behind some of our clinical practice is reducing. Paradoxically, the widespread development and advertisement of new appliances and philosophies is counteracting the effect of research evi- dence and uncertainty is increasing. 12 Vig and O’Brien This situation is unsatisfactory if we are to avoid returning to a low evidence base. The way forward is clear. Firstly, the drive for high quality research should continue. Secondly, orthodontists and dental practitioners need to read and interpret the scientific literature more critically. There is a need for increased education delivered in pre- and post-doctoral training programs. We should not underestimate the role of social media in providing information in the digital age where comput- er literacy in our current students typically exceeds that of their teachers and faculty. Dental and specialty organizations should consider making more use of this rapidly changing medium in education and curriculum revision. Meanwhile, the advertising industry makes use of social media and it will take time, effort and resources to make the necessary prog- ress in education and the academic environment. Continuing to accept the current situation in which clinical practice ebbs and flows, driven by the forces of clinical research and unsubstantiated advertising, we are in danger of returning to the days of the barber surgeons at the infancy of our profession. ACKNowLEDGEMENTs Some of the content of this chapter is based closely on Kevin O'Brien's orthodontic blog (www.kevinobrienorthoblog.com). REFERENCES Baccetti T, Mucedero M, Leonardi M, Cozza P. Interceptive treatment of palatal impaction of maxillary canines with rapid maxillary expansion: A randomized clinical trial. Am J Orthod Dentofacial Orthop 2009; 136(5):657-661. Caplan L. The double life of Richard Posner, America's most contentious legal reformer. Harv Mag 2016;Jan-Feb:56. D'Cruz L, Kaney H. Consent: A new era begins. Br Dent J 2015;219(2):57- 59. Damon DH. The Damon low-friction bracket: A biologically compatible straight-wire system. J Clin Orthod 1998;32(11):670-680. Dolce C, McGorray SP, Brazeau L, King GJ, Wheeler TT. Timing of Class Il treatment: Skeletal changes comparing 1-phase and 2-phase treat- ment. Am J Orthod Dentofacial Orthop 2007;132(4):481–489. 13 Making Rational Decisions Fleming PS, DiBiase AT, Sarri G, Lee RT. Comparison of mandibular arch changes during alignment and leveling with 2 preadjusted edgewise appliances. Am J Orthod Dentofacial Orthop 2009a;136(3):340-347. Fleming PS, DiBiase AT, Sarri G, Lee RT. Efficiency of mandibular arch alignment with 2 preadjusted edgewise appliances. Am J Orthod Den- tofacial Orthop 2009b;135(5):597–602. Fleming PS, DiBiase AT, Sarri G, Lee RT. Pain experience during initial alignment with a self-ligating and a conventional fixed orthodontic appliance system: A randomized controlled clinical trial. Angle Orthod 2009c;79(1):46-50. Fleming PS, Johal A. Self-ligating brackets in orthodontics: A systematic review. Angle Orthod 2010;80(3):575-584. Greenhalgh T, Howick J, Maskrey N; Evidence Based Medicine Renaissance Group. Evidence based medicine: A movement in crisis? BMJ 2014;348:g3725. Harrison JE, O'Brien KD, Worthington HV. Orthodontic treatment for prominent upper front teeth in children. Cochrane Database Syst Rev 2007;3:CD003452. Marshall SD, Currier GF, Hatch NE, Huang GJ, Nah HD, Owens SE, Shroff B, Southard TE, Suri L, Turpin DL. Ask us: Self-ligating bracket claims. Am J Orthod Dentofacial Orthop 2010;138(2):128-131. Miles PG. Self-ligating vs conventional twin brackets during en-masse space closure with sliding mechanics. Am J Orthod Dentofacial Orthop 2007;132(2):223-225. McNamara JA Jr. 17th Annual Robert E. Moyers Memorial Lecture: Reflec- tions on the Moyers Symposium: A Living History of Contemporary Orthodontics and Craniofacial Biology. In: McNamara JA, ed. The 40th Moyers Symposium: Looking Back ... Looking Forward. Craniofacial Growth Series, Center for Human Growth and Development, The Uni- versity of Michigan, Ann Arbor, MI 2014;50:1-28. McNamara JA Jr. Robert Edison Moyers: War hero, motivator, collabora- tor. Am J Orthod Dentofacial Orthop 2015;147:650-652. O'Brien K, Wright J, Conboy F, Appelbe P, Davies L, Connolly l, Mitchell L, Littlewood S, Mandall N, Lewis D, Sandler J, Hammond M, Chadwick S, O'Neill J, McDade C, Oskouei M., Thiruvenkatachari B, Read M, Robin- son S, Birnie D, Murray A, Shaw I, Harradine N, Worthington H. Early 14 Vig and O’Brien treatment for Class Il division 1 malocclusion with the Twin-block appliance: A multi-center, randomized, controlled trial. Am J Orthod Dentofacial Orthop 2009;135(5):573-579. Pandis N, Polychronopoulou A, Eliades T. Self-ligating vs conventional brackets in the treatment of mandibular crowding: A prospective clini- cal trial of treatment duration and dental effects. Am J Orthod Dento- facial Orthop 2007;132(2):208-215. Pavlin D, Anthony R, Raj V, Gakunga PT. Cyclic loading (vibration) accel- erates tooth movement in orthodontic patients: A double-blind, ran- domized controlled trial. Semin Orthod 2015;21(3):187-194. Prasad V, loannidis JP Evidence based de-implementation for contra- dicted, unproven, and aspiring health care practices. Implement Sci 2014:9:1. Sackett DL. Nine years later: A commentary on revisiting the Moyers Sym- posium. In: Trotman CA, McNamara JA Jr, eds. Orthodontic Treatment: Outcome and Effectiveness. Craniofacial Growth Series, Center for Hu- man Growth and Development, The University of Michigan, Ann Ar- bor, MI 1995;30:1-5. Sackett DL. The science of the art of clinical management. In: Vig KWL, Ribbens KA, eds. Science and Clinical Judgment in Orthodontics. Cra- niofacial Growth Series, Center for Human Growth and Development, The University of Michigan, Ann Arbor, MI 1986;19:242. Sackett DL, Rosenberg WM, Gray JA, Haynes RB, Richardson WS. Evidence based medicine: What it is and what it isn’t. BMJ 1996;312(7023):71- 72. Scott P. DiBiase AT, Sherriff M, Cobourne MT. Alignment efficiency of Damon3 self-ligating and conventional orthodontic bracket systems: A randomized clinical trial. Am J Orthod Dentofacial Orthop 2008; 134(4):470.e1-e8. Shawesh M, Bhatti B, Usmani T, Mandall N. Hawley retainers full- or part- time? A randomized clinical trial. Eur J Orthod 2010;32(2):165–170. Silvola AS, Arvonen P, Julku J, Lähdesmäki R, Kantomaa T. Pirttiniemi P. Early headgear effects on the eruption pattern of the maxillary ca- nines. Angle Orthod 2009;79(3):540-545. Thiruvenkatachari B, Harrison JE, Worthington HV, O'Brien KD. Orthodontic treatment for prominent upper front teeth (Class || 15 Making Rational Decisions malocclusion) in children. Cochrane Database Syst Rev 2013;11: CD003452. Tulloch JF, Medland W, Tuncay OC. Methods used to evaluate growth modification in Class Il malocclusion. Am J Orthod Dentofacial Orthop 1990;98(4):340-347. Tulloch JF, Proffit WR, Phillips C. Outcomes in a 2-phase randomized clini- cal trial of early Class Il treatment. Am J Orthod Dentofacial Orthop 2004;125(6):657-667. Vig KW. Nasal obstruction and facial growth: The strength of evidence for clinical assumptions. Am J Orthod Dentrofac Orthod 1998;113(6):603- 611. Vig KWL, O'Brien K, Harrison J. Early orthodontic and orthopedic treat- ment: The search for evidence—Will it influence clinical practice? In: McNamara JA, ed. Is the Benefit Worth the Burden? Craniofacial Growth Series, Center for Human Growth and Development, The Uni- versity of Michigan, Ann Arbor, MI 2007;44:13–38. Woodhouse NR, DiBiase AT, Johnson N, Slipper C, Grant J, Alsaleh M, Donaldson AN, Cobourne MT. Supplemental vibrational force during orthodontic alignment: A randomized trial. J Dent Res 2015;94(5):682- 689. 16 ANTERIOR OPENBITE: CRIB THERAPY IN CHILDREN AND NEWER STRATEGIES FOR ADULTS Greg J. Huang ABSTRACT Anterior openbite malocclusions are challenging to treat and even more chal- lenging to retain. This chapter presents information on two aspects of treat- ment for anterior openbite patients. First, crib use in children is discussed. Sec- ond, some of the newer modalities for management of openbite in adults are reviewed. Most of the literature on anterior openbite treatment and stability consists of lower-level evidence. However, until better studies are conducted, we should utilize the best available evidence as a foundation for our clinical rec- ommendations. KEY words: anterior openbite, crib, aligners, temporary anchorage devices, mandibular Surgery INTRODUCTION For decades, openbite malocclusions have been a challenge to orthodontists. They are difficult to correct and even more difficult to retain. This paper discusses two topics related to anterior openbite: the use of crib therapy in mixed dentition patients; and some of the newer treatment strategies that may be employed in adults. CRIB THERAPY In the mixed dentition, there are many possible reasons for an anterior openbite, including digit habits, tongue posture, airway issues and growth patterns. During early mixed dentition, children often are able to stop their digit habits without intervention from dental profes- sionals. However, even after cessation of digit habits, anterior openbites may persist. In these patients, an anterior tongue posture may play a sec- ondary role in the maintenance of an anterior openbite. If so, modifying 17 Anterior Openbite tongue posture may result in easier or even the spontaneous correction of the openbite, along with better long-term stability. This is the theory behind tongue Cribs that are used after the cessation of digit habits. What is the evidence for the efficacy of tongue cribs in aiding in the correction of anterior openbite? In 1990, an ar- ticle was published that investigated the long-term stability of anterior openbites treated with crib therapy (Huang et al., 1990). This retrospec- tive case series reported on a growing group of 26 patients and a non- growing group of seven patients. Most of the subjects were from the private practices of two practitioners, but several were contributed by other practitioners. Some patients had only early or partial treatment, while others received comprehensive treatment. Thus, the sample was mixed in terms of age, crib designs and orthodontic treatments that were rendered. Nevertheless, the success and stability rates in adolescents (88% success and 100% stability) and adults (86% success and 100% stability) were impressive. Of course, this study was conducted almost 30 years ago and we probably would do many things differently today. For in- stance, we would want to make sure all eligible patients were consid- ered consecutively for inclusion in the study to reduce selection bias. We also would wish to standardize the sample better in terms of age and treatment. Finally, comparing two different treatments (e.g., fixed ver- sus removable cribs, or cribs versus functional appliances) might have been helpful. Several studies have compared different crib therapies in chil- dren. Cozza and colleagues (2007) reported on quad helix/crib compared to an openbite biomator in a sample of 41 mixed dentition patients. They found that the quad helix/crib was more effective than the bionator for openbite correction. Giuntini and associates (2008) investigated fixed versus removable cribs in a sample of 40 mixed dentition subjects and found that the fixed appliance was more effective. Finally, Leite and co- workers (2015) investigated palatal cribs versus bonded spurs in a mixed dentition sample. They found that both bonded spurs and palatal cribs were effective. Perhaps collectively, these three articles suggest that fixed cribs or spurs are more effective than removable appliances for correction of openbites in mixed dentition. 18 Huang There also are a couple of systematic reviews that evaluated treatment for anterior openbite in children. A Cochrane review (Lenti- ni-Oliveira et al., 2014) found three randomized controlled trials (RCT) that investigated this issue. One trial compared a Frankel device and lip-sealing exercises to no treatment, another compared posterior bite blocks with and without repelling magnets, and the final RCT compared palatal cribs with high pull chincups to no treatment. In this last trial, the combination of palatal cribs and high pull chincup was found to be much more effective for closure of openbite compared to controls (80% closure compared to 13% closure during the study period; Torres et al., 2006). It was not possible to isolate the effects of the crib from the chin- cup, however, since all treated patients had both. The systematic review by Feres and colleagues (2017) reported that crib therapy “appears to be effective (for the treatment of anterior openbite) on a short time basis.” We also might ask what happens to young patients who have no treatment for their openbites. In an often cited cross-sectional study, the rate of spontaneous closure of openbite in mixed dentition has been reported to be 80% (Worms et al., 1971). However, NHANES III, a large cross-sectional study, reported almost no difference in the rates of openbite in mixed dentition and permanent dentition samples, even though subjects might have undergone orthodontic treatment (Proffit et al., 1998). Two longitudinal studies indicate that spontaneous open- bite closure may occur in 13–43% of mixed dentition patients (Pedrin et al., 2006; Jolley et al., 2010). These conflicting reports make it difficult to know what the true rate of closure may be. In general, longitudinal data may be more reliable than cross-sectional data, especially when the rates of a condition are relatively rare. For example, in the cross-sec- tional study by Worms (1971), the 80% reduction in “simple” openbites observed in the 10- to 12-year-olds was followed by a doubling of the rate of “simple” openbites in the next age group. It seems unlikely that openbite would be increasing in the early teens and it may have been a chance finding due to a few less openbites in the 10 to 12 age group or a few more openbites in the 13 to 15 age group. Also, the authors stated that the high rate of spontaneous closure in mixed dentition could be related to patients in the 7 to 9 age group being classified with openbite due to the incomplete eruption of the incisors. 19 Anterior Openbite One other factor that is important when conducting a study on openbite patients in the mixed dentition is attention to thumb or digit habits. There is a belief that digit habits that are arrested before eruption of the permanent incisors may allow self-correction of anterior open- bites. While this may be true in some children, it surely is not the case in all children and sometimes the tongue assumes a forward posture be- tween the incisors that will prevent their eruption. If patients with digit habits are included in studies, some of them may show spontaneous cor- rection of the openbite if they stop their digit habit during the study pe- riod. For that reason, it is important particularly to account for the digit habit status when conducting a study in mixed dentition. Ideally, it would be best to include only patients who have stopped their digit habits al- ready and have demonstrated no recent closure in their openbite. This would help to ensure that any closure would be due to treatment, rather than a discontinuation of a digit habit. In summary, crib therapy in mixed dentition is not associated with a large number of rigorously conducted studies. Most reports are case series, with a few cohort studies and randomized trials sprinkled in. There seems to be some consistency in the existing literature, however, that cribs can be effective, especially fixed ones, and that they have rela- tively good stability. NEWER STRATEGIES FOR ADULTS In adults, orthodontists have used strategies such as extractions, vertical elastics, multi-loop archwires and maxillary surgery to address an- terior openbites. However, some of the more recent approaches include aligners, temporary anchorage devices (TADS) and mandibular surgery. What do we know about these options for correcting anterior openbites? When the Invisalign” appliance became available commercial- ly, aligners were reported to deepen overbites in patients (Boyd et al., 2000). This tendency to deepen bites has been used advantageously in patients presenting with anterior openbites. The theory is that the posterior occlusal coverage acts as a bite block, thereby intruding mo- lars and allowing auto-rotation of the mandible. This, in turn, results in deepening of the anterior overbite. TADs also allow intrusion of the mo- lars, auto-rotation and deepening of the overbite. Thus, these two dif- 20 Huang ferent types of treatment seem to correct openbites with a similar ap- proach—molar intrusion and auto-rotation. To what extent does this oc- cur and how stable is the correction? Let's discuss aligners first. In theory, it makes sense that aligners could close openbites by intruding molars, as aligners have occlusal cov- erage, which almost always is heaviest on the posterior teeth. However, a recent study conducted at the University of Washington (Khosravi et al., 2017) found that even mild to moderate openbites are not closed with aligners. In fact, in their sample of twelve openbite patients who had a mean pre-treatment overbite of -1.1 mm, the overbite was deepened by only 1.3 mm to a final mean value of 0.2 mm. Four of the twelve patients did not achieve positive overbite. This was rather surprising, as was the fact that the molars did not show any intrusion, on average, nor did the mandibular plane angle change significantly. The overbite certainly im- proved, but the only significant vertical changes that were noted were extrusion of the upper and lower incisors. Why didn't the molars intrude in the studied sample? This re- quires further investigation, but one reason could be that openbite pa- tients do not have particularly strong bite force. Also, it is possible that even though molar intrusion was programmed into the aligners, incisor eruption was a relatively “easier” tooth movement, so those were the movements that were expressed. TADs have become a popular treatment modality for addressing anterior openbites and techniques have been proposed using maxillary buccal and/or maxillary palatal TADs, as well as mandibular TADs. The objective is the same, though, in all cases: intrude upper and/or lower molars to allow auto-rotation and closure of the anterior openbite. There are many cases reported in the literature demonstrat- ing successful openbite correction with TADs. However, the change in other vertical dimensions may be less than predicted, as illustrated by a recent article reporting on intrusion of molars with TADs and maxil- lary splints in 33 consecutive patients (Scheffler et al., 2014). The authors reported maxillary molar intrusion of 2.3 mm on average, but only 1.6 mm of change in anterior facial height. They listed two reasons why the changes in vertical facial dimension were attenuated despite substantial molar intrusion. First, intrusion of upper molars was accompanied by eruption of the lower molars. Second, there was slight extrusion of the 21 Anterior Openbite maxillary molars during post-intrusion orthodontic treatment. There also could be other reasons for diminished vertical facial change when other TAD systems are used. For example, less vertical changes may occur if intrusion of maxillary molars is associated with buccal flaring, causing the lingual cusps to plunge down. Another reason for less vertical facial changes may occur if intrusion of upper molars is associated with an ex- trusive force to the anterior teeth via a continuous archwire. This may result in the anterior openbite closing before significant molar intrusion is accomplished. Despite the many reports of successful openbite treatment with TADS, only a few articles address long-term stability (Sugawara et al., 2002; Lee and Park, 2008; Baek et al., 2010; Scheffler et al., 2014). With the exception of the most recent article (Scheffler et al., 2014), all report on small samples (nine to eleven patients) and all four studies indicate some degree of molar extrusion after orthodontic treatment. TADs cer- tainly have increased the range of possibilities for openbite correction without orthognathic surgery. They are less invasive, less risky and less costly than maxillary impaction surgery. However, we need good data on the long-term stability of this technique compared to maxillary impaction Surgery. The third option mentioned for adults is mandibular surgery with counter-clockwise (closing) rotation, which is not a new technique, but one that largely was abandoned decades ago because the results in open- bite patients were not stable. Surgeons turned to maxillary impaction surgery, which seemed to provide better stability. At that time, however, wire fixation was being used to stabilize segments. Over the past several decades, almost all surgeons have adopted rigid fixation techniques for orthognathic procedures. Proponents of mandibular surgery report that rigid fixation has helped to improve the predictability and stability of anterior openbite correction and they feel that the mandibular approach does afford some advantages. For example, mandibular surgery avoids any negative soft tissue changes in the midface that sometimes accompany maxillary sur- gery. It also allows for vertical and Class Il correction with surgery in only the lower jaw. These are both significant advantages and this technique is gaining traction in the northwest portion of the U.S. There are a few articles that discuss stability of treatment, the largest of which indi- 22 Huang cates that 90% of patients who presented with mild to moderate openbites were stable 4.5 years after treatment (Fontes et al., 2012). This is impressive and certainly not worse than maxillary impaction surgery, with reported Stability in the 80-85% range (Greenlee et al., 2011); however, more studies are warranted, especially with patients who have moderate to severe openbites. It was mentioned earlier that aligners and TADs are thought to correct openbites by intruding molars and allowing auto-rotation. This mechanism of correction also is shared with maxillary impaction Surgery, although the intrusion is accomplished surgically, rather than orthodon- tically. In all three of these techniques, we would expect a decrease in the mandibular plane angle. Mandibular surgery also decreases the man- dibular plane angle, but it is accomplished by rotating the distal fragment of the mandible during surgery, rather than by intruding molars. This may be a significant difference, as the upper molar vertical position is not changed with this technique, thereby minimizing any tendency for the molar to erupt post-treatment. This, in turn, might lead to less vertical relapse, or at least less relapse due to molar eruption post-treatment. These newer techniques seem promising, and aligners and TADs have expanded the realm of openbite patients that might be treated with orthodontics only. Surgery is costly, invasive and associated with inherent risks; more conservative options should be welcomed if the results are fairly equal. We should assess the predictability of these techniques carefully, however, along with their mechanism of action and long-term stability. Likewise, mandibular surgery, rather than maxillary surgery, seems to offer advantages to openbite correction. Again, if the treatment results are good and stability is similar to maxillary surgery, we should present this as a viable option for our adult anterior openbite patients to consider. CONCLUSIONS As with crib therapy, the literature on the efficacy of anterior openbite correction with most newer treatment strategies tends to consist of lower level studies. Until better evidence is generated, we must be familiar with the existing literature and use the best information available when discussing treatment options with our openbite patients. 23 Anterior Openbite A recent initiative in the U.S. to conduct a national network study on ante- rior openbite treatment and stability in adults should help provide better information to the specialty. Because openbites are a relatively rare mal- occlusion, these types of network studies have the advantages of accumu- lating patients from many practitioners in a reasonable period of time and having good generalizability. We need rigorously conducted long-term as- sessments of treatments in all age groups to better identify the most ef- fective and stable treatment modalities for our openbite patients. REFERENCES Baek MS, Choi Y1, Yu HS, Lee KJ, Kwak J, Park YC. Long-term stability of an- terior open-bite treatment by intrusion of maxillary posterior teeth. Am J Orthod Dentofacial Orthop 2010;138(4):396.e1-eg. Boyd RL, Miller RJ, Vlaskalic V. The Invisalign system in adult orthodon- tics: Mild crowding and space closure cases. J Clin Ortho 2000;34(4): 203-212. Cozza P, Baccetti T, Franchi L, Mucedero M. Comparison of 2 early treat- ment protocols for open-bite malocclusions. Am J Orthod Dentofacial Orthop 2007;132(6):743-747. Feres MF, Abreu LG, Insabralde NM, de Almeida MR, Flores-Mir C. Ef- fectiveness of open bite correction when managing deleterious oral habits in growing children and adolescents: A Systematic review and meta-analysis. Eur J Orthod 2017;39(1):31-42. Fontes AM, Joondeph DR, Bloomquist DS, Greenlee GM, Wallen TR, Huang GJ. Long-term stability of anterior open-bite closure with bi- lateral sagittal split osteotomy. Am J Orthod Dentofacial Orthop 2012;142(6):792-800. Giuntini V, Franchi L, Baccetti T, Mucedero M, Cozza P. Dentoskeletal changes associated with fixed and removable appliances with a crib in open-bite patients in the mixed dentition. Am J Orthod Dentofacial Orthop 2008;133(1):77-80. Greenlee GM, Huang GJ, Chen SS, Chen J, Koepsell T, Hujoel P. Stability of treatment for anterior open-bite malocclusion: A meta-analysis. Am J Orthod Dentofacial Orthop 2011;139(2):154-169. Huang GJ, Justus R, Kennedy DB, Kokich VG. Stability of anterior openbite treated with crib therapy. Angle Orthod 1990;60(1):17-24. 24 Huang Jolley CJ, Huang GJ, Greenlee GM, Spiekerman C, Kiyak HA, King GJ. Den- tal effects of interceptive orthodontic treatment in a Medicaid popu- lation: Interim results from a randomized clinical trial. Am J Orthod Dentofacial Orthop 2010;137(3):324–333. Khosravi R, Cohanim R, Hujoel P. Daher S, Neal M, Liu W, Huang G. Man- agement of overbite with the Invisalign” appliance. Am J Orthod Den- tofacial Orthop 2017;151(4):in press. Lee HA, Park YC. Treatment and posttreatment changes following intru- sion of maxillary posterior teeth with miniscrew implants for open bite correction. Korean J Orthod 2008;38(1):31-40. Leite JS, Matiussi LB, Salem AC, Provenzano MG, Ramos AL. Effects of pal- atal crib and bonded spurs in early treatment of anterior open bite: A prospective randomized clinical study. Angle Orthod 2015;86(5):734– 739. Lentini-Oliveira DA, Carvalho FR, Rodrigues CG, Ye O, Prado LB, Prado GF, HU R. Orthodontic and orthopaedic treatment for anterior open bite in children. Cochrane Database Syst Rev 2014 Sep 24;(9):CD005515. Pedrin F, Almeida MR, Almeida RR, Almeida-Pedrin RR, Torres F. A pro- spective study of the treatment effects of a removable appliance with palatal crib combined with high-pull chincup therapy in anterior open- bite patients. Am J Orthod Dentofacial Orthop 2006;129(3):418-423. Proffit WR, Fields HW Jr, Moray LJ. Prevalence of malocclusion and orth- odontic treatment need in the United States: Estimates from the NHANES III survey. Int J Adult Orthodon Orthog Surg 1998;131(2):97- 106. Scheffler NR, Proffit WR, Phillips C. Outcomes and stability in patients with anterior open bite and long anterior face height treated with temporary anchorage devices and a maxillary intrusion splint. Am J Orthod Dentofacial Orthop 2014;146(5):594-602. Sugawara J, Baik UB, Umemori M., Takahashi I, Nagasaka H, Kawamura H, Mitani H. Treatment and posttreatment dentoalveolar changes fol- lowing intrusion of mandibular molars with application of a skeletal anchorage system (SAS) for open bite correction. Int J Adult Orthodon Orthognath Surg 2002;17(4):243-253. 25 Anterior Openbite Torres F, Almeida RR, de Almeida MR, Almeida-Pedrin RR, Pedrin F, Hen- riques JF. Anterior open bite treated with a palatal crib and high- pull chin cup therapy: A prospective randomized study. Eur J Orthod 2006;28(6):610–617. Worms FW, Meskin LH, Isaacson RJ. Open-bite. Am J Orthod 1971; 59(6):589-595. 26 TREATMENT OF CLASS III MALOCCLUSIONS WITH TSADS: IS IT WORTH THE BURDENP Peter Ngan, Nick Maddux, Dobin Choi, Timothy Tremont ABSTRACT Protraction facemask has been used in the treatment of Class Ill malocclusions with maxillary deficiency. However, side effects have been reported with the use of tooth-borne anchorage devices including excessive proclination of the maxil- lary incisors and extrusion of the maxillary molars. Such side effects may be use- ful in treatment of patients with a hypodivergent growth pattern with excessive spacing. In addition, the use of temporary skeletal anchorage devices (TSADs) such as implants, on plants, mini-implants or mini-plates can provide additional anchorage for protraction of posterior teeth. The palate is an excellent area for placement of mini-implants rather than the inter-radicular area. The fixture is placed on denser cortical bone and there are no adjacent tooth structures. The present case report illustrates the use of mini-implants as skeletal anchorage for mesialization of the maxillary and mandibular posterior teeth and skeletal protraction of the maxilla. Skeletal, dental and facial changes in response to or- thopedic and orthodontic treatment are reported to illustrate the esthetic, func- tional and stability advantages of this treatment modality. KEY WORDS: Class III malocclusion, skeletal anchorage, miniscrews, hypodiver- gent, excess Spacing INTRODUCTION Maxillary protraction has been used in the treatment of Class Ill malocclusions with maxillary deficiency in growing patients (Ngan et al., 1998; Kim et al., 1999; Hägg et al., 2003; Turley, 2007). The use of face- mask for maxillary protraction has several shortcomings including exces- sive proclination of maxillary incisors, extrusion of maxillary molars and clockwise rotation of the mandible (Westwood et al., 2003; Mandall et al., 2010); however, these side effects may be useful in treating patients 27 Treatment of Malocclusions with TSADS with hypodivergent growth patterns and excessive spacing. The use of temporary skeletal anchorage devices (TSADs) such as osseointegrated titanium implants (Singer et al., 2000), onplants (Hong et al., 2005), ti- tanium mini-implants (Feng et al., 2012) and mini-plates (Baek et al., 2011; Cha et al., 2011; Kaya et al., 2011) can increase the anchorage value for protraction of posterior teeth. Several studies have examined the suitability of using the palate as a skeletal anchorage site other than the inter-radicular areas (Han et al., 2012; Lee et al., 2012; Ryu et al., 2012). Kook and colleagues (2010, 2015) placed palatal plates for mo- lar distalization in adolescents with almost no side effects on the palatal soft tissue. Nienkemper and colleagues (2012, 2013) reported that use of miniscrews with diameters of 2 to 2.3 mm and lengths of 9 to 11 mm has been associated with higher survival rates and stability. Success rates can be increased further by coupling two mini-implants (Liou, 2005). This design has many applications including protraction of a maxilla, mesial- ization and distalization of maxillary posterior teeth. The present case report illustrates the use of skeletal anchorage in the treatment of a Class Ill patient with a hypodivergent growth pattern and excessive spacing in both the maxillary and mandibular arches using the hybrid hyrax device and TSADs as anchorage. Skeletal, dental and facial changes in response to orthopedic and orthodontic treatment are reported to illustrate the esthetic, functional and stability advantages of this treatment modality. DIAGNOSIS An eleven-year, nine-month-old girl presented with a skeletal Class Ill malocclusion and a concave facial profile due to a combination of a retruded maxilla and protruded mandible. Intra-oral examination re- vealed an anterior crossbite, Class Ill molar relationship, a narrow maxilla and a 3 mm anterior shift of the mandible on closure (Figs. 1 and 2). Intra- oral photographs also were taken in centric relation to show the centric occlusion/maximum intercuspation discrepancy (Figs. 3 and 4). A lateral cephalometric radiograph was taken in centric relation and corrected for anteroposterior and vertical measurements without a functional shift (Fig. 5). Cephalometric analysis (Table 1) showed an ANB angle of -2.7°, a Wits appraisal of -6.8 mm and a deficient maxillary length (Condylion to ANS = 82.3 mm). Vertically, the patient presented with a hypodivergent growth pattern with a decrease in lower face height (ANS-Me = 53.8 mm) and mandibular plane angle (FMA = 18.4°). Dentally, the incisors were 28 Ngan et al. compensated due to the skeletal pattern. The maxillary incisors to Frank- fort plane (U1-FH) was 120.1° and the mandibular incisors to mandibular plane (IMPA) was 82.6°. The upper lip to E-plane was -6.9 mm and the lower lip to E-plane was –3.9 mm. There was no familial history of Class ||| malocclusions. Treatment Objectives Based on the above diagnosis, the treatment objectives were to reduce the skeletal discrepancy, correct the reverse overjet, establish a functional occlusion and improve facial esthetics. Treatment Alternatives The alternative treatment plan was to wait for completion of growth and to correct the skeletal and dental discrepancies with compre- hensive orthodontic treatment together with orthognathic surgery. Figure 1. Pre-treatment facial and intra-oral photographs in maximum inter- CuSpation. 29 Treatment of Malocclusions with TSADS Figure 4. Pre-treatment models in centric occlusion. Tredtment Plan The treatment plan for this patient included protraction of the maxilla, comprehensive orthodontic treatment with fixed appliance and use of TSADS as anchorage for mesialization of maxillary and mandibular posterior teeth. Considering patient age and the patency of the circum- maxillary sutures, the patient was informed that the maxilla can be pro- tracted without using TSAD as anchorage. However, excessive spacing in 30 Ngan et al. Figure 5. Pre-treatment radiographs. A. Lateral cephalogram. B: Panoramic radiograph. Table 1. Cephalometric values. Norm rejent ºn: Difference ANB (*) 2 –2.7 1.7 1.0 SNA (*) - 82 84.3 86.5 2.2 SNB (*) 80 87.1 88.3 1.2 Wits appraisal (mm) O –6.8 –6.5 0.3 Condylion to ANS (mm) 90 82.3 87.4 5.1 Mand plane to SN 32 24.1 23.0 1.1 FMA (MP-FH) 25 18.4 18.6 0.2 Upper face height (N-NS) (mm) 50 47.9 51.4 3.5 Lower face height (ANS-Me) (mm) 65 53.8 53.0 0.8 LFH/TFH (ANS-Me:N-Me) (%) 55 52.9 51.2 1.7 Anterior cranial base (SN) (mm) 73 66.3 68.7 2.4 Mand body length (Go-Me) (mm) 71 68.1 74.7 6.6 PT-H/AFH (%) 65 72.3 7.2.1 0.2 U1-NA (*) 22 30.0 24.5 5.5 U1-Palatal plane (*) 110 122.1 118.5 3.6 U1-FH (*) 111 120.1 122.4 2.3 IMPA (L1-MP) (*) 95 82.6 87.2 4.6 L1-NB (*) 25 13.8 18.4 4.6 Upper lip to E-plane (mm) –4 –6.9 —5.3 1.6 Lower lip to E-plane (mm) –2 –3.9 –3.2 0.7 both the maxillary and mandibular arches would require a skeletal an- Chorage device to mesialize the posterior teeth and avoid unwanted inci- Sor retraction. The patient consented to the placement of mini-implants 31 Treatment of Malocclusions with TSADS in both the palate and inter-radicular bone between the mandibular ca- nines and first premolars as skeletal anchorage for space closure. Treatment Progress and Results A Hyrax rapid palatal expansion appliance was constructed by placing bands on the maxillary premolars and first molars. These bands were joined by a heavy wire (0.043") to the palatal plate, which had a jackscrew in the midline. A maxillary expansion and constriction protocol was used to distract the maxillary sutures in order to facilitate forward movement of the maxilla (Liou, 2005). The appliance was activated four times daily (0.25 mm/turn) by the patient for one week. After one week of activation, the jackscrew was deactivated for constriction of the max- illa at the same rate. This process was repeated for seven weeks. Maxil- lary protraction was started after completion of maxillary expansion and constriction protocol with a force of 450 g (300 cm) to each side applied twelve to fourteen hours per day. At the same time, a 2x4 appliance was inserted in the mandibular arch for the patient to wear Class III elastics (6 oz/side) for eight hours per day. After six months of protraction therapy, the anterior crossbite was overcorrected to 2 to 3 mm of overjet and there was an improve- ment in facial esthetics and the occlusion (Fig. 6). The functional forward shift of the mandible was eliminated. Spacing was increased in the upper arch due to maxillary skeletal expansion. A decision was made to place two miniscrews in the midline of the palate connected by a BENEplate (psm Medical Solution, Tuttlingen, Germany) to serve as skeletal anchor- age for protraction of the maxillary posterior teeth (Wilmes et al., 2009). Two miniscrews were placed between the mandibular canines and first premolars inter-radicularly to protract the mandibular posterior teeth (Fig. 7). Comprehensive orthodontic treatment with fixed appliances was started. A button was bonded on the lingual of the mandibular first pre- molars together with elastic chain to help protract mandibular posterior teeth in a more bodily fashion. After eighteen months of treatment, all spaces were closed. The overbite and overjet were improved and the mid- lines were coincident (Figs. 8 and 9). Analysis of the post-treatment ceph- alometric radiograph (Fig. 10, Table 1) showed forward movement of the maxilla and mandible attributed to growth with minimal improvement of the skeletal base discrepancy (ANB from -2.7 to -1.7° and Wits appraisal from -6.8 to -6.5 mm). The mandibular plane angle remained the same 32 Ngan et al. Figure 6. Intra-oral photographs showing maxillary expansion and the protract- ion device to correct the anterior crossbite. Figure 7. A-C. E. Miniscrews placed between mandibular canines and first pre- molars as anchorage for protracting mandibular molars. D: Intra-oral photograph showing two miniscrews placed on the palate connected to the maxillary incisors as anchorage for protracting maxillary molars. after maxillary protraction. The maxillary incisors were retracted from 30° to 24.5° (U1-NA) and the mandibular incisors improved from an IMPA of 82.6° to 87.2°. Facial esthetics was improved with upper lip to E line in- Creasing from -6.9 to -5.3 mm and the lower lip changing from -3.9 to -3.2 mm. Superimposition of the pre- and post-facemask treatment radio- graphs showed harmonious parallel forward and downward growth of the 33 Treatment of Malocclusions with TSADs Figure 9. Post-treatment models. maxilla and mandible. Both the maxillary and mandibular molars were protracted as a part of the treatment plan without compromising the in- cisors (Fig. 11). 34 Ngan et al. Figure 10. Post-treatment radiographs. A. Lateral cephalogram. B: Panoramic ra- diograph. Figure 11. Initial (black) and final (green) cephalometric tracings are super- imposed on the anterior cranial base (A), skeletal structures of the maxilla ANS- PNS (B) and the lingual symphysis of the mandible (C). DISCUSSION The success of orthodontic treatment in patients with a develop- ing Class Ill malocclusion depends on individual growth and timing of or- thopedic intervention. In childhood or early mixed dentition, sutural ex- pansion can be accomplished with almost any type of expansion device. 35 Treatment of Malocclusions with TSADS By early adolescence or early permanent dentition, interdigitation of spicules in the circummaxillary suture has reached the point that a jack- screw with considerable force is required to create micro-fractures be- fore the suture can open. By the late teens or after puberty, interdigita- tion and areas of bony bridging across the suture develop to the point that skeletal maxillary expansion or protraction becomes impossible us- ing only a tooth-borne anchorage device (Sar et al., 2011). A combination of maxillary expansion and protraction has been advocated to distract the maxillary sutures in young Class Ill patients to facilitate the forward movement of the maxilla (Ngan et al., 1998; Kim et al., 1999; Hägg et al., 2003; Turley, 2007). Facemask protraction is a type of sutural protraction osteogenesis of the circummaxillary sutures (Liou, 2005). It is assumed that rapid maxillary expansion disarticulates the circummaxillary sutures so that facemask protraction can be more productive; however, the aver- age forward movement of the maxilla using this technique is only 1.5 to 3.0 mm (Ngan et al., 1998; Kim et al., 1999; Hägg et al., 2003; Westwood et al., 2003; Turley, 2007; Mandall et al., 2010). Liou (2005) proposed a protocol of weekly alternate rapid maxillary expansion and constriction (Alt-RAMEC) to disarticulate the maxilla without over-expanding the max- illa. Yen (2011) reported success in using this technique to treat a group of Class Ill patients with cleft lip and palate supplementing the facemask with daily use of Class Ill elastics to keep the sutures distracted when patient is not wearing the facemask. In the present case, the anterior crossbite was overcorrected to 2 to 3 mm of overjet using this technique. This was performed in anticipation of a disproportionate growth differ- ence between the maxilla and the mandible. The use of TSADs can increase anchorage for mesialization of posterior teeth. From a biomechanical standpoint, miniscrews allow more bodily tooth movement during space closure by placing the force vectors closer to the center of resistance of the teeth. The sites most often utilized for TSAD insertion in the maxilla include the buccal or lin- gual inter-radicular spaces, extraction space or the inferior surface of the anterior nasal spine (Poggioa et al., 2006). Several studies have examined the suitability of using the palate as a skeletal anchorage site other than the inter-radicular areas (Han et al., 2012; Lee et al., 2012; Ryu et al., 2012). Kook and colleagues (2010, 2015) placed palatal plates for molar distalization in adolescents with almost no side effects on the palatal soft tissue. Nienkemper and associates (2012, 2013) reported use of mini- 36 Ngan et al. screws with diameters of 2.0 to 2.3 mm and lengths of 9 to 11 mm have been associated with higher survival rates and stability. Success rates can be increased further by coupling two mini-implants. This design has many applications including protraction of the maxilla and mesialization and distalization of maxillary posterior teeth. In the present case, the incisors were connected to two miniscrews in the palate to serve as anchorage for protraction of the maxillary posterior teeth. To avoid the side effects of rotation and extrusion during forward movement of the maxillary pos- terior teeth, a transpalatal bar was soldered to the maxillary first molars and elastic chains were used to connect the lingual surface of the maxil- lary first molars to the plate of the miniscrews. In the mandible, the most common miniscrew placement sites are buccal or lingual inter-radicular spaces, lateral to the symphysis men- talis or extraction spaces (Poggioa et al., 2006). The most useful locations are the inter-radicular spaces, either buccal or lingual, between the sec- ond premolars and first molars in both arches. In the present case, space was opened up between the mandibular canines and first premolars for placement of miniscrews. Buttons also were placed on the lingual surfac- es of the first premolars for simultaneous protraction of the mandibular posterior molars on both the buccal and lingual sides. The clinical use of miniscrew anchorage is associated with some risks and complications, which occur during screw insertion, under orth- odontic loading and during removal (Kravitz and Kusnoto, 2007). Screw fracture during insertion or removal might be one of the most undesir- able side effects in the clinical use of miniscrew anchorage (Suzuki and Suzuki, 2011). A recent systematic review showed that the overall success rate of 4,987 miniscrews in 2,281 patients was 86.5% (Papageorgiou et al., 2012). A lot of factors are explored and suspected to be associated with the screw failure. Damages to soft tissues are temporary in most cases, but damages to hard tissues are irreversible; therefore, care must be taken to avoid damage to the periodontal tissues. Furthermore, pain and discomfort after miniscrew placement also are a concern with orth- odontic tooth movement using TSAD as anchorage. CONCLUSIONS The use of TSAD such as miniscrew anchorage has expanded the limit of clinical orthodontics greatly. It minimizes the need for patient 37 Treatment of Malocclusions with TSADS compliance and provides relative stationary anchorage for tooth move- ments in various directions which have been impossible with traditional orthodontic mechanics. The present case illustrates the use of TSADs for protraction of posterior teeth in both the maxillary and mandibular arches in a Class Ill patient with hypodivergent growth and excess spac- ing. Mesialization of maxillary and mandibular posterior teeth was ac- complished without compromising the position of the incisors and facial esthetics. REFERENCES Baek SH, Yang IH, Kim KW, Ahn H.W. Treatment of Class Ill malocclusions using miniplate and mini-implant anchorage. 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Semin Orthod 2011;17(2): 138-148. 40 SUTURAL LOADING DURING BONE-ANCHORED MAXILLARY PROTRACTION Ayman Al Dayeh ABSTRACT Bone-anchored maxillary protraction (BAMP) is an emerging orthopedic treatment modality to address midface deficiency. It includes fixing surgical miniplates into the maxilla and mandible and running intermaxillary elastics between them. It is believed that the forces generated by BAMP therapy cause greater circummaxillary sutural separation, more bone growth and better protraction compared to traditional reverse pull headgear (RPHG) treatment. Despite the increasing popularity of BAMP, its effects at the tissue level still largely are unknown. This can be attributed partially to lack of an appropriate animal model to study BAMP. The purpose of this study was to evaluate the use of minipigs as an animal model for BAMP and measure deformation and growth of circummaxillary sutures during BAMP Results presented are preliminary, based on three six-month-old mini-pigs. BAMP miniplates were placed surgically, similar to that in human subjects, and protraction forces were applied. Fluorescent bone labels were injected before and after protraction. During terminal surgery, displacement sensors were installed across the zygomatico-maxillary and naso- frontal sutures to measure their deformation during BAMP. After sacrifice, tissues were harvested and analyzed to determine effects of BAMP on mineral apposition and osteoblast differentiation. Our results indicate that minipigs can serve as a suitable animal model for BAMP No post-operative complications were noticed. Preliminary findings suggest that the zygomatico-maxillary and naso- frontal sutures are tensed highly during BAMP. Opening and closing of the mouth introduced an oscillatory component to sutural loading. BAMP also resulted in increased mineral apposition and osteoblast differentiation at the sutures. KEY WORDS: protraction, BAMP, zygomatico-maxillary, suture deformation, mid- facial deficiency 41 Sutural Loading INTRODUCTION For decades, the reverse pull headgear (RPHG) has been the most commonly used maxillary protraction device. It works by applying a posterior-to-anterior traction force on the maxilla using maxillary teeth as the point-of-force application (Nanda, 1980; Delaire, 1997). As the maxilla is protracted, circummaxillary sutures are separated and bone formation along sutural edges is stimulated (Kambara, 1977; Nanda and Hickory, 1984), resulting in improved anteroposterior maxillary growth (Ngan et al., 1998; Toffol et al., 2008; Yavuz et al., 2009). Although the RPHG treatment generally is effective, it is associated with several disad- vantages such as unwanted dental movements (Yavuz et al., 2009) and high rates of relapse (Hägg et al., 2003; Masucci et al., 2011; Seehra et al., 2012). Generally, it is recommended to start the RPHGs in the early stages of mixed dentition (Baccetti et al., 1998), as circummaxillary su- tures still are patent and better skeletal improvements can be achieved. This narrow time interval for intervention further limits the application of RPHG. Optimizing the outcome of orthopedic protraction is of great importance to the patients, especially when considering that other treat- ment alternatives are associated with several disadvantages. In order to overcome unwanted dental movements and op- timize the orthopedic outcome of RPHG, Kokich and associates (1985) suggested applying the protraction force using Skeletal units as a point- of-force application instead of teeth with positive results reported. Suc- cessful application of extra-oral traction to miniplates implanted in the zygomatic buttress (Cha et al., 2011) and the lateral nasal walls also has been reported (Kircelli et al., 2006). Another drawback of using extra- oral traction is its reliance on patient compliance, especially with the esthetically objectionable appearance of the extra-oral traction device. To overcome these problems, De Clerck and colleagues (2009) recom- mended the use of bone-anchored maxillary protraction (BAMP). It con- sists of fixing surgical miniplates into the infrazygomatic crest anterior to the zygomatico-maxillary suture (ZMS) and into the body of the mandible apical to the canines. The patient is instructed to attach intermaxillary elastics between the two plates. It is believed that the force from the elastics causes sutural separation, leading to stimulation of bone for- mation along sutural edges. Preliminary studies (De Clerk et al., 2009, 42 Al Dayeh 2010, 2012; Heymann et al., 2010; Nguyen et al., 2011) suggest favorable changes, which are better than traditional RPHG (Cevidanes et al., 2010; Hino et al., 2013). However, most of these results come from case-report and case-control studies using the same cohort of patients. The mechanism of action of BAMP at the tissue level still is un- derstood poorly. Although it is believed that BAMP causes better circum- maxillary suture separation and sutural growth compared to RPHG, this has not been investigated or validated. The optimal loading force mag- nitude in BAMP also has not been studied. The current practice is to use force levels between 100-250 gram force (g.f; De Clerk et al., 2009). How- ever, these numbers are rudimentary and there is no scientific evidence to support or challenge them. The poor understanding of the biologic effects of BAMP can be attributed to lack of an appropriate animal model to study this modal- ity of treatment. To date, only one animal study investigated the effects of BAMP at the tissue level (to et al., 2014). In their study, they applied BAMP for 60 days to five three-month-old dogs and used lateral cepha- lograms and fluorescent bone labels to assess BAMP effects on maxillary protraction. The results indicate that BAMP promotes anteroposterior maxillary growth and increases mineral apposition at the ZMS. Although this pioneering study offered insights into the biological effects of BAMP, it suffered several limitations. Dogs are characterized by faster bone for- mation relative to humans (Pearce et al., 2007; Štembírek et al., 2012). Animals used were three months old, which probably is too young to ap- proximate BAMP application in patients. Using dogs as an animal model for BAMP is complicated further by the sparse knowledge about the phys- iologic mechanical loading of craniofacial sutures in this species. Most importantly, Ito and coworker's study (2014) did not investigate the pat- tern and magnitude of sutural loading during BAMP. Characterizing the relation between mechanical loading and sutural growth is of great clini- cal relevance as it will help to determine the ideal BAMP loading force magnitude and pattern that will result in optimal treatment outcome. Thus, the main goals of this study are to develop an animal model for BAMP and to collect preliminary data regarding: 1. Deformation of zygomatico-maxillary (ZM) and naso- frontal (NF) sutures during BAMP; 43 Sutural Loading 2. Mineral apposition at the ZM and NF sutures during BAMP; and 3. Effects of BAMP on cellular proliferation and osteo- blast differentiation at ZM and NF sutures. The current study is pilot in nature and preliminary data from three ani- mals is reported in this manuscript. MATERIALS AND METHODS Animal Model and Justification Female Hanford minipigs (sus scrofa) were the animals of choice. Animals were around six months old, which corresponds to growing, skeletally immature human subjects, the usual candidates for BAMP. All procedures were approved by the Institutional Animal Care and Use Committee (IACUC) at University of Tennessee Health Science Center (UTHSC). Minipigs were chosen because of their appropriate size to ac- commodate placement of miniplates and sensors. Although the midface in pigs is more prominent than in humans, the overall arrangement of the maxilla and masticatory system is similar (Herring, 1976; Ström et al., 1986). In particular, the arrangement of circummaxillary sutures relative to the occlusal plane—a critical factor in maxillary protraction—is similar to that in humans (Fig. 1). Furthermore, data from the breeder (Sinclair BioFesources, MO; Fig. 2) and our study on minipig dry skulls (Al Dayeh and Herring, 2014) suggest that the growth of the midface in minipigs is constant relatively between one and eight months with no gender differ- ence, thus rendering minipigs a suitable animal model for investigating the BAMP therapy, while minimizing the confounding effects of growth burst and gender differences. Furthermore, rates of bone turnover and growth in minipigs is similar to that in humans (Štembírek et al., 2012), thus giving better approximation to growth than a dog model. Most im- portantly, an extensive body of knowledge exists on the functional de- formation and growth of sutures in minipigs (Rafferty and Herring, 1999, 2003; Herring et al., 2001; Sun et al., 2004; Herring, 2008; Al Dayeh et al., 2009), thus helping to validate the functionality of sensors used and relate findings of this study to overall skull biomechanics and growth. 44 Al Dayeh Figure 1. A. Lateral view of a five-year-old human skull. B: Lat- eral view of a seven-month-old minipig skull. Both illustrate the similar position of the ZMS (dotted black line) relative to the occlusal plane. Technical Aspects of Sutural Deformation Sensors Two types of sensors will be used to measure the deformation of the ZM and NF sutures during BAMP strain gauges (SG) and differential Variable reluctance transducer (DVRT, Fig. 3). Below is a brief description of each. 45 Sutural Loading Overall growth of Hanford minipigs 140 120 -Nose length (males) --Nose length (females) 100 5 -Head length = 80 (males) * -Head length º (females) sº ---Height (males) £ 60 B ---Height (females) : 40 20 - 2 4. 6 8 10 12 0. 14 Animal age (months) Figure 2. Scatterplot based on data provided by the breeder of the minipigs used in this study (cross-sectional) illustrating the change in nose length, head length and height in this strain of minipigs between one and twelve months of age. The growth was relatively steady with a short, slow growth period between the age of four and five months. There is no difference in growth rates between genders. Strain Gauge. In this study, foil SG (Vishay Micro-Measurements, Raleigh, NC) were used (Fig. 3A). They are comprised of a metallic wire bonded to a carrier matrix that is glued across sutures. Deformation of the underlying suture changes the resistivity of the wire. This change rep- resents the strain of the suture. Since the gauges are glued directly to the bone across the sutures, they provide an accurate measurement of the loading of the sutures with high resolution (0.1 pm). However, they have a limited range (~ 3,000 us). Differential Variable Reluctance Transducer (DVRT). The DVRT is a linear displacement transducer that is comprised of two parts, a rod and a coiled core, each fixed to the bone on each side of the suture using screws (Fig. 3B). The rod is free to slide within the core and its position is detected by measuring the coil's differential reluctance. This method pro- vides a relatively sensitive measure of rod movement (+1 um). Although 46 Al Dayeh Figure 3. Sensors used in the study. A: Picture of single element strain gauge, illustrating the resistor (zigzag wire) on a carrier matrix. Deformation of the su- ture will result in flexing the foil, the wire length will change and its resistivity is altered. This change is read by pre-calibrated software and the amount of de- formation is calculated accurately. B: Differential variable reluctance transducer (DVRT) is comprised of two parts: a rod and a core. The attachment screws are placed in bones across the sutural edges. Deformation of the suture will result in the rod sliding in (in compression) or out of the core (in tension). The core houses a coil such that sliding the rod in and out of the core will result in change in the core differential reluctance, enabling accurate calculation of the amount of movement of the core up to a resolution of +1 um. DVRT are less sensitive than SG (Al Dayeh et al., 2009), they are suited better to large magnitude of deformation. Animal Surgical Procedures Animals were housed at the animal facility at UTHSC and fed a regular pig diet. Seven days before the initial surgery, animals were se- dated with an intra-muscular injection of Telazol (6-8 mg/Kg), mask-anes- thetized with isoflurane (2-3%), then injected intravenously using 0.22 Millex-GP syringe (EMD Millipore, MA) with the first bone label calcein 47 Sutural Loading (Sigma, St. Louis, MO) prepared according to the manufacturer specifica- tions (12.5mg/Kg calcein dissolved in sterile 0.9% saline). Initial Surgery. On the day of the initial surgery, pigs were sedat- ed, mask-anesthetized then intubated. In one animal, two mucoperios- teal flaps were reflected to access the site of miniplate installation while in the other, two self-tapping, self-drilling miniscrews (Vector, Ormco, CA) were used. On each side, a miniplate (Synthes, West Chester, PA) was fixed to the zygomatic buttress 0.5 to 1.0 cm anterior to the ZM su- ture. A second plate was fixed to the body of the mandible apical to the root apex of the first premolar (Fig. 4). Two screws were used per each plate. The extensions of the plates were around the level of the muco- gingival junction. In each animal, ~2.0 N protraction force verified by a force gauge was applied on one side, while the other side acted as sham control (plates with no protraction force). In one animal, a custom-made nickel-titanium (NiTi) spring was used to generate the protraction force, while in the other two animals, latex-free orthodontic elastics were used. Immediately after surgery, animals were injected intravenously with the second bone label alizarin complexone (Sigma; 12.5mg/Kg alizarin dis- solved in sterile 0.9% saline) using a 0.22 Millex-GP syringe (EMD Mil- lipore, MA). Animals were monitored daily for signs of discomfort and for stability of plates and elastics. Animals were given oral Tylenol (10 mg/Kg, BID) and Cephalexin (10-15 mg/Kg; BID) during the entire post-operative time. Every other day, the animals were sedated and anesthetized and the elastics were replaced with new ones adjusted to release the same level of force. Seven days after initial surgery, the animals were anesthe- tized and a tertiary bone label (Calcein, Sigma) was injected as before. Two weeks after initial surgery, the animals were sacrificed. Terminal Surgery and Tissue Harvest. Pigs were sedated, mask- anesthetized and intubated as before. Miniplates were inspected for sta- bility. If the miniplates were unstable, they were replaced following the same steps used in the initial surgery. Two 2 cm incisions were made to expose the ZM and NF sutures. Bone on both sides of the suture was degreased and cleaned, dried and prepared (M-Bond 200 catalyst, Vishay Micro-Measurements, Raleigh, NC). A small piece of Teflon was placed on the suture before gluing of the SG to prevent the glue for leaking into the suture. Three single element SG (CEA-13-250UW-350/P2, Vishay) then were glued (M-Bond 200, Vishay) across the NF and dorsal part of ZM 48 Al Dayeh Figure 4. Lateral view of a seven-month-old Hanford minipig skull illustrating the position of BAMP miniplates and the relation of the protraction force to the oc- Clusal plane. A DVRT and a SG are placed across the ZM suture (marked with a lead pencil for visibility) only during the terminal surgery. Sutures. A hole was drilled on both sides of ZM and NF sutures and three DVRTS were installed, one per suture (Fig. 5). The length between the DVRT fixation screws was measured. DVRT wires were connected to a sig- nal demodulator (DEMOD-DC2, LORD Microstrain Inc., Williston, VT) and together with the SG, lead wires were connected to a wireless transmitter (V-link, LORD Microstrain Inc.). SG and DVRT signals were telemetered to a nearby computer operating Node Commander software and a USB base Station (LORD Microstrain Inc.). Elastics with variable force levels (150, 200, 300, 400 and 600 g.f) were attached to the miniplates while the deformation of the ZM and NF sutures was recorded. The mouth of the anesthetized animal then was manipulated: opened and closed to Stimulate chewing, while the deformation of the sutures was measured and recorded. The animals then were sacrificed by a lethal dose of Euthasol. The ZM and NF sutures were isolated using a bone saw and fixed in a glyoxal-based fixative (Prefer", Anatech LTD, Battle Creek, MI) for approx- imately ten days. Bone specimens were stored in a dark place to prevent fluorescent bone label from decaying. 49 Sutural Loading Figure 5. A. Lateral view of a seven-month-old Hanford minipig skull displaying the position of the DVRT (ventral) and SG (dorsal) across the ZM suture (marked with lead pencil for ease of visibility). The DVRT and SG were used only during the terminal surgery. B: Dorsal view of the same skull illustrating the position of the DVRT and SG across the NF suture (marked with lead pencil). Only one SG was used, either left or right depending on surgical accessibility. The DVRT and SG were used only during the terminal surgery. Tissue Processing and Slide Preparation ZMS specimens were cut in half along the anteroposterior direc- tion: the inferior half was left undecalcified while the superior half was decalcified in formic acid/sodium formate (18 ml of formic acid, 82 ml dis- tilled water, 3.5 g sodium formate) for approximately seven to fourteen days. The NF suture specimens were cut into two lateral and one central part. The lateral parts were left undecalcified while the central parts were decalcified as before. The undecalcified section were plastic-embedded in Methyl Methacrylate based resin (Technovit 9100 New, Heraeus Kulzer GmbH, Germany) following the manufacturer's instructions. The decalci- fied specimens were embedded in paraffin. All sections were cut using an automated rotary microtome. Undecalcified sections were cut at 25 pum and mounted on slides with DPX mounting medium (Fluka, Switzerland). Decalcified paraffin embedded specimens were cut at 6 um. Histological Analysis Undecalcified sections were examined to assess the mineral ap- position rate (MAR) while the decalcified sections were used for HC de- tection of osteocalcin. 50 Al Dayeh MAR. Two slides were used per each ZMS. Slides were examined using Axio Observer Z1 Microscope (Zeiss, Germany) connected to a com- puter running Zen 2012 (blue edition, Zeiss). Images were captured at 10x magnification using the microscope camera (Zeiss). Since calcein flu- oresces green and alizarin red, images of the slide were captured under green and red fluorescent light, and images were combined (Fig. 6). A grid with 500 x 500 pum squares was superimposed over the combined image and mineral apposition was measured as the distance between each of the color bands at the location where gridlines intersect with the sutural surface. MAR before and after BAMP, and at the protraction and control sides, was measured and compared. Immunohistochemistry. Sections were deparaffinized using the xylene substitute Clearene” (Surgipath Medical Industries, Richmond, IL) and then rehydrated using three consecutive washes of 100, 100 and 70% ethanol. Sections then were washed in phosphate buffered saline (PBS). PBS buffer was used to wash between all of the following steps. Endog- enous peroxidases were blocked by incubation with 3% hydrogen perox- ide for 20 minutes. Endogenous biotin, avidin and non-specific binding proteins were blocked by incubation with avidin, biotin and 1% BSA, re- spectively (Vector Labs, Burlingame, CA). Sections then were reacted with osteocalcin antibody (mouse monoclonal, Genetex, Irvine, CA) diluted in buffer at 1:150 for 90 minutes. Negative controls were incubated with isotype antibody. After washing, sections were treated with biotin-con- jugated secondary antibody for 30 minutes (anti-mouse or anti-rabbit, Vector Labs), washed and incubated with avidin-labeled peroxidase (ABC Elite, Vector Labs) for another 30 minutes. Chromogen development was performed by means of the peroxidase substrate diaminobenzidine (DAB; Vector Labs) for 120 seconds and stopped by thorough rinsing with water. Slides then were counterstained by Gill's hematoxylin (Vector Labs). Next, sections were dehydrated and coverslipped. Slides were examined using Axio Observer Z1 Microscope (Zeiss, Germany) connected to a computer running Zen 2012 (blue edition, Zeiss). The microscope is equipped with an automated motorized stage that allow tiling multiple images to produce a bigger overview of the slide. Images were captured at 16x. A 250 x 250 pum Square grid was superim- posed on the image (Fig. 7). Random squares at the sutural edges (yellow Squares in Fig. 7) were selected for cell counting. Osteocalcin-positive and 51 Sutural Loading Figure 6. Image illustrating the steps used in MAR. A and B: Images were captured under green and red fluorescent light, respectively. C. Images were merged. D: Images then were overlayed with the 500 x 500 pum grid. Colors on the final im- age were changed for better contrast. Mineral apposition was measured at the Intersection of the grid line with bone edges. -negative cells inside the bone and at the bone surface were counted separately (Fig. 8). Statistical Analysis Because of the pilot nature of the study and the limited sample size, no statistical analysis was performed. Only descriptive statistics are reported. RESULTS Animal Model Overall, minipigs proved to be a successful animal model of BAMP. The animals tolerated the procedure well with no signs of inflam- mation or infection. Implants were stable throughout the experiment, except in one pig where the maxillary left plate became loose two days before the terminal experiment. Animals responded well to the BAMP treatment as evidenced by increased bone formation and cellular prolif- eration at the suture. 52 Al Dayeh º: "Wºº - º º º º | º º º . | | | | | || º Figure 7. A tiled image of the ZM suture of pig 3 illustrating the zygomatic and maxillary bone and the sutural space. A 250 x 250 pum grid was superimposed on the image. At each sutural edge individual 250 x 250 pum Squares (yellow) were Selected for cell counting and analysis. In order to eliminate bias, for each image, One Square was selected and two were skipped starting from the edge of the Image. loo - º B Figure 8. A: A 16x image displaying osteocalcin-positive cells at the sutural edge and inside the sutural matrix. B: A cropped image showing osteocalcin in the bone proper. 53 Sutural Loading Deformation of the Sutures Since DVRT measures deformation linearly (um) while SG mea- sures deformation in strain (change in length/ initial length), results from the DVRT were converted to pue to allow comparison between the two Sensors, using the following equation: Strain (us)=(deformation recorded by DVRTſum]/DVRT length ſum]) x 10°. Detailed results are presented in Table 1. Positive values indicated tensile strain indicative of separation of the suture. Overall, BAMP resulted in tensile strain at the ZM and NF sutures (NFS). Increasing the magnitude of protraction force resulted in disproportional increase in sutural defor- mation. The effects of BAMP were more pronounced at the ZM compared to NF sutures. Manipulation of the jaw (open and closing) induced an oscillatory component to sutural deformation (Fig. 9). However, the ZMS and NF sutures responded to manipulation in opposite manner. While the ZMS underwent mild additional tension, the NFS underwent severe compression. Histology MAR. High variability in the results was noticed. Overall, mild in- crease in MAR was present at the ZMS during the first week of BAMP (Fig. 10), with the difference becoming more pronounced during the second week. Immunohistochemical Detection of Osteocalcin. Only data from two animals are reported here. BAMP resulted in the expression of os- teocalcin as evidenced by an increased number of osteocalcin-positive cells. No specific location of this cellular increase was noticed, with os- teocalcin-positive cells being present in the bone matrix, at the bone surface and inside the sutural connective tissue. Both BAMP and control sides displayed osteocalcin-positive cells. However, higher numbers were present at the protraction side at all three locations (Table 2). DISCUSSION BAMP is a promising new orthopedic treatment modality for midfacial retrognathia in growing patients. In this study, we present pre- liminary data about using minipigs as an animal model for BAMP and re- port, for the first time, in vivo deformation of one circummaxillary suture 54 i Table 1. Strain recorded at the ZM and NFS during application of various protraction forces alone and during BAMP force application while manipulation (opening and closing) of the mouth. DVRT values were recorded in micrometer. Strain was calculated by dividing the displacement by initial length of the DVRT and multiplying by 106. Negative val- ues indicate compression. Values were rounded to the nearest number. Force unit = gf. Manipulation 150 g.f + 200 g.f + 300 g.f + 400g.f + 600g.f + Site | Sensors alone 150 g.f manipulation 200 g.f manipulation 300 g.f manipulation 400 g.f manipulation 600 g.f manipulation RZMS º 6 + 3 9 + 2 11 + 6 9 + 5 8 + 5 12 + 1 14 + 4 14 + 6 15 + 9 17 £ 4 19 + 3 *" | 281*157 | *** | 523: 343 | ** | 386+274 | ** | 697: 32s 631:350 559: 421 783:269 659:401 (ue) 173 244 108 sG ſue) 287+164 | *** | 4724385 | ** 536+370 | ** | 687:513 | 8644613 || 564:161 | 920; $45 964342 274 270 439 LZMS º 5 + 1 10 + 8 13 + 10 6 + 5 7+ 5 19 + 18 22 + 20 21 + 20 17+ 13 35 + 40 25 + 13 DVRT 491 + 220 it 983 + 1195 + 1940 + (ue) 207: 91 416 622 + 535 140 270 + 222 864 797 it 665 930 865 + 531 2057 1353 + 1121 SG (ue) || 114 + 32 ** | 640:622 | *** | 400: 287 ** | 9343753 777+731 | 825+766 | 895 #797 | 967:798 579 241 767 NFS º 5 + 1 8 + 2 4 + 3 4 + 4 3 + 3 7 + 2 6 + 4 12 + 7 12 + 6 7+ 2 7 + 5 PVRT | 2s2 + 101 429* 2.11 + 98 *** | 153 + 113 ** 292: 181 485 + 134 407: 321 3964 134 252: 121 (ue) 152 143 134 381 + 318 : SG (ue) || -254 + 70 253 111 + 121 120 156 + 103 || 479 + 83 193 + 80 431 + 169 || 201 + 1.70 || 431 + 109 || 193 + 39 § Sutural Loading Manipulation effects on RZMS DVRT and NFSSG (300 gif) 1200 -RZMS DVRT --NFSSG 1000 800 600 400 200 1380 1390 1400 1410 1420 1430 1440 1450 Time (sec) Figure 9. Deformation data from right ZM and the NFS of pig 3.300 g.f was ap- plied. Jaw manipulation introduced an oscillatory component to the deformation at both the RZMS and NFS. At the RZMS, the oscillation was tensile in nature, while at the NFS, it was purely compressive in nature. 16 Mineral apposition rate at the ZMS Protraction - Control 12 – - 6 8 4. | 2 7 days before TO-T1 T1-T2 protraction Figure 10. Graph illustrating the daily MAR at the ZMS. TO = initial surgery; T1 = tertiary bone label injection; T2 = terminal. Each period corresponds to seven days: before protraction, first and second weeks of BAMP Error bars correspond to one standard deviation. 56 Al Dayeh Table 2. Percentage of osteocalcin- (OCN) positive cells recorded inside the bone and at the bone surface, presumably osteoblasts, and total number of osteocal- cin-positive cells in the sutural tissue. % of OCN + ve cells | 9% of OCN + ve cells osteoblast OCN + ve cells in the inside the bone (bone surface) sutural matrix (count) Protraction ZMS 42 + 23 67 + 8 22 + 18 Control ZMS 27 ± 13 41 + 15 14 + 9 (ZMS), one facial suture (NFS) and the effects of BAMP on osteoblast dif- ferentiation at the sutural edges. This study is an ongoing project and values presented here are preliminary and based on data from three ani- mals. Pattern and Magnitude of Strains at the NFS Strain measurements at the NFS were intended to serve two purposes: help validate our sensors; and determine if BAMP induces de- formation of facial sutures outside the circummaxillary sutural system. Previous studies on minipigs of similar age and strain have shown that the NFS is compressed heavily during mastication with strains averag- ing 1,000-1500 pie (Rafferty and Herring, 1999; Al Dayeh et al., 2009). Although strain reported in current study during manipulation still were compressive, they were 5x less (~250 pue) than those experienced during mastication. This finding was unexpected. One reason for this discrep- ancy can be attributed to manipulation failure to mimic masticatory con- ditions. Mastication involves muscle contraction and teeth impact that generate reaction that load the sutures (Herring, 1976). Manipulation performed in this study included gentle opening and closing that could have underestimated the real compressive strains, thus systematic instru- mentation malfunction is unlikely. Interestingly, the NFS was tensed heavily during BAMP. The mag- nitude of sutural separation was comparable to that at the ZMS and it increased as the BAMP loading force increased. This unexpected finding might be species specific as the NFS, lacrimomaxillary and ZMS are lo- cated at the same line on the pig's skull (Figs. 1, 4 and 5). Nonetheless, this further highlights the importance of understanding loading caused by orthopedic forces on the facial sutures, as such loads might have a favorable or unfavorable outcome. 57 Sutural Loading Manipulation with BAMP resulted in decreasing the amount of strain at the suture; however, the overall strain still was tensile. This decrease was expected somehow since manipulation alone resulted in compression at the sutures, while BAMP resulted in tension. Unfortu- nately, we cannot determine if this decrease happened while the mouth was opened or closed since our strain recording did not involve recording the EMG activity or a synchronized video to illustrate what movement resulted in the decrease in overall protraction. Manipulation seems to have introduced an oscillatory compo- nent to protraction (Fig. 9). Oscillation is believed to stimulate further sutural growth (Mao et al., 2003). The fact that BAMP load is more oscil- latory while RPHG is more static suggests that the oscillatory component might have contributed to the observed increased treatment effect of BAMP (Cevidanes et al., 2010; De Clerck et al., 2010; Hino et al., 2013), a possibility that requires further study. Pattern and Strain Magnitude of the ZMS The ZMS is believed to be the major site of midfacial growth. In- stalling miniplates across the ZMS in two-month-old minipigs resulted in severe retardation of midface growth and upward rotation of the snout (Holton et al., 2010). ZMS has been known as therapeutic target of pro- traction for a long time (Nanda, 1980; Nanda and Hickory, 1984; Smalley et al., 1988); however, no data exist on the in vivo deformation of this suture during protraction. Most of our information regarding ZMS deformation during pro- traction comes from finite element analysis (FEA; Holberg et al., 2007; Yo et al., 2007; Liu et al., 2015; Tanaka et al., 2016). In these studies, the reported numbers are much lower than those in the current study, which can be attributed to the differences in the experimental approaches used in the two studies. Mathematical modeling of skull loading is compli- cated by the lack of knowledge of mechanical properties of the differ- ent elements of the skull. Additionally, FEA approximates the mechanical properties of elements of craniofacial skeleton as homogenous uniform material, an approximation that is far from the anisotropic nature of the craniofacial skeleton. FEA also tends to underestimate the viscoelastic na- ture of sutures and the periodontal ligament (PDL). As an example, Hol- berg and colleagues (2007) did not include sutural mechanical properties in the mathematical model. A great body of evidence suggests that PDL 58 Al Dayeh and sutures are important determinants of the mechanical behavior of the skull and act as stress breakers, absorbing and redistributing loads (Jaslow et al., 1995; Toms et al., 2002; Rafferty et al., 2003; Al Dayeh et al., 2009), thus, not including them will result in erroneous findings. In Bright's study (2012), it was shown that inclusion of sutures in FEA of the pig skull will change the magnitude and direction of the reported strain. Additionally, inclusion of sutures was not sufficient to improve the overall accuracy of the model. It also was suggested that heterogeneity and lack of thorough knowledge of pig bone properties might be the cause of the discrepancy between the model and the reported in vivo strain. Thus, FEA, although useful in approximating stress distribution in uniform en- gineering material, is still far from being an accurate predictor of loading in the craniofacial area. To my knowledge, only two studies have reported on the me- chanical deformation of ZMS during protraction; both were done on ex vivo samples. Hata and associates (1987) presented a thorough study in- vestigating deformation of various facial sutures during facemask protrac- tion using a dry human skull of a twelve year old. They further investigat- ed how protraction force direction affects sutural loading. The study by Jackson (2012) was performed on six fresh, one-month-old minipig heads of similar strain to the one used in this study. They further investigated the relation between orthopedic maxillary expansion and loading of the sutures. Both studies used RPHG and protraction was applied using max- illary molars as a point-of-force application. Hata and Colleagues' study (1987) showed that the ZMS was under tension when the protraction force was at the level of the occlusal plane. Although the magnitude of protraction force used was almost double the highest magnitude used in our study (1000 versus 600 g.f), the deformation of the ZMS was around 20 pum, which corresponds well with our findings (~22 pum). This can be attributed to the difference in point-of-force application. In their study, molars were used as a point of protraction-force application. Although the skull was dry, some force decay is expected, resulting in a comparable amount of deformation despite doubling the protraction force. Results from Jackson's study (2012) are interesting, especially since they used fresh heads of similar strain of pigs to the one used in current study. Overall, the ZMS was tensed during protraction; however, the magnitude of deformation surprisingly was much lower (^10x) than 59 Sutural Loading current numbers. This finding also is interesting since the animals used were one month old, probably with more patent ZMS compared to our six-month-old animals. This difference might highlight the main method- ological difference between the mechanism of action of RPHG and BAMP. In RPHG, the loading force was applied through the maxillary molars and since the heads were fresh, the PDL probably was intact (at least me- chanically) and most of the protraction force was dissipated before be- ing transferred to maxillary bone and the ZMS. In BAMP, however, the loading force is applied directly to the maxillary bone, thus most of the protraction force is transmitted to the maxillary sutures, which results in more deformation of the sutures. Whether this higher separation can ex- plain the increased bone formation (Ito et al., 2014) and improved clinical outcome of BAMP (Cevidanes et al., 2010; De Clerck et al., 2010, Hino et al., 2013) will require more investigation including in vivo comparisons of the two techniques. Direction of protraction force plays a significant role in the effects of orthopedic treatment as well. Nanda (1980) suggested that protrac- tion force should pass through the maxilla center of resistance, which is estimated to be in the vicinity of maxillary premolars' root apices. Hata and coworker's results (1987) further highlight the importance of the re- lation between force direction and sutural deformation. In their study, they reported force at the level of maxillary occlusal plane to elicit ten- sion in the ZMS, while forces that were 5 and 10 mm above the occlusal plane resulted in compression of the suture. This is of a great clinical rel- evance, as proper direction of force application is needed to ensure the desired outcome (Keles et al., 2002). Since BAMP protraction force is be- low the center of resistance of the maxilla (Fig. 4), this theoretically might result in rotation of the maxilla. Clinical studies on BAMP suggest minimal maxillary rotation (Nguyen et al., 2011). In our experiment, DVRTs were installed on the ventral part of the suture, while SGs were on the dorsal part (Fig. 5), thus providing us with the opportunity to evaluate whether the maxilla is rotated during BAMP. Strain measurements provided by the DVRT and the SG were comparable, thus supporting bodily separation of the suture. However, the difference in the methodology of action between the two sensors might have masked difference in the strain measured. SGs are glued on the surface of the bone, thus providing a better estima- tion of deformation. On the other hand, DVRTs are linear displacement 60 Al Dayeh sensors and tend to underestimate deformation that does not happen along the long axis of the sensor (Al Dayeh et al., 2009). In our experi- ment, DVRTs were not exactly in line with the protraction force (Figs. 4 and 5). Although this angle was not measured, there was approximately 20-30° between the line of force and the log axis of the DVRTs. Applying the principles of trigonometry, it is suggested that the sutural deforma- tion measured by the DVRT might have been underestimated by 0.15, which is the cosine of 30°. Even if DVRT's reported values were adjusted for this, deformation recorded by both DVRTs will be higher, but still com- parable to SG values (20% higher). Thus, mild rotation might be 'present with the inferior portion of the suture subject to more tension. Measur- ing bone formation (MAR) on the dorsal and ventral parts of the suture would have ruled this question out. Unfortunately, in our experiment, the dorsal half was decalcified for IHC rather than to assess MAR, thus leaving this question unanswered. Mineral Apposition Rate (MAR) Protraction of circummaxillary sutures induced by BAMP is be- lieved to accelerate bone formation along sutural edges, which our pre- liminary results support. MAR on the control side might have been in- creased due to inadvertent bone Stimulation from the BAMP side. Masti- cation in pigs is bilateral with complex pattern of loading on the ipsi- and contra-lateral sides. This might result in the partial transmission of the protraction force to the control side. However, comparison of the MAR at the ZMS in our study to MAR recorded at other craniofacial sutures in minipigs (Sun et al., 2004) suggests that our MAR values are within the comparable range. Thus, any stimulation of the MAR at the control ZMS must have been minimal. BAMP increased the MAR by approximately 60%, which is much less than the "500% increase reported by Ito and col- leagues (2014). This difference can be attributed to the length of protrac- tion period and species used. In their study, protraction was applied for 60 days, thus the animals had sufficient time to recover from the surgical procedure, unlike our procedure in which protraction was performed for only days immediately following surgery. In addition, not only is bone for- mation in dogs faster than in pigs (Štembírek et al., 2012), but the animals used by Ito also were much younger than those used in our study and therefore, probably grew more rapidly. 61 Sutural Loading Osteoblast Differentiation Our approach used immunohistochemical detection of osteocal- cin to assess effects of BAMP on osteoblasts activity. Osteocalcin is as- sociated with the terminal stage of osteoblast differentiation (Kasai et al., 2009) and often is used in craniofacial research as an active osteoblast marker (Oztürk et al., 2012). In our study, BAMP force application result- ed in increasing the expression of osteocalcin. Although these findings are preliminary in nature, if validated through additional studies, it would suggest that BAMP promotes differentiation of osteoblasts and would coincide with previous reports of increased osteocalcin expression as a response of mechanical stimulation of sutures (Lai et al., 2013). Finding osteocalcin-positive cells in the sutural matrix was surprising as osteo- calcin usually is associated with later stages in osteoblast differentiation. However, it might indicate that BAMP stimulates undifferentiated sutural cells to differentiate into osteoblast, thus promoting bone formation at the sutures, a possibility that requires further investigation. Unfortunate- ly, we were unable to establish a relation between osteocalcin-positive cells and new bone formation and the sutures since IHC and MAR were performed in two separate sets of tissue. Future Directions These preliminary findings are part of an ongoing project. Future directions will include expansion of the sample size and supplementing in vivo deformation data with ex vivo data on pig heads. Additionally, the mechanical properties of the ZMS will be tested to understand further the relation between mechanical loading and sutural separation. At the tissue level, samples will be tested to determine the effects of BAMP on cellular proliferation. We also will attempt to double probe the section for osteocalcin and cellular proliferation markers to determine the rela- tion, if any, between cellular proliferation and osteoblast differentiation. CONCLUSIONS In this study, we established minipigs as an animal model for BAMP and reported the in vivo loading of the skull during BAMP for the first time. Additionally, we related the preliminary effects of BAMP on mineral apposition and osteoblast differentiation at the sutural edges. Our preliminary findings that require further validation suggest that: 62 Al Dayeh 1. Minipigs can be used successfully as an animal mode for BAMP; 2. BAMP tenses (separates) the ZMS and NF sutures; 3. Mastication and daily activities introduce an oscillatory component to BAMP loading; and 4. BAMP possibly increases osteoblast differentiation and bone formation at the sutures. 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It also emphasizes the role of evaluation of mediators in peri-implant crevicular fluid (PICF) to aid in the comprehension of bone and soft tissue remodeling processes around MSls at insertion or application of orthodontic forces when using MSls as direct or indirect anchorage. Various mediators including pro-inflammatory cytokines, in- terleukins (ILS; IL-13, -2, -6 and -8), tumor necrosis factors (TNF-o) and receptors such as osteoprotegerin (OPG) and B-receptor activator of nuclear factor kappa- B ligand (RANKL) already have been studied in PICF around MSls. Of these, only IL-1B has shown a significant increase immediately on loading, reaching peak at 24 hours, followed by a subsequent decrease in levels. There is still a wide scope of research related to the study of biomarkers or microbiologic studies that could play a significant role in determination of MSI stability as highlighted in this chapter. KEY WORDS: miniscrew implants, peri-implantitis, cytokines, biomarkers, stability INTRODUCTION Orthodontic miniscrew implants (MSIs) are being used extensive- ly as contemporary temporary anchorage devices (TADS) for a wide array of orthodontic tooth movements (OTMs). The upsurge in the use of MSIs lately is due to their affordable cost, small size, rationalized insertion 69 Peri-miniscrew Biomarkers and removal, as well as simplified surgical procedures with both immedi- ate and delayed loading modules (Bittencourt et al., 2011). Success of implants is attributed to the close proximity of MSI with bone that leads to enhanced immobility of MSI in bone-on application of reactive orth- odontic forces. It also is measured by its ability to augment the anchor- age potential without any impediments or side effects that can compro- mise the treatment effects. Literature evidence regarding quantification of success of implants was measured in the range of 57-95.3%, with an average survival rate of 84% (Shank et al., 2012). The terms primary and secondary implant stability are related perpetually to the success of im- plants in bone; primary stability signifies the mechanical retention of im- plant in bone, while the secondary (biological) stability is administered by the bone regeneration and remodeling phenomenon (Javed et al., 2013). The host bone thickness and quality, implant geometry, design, diameter, length of MSI and surgical technique govern the primary stability. On the other hand, peri-implant (PI) inflammation due to factors of oral hygiene and orthodontic mechanics may contribute to the loss of secondary sta- bility of MSIs (de Freitas et al., 2012). Hence, it is imperative to identify the cause of MSI failures distinguished by loss of bone-to-implant contact as it ultimately may compromise the orthodontic treatment results and lead to patient dissatisfaction. This chapter provides an overview of the factors determining primary and secondary stability of MSIs, and focuses on dynamic host- related factors affecting the interface between bone and soft tissue MSI. It also establishes the importance of peri-implant crevicular fluid (PICF) in understanding the remodeling of bone and soft tissue at cellular and biochemical levels before and after loading MSls. FACTORS INFLUENCING MSI STABILITY Host-, MSI- and Technique-related Factors Many of the factors that contribute to partial osseointegration of MSI with the bone surface and provide a successful outcome have been tabulated into host-, MSl- and technique-related categories (Table 1). In- creased primary stability of implants has been correlated directly with variables including cortical bone thickness and bone density, and are re- lated inversely to pilot hole diameter and use of self-drilling MSls (Shank et al., 2012). 70 Kharbanda et al. Table 1. Table depicting factors influencing MSI stability into host- (biological), MS- and technique-related categories. - Biological factors MS relate: Technique related * MSI location Implant material Incisionſ Mucosa type * Length | 19 nº Available bone - Diameter | Pre-drilling Bone density - Shape. | . Age Cylindrical or | OFCLE Value | Speed of Sex taper insertion Growth pattern Pitch Onset of loading Oral hygiene Flute immediate/ Periodontal Helix angle delayed health Self drilling | Anchorage General health Surface quality direct/indirect Smoking * Force value Ex perie n cle of the opera to r Evidence-based Research on Host-related Factors A systematic review by Papageorgiou and colleagues (2012) has furnished an evidence-based record of the risk factors determining the Success of orthodontic MSIs. The results indicate that the jaw in which the MSI is inserted may be a contributing factor, with failure in the man- dible occurring 1.5x more often than in maxilla. Other factors include Contact of MSI with the roots of adjacent teeth, which increases the fail- ure rate by approximately 3x. However, no significant association was detected with the time of force application (i.e., immediate or delayed loading) and MSI stability. Published results from an animal study sup- port greater stability of MSIs in the maxilla than in the mandible, but are inconclusive (Mortensen et al., 2009). The higher failure rate in human mandibles was attributed to the greater bone density of the mandible, resulting in the use of higher insertion torque values, bone overheat- ing and less cortical bone formation around the MSI, which also limited Cleaning of the area (Papageorgiou et al., 2012). The higher MS. failures in mandibles also was an outcome of a clinical study performed in the Centre for Dental Education and Research (CDER), All India Institute of Medical Sciences (AIIMS, New Delhi, India) in 2009, where 38 MSIs were placed in ten patients in both the maxilla and mandible; a survival rate of 100% was seen in the maxilla and 76.33% in the mandible. Critical risk factors associated with failure included placement in non-keratinized mu- COSa, as well as in soft and thin cortical bone with additional soft tissue in- flammation. This finding was supported by the quantification of implant 71 Peri-miniscrew Biomarkers stability by the implant stability quotient (ISO) using resonance frequency analysis (RFA) in a longitudinal study in beagle dogs (Ure et al., 2011). This study showed that MSIs placed in non-keratinized mucosa were associated with a large decrease in ISOs in the first three weeks of MS placement, indicative of greater bone loss around the MSls and peri- implantitis due to a lack of keratinized tissue and failure of these MSls. Cortical bone density was another factor analyzed for MS stability in the 2009 CDER, AIIMS study. Bone density was evaluated from high-quality images reconstructed from multiple, thin overlapping slices in a multi-detector-computed tomography (MDCT) scan in an axial section parallel to the occlusal plane, 5 to 8 mm apical to the alveolar crest. Results revealed cortical bone density values ranging from 503.8 to 1544.8 Hounsfield units (HU; mean = 1116.2 +/- 298.33 HU) in the mandible that were significantly higher than maxilla with values ranging from 506.7 to 1705.6 HU (mean = 929.27+/- 322.12 HU). Clinical success was found to be greater in the maxilla (100%) than mandible (77.8%), hence no definite association of MSI success could be established with bone density (Samrit et al., 2012). The site of MSI placement as a contributing factor for MSI success also was evaluated in records from the Department of Orthodontics, CDER, AIIMS. The results confirmed a success rate of 90% in 261 buccal and two palatal MSls placed in the maxillary second premolar-molar area. MSI loosening in the remaining 9.88% cases was observed mainly due to soft tissue inflammation, overgrowth and drifting of the MSIs. Apart from clinical assessment for the success of MSI, few stud- ies have been conducted on microbiological colonization in the gingival sulcus around anchorage devices inserted in the keratinized attached mu- cosa, which account for Pl inflammation or peri-implantitis and led to im- plant failure. The study by de Freitas and associates (2012) evaluated mi- crobial colonization of non-specific Streptococcus, Lactobacillus casei and Candida species colonizations, as well as Porphyromonas gingivalis in the mini-implant region from baseline to three months. Of these, only Strep- tococcus spp showed significant initial colonization between baseline and 24 hours. A similar outcome was observed in the preliminary study on MSIs by Mishra (2014), in which initial colonization by Streptococcus spe- cies was seen in the first 24 hours, but an association of failed MSls was 72 Kharbanda et al. established to a higher proportion of obligate anaerobes and Candida albicans species. Research data has provided substantial understanding of the factors that influence primary stability. However, parameters governing secondary stability leading to the long-term survival of MSI have to be ex- plored yet, of which the bone and soft tissue MSI interface are important components. MSI-BONE INTERFACE An immediate host response to the placement of MSIs in bone is the formation of a blood clot at the site where implants come in contact with viable bone. This clot area hosts a wide array of proteins including glycosaminoglycans and non-collagenous bone matrix proteins (e.g., os- teopontin and bone sialoprotein) apart from migration of osteoprogeni- tor cells and angiogenesis. This contributes to woven bone formation that may lead to secondary remodeling and lamellar bone formation (Naga- matsu, 2008). An excellent hypothesis of propagation of micro-cracks in bone upon the placement of MSIS has been put forward by Murakami and co- workers (2016; Fig. 1). The micro-crack propagation occurs primarily due to the difference in elasticity of bone and MSI, which leads to the ini- tiation of a physio-chemical as well as biologic response. The repair of these micro-cracks is proposed to occur by micro-callus formation that may be instigated by calcium phosphate supersaturating the local envi- ronment to yield mineralized bone, but a delay in ossification may occur due to acidification or release of biological mediators in the paracrine area that may hamper the calcification process. Evidence supporting typi- cal micro-cracks in bone distant to MSI, as well as diffuse damage in the bone region adjacent to insertion upon placement of MSIs was seen by epifluorescent photomicrographs in the canine mandible (Shank et al., 2012). In maxillary drilling and non-drilling specimens, similar staining of diffuse damage and micro-cracks was seen, but in mandibular specimens, greater diffuse damage and micro-cracks were witnessed in self-drilling MSIs compared with non-drilling MSIs in thickness greater than 2 mm (Fig. 2). Another animal experiment on the sheep mandible utilized a semi-automated digitized morphometric method to assess the correlation 73 Peri-miniscrew Biomarkers Drilling mini-screw into bone matrix Physicochemical reaction ! Biological reaction Arising cracks around Calcium phosphate -- - - supersaturating environment * the mini-screw -> | Reaction ºbone cells to mineralization (micro-cracks) Mechanical load ! |- Acidification The micro-crack repair by inhibition of calcification calcification * Reaction as ! mechanical stress Loosening of mini-screw Osseointegration - Figure 1. Figure depicting hypothesis of propagation on micro-cracks in bone on placement of MSIs. From Murakami et al., 2016. Reprinted with permission of Creative Commons (CC) license. of micro-cracks, diffuse damage and cross-hatch damage of bone with surface roughness and the configuration of MSIs (Bartold et al., 2011). The results showed that although all MSIs had an associated micro-dam- aged bone matrix, rough-cylindrical MSI witnessed a greater amount compared to rough-tapered, smooth-cylindrical and smooth-tapered MSIs (Bartold et al., 2011; Fig. 3). Additionally, the effect of temperature on the extent of micro-damage of bone on MSI placement was tested on four live white rabbit tibia that received MSls at 0.7°C, 22.0°C and at 60.0°C. Among the different temperature groups, no significant differ- ences were observed regarding the area of micro-cracked and displaced bone fragments, but cortical bone necrosis occurred in cold self-drilling MSls at 0.7°C (Nagamatsu, 2016; Fig. 4). The histochemical studies on rat tibia Cortical bone, approximately 1 mm thick, showed pH changes of the bone matrix around the MSI upon immediate loading by staining with basic aldehyde fuschin and observation under transmitted optical micro- scope (Murakami et al., 2016; Fig. 5). Hence, literature evidence proves that MS leads to formation of micro-cracks and diffuse damage when in contact with bone, the extent of which varies according to the MSI site of placement, shape and texture. 74 Kharbanda et al. - º º . . . S Periosteal bone surface Microdamage | Endocortical bone surface º Mini-implant surface º Diffuse damage Figure 2. Figure depicting micro-damage and diffuse damage as a result of micro-implant insertion. Reconstructed based on a pictoral represen- tation by Shank et al., 2012. Bone V" Implant Diffusedamage Region of analysis Micrºcracking Cross-hatch V" microdamage Figure 3. Experiment on sheep mandible utilizing semi-automated digitized mor- phometric method to assess correlation of micro-cracks, diffuse damage as well as Cross-hatch damage of bone with surface roughness and configuration of MSls. From Bartold et al., 2011. Reprinted with permission of CCC Republication. 75 Peri-miniscrew Biomarkers Contical Bone Microcracks and displaced bone Figure 4. Area of micro-cracks, displaced bone fragments and cortical bone ne- crosis as bone response to orthodontic MSI placement. Reprinted with permis- sion of Nagamatsu (2016). ". adaº Load area Figure 5. Histochemical changes of the bone matrix of rat tibia cortical bone loaded immediately using MSIs by staining with basic aldehyde fuschin and ob- servation under transmitted optical microscope. From Murakami et al., 2016. Reprinted with permission of Creative Commons (CC) license. MSI-SOFT TISSUE INTERFACE Histology of Normal Peri-MSI Mucosa To understand the biological variables affecting the primary stability of implants, it is important not only to have a thorough knowledge of the concept of osseointegration in implant bone interface, but equally important also to study the gingival seal of the MSI-soft tissue interface in the transmucosal region. The components of PI mucosa are similar to normal mucosa, consisting of keratinized stratified squamous oral 76 Kharbanda et al. epithelium and peri-implant sulcular epithelium (PISE) and non-keratin- ized peri-implant epithelium (PIE) with blood vessels and invading neu- trophils (Fig. 6; Yamaza and Kido, 2011). PIE is important for the bio- logical seal, which is comprised of a cellular arrangement parallel to MSI, with intercommunications via cytoplasmic processes, tonofilaments and desmosomes, and formation of wide intracellular spaces. It is the site for leakage of neutrophilic granulocytes from the blood vessels of sub- epithelial connective tissue (CT), as seen in inflammation or trauma. Hence, PIE serves as a pathway for the penetration of foreign molecules into the sub-epithelial CT of PI mucosa and from sub-epithelial CT to PICF (Yamaza and Kido, 2011). This region is critical for the short- and long-term stability of MSI, with clinically visible inflammation leading to peri-implantitis, as well as progressive destruction of the transmucosal region due to bacterial invasion. There is literature evidence to support peri-implantitis as the most common cause of MSI failure, with greater than 90% of failures occurring in the first four months (Miyawaki et al., 2003); Pl bacterial colonization and subsequent inflammation are poten- tial causes of MSI failure (Chen et al., 2008). Hence, a clinical diagnosis Should assess peri-implantitis as an integral factor to cause MSI failures, along with bacteriological and biochemical evidence, based on the con- tents of PICF that show alteration in inflammation. Gingival Crevicular Fluid (GCF) versus Peri-miniscrew Fluid (PICF) PICF is a crevicular fluid that emanates from the implant gingival vessel plexus as an osmotically driven inflammatory exudate. Its com- position is similar to other body fluids like GCF consisting of biological mediators of inflammation (e.g., cytokines, antibodies, host-derived en- zymes and their inhibitors, tissue breakdown products and host response modifiers) and may show variation with application of orthodontic forces (Monga et al., 2014). Slight differences occur in GCF representing a tran- Sudate in the unstimulated State that is released from the gingival plexus of blood vessels in gingival CT adjoining to epithelium lining the dento- gingival space. Study of the contents of PICF and GCF non-invasively at multiple observation times may serve as indicators of Pl inflammation due to disease or stresses of OTM. 77 Peri-miniscrew Biomarkers Healthy gingiva Peri-implant mucosa - Figure 6. Light micrographs depicting similarity in healthy gingiva and peri-im- plant mucosa in rats. A: Components of healthy gingiva comprising of epithelial component and connective tissue (CT). B-C: Components of peri-implant (PI) mucosa consisting of keratinized stratified squamous oral epithelium and peri- implant sulcular epithelium (PISE) and non-keratinized peri-implant epithelium (PIE) with blood vessels and invading neutrophils. From Yamaza and Kido, 2011. Reprinted with permission of InTech. ROLE OF PICF IN DETECTION OF BIOMARKERS OF MSI SUCCESS AND FAILURE Biomarkers in PICF There have been numerous studies on mediators in GCF that act as signals to initiate the process of bone and tissue remodeling, by sequential release at multiple stages during OTM, as documented in a systematic review by Kapoor and coworkers (2014). These may be con- sidered as a basis for determination of inflammatory mediators in PICF to evaluate the bone and soft tissue remodeling processes associated to MS placement and loading, and ultimately, to correlate with clinical success or failure of the implant. The mediators studied in PICF are as follows. Cytokines. The expression of various regulatory molecules in PICF has been documented in the literature, but the most widely acknowl- edged among them are pro-inflammatory cytokines that are low-molecu- lar weight proteins released in response to the application of stress in any 78 Kharbanda et al. form—either of implant drilling or its loading—in the autocrine or para- crine environment (Kapoor et al., 2014). Among these cytokines, inter- leukins (ILs; IL-13, -2, -6 and -8), tumor necrosis factors (TNF-o) and re- ceptors osteoprotegerin (OPG) and B-receptor activator of nuclear factor kappa-B ligand (RANKL) have been studied in MSls. Interleukins (ILS). ILs, specifically IL-13, is a potent marker of bone resorption working synergistically with TNFs in mediating the binding of RANK to its ligand (RANKL) expressed by osteoblasts and periodontal ligament (PDL) cells, for facilitating osteoclast differentiation (Kapoor et al., 2014). A study on the levels of IL-13 in PICF was performed by Sari and Uçar (2007). PICF was collected from 20 implant sites in the implant group where implants were used as direct anchorage for the retraction of canines in the maximum anchorage group. In addition, GCF was collected from canines undergoing retraction in the treatment group. Both were evaluated at different observation times: initiation of tooth movement (two weeks post-MSI insertion), 24 hours, 48 hours, 168 hours, 14 days and 21 days. However, the results showed demonstrable changes in lev- els of IL-13 in the treatment group only, thus favoring the use of MSIs as absolute anchorage devices. Kao and associates' study (1995) comparing healthy and diseased implants in 12 patients showed levels of IL-13 in the crevicular fluid of diseased implants to be approximately 3x that of that in healthy sites. Monga's thesis (2011) and published article (Monga et al., 2014)—where MSIs were used as an indirect anchorage for en mass re- traction and delayed loading of the implant—showed contradicting re- sults. IL-13 levels in PICF showed a significant rise at insertion of MSI, followed by a decrease during three weeks of delay in loading. On MS loading, levels increased in one hour, reached peak in 24 hours and fur- ther decreased close to baseline for the remaining study period of 300 days (Figs. 7-8). They also correlated it with clinical success based upon repeated assessment of implant mobility by Periotest, as well as level of gingival inflammation of Pl tissue by a modified Loe & Silness index. In peri-implantitis cases, the levels in IL-13 were significantly higher at 14 days, which coincided with clinical failure of the MSI. Another study by Hamamci and coworkers (2012) evaluated IL-2, -6 and -8 in PICF of implants used as direct anchorage for en mass retrac- tion, as well as in GCF collected from maxillary canines being retracted 79 Peri-miniscrew Biomarkers 300 66.33 *Significance: p < 0.05 250 \ N 200 - Tö \ N. 3. E. 150 Y 153.57 75 131.95 137.77 # 100 123.75 115.47 120.01 $2. 'i T 50 0 I t I I i I I I 1 hour 3 1 hour 24 21 72 120 180 300 after weeks after hours days days days days days insertion loading Figure 7. Depiction of trend in upregulation and downregulation of IL-13 levels (pg/ml) in PICF on MSI placement and loading. Levels show increase in one hour of loading, peak in 24 hours, further decreasing close to baseline for remaining study period of 300 days. Reprinted with permission of Monga (2011). k. IN N - 76 5. N 3. # 150 º 153.57 # 13:1.95 137.77 § 100 – 50 0 I i I I I 1 hour after 3 1 hour after 24 21 72 insertion weeks loading hours days days Figure 8. Depiction of increase in levels of IL-13 in PICF on loading of MSIs fol- lowed by peak in 24 hours. Reprinted with permission of Monga (2011). 80 Kharbanda et al. and maxillary second premolars as control teeth. Of these, IL-2 was the mediator studied due to its association with osteoclast activity stimula- tion, which led to bone resorption, and as an inflammatory biomarker owing to raised levels in patients with periodontitis. Levels of IL-6, a multi-functional cytokine, are known to increase in bone destruction. IL-8, which is a strong inflammatory mediator, is known to play a ma- jor role in the pathogenesis of periodontal disease. The results of this study, however, do not show any significant increase in levels of any of the mediators in PICF in the implant group, but a definite increase in GCF in the treatment group. Only IL-2 levels showed an increase in initial days, which correlated with early MSI failures. In association with cytokines, studies on receptors like OPG and RANKL that facilitate bone resorption and remodeling also have been explored in PICF. Enhos and associates' study (2013) compared levels of OPG and RANKL in 16 loaded and 20 unloaded implants before loading, at 24 hours, 48 hours, 168 hours and 30 days after loading and showed that RANKL was elevated significantly upon loading, which indicates that bone resorption and the corresponding OPG/RANKL ratio were decreased at all time periods in PICF. Tumor Necrosis Factors (TNFs). Cytokines other than ILs that have been documented widely in GCF in OTM are TNFs. They work synergisti- cally with ILs causing bone resorption, as well as release of collagenase on stimulation of fibroblasts (Kapoor et al., 2014). They also have a defi- nite role in the regulation and amplification of periodontal and Pl inflam- mation (Scierano et al., 2008). Levels of TNF-0 in PICF were assessed by Kaya and colleagues (2011) during canine distalization with a 150-g force nickel titanium (NiTi) closed-coil spring where MSIs were used as direct anchorage. Although PICF levels of TNF-o were found to increase in ini- tial activation in 24 and 48 hours, probably due to release of orthodontic forces, this increase was not found to be significant statistically. It later decreased in 21 days due to inherent feedback mechanisms and adapta- tion of periodontal architecture to forces. Secretory Proteins and Enzymes. Other potential markers for study in PICF were secretory proteins and enzymes, of which glycosami- noglycans—particularly chondroitin sulphate (CS)—is significant due to its role in bone and cartilage destruction (Intacha et al., 2010). Evi- dence in the literature also correlates CS expression in GCF with the level 81 Peri-miniscrew Biomarkers of inflammation, disease status and hyalinization of periodontal tissue (Shibutani et al., 1993). In the study by Intachai and associates (2010), CS(WF6 isotope) was assessed in PICF from 20 MSls placed in ten patients who required all first premolar extractions and retraction was done by a 50 g closed Sentalloy coil spring using MSls as direct anchorage. PICF in this study was collected at multiple observation times: at days 1, 3, 5 and 7 after MSI insertion and days 14, 21, 28 and 35 after MSI loading. The median levels of CS WF6 epitope did not show a statistically signifi- cant difference in the loaded and unloaded phases; however, the clinical correlation of two failed implants due to mobility showed high levels of CS, 14 days prior to implant failure, which suggests a role of CS in bone resorption. Biochemical and Microbiologic Evidence Related to MSIs There have been a series of studies conducted at AIIMS on bio- chemical mediators in PICF in an attempt to understand the biology of remodeling in the bone MSI and soft tissue MSI interface. The choice of mediators in these studies were based on an extensive literature search and collection of evidence from a series of systematic reviews (published as well as unpublished); this knowledge led to the formulation of a model that has attempted to explain temporally the role of various mediators in remodeling after MSI placement and loading, leading to bone healing, bone dust clearing and extracellular matrix degradation (Table 2). Besides studies on mediators of inflammation and contents of PICF, efforts also have been directed toward the modification of surface characteristics of implant surface to improve the biological seal, thus lim- iting implant failures. The various mediators considered for evaluation in PICF are as follows. Interleukin-16 (IL-16). The first studies in the AllMS series were Monga's thesis (2011) and the research by Monga and coworkers (2014) on IL-13 in PICF where indirect loading of implants led to an increase in levels in 24 hours, suggestive of initial inflammation around MSI, only to fall in subsequent observation intervals at 300 days. In this study, a clini- cal correlation of implant failure was established with higher levels of IL- 13 in 14 days, which may be reminiscent of IL-13 being a potential marker of implant stability (Figs. 7-8). 82 CO U.J. Table 2. Overview of release of various mediators and their role in remodeling after MSI placement and loading. MIS placement Regulatiºn by High º box protein (HMG-81) Release-in extra-ceºlar space aftercelysis Acute inflammation Trauma to oral mucosa and alveolar bone Paractine environment Macrophage Colony- StimulatingFactor (M-CSF) Early Osteocastic ACP. B- Precursor (OCP) to Glucuronidase mature osteocasts expressed in - osteocasts Bone dustclearing Enzyme (ALP) Ny Alkaline phosphatase Release of mediators from activated monocytes, macophages Released from PMNLS, fibroblasts, bone. plasma cells Matrix metalloproteinases (MMP-1,2,3,8,9,13) Collagenases Gelatinases (MMP13) - Downregulation of RANKL Osteoprotegrin (OPG) Growth factors (IGF Bºº, Local increase of phosphate ions Enzyme - Lysosomal protease Cathepsin B) | Organic matrix Bone healing breakdown osteoprotegerinigand (OPGL) or NF-related activation-induced cytokine (FRANCE) upregulation RANKL expression or osteocast differentiation factor(CCF) by Osteoblastic cells Extracellular matrix degradation Peri-miniscrew Biomarkers High Mobility Box Protein (HMG-B1). Another closely related protein is extracellular high mobility box protein (HMG-B1) that works through the induction of various pro-inflammatory and osteoclastogenic cytokines such as IL-13, -6, -17 and RANKL, as well as vascular adhesion molecules. Ilancheralathan and colleagues (2015) evaluated HMG-B1 in PICF at one hour, 24 hours and three weeks before loading the implant and one hour, one day, one week, three weeks and six weeks after load- ing. Results showed an initial rise in levels on MSI placement due to tissue damage causing the release of inflammatory mediators. Due to a three- week delayed loading protocol, the levels fell, indicating cessation of in- flammation caused by trauma during MSI insertion. However, the levels increased again one hour after loading, reaching peak at 24 hours, due to the orthodontic stresses of a 200 g Niſi closed-coil spring used for en mass retraction in both the maxilla (Fig. 9) and the mandible (Fig. 10). This study also reported an increase in HMG-B1 levels in two separate cases of mucositis, again indicating inflammation (Fig. 11). Microbiological Colonization of MSI. Assessment of implant sta- bility has been based mainly on the clinical correlation of implant mobil- ity and gingival inflammation with levels of biomarkers in GCF. Recent emphasis on the correlation of implant stability with microbial coloniza- tion led to the study of variation in microbiological constituents of 24 successful and eight failed implants versus non-implant areas (Mishra, 2014). Results depicted an initial microbiological colonization of MSI by Streptococcus species in the first 24 hours. Failed MSls showed a higher proportion of obligate anaerobes and Candida albicans compared to suc- cessful MSIs. Hence, evaluation of microbial flora may be explored as a measure to anticipate the success of the implant. Matrix Metalloproteinases (MMPs). Another factor responsible for extracellular matrix degradation and turnover are matrix metallopro- teinases (MMPs). These are a family of zinc-dependent endopeptidases stored dormantly in granules of polymorphonuclear leukocytes (PMNs), whose release is triggered in inflammatory tissue destruction. Of these, MMP-8 or collagenase 2 is associated with non-PMN lineage cells, namely endothelial cells, odontoblasts, dental pulp cells, and gingival and PDL fi- broblasts, and has an established association in periodontitis and peri-im- plantitis (Ingman, 1996). OTM also has led to a variation in levels of MMPS 1, 2, 3, 7, 8, 9, 12 and 13 and MMP9/neutrophil gelatinase-associated 84 Kharbanda et al. 25 00 Before loading After loading 2040 2000 1500 1000 58 500 T1 T2 T3 T4 T5 T6 TZ T8 Observational time Figure 9. Figure depicting HMG-B1 (pg/ml) levels in PICF at different time inter- Vals in the maxilla. Levels were shown to increase at T4 (one hour after loading), followed by peak at T5 (24 hours after loading). Reprinted with permission of |lancheralathan (2015). Beforeloading After loading 2000 - 1500 1000 500 T1 T2 T3 T4 T5 T6 TZ T8 Observational time Figure 10. Figure depicting HMG-B1 (pg/ml) levels in PICF at different time inter- Vals in the mandible. Levels were shown to increase at T4 (one hour after load- ing), followed by peak at T5 (24 hours after loading). Reprinted with permission of lancheralathan (2015). lipocalin (NGAL) in GCF, thus potentiating their role in ECM destruction and remodeling process. A 62-day study on 40 sites of MSI placement was Initiated by Neg (2016) to evaluate MMP8 in PICF at multiple observation Points. PICF collection was done at one hour, one day and three weeks 85 Peri-miniscrew Biomarkers Maxilla 2500 2000 1500 1000 500 T1 T2 T3 T4 T5 T6 T T8 -O-case ID 79 -O-Mean Mandible 2000.00 1500.00 1000.00 500.00 0.00 T1 T2 T3 T4 T5 T6 T. T8 -º-case D 68 -o-Mean Figure 11. Figure depicting increase in HMG-B1 (pg/ml) levels in two separate cases of mucositis. Reprinted with permission of Ilancheralathan (2015). after implants placement before MS loading, followed by one hour, one day, one week, three weeks and six weeks after loading. Results showed an increase in MMP8 immediately after MSI placement that was attrib- uted to surgical trauma, further showing a fall in levels during the delayed loading period of three weeks, a subsequent increase one hour after MS loading and attainment of peak levels 24 hours after loading (Fig. 12). Circulating Nucleic Acids (CNA). CNA (DNA and RNA) that are re- leased into plasma and blood circulation after apoptosis of lymphocytes and other nucleated cells (e.g., T cells, haemopoeitic cells; Swarup and Rajeswari, 2007) also are probable biomarkers to be considered. Hence, in severe inflammation after MSI insertion, the levels of CNA are ex- pected to rise and have been considered for study in PICF in Tabassum's 86 Kharbanda et al. 16 14 12 º - 1 2 3 4. 5 6 7 8 Obsevational time in hours —- Figure 12. Depiction of MMP-8 (pg/ml) levels in PICF at different time intervals in the maxilla. Levels are shown to increase at T4 (one hour after loading), followed by peak at T5 (24 hours after loading). Reprinted with permission of Negi (2016). thesis (2015), where collection of PICF would be done by micropipette and determination of CNA by real-time PCR at multiple observation points. Pentraxin 3 (PTX3). Pentraxin 3 (PTX3), a novel member of the PTX Super family that also is known as TNF-stimulated gene 14 (TSG-14), has a potential to be researched as a biomarker of PDL inflammation as it is secreted by an array of cells found in and around PDL tissue, namely heutrophils, fibroblasts, monocytes/macrophages, dendritic cells, epi- thelial cells, endothelial cells and vascular smooth muscle cells. Studies in the literature have assessed PTX3 in GCF in periodontal inflammation (Pradeep et al., 2011), as well as in OTM (Surlin et al., 2012). Levels in GCF in young and adult patients have been found to increase when ca- nine distalization was initiated, reach peak levels in 24 hours and fall later (Surlin et al., 2012). The literature lacks information on levels of PTX3 in PICF following MS placement and loading, although its role in periodon- tal inflammation and orthodontic force application is established. Hence, it is being studied as the marker of interest in PICF evaluated in en mass ºtraction of anterior teeth in samples requiring maximum anchorage (Ji- tender, 2015). 87 Peri-miniscrew Biomarkers Macrophage-colony Stimulating Factor (M-CSF). Macrophage- colony stimulating factor (M-CSF) is another potential biomarker with a role in osteoclast differentiation by mediating the survival, proliferation and differentiation of mononuclear phagocyte lineage populations with their precursors. Kaku and associates' study (2008) in GCF on experimen- tal tooth movement in mice showed a significant increase in MCSF levels at one day and seven days when compared to baseline. This conceptual- ized the basis of another research protocol by Katiyal (2015) with the aimed of evaluating MCSF in PICF as a prognostic marker for implant re- tention. SUMMARY This chapter highlights factors that may be considered instru- mental for the secondary stability of micro-implants governed by bone and tissue remodeling around MSI. Hence, to facilitate understanding of MSI placement and loading at a biochemical level, estimation of an array of biochemical mediators in PICF has been attempted, along with their correlation with clinical parameters of peri-implantitis or MSI mobility. Cytokines—mainly IL-13, -2, -6 and -8–have been studied in PICF at dif- ferent time periods before and after loading the implants. Of these, a significant increase in IL-13 levels has been associated with MSI loading, as well as in cases of peri-implantitis with peak levels 24 hours after load- ing. Among the receptors OPG and RANKL, the latter was found to be el- evated significantly on MSI loading, while OPG/RANKL ratio lowered at all observation times in PICF. TNF-0 levels were not significant statistically, though they increased in initial activation in 24 and 48 hours. Glycos- aminoglycans CS levels were found to increase significantly in two failed implants 14 days before implant failure. HMG-B1 levels showed an initial rise on MSI placement, followed by a fall in a three-week delayed load- ing protocol, which ultimately led to an increase again after loading and reached peak in 24 hours. In addition, increased HMG-B1 levels also were seen in two separate cases of mucositis, indicating inflammation. MMPS, specifically MMP8, showed a similar trend with increase immediately after MSI placement, subsequent decrease in levels during a delayed loading period of three weeks, followed by an increase after MSI loading which reached peak 24 hours after loading. Microbiologic studies have indicated correlation of failed MSls with a higher proportion of obligate anaerobes and Candida albicans compared to successful MSls. 88 Kharbanda et al. SCOPE OF FUTURE RESEARCH Further potential areas of research include assessment of other biomarkers in PICF indicative of bone and tissue remodeling processes, as well as inflammation. In addition, surface alteration of the implant to improve primary stability and epithelial attachment to the implant may be undertaken. Microbial colonization of the PI area is a prospective re- Search area to be explored for MSI stability. Delayed loading of the im- plant may yield alteration in the levels of enzymes (e.g., AST, ALP, gluc- uronidase), but still has not been evaluated in PICF. Extracellular matrix degradation regulated by MMPs (MMP-1, -2, -3, -8, -9 and -13)—both collagenases and gelatinanses that are released from PMNLS as well as lysosomal proteases responsible for organic matrix degradation—also are further probable areas of research. The current literature indicates that only 1% of biochemical and microbiological evidence regarding the Success of MSIs has been explored. 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Angle Orthod 2011;81(6):994-1000. Yamaza T, Kido MA. Biological sealing and defense mechanisms in peri- implant mucosa of dental implants. In: Turkyilmaz I, ed. Implant Dentistry: The Most Promising Discipline of Dentistry. Open access 2011:219–242. Published in [short citation] under CC BY-NC-SA 3.0 li- cense; available from http://dx.doi.org/10.5772/18998. 92 MYTHS AND LEGENDS: UNRAVELING THE COMPLEX ASSOCIATIONS BETWEEN VIBRATIONAL FORCE, TOOTH MOVEMENT AND PAIN DURING INITIAL ALIGNMENT WITH FIXED APPLIANCES Martyn T. Cobourne, Andrew T. DiBiase, Neil R. Woodhouse, Spyridon N. Papageorgiou ABSTRACT Contemporary advances in orthodontic treatment with fixed appliances have led to increased sophistication and predictability in the treatment response. Despite relatively consistent treatment results when using these appliances, treatment times have remained unchanged. In recent years, there has been increasing in- terest in adjunctive methods designed to speed up the process of orthodontic tooth movement and, therefore, reduce the length of treatment. One method that has emerged is the use of supplemental vibrational force during orthodon- tic treatment. In this chapter, we summarize the current evidence base relating to the use of vibrational force in orthodontics and describe some aspects of a large multi-center randomized controlled trial (RCT) that was carried out in the United Kingdom to investigate clinical efficiency of the market-leading Accele- Dent device during initial alignment with fixed appliances. Specifically, we focus on the rate of initial tooth alignment and the pain and discomfort experienced by subjects using functional or sham vibrational devices in conjunction with fixed appliances, compared to patients with fixed appliances alone. KEY WORDS: vibration, orthodontic tooth movement, pain, AcceleDent, random- ized controlled trial (RCT) INTRODUCTION Orthodontic treatment with fixed appliances has become in- creasingly sophisticated since the introduction of edgewise mechanics and a wide range of systems now are available that offer precise control of tooth movement. However, despite the many technical advances that the fixed appliance has undergone, treatment times remain relatively 93 Myths and Legends long (Tsichlaki et al., 2016). In recent years, there has been increasing interest in adjunctive methods designed to speed up the process of orth- odontic tooth movement and, therefore, reduce treatment times (Long et al., 2013). One procedure is the application of supplemental vibration- al force during fixed appliance treatment. In this chapter, we summarize the current evidence base pertaining to the use of vibrational force in orthodontics and describe some components of a large multi-center ran- domized controlled trial (RCT) that was carried out in the United Kingdom to investigate the clinical efficiency of the market-leading AcceleDent” (OrthoAccelº Technologies, Inc., Houston, TX) device. VIBRATIONAL FORCE IN ORTHODONTICS Biological Basis of Vibrational Force Application Since the work of Julius Wolff in the 17th century, it has been recognized that bone mineral density can be influenced by environmen- tal stimuli. High-frequency, low-magnitude mechanical stimulation has been used in individuals prone to reduced bone density as a method of increasing bone and muscle mass in the axial skeleton (Rubin et al., 2004; Ward et al., 2004; Holguin et al., 2009; Wang et al., 2012). This principle also has been applied to the craniofacial region where cyclic loading can promote suture growth and remodeling (Mao et al., 2003; Peptan et al., 2008) and can increase expansion and space closure rates in rat models of orthodontic tooth movement (Darendeliler et al., 2007; Nishimura et al., 2008). Moreover, it has been suggested that vibrational force may enhance tooth movement with fixed appliances by reducing the frictional resistance to sliding between bracket and archwire (Olson et al., 2012; Seo et al., 2014). There also is some evidence indicating that vibrational stimulation could be effective in providing relief for acute and chronic musculoskeletal pain (Lundeberg et al., 1987, 1988), sinus pain (Lundeberg et al., 1985) and pain of dental origin (Ottoson et al., 1981). These effects may be explained by an increased vascularity, reduction of ischemic areas and the activation of large-diameter sensory nerve fibers (Lundeberg et al., 1984). The concept of vibratory stimulation as a meth- od of pain alleviation following the adjustment of orthodontic appliances has been described (Marie et al., 2003). Collectively, these findings have prompted the development of vibrational devices for use in human sub- jects during orthodontic treatment as a method of increasing the rate 94 Cobourne et al. of tooth movement, while at the same time reducing pain and discom- fort. Vibrational Force in Orthodontics A number of devices designed to provide supplementary cyclic- force directly to the dentition during orthodontic treatment have been introduced to the market. Predominant among these are the Tooth Mas- Seuse and AcceleDent appliances. The Tooth Masseuse is a one-com- ponent device providing a vibrational frequency of 111 Hz and force of 0.06 N. AcceleDent is a hands-free device consisting of a removable mouthpiece attached to an activator unit that provides a vibrational fre- quency of 30 Hz and force of 0.2 N to the dentition (Fig. 1). Both devices require the patient to bite gently onto a vibrating thermoplastic wafer, which touches the occlusal surface of both the maxillary and mandibu- lar dentitions. It is recommended that subjects use them for around 20 minutes/day as a supplement to their fixed-appliance treatment. Both of these devices have been proposed to reduce pain and discomfort during fixed appliance treatment, while the manufacturers of the AcceleDent appliance also claim that vibrational force can increase the rate of tooth movement. However, there currently is limited evidence on their clinical efficiency. Orthodontic Tooth Movement The first published report on AcceleDent was a preliminary inves- tigation of a prototype device, which demonstrated higher rates of tooth movement than previously published norms (Kau et al., 2010). These data should be treated with caution, however, due to the retrospective design, Small sample size and lack of Control group. More recently, a prospective RCT conducted in Australia ran- domized 66 patients either to fixed appliances alone or fixed applianc- es supplemented with use of the Tooth Masseuse. In this investigation, there were no significant differences in alignment rates between the two groups during a ten-week period of treatment with 0.014" nickel-titani- um (Niſi) archwires (Miles et al., 2012). The effects of vibration using AcceleDent have been evaluated during leveling and alignment with fixed appliances (Bowman, 2014). This retrospective investigation used a cohort of over 100 consecutively treated 95 Myths and Legends Figure 1. A: The Tooth Masseuse vibrational device. B: The AcceleDent" vibra- tional device. Tooth Masseuse photo courtesy of Peter Miles. Class Il patients undergoing concurrent temporary anchorage device (TAD)-supported maxillary molar distalization and mandibular leveling and alignment. Within this sample, 30 were enrolled into an AcceleDent vibration group and 37 into a similar-aged control group. Mean times to achieve alignment in the group provided with AcceleDent were shorter than in the controls (ranging from 27 to 38 days, which approximates to between 29–40% faster, on average). Moreover, the average time to achieve leveling also was reduced in the vibrational group (ranging from 48 to 55 days, which approximates to between 30-35% faster, on aver- age). The results of this study were impressive, but they need to be Con- sidered in context. As a retrospective study, there is a real risk of bias and over-estimation of treatment effects. A major issue is the incomplete reporting and integration in the statistical analysis of baseline characteris- tics (e.g., patient gender, age, initial irregularity and curve of Spee), which makes it difficult to make any meaningful conclusions. How can we Con- clude that more rapid alignment seen in the group exposed to vibration actually was due to the vibration, when we do not know how crowded the two groups were prior to the start of treatment? Moreover, align: ment and leveling were judged subjectively and this also is susceptible to bias, particularly as it was not conducted blindly. These issues emphasize why it is important to have pre-treatment equivalence and prospective randomized allocation of any intervention in clinical studies. Finally, no a priori sample size was undertaken, which resulted in the study being underpowered severely. As such, the study only had a power of 48% to detect the observed differences in alignment between groups, which in 96 Cobourne et al. asSociation with the risk of bias arising from the study design critically endangers the reliability of the results (Schulz and Grimes, 2005). Although not focusing on rate of alignment, a recent prospec- tive RCT investigated the influence of vibrational force on tooth retrac- tion (Pavlin et al., 2015). A mixture of subjects undergoing TAD-supported individual canine or en masse retraction with fixed appliances were al- located to supplementary vibrational force with a functional AcceleDent appliance or non-functional sham device. The analysis was complicated slightly by having combined intention-to-treat (ITT) and per protocol (PP) Cohorts, a mixture of single tooth retraction and en masse retraction within the samples and the need to exclude cases with loose TADs. In ad- dition, measurements were taken directly from the mouth, which meant that reliability could not be assessed properly. However, these problems notwithstanding, there was a statistically significant increase in tooth movement in both ITT and PP groups of 0.37 and 0.36 mm/month, re- Spectively. Although interesting, these results should be evaluated in ac- Cordance with their statistical and clinical relevance. The study was pow- ered on the basis of increasing weekly tooth movement from 0.24 to 0.35 mm (or 0.15 mm/week) through the use of vibration. In reality, the ITT and PP AcceleDent groups achieved only a total movement of 1.16 and 1.25 mm per month, respectively (which equates to approximately 0.29 and 0.31 mm/week, assuming a four-week month). This makes the ob- served results incompatible with the initial goals of the sample size calcu- lation, which means this study is underpowered severely (it has a power of around 40%). These data also invite the question of what the clinical relevance of a 0.37 mm difference/month is when viewed in conjunction With both the Standard error of the difference and the error associated with the intra-oral measurements. Does it justify using an intra-oral vi- brational device for 20 minutes every day? Finally, the authors analyzed their data with a multi-variable model for multiple explanatory variables, which might render their results unstable, as no initial univariable model was reported and the limited study sample might not support the addi- tion of many covariates. Pain and Discomfort Pain is experienced commonly during orthodontic treatment with fixed appliances, particularly in the immediate stages following 97 Myths and Legends appliance placement (Kvam et al., 1989; Scheurer et al., 1996; Johal et al., 2014). Pain generally increases during the first few days after the appliance has been fitted and then begins to reduce (Jones and Chan, 1992; Otasevic et al., 2006; Scott et al., 2008; Pringle et al., 2009; Johal et al., 2014; Abdelrahman et al., 2015; Rahman et al., 2016). This cycle is repeated regularly during archwire progression and often requires the consumption of oral analgesics (Brown and Moerenhout, 1991; Johal et al., 2014). A number of studies have evaluated variations in appliance de- sign and their relationship to orthodontic pain, but little evidence exists of any clinically significant differences during alignment (Scott et al., 2008; Fleming et al., 2009; Pringle et al., 2009; Bertl et al., 2013; Rahman et al., 2016). Archwire materials also have been investigated, with martens- itic-active copper Niſi associated with greater pain intensity compared with martensitic-stabilized (Mandall et al., 2006; Ong et al., 2011) and super-elastic Niſi having a significantly higher peak pain when compared to multi-strand stainless steel (Sandhu and Sandhu, 2013). However, the effects of archwire type have been marginal in other studies (Sandhu and Sandhu, 2013; Abdelrahman et al., 2015) and while more evidence is needed (Riley and Bearn, 2009; Papageorgiou et al., 2014), it seems that clinically significant differences are unlikely to be seen in association with variation in archwire material. It has been suggested that supplemental vibrational force may have the ability to reduce pain and discomfort as- sociated with fixed appliance treatment. Until recently, the evidence for this was largely anecdotal, but in the last few years, several studies have been published that specifically investigate the effect of vibrational force on orthodontic pain and discomfort experienced during the early stages of fixed appliance treatment (Miles et al., 2012; Lobre et al., 2015; Wood- house et al., 2015a). Encouragingly, these studies all have adopted a pro- spective randomized methodology and we will consider them further. Pain and discomfort were investigated in association with use of the Tooth Masseuse vibrational appliance during the first week of treat- ment with fixed appliances in the study by Miles and colleageus (2012). Subjects completed a discomfort score chart using a Visual Analogue Scale (VAS) at five time points: immediately following appliance place- ment, at six to eight hours, one day, three days and one week. In addition, the subjects were asked to refrain from the consumption of analgesicS 98 Cobourne et al. containing lbuprofen because of the negative associations between non- Steriodal anti-inflammatory drugs and orthodontic tooth movement. In- terestingly, no significant differences in pain levels at any of the included time points could be found (Miles et al., 2012). Pain control in association with the use of AcceleDent in conjunc- tion with fixed appliances also was investigated as a primary outcome in a block RCT (Lobre et al., 2016). Specifically, overall and biting pain data were collected on a daily basis using a VAS for the first seven days of each month following appliance adjustment and averaged to provide a “first week” score. Pain was scored once weekly for the remainder of each month and averaged to give a monthly score. Data collection proceeded over a four-month period to give a total data set of 40 pain scores for each Subject. There was a dropout of 17% in each group during the four-month period of the trial. Interestingly, some of these subjects were excluded because of excessive use of pain medication, which seems somewhat Counterintuitive in an investigation of pain experience associated with a particular intervention. Usage compliance was verified electronically through a USB interface within the appliance itself, although no specific data was presented. Interestingly, there was a consistent and significant reduction in the perception of overall and biting pain in subjects using the AcceleDent device when compared to control groups (Lobre et al., 2016). When considering this investigation, it is useful to remember that the fundamental reason for adopting a prospective and randomized methodology for any clinical trial is to establish pre-treatment equiva- lence between experimental groups. This increases the likelihood that the experimental intervention is the sole difference between groups and, therefore, minimizes potential bias. Unfortunately, a number of impor- tant patient characteristics were not reported in this trial, which makes it impossible to know whether the groups were balanced and if randomiza- tion actually was successful. Were the two groups balanced in terms of Sex and age to avoid any ‘noise' in measured pain (Krishnan, 2007; Sand- hu and Sandhu, 2013)? Did the groups have similar amounts of crowding before treatment? Did any of the patients have dental extractions carried out prior to or during treatment? If so, could these factors have influ- enced subsequent pain perception? Did the two groups have identical appliances and archwire sequences during treatment? These important baseline demographics are not reported. 99 Myths and Legends A number of other issues also exist which, according to empirical evidence, are likely to introduce bias (Higgins et al., 2011). Using block randomization with a fixed rather than an unpredictable block size can compromise the success of this process (Schulz and Grimes, 2002b). Ad- ditionally, the authors did not indicate if the outcome assessment was reliable and valid; indeed, if the outcome assessors were blinded, even though in trials with subjective outcomes, a greater effect than appropri- ate randomization and allocation concealment can take place (Savović et al., 2012). There also are concerns about the possibility of selective out- come reporting, both in terms of elective post hoc reporting of outcomes (other data were compared graphically and, if indicated, statistically over the various time points; Lobre et al., 2015) and incomplete reporting (no standard deviations are given). Furthermore, subjects were selected from those presenting for initial orthodontic treatment — how were they selected? How many declined to participate? The casual mixing of pre- adolescent, adolescent and adult patients also may have confounded the trial results (Brown and Moerenhout, 1991; Krishnan, 2007). In addition, there are potential concerns relating to how the pain data was measured. The authors averaged pain data across the first seven days and then again within each month. There is good evidence that perceived pain dimin- ishes greatly during the first week of orthodontic treatment following appliance placement or adjustment (by approximately 30 mm on a VAS scale; Scott et al., 2008; Pringle et al., 2009; Abdelrahman et al., 2015; Woodhouse et al., 2015b). Averaging across time points dilutes the actual pain perceived, thereby explaining the considerably lower VAS scores re- ported in this trial and compromising the clinical relevance of this trial. SUPPLEMENTAL VIBRATIONAL FORCE DURING INITIAL ALIGNMENT WITH FIXED APPLIANCES: A RANDOMIZED CLINICAL TRIAL We carried out a three-arm parallel RCT to investigate the effects of a 20-minute regime of supplemental vibrational force using an Accele- Dent vibrational device during initial alignment with fixed appliances. The primary outcome for this investigation was initial rate of tooth align- ment in the mandibular arch. A secondary outcome was pain and dis- comfort during the week following placement of the fixed appliance and insertion of the initial 0.014" NiTi archwire. The results of this trial have 100 Cobourne et al. been reported in detail elsewhere; here we will present an overview of the data relating to the period of initial tooth alignment. Materials and Methods Ethical approval was obtained from the United Kingdom National Research Ethics Service (South East London REC 3: 11/LO/0056) and writ- ten informed consent was received from all parents, guardians and chil- dren. The trial was registered at www.ClinicalTrials.gov (NCT02314975) and is reported according to the CONSORT statement (Moher et al., 2010). Mandibular dental study casts were obtained at baseline (place- ment of upper and lower fixed appliances and insertion of a 0.014" Niſi archwire) and at initial alignment (placement of a 0.018” NiTi archwire). Tooth alignment was measured from dental stone casts using Little's Ir- regularity Index (1975). Rate of initial alignment was calculated as the difference in irregularity index of casts taken at baseline and initial align- ment divided by the number of days between measurements. Subjects reported pain and discomfort using a questionnaire: im- mediately after, four hours, 24 hours, three days and one week following their appointment by means of a 100 mm VAS using the terms “very com- fortable” and “very uncomfortable” as peripheral weightings (Seymour, 1982). Each subject was free to take non-prescription oral analgesics as necessary. Maximum pain, mean pain, reported analgesic usage and the number/type of oral analgesics taken during this period of treatment were recorded. Participants were recruited from the orthodontic departments at King's College London Dental Institute, UK (Guy's Hospital); Royal Alexan- der Children's Hospital (Brighton, UK); and William Harvey Hospital (Ash- ford, UK). Eligibility for the participants included the following require- mentS: 1. Under 20 years of age at treatment start; 2. No medical contraindications, including regular medi- Cation; 3. In the permanent dentition; 4. Mandibular arch incisor irregularity; and 5. Extraction of four premolars as part of the orthodon- tic treatment plan. 101 Myths and Legends Subjects were assigned randomly following recruitment independently from the clinical operators (allocation concealment; Schulz and Grimes, 2002a) to one of three groups: 1. Pre-adjusted edgewise fixed-appliance treatment with adjunctive daily use of a functional AcceleDent vibrational device (Accel group); 2. Pre-adjusted edgewise fixed-appliance treatment with adjunctive use of a non-functional (sham) AcceleDent device (Accel sham); and 3. Pre-adjusted edgewise fixed-appliance treatment alone (fixed-only group). Subjects allocated to functional or sham.devices were given direct verbal and written instruction on operation and usage. The fixed appliance was standardized between groups (MBT prescription pre-coated 3M Victory series, 3M Unitek, Monrovia, USA) and a pre-determined sequence of 0.014" and 0.018” NiTi archwires was used during the period of study. Archwire progression occurred only if full-bracket engagement was achievable; this required the relevant archwire to be tied fully into the base of the bracket slot adjacent to each tie-wing using elastomeric ligation. Results Eighty-one subjects were recruited to the study with 29 allocated to the Accel group, 25 to the Accel sham and 27 to the fixed only. The total sample (40 males and 41 females) had a mean age of 14.06 years [SD = 1.90]. Baseline demographics and characteristics of the randomized groups are shown in Table 1. A CONSORT diagram demonstrating subject flow through the initial alignment component of the trial is shown in Figure 2. A full dataset was obtained at initial alignment (placement on an 0.018” NiTi archwire), except for one subject allocated to the fixed- only group where the mandibular cast was lost. All subjects returned a completed pain questionnaire for the week following appliance placement, except for one (different) subject allocated to the fixed-only group. Missingness was not regarded as substantial and, therefore, was classified as missing at random. 102 Cobourne et al. Table 1. Baseline demographics and characteristics of randomized groups. SD = Standard deviation; Cl = confidence interval. Characteristic Accel group Accel sham Fixed only Mean age (years) [SD] 13.9 [1.6] 13.8 (1.7) 14.4 [1.9] Male/female 15/14 13/12 12/15 Trial site, n Guy's 5 5 8 Brighton 11 11 11 Ashford 13 9 8 Irregularity (mm) - mean [95% CI) Baseline (T1) 8.3 [6.7-9.9] 8.1 [6.8-9.5] 8.9 [7.4–10.5] Initial alignment (T2) 2.8 (1.8-3.8] 2.2 [1.4-3.0] 3.3 [1.9–4.7] Initial Alignment For the total sample, mean baseline irregularity index was 8.5 mm [SD = 3.8; 95% CI = 7.6 to 9.3] with no significant difference between groups (p = 0.73). Mean irregularity index for each experimental group at baseline and initial alignment is shown in Table 2. For the total sample, mean irregularity-index at initial alignment was 2.7 mm [SD = 2.8; 95% Cl = 2.2 to 3.4] with no significant difference between groups (p = 0.40). Change in irregularity index from baseline to initial alignment is shown in Table 2, with no significant differences between groups (p = 0.39). For the total sample, mean time to initial alignment was 59 days [SD = 25; 95% CI = 54.5 to 65.6]. Mean times (in days) to reach initial alignment from baseline are shown in Table 2; likewise, no significant differences between groups were found (p = 0.80). A representative subject is illus- trated in Figure 3. We also conducted multi-variable linear regression to control the effect of initial irregularity, age and intervention on initial rate of align- ment using baseline irregularity index as the covariate. Overall, there was no statistically significant difference on alignment rate in mm/day among the three study groups (Fig. 4). The most important influence on initial alignment was initial irregularity index. For each mm of initial irregular- ity, initial rate of alignment increased by 0.01 mm/day [95% CI = 0.005 to 0.01; p < 0.0001]. 103 Myths and Legends Assessed to eligibility in-89) Excluded [n=8] Declined to participate (n=3| | domized in-81 º B | & | C. º Acceledent (n=29] Sham (n=25] Fixed-only [n=27] Received intervention (m=29] Received intervention (n=25] Received intervention (n=27] º O -- a 5 - E. J. ; : C c Follow-up (n=29] Follow-up (n=25] Follow-up (n=26] G E Lost to follow up [n=0} Lost to follow up [n=0} Failed to complete pain diary (n=1 -- ſº E º c. º g º Analysed (n=29] Analysed In=25] Analysed (n=26] º * -- - -, * # = à º Follow-up (n=29] Follow-up (n=25] Follow-up [n=26] º º Lost to follow up [n-0) Lost to follow up [n=0} No initial alignment model (n=1} tº .ſº E º: º º - º Analysed In=29] Analysed In=25] Analysed (n=26] º Figure 2. CONSORT diagram showing the flow of subjects through the initial align: ment phase of the trial. 104. Cobourne et al. Table 2. Irregularity and time to initial alignment by randomized group (Wood- house et al., 2015a). Group n ſº (...) ". 95% CI Irregularity index [baseline] Accel-group 29 2.4 23.3 8.3 6.7 9.9 Sham-group 25 4.2 18.4 8.1 6.8 9.5 Fixed-only group 27 0.4 16.6 8.9 7.4 10.5 Irregularity index [initial alignment] Accel-group 29 O 11.0 2.8 1.8 3.8 Sham-group 25 O 9.7 2.2 1.4 || 3.0 Fixed-only group 26 O 11.2 3.3 1.9 4.7 Change in irregularity index [baseline to initial alignment] Accel-group 29 1.7 14.6 5.5 4.4 6.6 Sham-group 25 1.7 11.8 5.9 4.8 7.0 Fixed-only group 26 0.4 13.9 5.7 4.5 6.8 Time from baseline to initial alignment Group n º ſº ) ſº 95% CI Accel-group - 29 28 109 56.3 48.3 71.3 Sham-group 25 30 132 59.8 49 63.4 Fixed-only group 26 40 136 61 51.8 70.6 Pain and Discomfort Mean maximum pain for the total sample was 72.96 mm [SD = 21.59; 95% CI = 68.19 to 77.74 mm) with no significant differences among groups (Table 3; p = 0.282). Multi-variable regression for maximum pain indicated that even after accounting for all confounders (gender, irregu- larity index, use of oral analgesia and alignment rate; p > 0.05 in all cases), there were no significant differences between the Accel-sham or Accel- group and the control group (p = 0.978 and 0.121, respectively). However, Subject age was significant marginally, with younger subjects reporting higher maximum pain (p = 0.047). 105 Myths and Legends Figure 3. Treatment progress of a representative case from the trial. Subgroup analysis according to the use of oral analgesics (yes Of no) indicated that subjects taking analgesics reported slightly higher max imum pain compared to those who did not (75.24 mm versus 68.15 mm. respectively), although this was not significant statistically (Table 3; p * 0.170). Finally, the effect of intervention among groups was independent of whether or not oral analgesia was taken (p = 0.883). 106 Cobourne et al. Sham P = 0.200 Acceledent P=0.660 t t i i -0.02 -0.010 -0.005 o 0.005 0.020 0.040 Alignment rate (mm/day) - Figure 4. Forest plot of mean difference in tooth alignment rate (mm/day) in the Accel-group and Accel-sham patients compared to the control group. Horizontal lines for each box indicate the 95% confidence intervals of the difference. Table 3. Reported maximum pain from each subject and subgroup analysis ac- Cording to use of oral analgesia (Woodhouse et al., 2015b). SD = standard de- Viation; * = p value for differences among experimental groups from one-way ANOVA; = p value for differences between subgroups no/yes pain medication from independent t-test; t = p value for interaction between use of pain medica- tion and the three experimental groups from two-way ANOVA. Total Accel-group Accel-sham Fixed-only Sub p p upgroup n Mean (SD) value " Mean (SD) n Mean (SD) n Mean (SD) value Overal 81 72.96 (21.59) 29 76.28 (18.86) 25 67.32 (23.81) 27 74.63 (21.95) 0.282* Oral analgesia: No 26 68.15 (24.15) 0.170 8 71.63 (27.42) 10 61.80 (1833) 8 72.63 (28.38) 0.883' Oral analgesia: YES 55 75.24 (2010) 21 78.05 (14.93) 15 71.00 (26.82) 19 75.47 (1949) Mean pain intensity and reported use of oral analgesics among Éſoups also are shown in Table 4. Mean pain intensity varied consider- ably at the individual time points during the week after appliance place- "ent. Overall, a total of 55 patients (69%) reported taking any kind of oral analgesia. For all outcomes studied, no statistically significant difference Could be found among the three experimental groups (p → 0.003, due to Bonferroni Correction). 107 Myths and Legends Table 4. Alignment rate, mean pain and analgesia usage at each time point (Woodhouse et al., 2015b). SD = standard deviation; * = p value for differences among the three experimental groups from one-way ANOVA (except for analge- sia use, where chi-square test was employed). Due to the application of Bonfer- roni correction for the existence of 17 tests, p values < 0.003 are regarded as significant. Total Accel-group Accel-sham Fixed-only Time n Mean (SD) n Mean (SD) in Mean (SD) n Mean (SD) wº Alignment rate 80 0.10 (0.05) 29 0.10 (0.05) 25 0.11 (0.06) 26 0.10 (0.05) 0.655 Mean pain 0 hours 80 27.59 (24.44) 29 25.97 (22.80) 25 28.76 (24.68) 26 28.27 (26.74) 0.905 4 hours 80 48.15 (25.50) 29 46.34 (24.65) 25 48.56 (25.46) 26 49.77 (27.29) 0.882 24 hours 80 54.26 (27.04) 29 59.10 (22.39) 25 45.12 (28.89) 26 57.65 (28.71) 0.122 72 hours 80 36.26 (27.59) 29 40.14 (29.50) 25 28.88 (24.54) 26 39.04 (27.80) 0.272 1 week 80 19.65 (22.87) 29 22.03 (23.24) 25 15.68 (19.14) 26 20.81 (25.93) 0.573 Analgesia usage 80 55/80 (69%) 21/29 (72%) 15/25 (60%) 19/26(73%) 0.533 Ibuprofen taken 80 0.53 (1.18) 0.45 (0.74) 0.16 (0.47) 0.96 (1.80) 0,046 Paracetamoi taken 80 1.55 (2.43) 1.62 (3.09) 1.04 (1.27) 1.96 (2.44) 0.397 Multi-variable linear regression for mean pain intensity indicated that the only significant predictor was time (Table 5). A statistically and clinically significant increase in pain was seen at four and 24 hours follow- ing appliance placement, which declined at 72 hours and became insignif- icant at one week (Fig. 5). When taking into account possible confounders through multi-variable logistic or linear regression, the use of a function- al or sham AcceleDent device had no significant effect on reported use of oral analgesia or the number of oral analgesics taken after appliance placement. A marginally significant effect of subject age on number of paracetamol (acetaminophen) taken was seen during the first week after appliance placement (p = 0.043; data not shown; refer to Supplementary Table S4 in Woodhouse et al., 2015b), with older patients taking less an- algesia on average. DISCUSSION Woodhouse and associates' RCT (2015a,b) found that supple- mental vibrational force does not increase the rate of tooth movement significantly or reduce pain during initial alignment with a fixed appliance. Our findings are not in agreement with other clinical data showing AC- celeDent increasing rates of tooth movement in subjects who had under- gone fixed appliance therapy (Kau et al., 2010; Bowman, 2014; Pavlin et al., 2015). However, only one of these studies was prospective and meth- odological issues exist with them all, which make them susceptible to bias 108 Cobourne et al. Table 5. Multi-variable regression for mean pain (Woodhouse et al., 2015b). In- teraction term of time with group: after first visit; p = 0.566; after second visit: p = 0.549. Cl - confidence interval. T1 (n=80) Coefficient (95% CI) P value Gender –3.24 (-10.85,437) 0.404 Age –0.06 (-2.31,2.19) 0.959 Irregularity –0.06 (-1.14, 1.02) 0.913 Painkiller use 3.06 (-5.85,11.98) 0.501 - Accel group –0.18 (–9.46,-9.10) 0.970 Accel sham –4.11 (-13.63,542) 0.398 Fixed only Reference 0 hours Reference 4 hours 20.56 (14.04,27.08) <0.001 24 hours 26.68 (18.79,34.56) <0.001 72 hours 8.68 (1.19,16.16) 0.023 1 week –7.94 (–14.00,-1.88) 0.010 c n- T —e- Accel group (n=29] - o | | | | ------ Sham group (n=25 º co º ------ Fixed only group (n=26) º C O) Lo E - O º - C º 5 c ſu - C. co c ſu Q Q) CN s c - - º - I i I Oh 4h 24h 72h 1Whº º 5. Mean pain intensity scores during the first week following appliance .." according to the intervention administered. Vertical whiskers indicate * 95% confidence intervals of the mean. 109 Myths and Legends and a possible overestimation of treatment effects (Pandis, 2011). In- deed, our investigation, together with an additional prospective ran- domized evaluation of another vibrational device, found no differences in initial tooth alignment rates (Miles et al., 2012; Woodhouse et al., 2015a). We found no evidence of significant differences in orthodontic pain during initial alignment between subjects supplemented with wi- brational force and those treated with fixed appliances alone. The use of vibrational force also had no significant influence on reported use of analgesics. The only significant predictor of pain intensity was time, with marginally significant effects identified between maximum reported pain and subject age. Woodhouse and colleagues' RCT (2015a,b) represents high-qual- ity evidence regarding vibrational force supplementation and fixed appli. ance treatment. Subjects were allocated prospectively and randomized appropriately with allocation concealment. Relatively few subjects were lost to follow-up and the sample retained appropriate power. All three randomized groups were comparable for age, sex, recruitment site and irregularity index. The a priori sample size calculation was based upon the outcome of tooth alignment and not on the outcome of orthodontic pain. However, a previous investigation on fixed appliances during initial alignment indicated that a difference of 20 mm on the VAS scale would be significant clinically (Pringle et al., 2009). Post hoc power analysis, us- ing a three-group one-way ANOVA to identify the above-mentioned dif- ference indicated that our study had a power of >80% to detect a clini- cally meaningful difference in pain. Due to the broad inclusion criteria used, the balanced character- istics of the three groups and the internal validity of our study the results of this trial are applicable to most subjects under 20 years of age under- going routine orthodontic treatment with fixed appliances for the correc- tion of mandibular crowding. This is the first clinical trial to investigate orthodontic pain in association with use of the market-leading supple- mental vibrational device that adopts a RCT design and provides a high- level of evidence to inform clinical practice (Woodhouse et al., 2015a,b). No clinical study is perfect and inevitably there are limitations with the one described here. First of all, definitive compliance data relat- ing to use of the active and sham devices would have been desirable. Both appliances were provided directly by the manufacturer and fitted with electronic timers designed to measure usage. Unfortunately, these 110 Cobourne et al. timers proved to be unreliable and obtaining a definitive dataset to in- form the analysis was not possible. However, subjects were monitored Carefully for compliance during the trial, being asked to bring the appli- ance with them for use prior to each appointment, demonstrate con- tinued familiarity with operation and allow inspection for evidence of use. This was a pragmatic Study designed to investigate Supplementary vibrational force during routine everyday orthodontic practice as part of the overall management of subjects with malocclusion. It also should be noted that the first dataset relating to pain and discomfort was obtained during the week immediately following appliance placement. It might be expected that compliance levels with the vibrational device would be high in the period immediately after it had been provided to patient. Indeed, if they were not using it each day during this period of time, it might be reasonable to ask how usable such a device is in the ‘real world' in this age group of patients. A true blinding for the operators and pa- tients could not be performed due to practical reasons, but subjects were blinded to the allocation of functional or sham devices—even if the lack of vibration associated with the sham appliance meant that the specific allocation became apparent for some. However, outcome measurement and data analysis was masked completely. The presence of a sham group was important to eliminate the possibility of a placebo effect, particularly in relation to pain and discomfort. Despite these limitations, we believe that this investigation offers the highest level of evidence relating to clini- cal use of the AcceleDent vibrational device. CONCLUSIONS There currently are a number of adjunctive devices and tech- niques being advertised to both orthodontists and patients, all of which claim to increase treatment efficiency. It is important that the evidence base underlying these interventions is robust, otherwise patients and cli- nicians are being misled. The RCT described here found that supplemen- tal vibrational force does not increase the rate of tooth movement sig- nificantly or reduce pain during initial alignment with a fixed appliance. ACKNOWLEDGEMENTS The authors acknowledge the contributions of Nicola Johnson, Carmel Slipper, James Grant, Maryam Alsaleh and Nora Donaldson during 111 Myths and Legends the conduct of this trial (Woodhouse et al., 2015a,b). We also are grate- ful to Peter Miles for providing the Tooth Masseuse image and discussing unpublished data, and to Jay Bowman for an interesting discussion on his trial and all things rock 'n roll. 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Supplemental vibrational force does not reduce pain experience during initial alignment with fixed orth- odontic appliances: A multicenter randomized clinical trial. Sci Rep 2015b;5:17224. 117 118 A VIEW FROM THE CLINICAL TRENCHES: VIBRATION AND TOOTH MOVEMENT S. Jay Bowman ABSTRACT objective: The intent of the present study was to determine if the application of vibration would increase the rate of orthodontic maxillary first molar distal movement and reduce the time required for mandibular leveling. MATERIALS AND METHODS: Sixty adolescent Class Il patients, selected to undergo treatment with a miniscrew-supported molar distalization appliance, were split equally into two groups of similar demographics: 1) vibration patients (V) were asked to use a vibrational device 20 minutes/day (frequency of 30 Hz; force of 0.25 N); and 2) control patients (C) received the same distalization, including adjustments at four-week intervals, but without vibration. Pre- and post-distalization cephalo- grams were traced independently and superimposed to determine any differ- ences. Subsequently, a retrospective evaluation of the vibrational effects on time required to achieve mandibular leveling also was conducted. RESULTS: There was a trend for faster molar movement during distalization in the vibration group, but it was not significant statistically (1.12 mm/month versus 0.88 mm/month; V versus C; P = 0.053). Leveling of the mandibular dentition was achieved 30% faster (160 days versus 208 days; V versus C; P = 0.017). CONCLUSIONS: Faster mo- lar movement for the vibration group was not found to be significant statistically; however, 48 fewer days to achieve lower arch leveling with the vibration device was significant statistically. KEY WORDS: orthodontics, molar distalization, vibration, accelerated treatment, orthodontic leveling INTRODUCTION A variety of methods to accelerate the speed of orthodontic tooth movement and potentially decrease treatment time have been introduced in recent years; however, data thus far has been sparse to Support most (McNamara et al., 2011; Liou, 2012). There appears to be 119 Vibration and Tooth Movement interest from patients and practitioners for more effective biomechanics and shorter treatments (Uribe et al., 2014), but this does not imply that in pursuing those objectives, results of a lesser standard also would be acceptable to either group. The present chapter evaluates one method proposed for increasing the rate of tooth movement: vibration. Vibrational Effects on Tooth Movement Curiosity regarding the application of vibration to stimulate orth- odontic tooth movement began more than 30 years ago. Shapiro and colleagues (1979) described preliminary results using pulsating force- induced piezoelectricity to encourage tooth movement. In 1982, Craven Kurz was awarded a patent for a vibrating headgear/mouthpiece device. Four years later, Krishtab and co-investigators (1986) reported a 1.5 to 2.0.x increase in the rate of tooth movement with vibration (50 Hz for 60 to 360 seconds applied every two to three days). At the turn of the 21st century, attention turned to the biologic stimulation of tooth movement with vibration, which was evaluated with animal models. Investigators reported increased sutural responses (Ko- pher and Mao, 2003; Peptan et al., 2008) and more rapid tooth move- ment (Darendeliler et al., 2007; Nishimura et al., 2008). However, there also has been a hypothesized osteogenic effect from vibration (Alikhani et al., 2012). Kalajzic and associates (2014) and Yadav and colleagues (2015) described inhibition of tooth movement with vibration for rats during brief, two-week intervals. In contrast, Liu (2014) described 40% increased tooth movement over a four-week experimental period using mice. Orthodontic force coupled with cyclical force (i.e., vibration) ap- pears to affect tooth movement, but caution certainly is merited when attempting to apply the results from animal models to humans. Vibration may work both on a biological and a biomechani- cal level to affect Orthodontic tooth movement. Braun and coworkers (1999) credited the dynamic environment of the oral cavity (i.e., “vi- brational” perturbations) as the primary factor in moderating the rate of tooth movement with braces. Kennedy (2014) reported mechanical vibration-reduced sliding friction, whereas Seo and colleagues (2015) concluded there was reduction in both static and kinetic friction. Work- ers at the University of Missouri-Kansas City (Olson et al., 2012) reported that the amplitude of archwire vibrations was most important, which 120 Bowman refutes the simplistic claims that “reducing (elastic) friction” trims treat- ment time by merely choosing different brands of braces. Rather, it is inelastic friction (e.g., “notching” or stick-slip) that must be overcome with perturbations and all brackets are subject to that factor—we are not just sliding pearls along a String. Consequently, it appears that vibra- tion theoretically could affect the rate of orthodontic tooth movement in two ways: reducing the “lag" phase in tooth movement by stimulating changes in the periodontal apparatus; and/or by way of mechanical per- turbations. A pilot clinical trial at The University of Texas Health Science Center at Houston (Kau et al., 2010) was performed with fourteen pa- tients that were prescribed vibration (prototype AcceleDent device: fre- quency = 30 Hz, force = 0.25 N, duration = 20 minutes/day) concurrent with orthodontic treatment. With a 67% measured patient compliance, an increased rate of tooth movement (2.1 mm/month in the mandibular arch and 3 mm/month in the maxillary arch) compared favorably to the typically acknowledged rate of 1 mm/month. A follow-up randomized controlled trial (RCT) was conducted at The University of Texas Health Sci- ence Center at San Antonio (Pavlin et al., 2015) using the same vibrational characteristics; it demonstrated statistically significant reduced time to achieve both dental alignment and cuspid retraction. Both studies also reported no adverse effects from the process (e.g., additional root re- Sorption, pain or more loss of miniscrews). Workers at the Prince of Sonk- la University (Leethanakul et al., 2016) described a split mouth investiga- tion of greater rate of cuspid retraction and enhanced Interleukin-1 beta Secretion in crevicular fluid with the application of vibration. As a counterpoint, the effects of vibration using different proper- ties (111 Hz; 0.06 N; 20 minutes/day) on initial orthodontic alignment were examined using a split sample of 66 consecutive orthodontic pa- tients (Miles et al., 2012). No significant difference in the rate of align- ment between the two groups was found for patients appointed every five weeks over a brief 2.5-month period. In a follow-up investigation of the AcceleDent Aura device, no greater rate of increased arch pe- rimeter or improvement in Irregularity Index were found; however, the evaluation was only ten weeks in duration (Miles and Fisher, 2016). A prospective RCT from the United Kingdom (UK) also found no evidence that supplemental vibrational force significantly increased the rate of 121 Vibration and Tooth Movement tooth movement or reduced intervals to achieve dental alignment (Woodhouse et al., 2015a). Unfortunately, no information regarding pa- tient compliance using the vibrational devices was provided in either of these investigations. As a potential side benefit, the application of vibra- tion during orthodontic treatment may reduce the pain associated with the processes (Marie et al., 2003; Lobre et al., 2015), or it may not (Miles et al., 2012; Woodhouse et al., 2015b). Maxillary Molar Distalization and Mandibular Leveling Maxillary first molar distalization has been a commonly used method as part of the orthodontic correction of Class Il malocclusions. As a result, a significant number of reports describing the effects of distal- ization have been generated for a variety of techniques and the devices commonly employed (Ghosh and Nanda, 1996; Byloff and Darendeliler, 1997; Byloff et al., 1997; Patel, 1999; Runge et al., 1999; Brickman et al., 2000; Bussick and McNamara, 2000; Huerter, 2000; Davis, 2001; Guiter- rez, 2001; Lee, 2001; Ngantung et al., 2001; Bolla et al., 2002; Nishii et al., 2002; Chiu et al., 2005; Ferguson et al., 2005; Kinzinger et al., 2005, 2009; Kircelli et al., 2006; Escobar et al., 2007; Gelgor et al., 2007; Oberti et al., 2009; Cali, 2011; Caprioglio et al., 2011; Maino et al., 2013; Bowman, 2016b). The purpose of the present study was to determine if vibration would increase the rate of molar distalization and decrease the time to level the mandibular dentition. MATERIALS AND METHODS This exploratory prospective investigation was initiated with 65 Class Il patients, consecutively selected for treatment specifically using maxillary molar distalization (Bowman, 2016a). The patients were sepa- rated into two groups for comparison: vibration (V) and control (C). Thir- ty-four patients initially comprised the vibration sample; however, four were lost in the process: one declined to participate, one transferred away from the area and two withdrew (V, N = 30). The C group enrolled 31 patients; however, one was lost due to a change in treatment plan to extraction (C, N = 30). The final sample of 60 patients (Table 1) all were characterized as Class II (e.g., minimum of a unilateral half- to full-step Class Il mo- lar relationship) with mild to moderate crowding. They were treated 122 Bowman Table 1. Study Sample demographics and baseline characteristics. a = Fisher's exact test; b = two-sample t-test. Vibration Control P value N 30 30 Male 13 (43.3%) 13 (43.3%) Gender 1.00° Female 17 (56.7%) 17 (56.7%) Mean 13.1 12.9 Age (years) * ~ * 0.559 Standard deviation 1.3 1.1 Unerupted 5 (16.7%) 16 (53.3%) º Partially erupted 7 (23.3%) 3 (10.0%) 0.01. Erupted 18 (60.0%) 11 (36.7%) 3rd molar Present * * 27 (90.0%) 26 (86.7%) 1.00% Status Congenitally missing 21 3rd 3 (10.0%) 4 (13.3%) g molar Unerupted 8 (26.7%) 7 (23.3%) Maxillary Partially erupted 2 (6.7%) 0 (0%) 0.59% Canine status Erupted 13 (43.3%) 16 (53.3%) g Erupted facially 7 (23.3%) 7 (23.3%) non-extraction using a miniscrew-supported (6 mm thread length and 1.5 mm thread diameter), maxillary molar distalization device (Horseshoe Jet, AOA Labs, Racine, WI; Bowman, 2014c) and simultaneously treated with pre-adjusted 0.022” brackets (i.e., Butterfly System, American Orthodontics, Sheboygan, WI; Bowman and Carano, 2004; Figs. 1-4). Only the mandibular dentition received fixed brackets during the period of the present investigation. After the completion of distalization, the Horseshoe Jet then was "locked” to serve as indirect miniscrew anchorage for Subsequent retraction of the remaining maxillary teeth using upper brackets to complete treatment (Bowman, 2014c). It should be noted that all patients received the same treatment mechanics and were treated by the same practitioner. Orthodontic adjustments were prescribed Specifically at four-week intervals to ensure consistent management and timely evaluation of treatment progress. At the start of treatment, the 30 patients in the V sample were provided an AcceleDent vibrational device (frequency of 30 Hz, force of 123 Vibration and Tooth Movement Figure 1. Initial intra-oral photographs for patient in the late mixed dentition with deep anterior openbite. Figure 2. A: Vibrational device (AcceleDent) prescribed for use 20 minutes/day and patient appointed at four-week intervals. AcceleDent vibrational device de- livered a force of 0.25 N at a frequency of 30 Hz and was prescribed to be held between teeth 20 minutes/day. B: Patient from Figure 1 had Horseshoe Jet max. illary molar distalization supported with miniscrews with concurrent mandibular pre-adjusted fixed appliances. C. Cephalometric radiograph taken upon insertion of miniscrews, delivery of the distalizing appliance and lower fixed braces. 0.25 N, duration of 20 minutes/day; OrthoAccel, Bellaire, TX) with direct tions to hold the mouthpiece between their teeth 20 minutes/day during the course of their orthodontic treatment (Fig. 1). Except for receiving the vibrational device, all patients in both groups received the same pro- tocol for activating the Horseshoe Jet (i.e., the 240-gram open coil springs were re-compressed at each visit to maintain consistent force to push molars posteriorly). In a subsequent retrospective investigation of the effects of Viº bration on mandibular arch leveling (Bowman, 2004), the V sample Was compared to 37 control patients who received the four-week appoint- ment regimen of changing orthodontic archwires in the same sequence, 124 Bowman Figure 3. A-B: Class I molar relationship achieved in 167 days with a 2.0 mm/month rate of molar movement. C. Distalizing appliance "locked” to prevent further molar movement to support maxillary space closure With fixed appliances. Note eruption of previously impacted canine. D: Cephalometric radiograph taken at the completion of molar distaliza- tion to a “super” Class I molar position. Figure 4. A-B: Horseshoe Jet was converted to miniscrew-supported holding arch anchoring maxillary space consolidation. C. Horseshoe Jet and miniscrews re- moved after spaces closed. Treatment eventually was completed in 21 months With 19 visits (with no missed appointments or broken braces). exchanging wires to the next largest dimension that comfortably could be Seated completely into pre-adjusted 0.022.” brackets. The intent was to de- termine the time necessary to advance to rectangular wires of particular dimensions with and without the application of vibration. Neither distaliza- tion nor leveling results were dependent upon patient cooperation; how- *Yeſ, compliance in regularly applying vibration was an unknown variable. 125 Vibration and Tooth Movement Cephalometric Methods Standard digital lateral cephalometric radiographs were taken for all 60 patients immediately after the concurrent insertion of two miniscrew implants and delivery of the Horseshoe Jet appliance. At the completion of maxillary first molar distalization—determined by clinical observation (i.e., the mesiobuccal cusp of the first molar located distal to the buccal groove of the mandibular first molar: super-Class I)—post- distalization cephalograms were taken. All cephalograms were enhanced digitally for best hard tissue analysis and printed 1:1. Each cephalogram pair was hand traced in a single sitting by an independent cephalometrician with over 55 years of experience; this professional was blinded to the type of treatment pro- vided to each patient. Coordinated tracings of each pair (pre- and post- distalization) were based on Björk's putatively stable structural landmarks in the cranial base and midface, and were superimposed regionally using fiducial lines of the Pitchfork Analysis (Johnston, 1996). All measurements were made to the nearest 0.1 mm with digi- tal calipers; changes in position of the maxillary first molar relative to a common Mean Functional Occlusal Plane (MFOP) and cranial base were recorded (Tables 2 and 3; Fig. 5). Intra-examiner reliability was tested by random selection, using a table of random numbers, often subjects for a second set of cephalometric tracings and superimpositions. A Intraclass Correlation (Portney and Watkins, 1993) was calculated for each pair of cephalometric measurements and demonstrated individual measure- ment reliability (Table 4). Leveling Assessment As this was a retrospective investigation, there was no fore- thought to collect records at time points representing the completion of the leveling. Therefore, no objective comparative analyses (e.g., PAR, Irl or ABO scores) were possible. Consequently, for the purposes of the present study, a different definition for achieving leveling was required. Definition of Leveling The time to attain leveling of the mandibular dentition was designated by the duration required for vertical and rotational dental discrepancies to be oriented sufficiently to allow complete seating of a rectangular stainless steel archwire with a minimum dimension of 126 Bowman Table 2. Cephalometric values. a = two sample t-test, NS = non-significant; * = P × 0.1. Vibration Control (N = 30) (N = 30) Mean SD | Mean SD P value | Sig U6 distalization (U6-MFOP; mm) 6.9 2.21 6.0 2.50 0.161° NS U6 distalization (PTV-U6 centroid; mm) TO 22.0 3.77 21.5 3.41 0.643° NS T1 15.2 4.37 15.7 4.43 0.661° NS U6 distalization (T1-T0) –6.8 1.91 –5.9 2.26 0.090° -k U6 vertical change (PP-U6; mm) TO 19.1 2.41 19.2 2.38 0.809a NS T1 17.0 2.66 17.1 2.94 0.836° NS U6 intrusion (T1-T0) –2.2 1.43 –2.2 1.72 0.968° NS U6 tipping (SN-U6; degrees) TO 71.4 6.53 74.3 6.63 0.0954 sk T1 58.6 7.88 59.4 6.54 0.327° NS Tipping (T1-T0) -12.6 8.15 –14.5 6.38 0.809° NS Table 3. Rates of distalization. A = two sample t-test; NS = non-significant; ** = P < 0.05. Vibration Control (N = 30) (N = 30) Mean SD Mean SD P value | Sig U6 root apex distalization (mm) 2.9 1.58 1.7 2.43 0.032a | ** Days to distalize to super-Class | 200.1 || 45.10 227.2 || 71.61 || 0.085° NS Daily rate of distalization (mm/day) 0.04 .016 || 0.03 .014 || 0.053° NS Monthly rate of distalization (mm/month) 1.12 0.497 || 0.88 0.439 || 0.053" | NS Figure 5. Distal movement of the maxillary first molar mea- Sured from a line perpendicular to the Mean Functional Occlu- Sal Plane (MFOP) to the molar's mesial contact point. 127 Vibration and Tooth Movement Table 4. Cephalometric error study. Intra-class correlation. U6 Apex Distalized SN-U6 PP-U6 PTV-U6 Distal Error . Apex- |CC 0.845 O.937 0.946 0.849 0.724 0.779 O.796 0.899 0.019" x 0.025" or larger into 0.022” x 0.028” slot orthodontic brackets (Bowman, 2014c). All patients began tooth movement with the insertion of a 0.016" nickel titanium (NiTi) wire, most often followed by 0.017" x 0.025" Niſi, before inserting the larger steel working wire. The same orthodontist made the clinical decisions for all patients who were chosen for the same type of treatment mechanics and treated consecutively. Therefore, it seemed reasonable that reliable comparisons could be made. RESULTS Molar Distalization Analysis of variance (ANOVA) demonstrated no statistically sig- nificant differences between the V and C groups in terms of gender, age, cuspid eruption or third molar status. There was a significant difference, however, in regard to second molar eruption status (P<0.01): 25 patients from the V group began distalization with second molars partially or com- pletely erupted, whereas the C group had fourteen (Table 1; Bowman, 2016a). There were no statistically significant differences in cephalo- metric parameters between the two treatment groups in regard to the amount of upper first molar tipping (1/SN), intrusion (vertical 6/MFOP), amount of molar distalization (horizontal 6/MFOP; 6/NiTi) or the number of days required to achieve a super-Class I molar relationship (Tables 2 and 3). The patients using vibration demonstrated a trend toward faster molar movement (1.12 mm/month versus 0.88 mm/month; V versus C); however, the difference was not significant statistically (P = 0.053). There was 71% greater rate of first molar root apex movement with vibration (2.9 versus 1.7 mm; V versus C; P = 0.03) that was sig- nificant statistically. Therefore, for each millimeter of distalization there 128 Bowman was approximately 0.4 mm of root movement and 1.8° of crown tipping with vibration compared to 0.3 mm of root movement and 2.4° of tipping for the Controls. Mandibular Leveling The interval to achieve leveling for the V group was less than the C sample (160 versus 208 days). Specifically, the rate of leveling with vi- bration was 30% faster than without (requiring slightly more than five months to achieve the goals, compared to seven months for controls). Consequently, the differences in the rate of leveling were significant both clinically and statistically (Table 5; Bowman, 2014c). DISCUSSION Molar Distalization Moving Class || molars distally into Class | typically requires ap- proximately four to eleven months and results in 15-60% anchorage loss (Bolla et al., 2002). Interestingly, Burkhardt and coworkers (2003) re- ported that the contribution from mandibular response for either molar distalization (Pendulum) or fixed functionals (Herbst) was nearly identi- Cal. This reiterates the conclusion that the Correction of Class II for the growing individual is not due primarily to moving molars back or tugging mandibles forward, but rather from the interruption of dentoalveolar Compensation (Bowman, 2014a). The Distal Jet appliance (American Orthodontics, Sheboygan, WI) and modifications of this device have been the subject of a num- ber of publications (Table 6; Patel, 1999; Huerter, 2000; Davis, 2001; Table 5. Time to achieve mandibular dental aligning and leveling. * = P × 0.05; AD = AcceleDent. Parameter AcceleDent Control P value” Time to NS (0.1005 N 30 37 Time to N 129 Vibration and Tooth Movement Table 6. Comparisons among various distalizing methods. investigators Appliance Distalization | Tipping | Months ſº o) Brickman et al., 2000 Jones jigs 2.7 7.1 6 0.45 Pendulum 3.4 14.5 4.1 0.83 Byloff et al., 1997 g Pendulum modification 4.1 6.1 6.8 0.69 Runge et al., 1999 Jones jigs 2.2 2.1 5 0.40 Bººk and McNamara. Pendulum 5.7 10.6 7 0.81 Distal jet/ braces 2.8 5.0 10 0.28 Chiu et al., 2005 Distal jet 3.4 3.8 10.5 0.32 Pendulum 6.1 10.7 7 0.87 Bolla et al., 2002 Distal jet 3.2 3.1 5 0.64 Patel, 1999 Distal jet 1.9 2.2 10.5 0.18 Distal jet/ Huerter, 1999 braces 3.1 5.6 6.8 0.46 Distal jet 3.7 7.3 5.6 0.66 Gutierrez. 2001 & * p Distal jet/ braces 2.6 4.7 7.8 0.33 Ngantung, 2001 Distal jet 2.1 3.3 6.7 0.31 Lee, 2001 Distal jet 3.2 2.8 7 0.46 Davis, 2001 Distal jet 3.0 6.0 7.9 0.38 Greenfield 3.9 6.5 11 0.35 Ferguson et al., 2005 Distal jet 3.4 3.2 8 0.43 Sagittal/ headgear 2.1 13.5 7 0.30 Fast-back 4.2 2.2 9 0.47 Caprioglio et al., 2011 Pendulum 5.2 9.7 8 0.65 & MGBM Maino et al., 2013 System 4.1 10.5 8 0.51 Nishii, 2002 Distal jet 2.4 1.9 6.4 0.38 Ghosh and Nanda, 1996 Pendulum 3.4 8.4 6.2 0.55 Kinzinger et al., 2005 Pendulum K 3.5 4.2 5.5 0.64 Kircelli et al., 2006 Penºm/ 6.4 10.9 7 O.91 Escobar et al., 2007 renºm/ 6.0 11.3 7.8 0.77 130 Bowman Table 6, Continued Investigators Appliance Distalization | Tipping | Months tºo Gelgor et al., 2007 Nance/TAD 3.9 0.8 5.4 0.72 Kinzinger et al., 2009 Distal jet/TAD 3.9 3.0 6.7 0.58 tº Dual-force/ Oberti et al., 2009 TAD 5.9 5.6 5 1.18 Frog/TAD 2.6 4.4 7.5 0.34 Cali, 2011 Distal jet 2.7 4.7 7 0.39 Bowman modification jet 3.9 4.6 7.7 ,0.51 Horseshoe jet/ Present sample TAD 6.0 14.5 7.6 0.88 (Bowman, 2016) Horseshoe jet TAD/vibration 6.9 12.6 6.7 1.12 Guiterrez, 2001; Lee, 2001; Ngantung, 2001; Bolla et al., 2002; Nishii et al., 2002; Chiu et al., 2005; Ferguson et al., 2005; Kinzinger et al., 2009; Cali, 2011; Bowman, 2016b). More recently, miniscrew anchorage has been added to reduce untoward anchorage loss as a result of recipro- Cal forces applied to the anterior dentition in the original design of this device. When miniscrews have been incorporated into appliance designs that include support from premolars, anchorage loss still occurs (Kinz- inger et al., 2000, 2006). This is due to the fact that miniscrews do not provide absolute anchorage and as forces are applied, Screws move (Liou et al., 2004; El-Beialy et al., 2009; Alves et al., 2011; Chatzigianni et al., 2011)—tipping forward in response and allowing the premolars to move anteriorly (Kinzinger et al., 2006; Bowman, 2014c). The current design of the Horseshoe Jet used in this study eschews any premolar supports, thereby ensuring that anchorage support is derived exclusively from the miniscrews and prevents anterior anchorage loss, despite the inconse- quential fact that the miniscrews are free to tip. Although miniscrews can be inserted in a variety of favorable palatal locations with the Horseshoe Jet design (Ludwig et al., 2011), all were placed in the palatal alveolus between the maxillary first molars and Second premolars about 5 mm from the marginal gingiva. A total of 120 miniscrew implants (6 mm thread length and 1.5 mm thread di- ameter) were inserted, two per patient, to provide anchorage for the 131 Vibration and Tooth Movement Horseshoe Jet appliances. The overall failure rate was 8% with a total of ten miniscrews lost (six for V versus four for C) during the course of time required to complete this study. There was no significant difference in the number of screws lost between the two experimental samples, confirm- ing previous reports that vibration does not appear to increase the risk of miniscrew failure (Miura et al., 2014; Pavlin et al., 2015). Effects of Vibration on the Rate of Distal Molar Movement The 60-patient sample (Table 1) examined in the present study was treated in the same practice with the same device (Horseshoe Jet) by the same practitioner and included a well-matched, consecutively treat- ed group of 59 Caucasian and one Asian adolescents featuring similar Class II malocclusions. There was one exception: half of the sample (N = 30) was prescribed a vibration device to use 20 minutes/day. Unfortu- nately, a split-mouth experimental design was not feasible for this study for two reasons: 1. It is difficult to delineate between the right and left molars in cephalometric tracings; and 2. The effects of vibration appear to be transmitted across the palate to the contralateral dentition (Liu et al., 2013). Five patients were lost from an initial enrollment of 65, meaning that every consecutive adolescent patient that presented with charac- teristics typically chosen for distalization initially agreed to participate. Subsequently, three withdrew due to their inability to comply with the regimen of regular four-week appointments. One patient was lost due to a change in treatment plan involving extractions and another transferred out of the area. The remaining 60 patients were treated consecutively with molar distalization, a method consistently prescribed for more than 800 patients in the same private practice over the past eighteen years. These factors reduced the potential for sample selection bias. The results of molar distalization for both groups was similar, as demonstrated by the minimal differences in cephalometric values for the amount of distalization, molar tipping and molar intrusion (Table 2); this perhaps confirms little potential for Observer or Hawthorne effects 132 Bowman especially since the tested mechanism involved only simple re-compres- Sion of Coil springs at each visit and no reliance on patient compliance. In addition, all pairs of cephalograms were traced by hand independently and Superimposed to eliminate bias by an independent cephalometrician who was blinded as to the treatment provided. Although slightly more molar movement on average was achieved in the vibration group (6.9 mm versus 6 mm), there was 2" more molar tipping for the control group, but these findings were not signifi- cant statistically. Despite the difference in the number of patients with partially or completely erupted second molars (25 versus 14; V versus C), the characteristics of distalization appear to be affected minimally, con- firming previous findings (Bolla et al., 2002; Maginnis, 2002; Flores-Mir et al., 2013). On average, molars in both samples were intruded about 2 mm and tipped 11-15" due to the cantilever nature of the Horseshoe Jet appliance, which is the apparent trade-off for the benefits of precluding any possible anchorage loss by avoiding premolar supports in the design of this appliance. Reporting on the time required to achieve molar distalization is Subjective as there is no consensus as to the exact determination of the final molar position designated as “distalized.” For instance, molars in the V Sample could have been declared as Class I earlier than C group molars or vice versa if there was an intent to bias. In actuality, all molars were pushed beyond Class I in an attempt to avoid any concerns of such biases. In terms of the time required to distalize, the V sample achieved super- Class I molar relationship in 200 days, compared to 227 days for the C group; however, this 27-day difference was not significant statistically (P = 0.08). The average 6.7 months to distalize the molars for the vibration group was much the same as described in previous Distal Jet distalization Studies (five to eleven months; Table 6), but the 6.9 mm of distalization was nearly 2x that described in prior reports (2.1 to 3.9 mm; Patel, 1999; Huerter, 2000; Davis, 2001; Guiterrez, 2001; Lee, 2001; Ngantung et al., 2001; Bolla et al., 2002; Nishii et al., 2002; Chiu et al., 2005; Ferguson et al., 2005; Kinzinger et al., 2009; Cali, 2011; Bowman, 2016b). The current Vibration Sample using the Horseshoe Jet appliance also can be compared to other types of molar distalizing appliances (Table 6). 133 Vibration and Tooth Movement The purpose of this investigation was to determine if the daily application of vibration during maxillary first molar distalization could af. fect the rate of tooth movement. There was a trend toward a significant difference between the treatment groups for distalization rate (P = 0.053) with average rates of 1.12 and 0.88 mm/month for V and C subjects, re- spectively, with the V group demonstrating 27% greater rate of distaliza- tion (Table 4). Interestingly, a statistically significant 71% increased rate of first molar root apex movement also occurred with vibration (2.9 versus 1.7 mm; V versus C; P = 0.03). Effects of Vibration on the Rate of Leveling and Alignment In the present study, a three-wire sequence (similar to that used in previous investigations; Mandall et al., 2006; Flores-Mir, 2007) was used to reach a “working” rectangular steel wire in the mandibular den- tal arch. This leveling process required five months with AcceleDent and up to seven months for the controls, which was a statistically significant difference between the two groups (160 days [V] versus 208 days [C]; P = 0.02; Table 5). This was less time to level than Mandall and associates reported (2006), but more than reported by Ong and coworkers (2001). It should be noted that both of these groups were evaluating treatments without supplemental vibration. The variation between the current re- sults and those of Ong and colleagues (2001) may have confirmed their supposition that the difference in tolerances between 0.022” versus 0.018” slots affected the rate of alignment, especially since succeeding wires were inserted as soon as deemed possible during both studies. Un- fortunately, no prospective plans had been made prior to gathering re- cords in the present study for comparisons of objective scores for leveling and alignment. Nevertheless, as a retrospective analysis, there was no in- troduction of Hawthorne Effect or bias (e.g., altering archwire sequences preferentially among the two samples). Kau and coworkers (2010) conducted a preliminary clinical trial with fourteen patients who were prescribed 20 minutes/day of vibration with an AcceleDent prototype with a 67% measured rate of compliance. The rate of mandibular tooth movement was reported to be 2.1 mm/ month or 2x the traditionally reported rate and 3 mm in the maxillary arch. Pavlin and colleagues (2015) directed a more comprehensive fol- low-up RCT and reported the rate of initial maxillary dental alignment for 23 premolar extraction patients was 2.7 mm/month when using 134 Bowman AcceleDent. This resulted in a 51% time savings to achieve maxillary den- tal alignment Compared to controls and had no adverse findings (e.g., additional root resorption or pain). In comparison to Kau and associates (2010), the present results also demonstrate more rapid mandibular “alignment” with vibration, but the differences were not significant statistically (vibration seemed to con- tribute to 29% faster alignment, at approximately 27 days less; P = 0.1; Table 5). It is important to note that without some reduction in time to accomplish alignment with vibration, there would not have been a statis- tically significant, cumulative reduction in time to complete leveling. Per- haps, it requires some treatment time for the effects to be seen, as teeth do not just suddenly "jump” after a few vibration applications. In contrast, Miles and associates (2012) evaluated the initial den- tal alignment of 66 consecutive orthodontic patients, appointed every five weeks over a brief 2.5-month period. Half of the patients were given a Tooth Masseuse vibrational device (111 Hz; 0.06 N) to use 20 minutes/ day. No significant difference was found in the amount of alignment be- tween the two groups. However, the investigators acknowledge the dif- ference in results from the previously mentioned studies may have been due to the fact that their RCT used: 1. Consecutive patients rather than a more homoge- neous sample; 2. The duration of the investigation was only ten weeks; and 3. The vibrational forces were applied at a high frequen- cy and lower force. The present results, in contrast to those of Miles and associates (2012), demonstrated faster alignment with vibration; however, differenc- eS from both studies were not significant statistically (Bowman, 2014b). It is important to note that Miles' team discontinued data collection strictly at the end of ten weeks of treatment, whereas the present investigation Spanned more than 30 weeks. In addition, the force and frequency of Vibration was different substantially for the two studies, with a lower frequency and higher force employed in the present study. As yet, it is unknown how altering these vibrational properties (e.g., force, frequent, duration) may factor into the effects on the rate of tooth movement. 135 Vibration and Tooth Movement A subsequent evaluation of the AcceleDent Auradevice (Miles and Fisher, 2016) elected to forgo measuring dental alignment in this fol- low-up of a previous vibration study (Miles et al., 2012). Instead, they re- ported no effects of vibration on the speed of increasing mandibular arch perimeter and irregularity. They examined only six lower, bracketed ante- rior teeth with only a 0.014" Niſi wire during an abbreviated ten-weekin- vestigation. It is noteworthy that there was no change in biomechanics or archwire changes and that the investigators chose a study period often weeks, despite previous findings showing no statistically significant ef- fects of vibratory stimulation, even after 90-120 days of alignment (Miles et al., 2012; Bowman, 2014b; Miles and Fisher, 2016). It was not until a period of 160 days for leveling that effects rising to significance were noted (Bowman, 2014b). Perhaps some effects may have been noted (or not) if the observations had been made for a more extended period of time; otherwise, it seems the lack of results they obtained were simply as one would expect from previous observations (Miles et al., 2012; Bow- man, 2014b; Miles and Fisher, 2016). Woodhouse and colleagues (2015) conducted a prospective RCT with three samples: vibration (N = 29); “sham” non-working vibrator (N = 29); and no device (N = 27)—all treated with fixed edgewise appli- ances and premolar extraction treatment. They found no reduced time to achieve final alignment (e.g., insertion of a 0.019" x 0.025" archwire into a 0.022" slot) accompanying vibration (averaging 209 +/- 65 days). Interestingly, no change in biomechanics was attempted in this study as patients were appointed in loose, six-week intervals with no reporting of missed appointments in multiple practices. If there was an expectation of more rapid tooth movement, it would seem likely at least that there should have been an anticipation of changing archwires and evaluating the effects more frequently. Perhaps periods of increased tooth move- ment might have been missed (Grauer, 2015). It was noted by Cobourne (2016), an author in the Woodhouse group at the 2015 Moyers Symposium, that patients given one of two devices (functioning or sham) were informed that the one they received “might be non-functional.” Unfortunately, Cobourne stated that compli- ance data was incomplete because they found that the built-in timers “proved to be unreliable” and working replacements were not delivered to the patients. Just because devices are dispensed to patients does not 136 Bowman guarantee even sporadic use. It would have been handy to know if any of those folks with active vibration devices used them consistently. Effects of Compliance As an aside, the total number of missed appointments from about 600 visits (60 patients seen every four weeks over approximately ten months) in the present evaluation was only six for the V sample and ten for the C patients. There also were no differences in orthodontist- assessed oral hygiene, graded at each visit, between the groups. Addi- tionally, the V group had four broken brackets, whereas the C sample had two from the 600 bonded braces placed in the mandibular arch for 60 patients. These factors describe a reasonably cooperative group overall, although neither distalization nor leveling procedures are driven by com- pliance. Therefore, any effects from the application of vibration should be apparent readily. The AcceleDent unit featured a charging base that recorded the number of daily uses of the device during a 30-day interval of treatment. All 30 V patients were instructed to bring the device to appointments every four weeks so that data could be collected. The average number of uses of the device for the entire group was 16.7 days/month over ten months of gathering data. In other words, the V group used the devices on average about 56% of the prescribed time—with some patients dra- matically more compliant than others (Table 7; Bowman, 2016a). Woodhouse and coworkers (2015a) reported that final align- ment (i.e., leveling) required 209 days to achieve for both those using Vibration and those who did not. In contrast, patients in the present study Table 7. Compliance with vibration versus effects. The top 20% most and 20% least compliant patients compared in terms of average number of vibration ap- plications/month, rate of distalization, time to achieve Class I by distalization and time to align the mandibular dentition (Bowman, 2016a). * | 29.6 ſ 27s | 260 l 25.3 || 24.1 | 24 26.1 | 2.8 3s 5.7 | 60 | 8.0 | 10s s.1 0.796 || 0.782 2.116 0.859 0.811 || 2.003 || 1.230 | 1.297 || 0,581 || 0.863 || 0.599 || 1.141 || 0.849 0.888 191 175 115 245 225 167 186 211 288 229 254 120 215 220 67 37 90 55 57 84 65 119 228 80 60 48 100 105 137 Vibration and Tooth Movement used vibration an average of 17x/month and achieved leveling in 160 days. Curiously, the current control group required 208 days—nearly identical to the vibration group from the UK (Woodhouse et al., 2015a). Since compliance was not measured in the UK study, we simply may be left with the difference in reported effects possibly being due to a lack of cooperation in using the vibration device. The present results appear to compare favorably with other re- ports describing the effects of vibration on orthodontic tooth movement: 1. Nearly 3x the typically reported rate of tooth move- ment of 1 mm/month in the maxilla (Kau et al., 2010); 2. 1.5 to 2.0x decreased duration required to move a tooth (Krishtab et al., 1986); '. 3. More rapid canine retraction 1.4 versus 0.9 mm/ month (Leethanakul et al., 2016); and 4. A 38–50% increased rate of extraction space closure (Pavlin et al., 2015). Pavlin and coworkers (2015) reported that vibration cut 28 days from the typical six to seven months required for maxillary extraction space clo- sure. These findings are similar to the 27-day reduction with vibration from the characteristic seven to eight months required to achieve molar distalization for patients found in the present investigation. Although the current results indicate a positive increase in the rate of orthodontic tooth movement accompanying the application of Wi- bration, extrapolating those effects to a reduction in overall clinical treat- ment time warrants additional investigation considering the multi-facto- rial and subjective nature of what constitutes “finished” results. In addi- tion, the positive effects from vibration may be dependent substantially upon patient compliance with consistent, daily application as a key. Until we have more definitive results, we are left with a cost/benefit analysis for the clinical application of vibration, one that depends upon the time value of money and money value of time (Iyer, 2003; Uribe et al., 2014). Limitations to the current investigations include no blinding of assessors (except the cephalometrician) and no sham device in the con- trol group. 138 Bowman CONCLUSIONS In the present prospective investigation, the rate of maxillary first molar distal movement produced using a miniscrew-supported molar distalizing appliance (Horseshoe Jet) was increased modestly—but not significant statistically—by 20-minute/day application of vibration (Ac- celeDent). Specifically, the rate of molar movement was 1.12 mm/month with vibration versus 0.88 mm/month without, with a P value of 0.053. However, a 71% increased rate of first molar root apex movement with vibration (2.9 versus 1.7 mm; V versus C; P = 0.03) was significant statisti- cally, as was a 30% increased rate of leveling of the mandibular dentition (160 versus 208 days; V versus C; P = 0.02). 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J Orthod 2001;38(1):32-39. Patel AN. Analysis of the Distal Jet appliance for maxillary molar distal- ization [Master's Thesis]. Oklahoma City, OK: University of Oklahoma 1999. Pavlin D, Anthony R, Raj V, Gakunga PT. Cyclic loading (vibration) accel- erates tooth movement in orthodontic patients: A double-blind, ran- domized controlled study. Sem Orthod 2015;21(3):187-194. Peptan Al, Lopez A, Kopher RA, Mao JJ. Responses of intramembranous bone and sutures upon in vivo cyclic tensile and compressive loading. Bone 2008;42(2):432-438. Portney LG, Watkins MP. Foundations of Clinical Research: Applications to Practice. Norwalk, CT: Appleton & Lange 1993;509-516. Runge ME, Martin JT, Bukai F. Analysis of rapid maxillary molar distal movement without patient cooperation. Am J Orthod Dentofacial Or- thop 1999;115(2):153-157. Seo Y!, Lim BS, Park YG, Yang IH, Ahn SJ, Kim TW, Baek SH. Effect of tooth displacement and vibration on frictional force and stick-slip 145 Vibration and Tooth Movement phenomenon in conventional brackets: A preliminary in vitro mechan- ical analysis. Eur J Orthod 2015;37(2):158-163. Shapiro E, Roeber FW, Klempner LS. Orthodontic movement using pulsat. ing force-induced piezoelectricity. Am J Orthod 1979;76(1):59-66. Uribe F, Padala S, Allareddy V, Nanda R. Patients', parents', and orthodon- tists’ perceptions of the need for and costs of additional procedures to reduce treatment time. Am J Orthod Dentofacial Orthop 2014;145(4 Suppl):S65-S73. Woodhouse NR, DiBiase AT, Johnson N, Slipper C, Grant J, Alsaleh M, Donaldson AN, Cobourne MT. Supplemental vibrational force during orthodontic alignment: A randomized trial. J Dent Res 2015a;94(5): 682-689. * Woodhouse NR, DiBiase AT, Papageorgiou SN, Johnson N, Slipper C, Grant J, Alsaleh MM, Cobourne MT. Supplemental vibrational force does not reduce pain experience during initial alignment with fixed orth- odontic appliances: A multicenter randomized clinical trial. Sci Rep 2015b:27(5);17224. Yadav S, Dobie T, Assefnia A, Gupta H, Kalajzic Z, Nanda R. Effect of low- frequency mechanical vibration on orthodontic tooth movement. Am J Orthod Dentofacial Orthop 2015;148(3):440-449. 146 PIEZO-CORTICISION-ASSISTED ORTHODONTICS: TRUTH AND MYTHS Clarice Nishio, Julien Strippoli, Robert Durand ABSTRACT Piezo-corticision is a new type of corticision-assisted orthodontic treatment, which consists of performing corticotomies on the alveolar bone using a piezo- electric device, without the need for a full gingival flap. The purpose of this meth- od is to create injuries in the bone, which consequently will induce the regional acceleratory phenomenon (RAP). The RAP is characterized by a confluence of biological events that include the stimulation and activation of the periodontal cells. This phenomenon accelerates the physiologic healing, decreases hyaliniza- tion areas, creates a transitory osteopenia and an increase in the bone turnover rate. Consequently, the acceleration of existing biological mechanisms leads to a hastening in tooth movement. While there is evidence to show that piezo-corti- cision is an effective and safe method to accelerate the rate of orthodontic tooth movement, few studies with low risk of bias have been published to assess the effectiveness of this technique in reducing the treatment length, potential iat- rogenic effects and long-term stability. The purpose of this chapter is to provide an updated review of the literature on piezo-corticision, to describe the mecha- nisms by which this method increases the rate of tooth movement and to discuss the issues of patient acceptance, safety and the cost/benefit ratio of this new type of corticision. KEY WORDS: piezocision, corticision, accelerating tooth movement, bone remod- eling INTRODUCTION The development of methods to accelerate tooth movement has been one of the main goals in the contemporary research field. Diverse factors have contributed to this increased interest in reducing treat- ment duration. There is ample evidence to show that prolonged treat- ment can be associated with the development of caries, decalcification, gingival recession, root resorption, alveolar bone loss and discomfort 147 Piezo-corticision-assisted Orthodontics (Gkantidis et al., 2014). While the number of adult patients seeking orth- odontic treatment to improve esthetics and/or a functional occlusion has increased significantly in recent years, long treatment time still rep- resents an important reason that discourages this specific group of pa- tients from proceeding with orthodontic treatment (Nimeri et al., 2013; Aksakalli et al., 2016; Tsichlki et al., 2016). Reducing the length of treat- ment, therefore, has become a key goal for Orthodontists, as it not only would decrease the risk of negative side effects, but also would increase patient satisfaction. The novel techniques introduced to accelerate tooth move- ment can be categorized briefly as non-surgical and surgical. The non- surgical approaches include laser therapy, photobiomodulation (Ya- maguchi et al., 2010), pulsed electromagnetic fields (Showkatbakhsh et al., 2010), pharmacological treatment (McGorray et al., 2012) and resonance vibration (Nishimura et al., 2008). The surgical techniques include distraction of the dentoalveolar bone (Kišnisci et al., 2002) and/ or periodontal ligament (Liou and Huang, 1998), corticotomy (Wilcko et al., 2001), corticision (Kim et al., 2009) and micro-osteoperforation (Alikhani et al., 2013). Piezo-corticision is a new type of corticision that consists of creating damage to the alveolar bone by perforating the interproximal cortices with a piezo-electric device. It is considered a minimally inva- sive technique because it does not require any gingival flap unlike other surgical approaches such as corticotomy (Dibart et al., 2009, 2014; Fig. 1). It may reduce the risk of undesirable side effects commonly associ- ated with corticotomy (e.g., swelling and discomfort, crestal bone re- sorption and bone dehiscence). If hard- and/or soft-tissue grafting are necessary to correct bone deficiencies or gingival recession, these pro- cedures can be carried out simultaneously by using selective tunneling technique (Dibart et al., 2014). Another advantage of piezo-corticision is that unlike corticotomy, the technique is performed only on the the buccal side, eliminating the need for a surgical intervention on the pala- tal or lingual side (Aksakalli et al., 2016). While both corticotomy (Bus- chang et al., 2012; Long et al., 2013; Gkantidis et al., 2014; Hoogeveen et al., 2014; Patterson et al., 2016) and low laser therapy (Gkantidis et al., 2014) already have been reported to be safe and effective methods for accelerating tooth movement, the lack of evidence regarding the effec- tiveness and safety of corticision confirms the necessity for further stud- 148 Nishio et al. Figure 1. Thirty-one-year-old female patient. A: Piezo-corticision surgical plan- ning from a cone-beam CT (CBCT) image. B: Interproximal mucoperiosteal inci- Sion with blade through the surgical guide. C. Bone incision with piezo-surgical knife, D: Post-surgery. ſes to assess the outcomes of this new technique since to date, few con- trolled randomized clinical trials (RCT) have been published on piezo-cor- ticision other than several case reports (Charavet et al., 2016). The im- Pact of this new surgical technique on the inflammatory events of bone "emodeling and on the periodontal status remains unclear. This chapter Provides a review of the literature with the most updated information ſegarding this novel piezo-corticision approach and is divided into a dis- °ussion of five major topics. HOW DOES PIEZO-CORTICISION PRODUCE THE ACCELERATION OF TOOTH MOVEMENTP The biomechanical basis of orthodontic treatment consists of the application of forces to the teeth, which leads to a cascade of cellular *Vents and changes in the periodontal tissues. Two fundamental biologi- cal requirements to allow tooth movement are the cellular activity of the periodontal ligament and the bone turnover Briefly, the mechani- Cal stimuli promote a “controlled" tissue damage which, in turn, leads 149 Piezo-Corticision-assisted Orthodontics to osteoclastogenesis and increases the production of inflammatory me- diators in the periodontium (e.g., neurotransmitters, cytokines, growth factors, colony-stimulating factors and metabolites of arachidonic acid). The pathways inherent to these inflammatory processes are fundamental for the regulation of the healing process and bone remodeling. A complex cascade of protein markers determines the formation of cells responsible for the bone turnover. Osteoclast progenitor cells appear more abundant- ly at the compression sites and osteoblasts dominate in the tension sites, developing areas of bone resorption and apposition, respectively. This dynamic coupling between the osteoclast-osteoblast activities induces the bone remodeling and subsequently, the tooth movement (Krishnan and Davidovitch, 2006; Baloul et al., 2011; Huang et al., 2014). Alveolar corticision and orthodontic tooth movement are not simply two independent procedures, but likely combine to produce a so- phisticated synergy on both periodontium cell activities and on bone re- modeling. The acceleration of tooth movement caused by the piezo-cor- ticision is believed to be based on three concomitant biological processes (Fig. 2). The first is that by promoting an injury on the cortical bone, this damage accelerates the physiologic healing process by increasing the activity of the periodontal cells and enhancing the alveolar cancellous bone turnover. The healing process associated with corticision is similar to those observed following corticotomy, tooth extraction and bone frac- ture. It includes three phases: reactive, reparative and remodeling (Wang et al., 2009; Buschang et al., 2012; Huang et al., 2014; Verna, 2016). This process, called regional acceleratory phenomenon (RAP), was first de- scribed by Frost (1983) and is characterized by a tissue reaction to a del- eterious stimulus that increases the healing capacities of the damaged soft and hard tissues (Verna, 2016). This acceleration of existing biologi- cal mechanisms has been shown to promote the hastening of orthodon- tic tooth movement (Baloul et al., 2011). Studies at the cellular level have described that tissue damage and changes in the blood flow stimulate the production of macrophage colony-stimulating factor (M-CSF) and increase the ratio between the receptor-activator nuclear factor kappa-3 ligand (RANKL) and osteo- protegerin (OPG). These two events, in turn, promote the formation and function of osteoclasts by producing cytokines (e.g., VEGF, TNF-0, interferon-3, interleukins, matrix metalloproteinases). The mesenchymal 150 Nishio et al. Piezo-corticision A bone remodeling - Accelerated tooth movement W2 Decreased treatment time V hyalinization sites figure 2. Diagram showing the biological processes involved in the acceleration of tooth movement following piezo-corticision-assisted orthodontic treatment. RAP = regional acceleratory phenomenon. Stem cells also are stimulated to differentiate into osteoblasts through Cytokines (i.e., TGF-B, BMPs, VEGF). Although the role of the osteocytes is not understood well yet, it has been suggested that this most abundant $90ſce of bone cells may participate in the process of accelerating tooth "Ovement by inducing osteoclast formation through apoptosis (Huang et al., 2014). The intensity and duration of the RAP have been reported to be Proportional to the nature and magnitude of the injury on the hard and sºft tissues (Cohen et al., 2010; Farid et al., 2014; Verna, 2016). Since Pezo-corticision minimizes the extent of the surgical injury by eliminat- "8 the gingival flap, it is tempting to hypothesize that the duration of 151 Piezo-corticision-assisted Orthodontics the RAP produced by piezo-corticision may be shorter than the one caused by corticotomy. It has been described that the RAP produced by the piezo-Corticision starts within a few days of the surgery, usually peaks in one to two months and then slows down and ceases once the remin- eralization process sets in (Keser and Dibart, 2013; Dibart et al., 2014). In general, studies have shown that the tissue reaction can vary from two to four months (Yaffe et al., 1994; Wilcko et al., 2008; Buschang et al., 2012; Keser and Dibart, 2013). In fact, a mucoperiosteal flap reflection by itself, without any decortications, already would promote a RAP. This procedure could result in the widening the periodontal ligament space and tooth mobility without any force application (Yaffe et al., 1994); however, whether piezo-corticision sufficiently stimulates the RAP to ac- celerate tooth movement is one of the main topics of this chapter. In order to extend the duration of the RAP and optimize the outcomes dur- ing the biological stimulus, repeated surgeries have been recommended throughout the treatment (Kim et al., 2009; Safavi et al., 2012; Dibart et al., 2014). Nevertheless, the outcomes and risk/benefits of this repetitive method remain to be elucidated. Because RAP is considered a transient phenomenon, the piezo-corticision protocol recommends that patients be seen every two weeks during the first four months following surgery for appliance reactivation, in order to optimize the outcomes from the biological changes caused by the corticision (Dibart et al., 2010, 2014; Aksakalli et al., 2016). The second biological mechanism in which piezo-corticision is implicated is its association with the increase in catabolic and anabolic periodontal remodeling. This phenomenon is believed to produce a fast- er removal of the hyalinized zone formed soon after mechanical force application and to allow for earlier bone resorption required for tooth movement (Kim et al., 2009; Baloul et al., 2011). Moreover, the diminu- tion of the cortical resistance and/or the augmentation of bone turnover also may prevent excessive pressure buildup in the periodontal ligament and, consequently, the formation of hyalinization areas (Hoogeveen et al., 2014). Finally, some studies have stated that the third biological pro- cess in which corticision participates is to promote a transitory osteope- nia condition with an augmentation of calcium release and a decrease in bone density. This reduction of bone resistance not only would ac- celerate tooth movement (Wilcko et al., 2008; Keser and Dibart, 2013; 152 Nishio et al. Dibart et al., 2014), but it also would minimize the risk of root resorption by facilitating the remodeling of the alveolar bone instead of the root Surfaces (Murphy et al., 2016). It is clear that all this evidence taken together demonstrates that piezo-corticision, like corticotomy, does cause RAP. This phenomenon re- Sults in the reduction of alveolar resistance to tooth movement and in the acceleration of bone turnover rate, thus leading to the acceleration of orthodontic tooth displacement. DOES PIEZO-CORTICISION RESULT IN ACCELERATION OF ORTHODONTIC TOOTH MOVEMENTP Although previous studies have shown no significant improve- ment following minimally-invasive surgical procedures without gingival flap (Safavi et al., 2012; Murphy et al., 2016), others have reported a sig- nificant acceleration of tooth movement caused by the corticision (Dibart et al., 2014; Aksakalli et al., 2016; Tsai et al., 2016). Aksakalli and colleagues' study (2016) on canine distalization demonstrated that piezo-corticision approximately doubled the rate of tooth movement compared to conventional treatment and decreased the anchorage loss for posterior teeth by maintaining the molars in a more stable position. No maxillary constriction was observed in this study and the authors concluded that this technique could be used safely in terms of avoiding any narrowing of the transversal dimensions. Similar results were observed in Tsai and associates' study (2016), which com- pared the effect of corticision and micro-osteoperforation on the rate of tooth movement in rats. These authors described that these two flapless methods showed similar results, by increasing bone remodeling and os- teoclast activity and by inducing faster orthodontic tooth movement for at least two weeks. It is important to consider, however, that the varia- tions in acceleration rates reported among the studies likely are due to the different experimental method designs (e.g., differences in the corti- Cision procedures, magnitude and duration of the applied force, type of tooth movement and protocols for appliance reactivation; Patterson et al., 2016). Murphy and colleagues' study (2014) in a rat model, which had the aim of evaluating the effect of different force magnitudes with and Without Corticision on the rate of tooth movement, showed converse 153 Piezo-Corticision-assisted Orthodontics results. Although light force significantly decreased the bone volume fraction, no differences in tooth movement or alveolar response were observed. In this study, the corticision did not induce clinical or histologic changes after two weeks of orthodontic tooth movement, regardless of the force magnitude. This might be explained by the fact that the cortici- sion carried out in this study was minor and localized. A more significant alveolar injury, therefore, should have been considered in order to in- crease the rate of tooth movement (Murphy et al., 2014). A clinical study on the effect of piezo-corticision on the duration of treatment is underway in the Orthodontic Section of the University of Montreal's Faculty of Dentistry. Thirteen adult patients (ages 18 to 40; ten females, three males) were selected.for this study according to the following inclusion criteria: skeletal Class I, complete permanent denti- tion, dental Class I and/or mild Class II (< 3 mm of discrepancy), irregular- ity index of s 4 mm, healthy periodontal status and systemically healthy patients. While final results are not available yet, preliminary results have revealed that this new surgical method accelerated the rate of dental alignment mainly during the first eight weeks after the procedure (Figs. 3 and 4). Although the evidence clearly has shown that piezo-corticision is an efficient technique to accelerate tooth movement, the fundamen- tal question whether this increase in the rate of tooth displacement can reduce the duration of treatment significantly remains to be answered. To address this issue, one would need to carry out a RCT to compare the length and the quality of the treatment between piezo-corticision and conventional orthodontic methods. Charavet and associates' study (2016) reported a significantly reduction of 43% in the overall piezo- corticision-assisted orthodontic treatment time when compared to the conventional orthodontic treatment. Further RCTs are necessary to vali- date the effectiveness of the piezo-corticision in reducing the treatment length and the average duration of piezo-corticision-assisted orthodontic treatment. WHAT IS THE PATIENT'S ACCEPTANCE OF PIEZO-CORTICISION-ASSISTED ORTHODONTICSP The piezo-corticision has been developed as an alternative to the corticotomy, not only because it is a less invasive approach, but also 154 Nishio et al. - - - - - - - º Lº - - - - - … - - Figure 3. Thirty-five-year-old male patient. Progression of dental alignment and leveling at two different time points, eight and sixteen weeks. The piezo- Corticision procedure was performed on the buccal side of the entire maxillary and mandibular arches. A. Frontal. B: Maxillary occlusal. C. Mandibular occlusal intra-oral photographs. because the latter has been demonstrated to have a lower acceptance among patients. Fear of the surgery required has been reported to be the major reason for rejection of this technique (Zawawi, 2015). In order to assess the patient's acceptance of piezo-corticision, a Survey was conducted at the University of Montreal after surgery using * numerical visual scale regarding patients’ pain and other oral health- related quality-of-life issues. The participants described less discomfort than they had expected and did not report any remarkable change in their quality of life. The acceptance toward the new surgical technique Was high and the majority of the participants (12 out of 13 patients) re- *Ponded that they would redo the procedure if needed. In case some still may consider piezo-corticision of the entire "outhto be relatively aggressive, less invasive treatment can be offered to Patients. Some authors have demonstrated that piezo-corticision can be 155 Piezo-corticision-assisted Orthodontics and leveling at two time points, eight and sixteen weeks. The piezo-corticision procedure was performed on the buccal side of the entire maxillary and mandibular arches. A: Frontal. B: Maxillary occlusal. C. Mandibular occlusal intra- oral photographs. used on limited mouth regions in order to close spaces, control anchor- age, protract molars, intrude and/or upright teeth, obtain unilateral arch expansion and facilitate any difficult tooth movement (Wang et al., 2009, Dibart et al., 2014, Tsai et al., 2016). Such conservative alternative ap- proaches may increase the level of patients' acceptance toward piezo- corticision and allow the orthodontist to optimize treatment outcomes by using this new method. IS PIEZO-CORTICISION A SAFE TECHNIOUEP The purpose of piezo-corticision is to produce an injury in the alveolar bone by performing cuts on the cortical bone with a piezo- electric device. Because of its micrometric and selective incision, this technique is believed to create safe and precise osteotomies with reduced risk of osteonecrotic damage (Keser and Dibart, 2013). Because a 156 Nishio et al. gingival flap is not necessary, the piezo-corticision is believed to cause less post-surgical discomfort and less post-operative complications when Compared to other surgical approaches (e.g., corticotomy; Keser and Di- bart, 2013). Hoogeveen and coworker's systematic review (2014) of different Surgical techniques used to facilitate orthodontic treatment, including Corticotomy, piezo-corticision, micro-osteoperforations and periodontal distraction has shown that all of these methods were considered safe. They were not associated with undesirable side effects (e.g., loss of tooth Vitality, periodontal problems and severe root resorption). Nevertheless, the conclusion of this review should be interpreted with caution due to the small sample sizes, the high risk of bias and the lack of homogeneity of the included studies. Even though piezo-corticision is considered a less invasive meth- Od because it does not involve a gingival flap, this procedure still requires perforations of the oral mucosa, which likely could cause bacteremia. Ileri and Colleagues' study (2014) investigated the influence of piezo-cortici- Sion procedures on bacteremia, but did not find a significant difference between the pre- and post-operative blood samples. However, while all patients did not present with any transient bacteremia in their pre-oper- ative samples, three subjects showed positive bacteremia in their post- operative blood exams. The authors concluded that orthodontists still should consider the possibility of bacterial endocarditis in at-risk patients and adopt preventive measures (e.g., prophylactic antibiotics) if Cortici- Sion is considered in the treatment plan (lleri et al., 2014). In our current pilot study, we have noticed that the gingival healing following piezo-corticision occurred normally within the ex- pected patterns. The patients showed rapid gingival healing within the Seven post-procedure days without any periodontal complications; how- ever, Some revealed a fibrous healing (“scars”) in the piezo-corticision sites (Fig. 5). This evidence also has been described by Charavet and Coworkers (2016). Although the participants did not complain about this unexpected side effect, the scars are not pleasing aesthetically. Therefore, it is important that patients be informed about the risk of developing such fibrous healing. The piezo-corticision employed by Di- bart and colleagues (2009) used a piezo-electric tip of 0.5 mm width 157 Piezo-corticision-assisted Orthodontics - - - - - Figure 5. Periodontal healing ten months after the piezo-corticision procedure. The arrows indicate the fibrous healing (“scars”) at the corticision sites. to perform the incisions in the alveolar bone. In our study, a thinner tip of 0.35 mm width was chosen in order to avoid contact with the roots, to provide thinner surgical lines and permit faster gingival healing. Whether the fibrous healing may be associated with this variation in technique in our study, or might disappear later through soft tissue remodeling, or is a common effect that has not been reported previously, merits further in- vestigation. While the evidence has demonstrated that corticision does not lead either to pathologic changes in the periodontal tissues (Aksakalliet al., 2016) or to root resorption (Kim et al., 2009), adequately designed clinical trials are necessary in order to provide more scientific evidence to support these claims. Prospective studies with a minimum five-year follow-up after the removal of orthodontic appliances are necessary in order to assess the risks to the periodontal health and long-term tooth vitality (Mathews and Kokich, 2013). WHAT IS THE COST/BENEFIT OF PIEZO-CORTICISION-ASSISTED ORTHODONTICSP The efficiency of a specific clinical technique depends upon the value received relative to the cost of the treatment in relation to the time saved, money expended and morbidity experienced (Mathews and KO- kich, 2013). According to our study, the piezo-corticision technique peſ: formed on the entire buccal side of the maxillary and mandibular arch: es necessitated an additional treatment fee of approximately 40%. Al- though the sums can vary greatly depending on the extent of the proce: 158 Nishio et al. dure (e.g., total or segment arch; one or two arches), this additional cost Can be a major reason for the low acceptability in clinical private prac- tice. Taking this into consideration, the orthodontist may consider the feasibility of reducing the cost of the orthodontic treatment in order to render the piezo-corticision-assisted technique more accessible to pa- tients. Undeniably, there also is a financial advantage to the orthodontist in delivering more efficient treatment by reducing both the number of visits and the time required chairside, thereby shortening the duration of treatment. There is no doubt that piezo-corticision can be effective in ac- celerating orthodontic movement, but is the treatment time difference justifiable when considering the additional cost? A systematic review has Suggested that conventional orthodontic treatment takes an average of just under two years to be completed with a mean number of required Visits of 17.81 (Tsichlaki et al., 2016). It is obvious that a wide range of treatment lengths should be expected due to the influence of many di- Verse variables including rate of tooth movement, case severity, need for extraction versus non-extraction treatment, necessity for orthognathic Surgery, the orthodontist's clinical expertise and to a great degree, the patients' cooperation (Mavreas and Athanasiou, 2008; Fisher et al., 2010; Murphy et al., 2014). Although some case reports have shown that the piezo-corticision can reduce the treatment length by 50% (Dibart et al., 2009, 2010; Keser and Dibart, 2013), further randomized clinical studies focusing on the treatment time of piezo-corticision-assisted orthodontics should be conducted. Therefore, it is not possible so far to draw definitive conclusions on the effect of piezo-corticision on this outcome. In terms of number of visits, we have noticed in our study that due to the recommended shorter intervals between checkups, the num- ber of appointments and amount of chair time needed to finish the treat- ment did not differ significantly from conventional orthodontic treat- ment. By following the piezo-corticision protocol guidelines, the patients were seen every two weeks for the first four months and every six weeks for the rest of treatment, thereby totaling twelve appointments over a ten-month period. A survey of patients' and orthodontists' perspectives on orth- odontic treatment duration has shown that most orthodontists would 159 Piezo-corticision-assisted Orthodontics sacrifice up to 20% of their treatment fee in order to use technologies to reduce treatment time, while most patients and parents were willing to pay only up to an additional 20% in fees for these approaches. Inva- sive clinical methods (e.g., piezo-corticision, corticotomies and intra-oral drugs) have lower acceptability among patients and professionals. More- over, although 70% of orthodontists were interested in using methods to accelerate tooth movement, they were not aware of the different avail- able approaches (Uribe et al., 2014). Cost-effectiveness analyses should be conducted in conjunction with the clinical trials. Prospective trials with proper methodology and larger samples still are recommended and should put an emphasis on comparing different surgical approaches with respect to their efficiency, complications, patients' perception and long-term stability. This will help both clinicians and patients consider the economic versus clinical impact, which will facilitate making informed decisions. Finally, due to the fact that the adverse effects of this technique have not been evaluated in the long term and that the overall reduction in the total treatment time still is questionable, the cost/benefit ratio of piezo-corticision for the patient and the doctor likely is not justifiable at this time. CONCLUSIONS Based on current evidence, piezo-corticision has been shown to be an effective and a safe method to accelerate the rate of Orthodontic tooth movement. The patients' acceptance of piezo-corticision-assisted orthodontic treatment has been good relative to their pain experience and other quality-of-life issues. However, the additional expense of the procedure and the lack of studies demonstrating a definitive reduction in treatment length suggest that the cost/benefit of piezo-corticision- assisted orthodontic treatment still is not sufficiently positive, either for the patient or the orthodontist. Controlled randomized clinical studies are necessary to assess the efficiency of piezo-corticision in reducing treatment time, potential iatrogenic effects and long-term stability. It is unclear presently whether any reduction in treatment duration by using this new technique would outweigh the extra cost of the surgical proce- dure. Finally, further experimental studies are needed to better under- 160 Nishio et al. Stand the cellular and biological mechanisms involved in bone remodel- ing following piezo-corticision. 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Traditionally, maxillary Orthopedics has been performed using the dental units only as anchorage (e.g., Hyrax or Haas appliances). Dental anchorage not only has created limited Skeletal orthopedic change, but also can cause significant adverse periodontal Outcomes and unstable side effects. There is a clear correlation between buccal tooth movement and gingival recession and bone dehiscences. These adverse periodontal responses with RPE indicate the importance of early treatment. The beneficial periodontal effects of transverse skeletal correction have been a primary focus of our research for the past 35 to 40 years. We have emphasized the importance of correcting transverse skeletal discrepancy to: 1) prevent periodontal problems; 2) achieve greater dental and skeletal stability; 3) improve dentofacial esthetics by eliminating or improving buccal corridors; and 4) improve airway resistance. When it may be critical to save the natural dentition, we do not want to introduce adverse dental/skeletal changes for adolescent patients and/or patients with advanced periodontal disease. New advances in skeletal anchorage should permit orthopedic change without adverse dental changes by applying force directly to the maxillary bone; an innovative technique to maximize the skeletal maxillary changes in the transverse dimension is explained in this chapter. Furthermore, diagnosis of the transverse dimension—the use of Cone-beam computed tomography (CBCT) for 3D evaluation of skeletal changes, the benefits of the skeletal transverse changes of the whole maxillofacial complex and its periodontal response, the changes in airway and non-surgical RPE with bone-anchored appliances utilizing temporary anchorage devices (TADs)—is described and discussed. KEY WORDS: expansion, transverse dimension, TAD RPE, orthopedics, hyrax 167 Correction of the Transverse Dimension INTRODUCTION Diagnosis in orthodontics must be performed with respect to all three planes of space. These include the sagittal, vertical and transverse planes in both the dental and skeletal dimensions. While our specialty always has been focused on profile views and a diagnosis on the Sagittal plane, the vertical and transverse dimensions also are of critical impor- tance. When Broadbent (1931) introduced cephalometric radiography at Case Western, the frontal postero-anterior cephalometric radiograph was included; however, its use in orthodontics was limited to asymmetric types of cases. It is essential to examine and quantify the degree of discrepancy of the radiographic films to determine the skeletal pattern in these three planes. It has been shown that clinical inspection of transverse maxillary deficiency is inadequate for diagnostic value (Crosby et al., 1992; Flick- inger et al., 1995) and can mislead the clinician. Likewise, a panoramic film is not sufficient for a complete orthodontic diagnosis. At present, the new technology, digital dentistry (Blasi et al., 2016) and three-dimen- sional (3D) radiographs (e.g., cone-beam computed tomography [CBCT) allow the orthodontist to evaluate the patient in 1:1 proportions and in three dimensions. However, visualizing these beautiful images is not enough and there is a need to quantify the skeletal and dental compo- nents for a proper diagnosis. For example, two different cases could have the same amount of dental overjet when measured and quantitated us- ing a lateral cephalogram; however, one case could be a Class I skeletal pattern and the other a Class II skeletal pattern. The same might occur for two different cases with different dental overjets and the same Class Il skeletal relationship (Fig. 1). Therefore, a skeletal diagnosis must be performed regardless of any dental compensation, since measuring teeth is not diagnostic for the skeletal component. The purpose of this chapter is to emphasize the importance of a 3D diagnosis and the impact of the transverse dimension in our treatment outcomes. TRANSVERSE SKELETAL PATTERN AND DIAGNOSIS Traditionally, the transversedimension has been addressed in cas- es of dental crossbites, tapered arches and skeletal asymmetries without an appropriate skeletal diagnosis. It is critically important to diferentiate 168 Vandrsdalſ and Blasi Figure 1. Two different cases with the same class II skeletal relationship and different dental overjet A-B: Patient with excessive overjet and a 79 ANB Class | skeletal discrepancy. C-D: A different patient with no dental overjet and a 79 ANB Class II skeletal pattern. Note that dental compensation hides a skeletal discrepancy on the Sagittal plane. and quantitate between the width of the maxilla and the width of the "landible, and it is essential that both jaws be measured to make a Skeletal diagnosis (Vanarsdall, 1999). Measuring only the upper jaw has no Value. Undiagnosed transverse discrepancy leads to adverse periodontal *Sponse, improper occlusal function, unstable dental correction and less-than-optimal dentofacial esthetics (Vanarsdall et al., 2017). The presence or absence of clinical posterior dental crossbite does not indicate the absence of a transverse skeletal discrepancy or 169 Correction of the Transverse Dimension skeletal crossbite. In many clinical scenarios, a skeletal discrepancy is ac- companied by dental compensation and lack of a dental crossbite (Fig. 2A). The upper posterior dentition is inclined buccally and the lower pos- terior inclined lingually, dentally compensating for a narrow maxilla. The lower teeth may be collapsed leaning inward, thus creating a crowded lower arch. These compensations may create an exaggerated curve of Wilson and consequently, posterior interferences on the non-working side as the patient goes into lateral excursions, which can predispose the patient to TMD symptoms, tooth wear and periodontal problems. Two of the most significant factors in determining the proper treatment (orthodontics, orthopedics or surgery) of the transverse di- mension and its prognosis are the severity of the skeletal discrepancy and the skeletal maturation of the patients. Established skeletal landmarks must be compared to diagnose the severity of the skeletal width of both the maxilla and mandible. The differential between the width of the max- illa and mandible is a critical evaluation for the individual patient. The posterior-anterior (PA) cephalogram, or a perfectly extracted PA cephalo- gram from a CBCT image (Fig. 2B-C), not only will show the existence of a discrepancy between the maxilla and mandible, but also will show the severity of such a discrepancy. Most treatment modalities (e.g., fixed and functional applian- ces) are used to correct the transverse plane, where treatment poten- tials are limited much more than in other planes. Orthodontics used to achieve unstable dental camouflage of the underlying skeletal discrep- ancy in the transverse dimension have been shown to lead to unsatis- factory treatment outcomes (Vanarsdall and White, 1994; Vanarsdal et al., 2017). Rapid palatal expansion (RPE) produces an orthopedic (skeletal) correction of the transverse dimension when used properly (at the correct skeletal age and with the proper appliance selection). Orthopedic maxillary expansion is the result of skeletal (sutural open- ings), dental (tipping) and alveolar (bending and remodeling) alterations. As a child (7 to 9 years) grows and matures skeletally, more force may be required to achieve proper expansion. The more mature the child, the less skeletal expansion is achieved and the more dental tipping oc- curs. Krebs (1964) reported such changes using metal markers during orthopedic expansion in children and adolescents. He demonstrated that children had 50% skeletal and 50% dental expansion, while the 170 Vanarsdalſ and Blasi Figure 2. A: A patient with absence of dental crossbite and a narrow max- illa. Note the upper posterior teeth are inclined buccally, creating an exag- Éerated curve of Wilson; the lower posterior dentition is inclined lingually, dentally Compensating the narrow maxilla. B-C: Posterior-anterior view of a 3D-rendered image of a CBCT and a perfectly extracted PA cephalogram (C) from the same CBCT to evaluate the skeletal transverse dimension. adolescent group exhibited 35% skeletal and 65% dental expansion. A tendency of dental tipping and alveolar bending to relapse was observed after appliance removal. 171 Correction of the Transverse Dimension Diagnosing the transverse plane must be based on skeletal, not dental, components. A dental diagnosis cannot provide information for skeletal correction. Moreover, separation of the midpalatal suture does not mean that the skeletal discrepancy has been corrected. There is a need to calculate the amount of skeletal discrepancy and to know what the appliance will provide in correction of such discrepancy. This will guide the practitioner in setting up realistic goals and objectives to correct the transverse dimension without estimating, guessing or eyeballing. There- fore, treatment planning for the transverse skeletal problem requires a comprehensive diagnosis differentiates between the skeletal and dental components, a determination of the severity of the skeletal discrepancy and maturity of the facial skeleton (skeletal age), an understanding of the patient's periodontal susceptibility and biotype, and selection of the ap- propriate appliance for the orthopedic/orthodontic correction. PERIODONTAL IMPLICATION Orthodontics is the most conservative and predictable treatment to improve many of the local etiologic factors that contribute to periodontal susceptibility and breakdown (Vanarsdall et al., 2017). It is important intrinsically as a clinician to identify the peri- odontally susceptible patient (Vanarsdall et al., 2017). When examining the patient clinically, evaluation of the gingival tissues—specifically bio- type—is critical to be able to provide optimal treatment. A patient with thin biotype (thin periodontal tissues) should be evaluated carefully. The biotype of both the soft and hard tissue has a crucial role in the outcome of the treatment (Lindhe et al., 2008). Orthodontic movement of teeth should be made carefully within the alveolar housing. Even though gin- gival recession has a multi-factorial etiology (Helm and Petersen, 1989; Offenbacher, 1996; Kornman and Van Dyke, 2008), a failure to make a correct diagnosis could cause orthodontics to be a contributing etiologic factor to periodontal breakdown and gingival recession (Vanarsdall et al., 2017). A study at the University of Pennsylvania (Saacks and Vanars- dall, 1994) showed that buccal gingival recession is correlated directly with maxillary transverse deficiency as measured in a group of untreat- ed patients with a transverse discrepancy of 5 mm or greater (than the 172 Vanarsdall and Blasi normal 19.6 mm maxillomandibular differential). Moreover, Anzilotti (2002) compared a group of patients treated with orthopedics (Haas RPE) and an edgewise appliance, a group treated only with an edgewise ap- pliance and a control group of untreated subjects from the Center for Human Growth and Development at The University of Michigan. The or- thopedic group was evaluated at time point 1 (T1)-11.3y and time point 2 follow-up records (T2)-20.7y; the edgewise-only group at T1-12.3y and T2-19.3y; and the control group records at T2-17.2y. All three groups re- Vealed gingival recession when the differential between the maxilla and mandible was greater than 5 mm of transverse discrepancy. A negative transverse differential - 5 mm from the Rocky Mountain analysis norm may be a risk marker for gingival recession (Anzilotti, 2002). This data may help identify patients at greater risk of gingival recession (Figs. 3 and 4). Garib and associates (2006) evaluated the periodontal out- Comes of RPE with a tooth-tissue-borne (Haas RPE) and a tooth-borne (Hyrax) appliance. Utilizing CBCT images, they observed that both RPEs decreased the buccal plate thickness of the maxillary posterior teeth and induced bone dehiscences on the buccal aspect. Furthermore, the Hyrax appliance created a greater decrease of the buccal alveolar crest level than did the Haas RPE expander. Several other studies evaluating the Hyrax appliances demon- strated a decrease in thickness of the buccal bone on the anchorage teeth area and dental tipping (Rinderer, 1966; Oliveira et al., 2004; Garrett et al., 2008), thus indicating major recession with potential damage to the buccal cortical plate. It can be concluded that the Hyrax appliance is a "tooth tipper” and may predispose the patient to greater gingival reces- Sion (Fig. 5). Dental expansion and alveolar bending predispose the pa- tient to recession and dental instability if treated beyond the limits of the transverse envelope of discrepancy. Even when the gingiva is nor- mal in thickness, recession can be present if the transverse dimension is violated by tooth movement alone. Therefore, it is critical to make a proper diagnosis and a proper selection of the type of appliance needed. Gingival recession also may occur in cases of excessive lingual inclina- tion of the lower teeth, leaving alveolar support in the apical third only and/or excessive buccal inclination of the upper teeth that can result in alveolar support limited to the apical third of the teeth. When the tissue becomes inflamed, it recedes and the soft tissue and the roots become 173 Correction of the Transverse Dimension R. S. Coucosion | Mole - - Age: 14.5 Tronsverse Deficiency Skel: 13 Potient Norm Mx-MX: 58,0mm Mx-MX: 64.8mm Ag-Ag: 85.4mm Ag-Ag: 82.9mm Norm - Patient –9.3mm Dif: 27.4mm Dif: 18.1mm Figure 3. Case 1. Patient treated without proper diagnosis of the skeletal tranº verse dimension. A. PA cephalometric analysis indicating a severe skeletal diº crepancy on the transverse plane: transverse deficiency of > 9.3 mm betwee' the upper and lower jaws with a narrow maxilla and a wide mandible. B: Initial cast of the patient before treatment. C. Final cast after two years of orthodo" tic treatment. The patient was treated with two expanders and four premolaſ extractions. D: One year after treatment cast. Note evidence of recession that starts to appear and relapse of the dental correction. E. Two years post-orth- odontic treatment. The case was treated beyond dental camouflage which ſº sulted in further dental relapse and gingival recession. 174 Vandrsdalſ and Blasi Ironsverse Deficiency Potient Norm Mx-MX: 55.0mm Mx-MX: 66.2mm Ag-Ag: 81.0mm Ag-Ag: 85.8mm Norm - Patient -6.4mm Dif: 26.0mm Dif: 19.6mm Figure 4. Case 2. Patient seeking orthodontic treatment for a second time. A: PA Cephalometric analysis exhibited a transverse skeletal deficiency of > 6.4 mm. B-C Intra-oral pictures. The patient was treated orthodontically with four pre- molar extractions. Note severe gingival recessions with normal thickness archi- tecture of the soft tissues. Figure 5. A. Hyrax expander with a metal framework anchored to the dentition ºnly B: CBCT coronal cut at the level of the first maxillary molar on a mix denti- tion patient after expansion with a Hyrax. Note the clear buccalangulation (den- tal tipping) of the anchored teeth, even in a skeletally immature patient. 175 Correction of the Transverse Dimension exposed. In cases of partial edentulism and implant rehabilitation treat- ment, the implant fixtures can be affected severely and even lost if there is a significant transverse skeletal problem (Vanarsdall, 1999). Placing im- plants in a narrow maxilla could be a challenge. In many cases, there is a need to augment the bone with guided bone regeneration (GBR) or sinus lift augmentation. If not grafted, the lack of buccal bone could be a limita- tion and the implants may be at risk to be lost. Moreover, when implants are placed in patients with a severe transverse skeletal discrepancy, even if grafted, they have to be angulated excessively in order to meet the occlusal requirements of correct dental buccal-lingual landmarks. When angulated in such a manner, the occlusal forces may create additional stress on the implant units. If the transverse dimension is not corrected orthopedically/surgically, the implant units should be placed at the cen- ter of the alveolus and the posterior restorations in dental crossbite. Currently, many adult patients are seeking orthodontic treatment for the second or third time (Fig. 4). Many of them have been treated in the past with extractions and present with normal tissue, but with gingi- val recession. Some cases will present with: 1. Only upper premolar extraction treatment decision due to a narrow maxilla and consequently crowding on the upper arch; 2. Lower premolar extraction treatment decision due to a narrow maxilla and crowding on the lower arch (crowding occasioned by lingually inclined teeth to compensate dentally for a narrow upper jaw); or 3. A combination of both, upper and lower premolar ex- tractions. The majority of these cases lacks an orthopedic transverse skeletal Cor- rection and can result in partially exposed roots, with only soft tissue COV- erage around the remaining apical root and no buccal bone. Whether the type of treatment is extraction or non-extraction, the patient is predis- posed and more susceptible to gingival recession if there is a mismatch on the transverse dimension. We have reported that the transverse dimension may be the most crucial risk marker for facial gingival recession (Vanarsdall et al., 2017), yet there are other significant factors (e.g., gingival bleeding from 176 Vanarsdall and Blasi probing, tooth mobility and thin, friable gingival tissue). These all are Critical reasons to make the skeletal correction in the transverse dimen- Sion based on skeletal landmarks and not on dental landmarks (e.g., the lingual of the upper teeth contacting the buccal surfaces of the lower). ENVELOPE OF DISCREPANCY: LIMITS FOR DENTAL EXPANSION As stated earlier in this chapter, there are noticeable definitive limits to dental expansion. If these boundaries are violated, there are adverse consequences. Establishing the envelope of discrepancy and delineating the limits of these boundaries is highly relevant and should be made for each individual patient. Proffit and Ackerman (1982) first introduced and developed the sagittal and vertical envelope of discrep- ancy concept. We later added the transverse envelope of discrepancy (Vanarsdall and Musich, 2017). Figure 6 helps simplify and visualize the limits of the three major treatment modalities for skeletal discrepancies. The inner envelope illustrates the limits of camouflage with orthodontic treatment alone; the middle envelope establishes the limits of orthodon- tic treatment combined with orthopedics and growth modification; and the outer circle represents the limits of the correction with orthodontics and orthognathic surgical procedures. The numbers on the diagram are simple guidelines and may under-/overestimate the potentials for any given patient; nevertheless, they help place the potential of the three major treatment options in perspective. It is important to note that the envelopes of discrepancy for the transverse dimension are much smaller (Fig. 6); the premolar areas are Smaller considerably than those for incisors in the anterior-posterior (AP) plane. When violating these limits, teeth are placed in a position where they could be traumatized and possibly lost. Clinicians need to develop an envelope of discrepancy concept for the transverse dimension, as well as for the Sagittal and vertical dimension for every case. Orthopedic transverse correction, utilizing growth in children, is the most desired approach to any skeletal discrepancy when growth potential exists (DeGeorge, 2015). The envelope of discrepancy is in- Creased greatly with orthopedics and may allow the clinician to provide a non-extraction treatment if the transverse skeletal discrepancy is cor- rected. In adolescents and young adults, an orthopedic correction may 177 Correction of the Transverse Dimension —- 10 - BUCCAL LINGUAL BUCCAL PALATAL 10 A MAXILLA B MANDIBLE Figure 6. Envelopes of discrepancy for the transverse dimension of the maxilla (A) and mandible (B). The inner circle establishes the limits of orthodontic treat ment alone; the middle circle exhibits the limits of orthodontic treatment Com- bined with growth modification; and the outer circle illustrates the limits with orthodontics and surgical procedures. be possible utilizing bone-anchored RPEs. In adults, when the sutures al. ready are closed, the clinician may choose to correct the skeletal patterſ using surgically-assisted palatal expansion (SARPE) or to leave the patient in a dental crossbite distal to the premolars (Betts et al., 1995). Camouflaging the transverse skeletal deficiency by moving only the teeth may cause periodontal problems and instability of the occlusal scheme. Consideration of camouflage requires careful examination of the patient's ultimate periodontal status, occlusal function and stability, and facial esthetics. If the clinical and radiographic analysis indicates less Sig nificant transverse maxillary deficiency in the mature patient, howeveſ sufficient buccal maxillary bone may remain to allow dental tipping and camouflage of the transverse skeletal dimension. Additionally, this envelope of discrepancy may be expanded with periodontally-accelerated osteogenic orthodontics (PAOO), alveo lar decortication and augmentation bone grafting. In selected cases, the procedure will help expand the boundaries of dental movement with reduced loss of attachment. This novel approach changes only the al- veolar bone and not the basal structures. It also does not substitute for 178 Vanarsdall and Blasi Orthopedic expansion; however, it may be indicated for mild transverse discrepancies with dental camouflage for changes of arch form (Vanarsdall et al., 2017). EARLY TREATMENT It is important to initiate early treatment, since the transverse growth of the maxilla is completed sooner than in most of the other maxillofacial structures and its growth slows first (Korn and Baumrind, 1990; Edwards et al., 2007). This growth is differential, with the man- dible outgrowing the maxilla. The Burlington template for the transverse demonstrates that from ages 4 to 20, the normal maxillary (Mx) growth is down, following a continuous pattern with minimal increase in width and the normal mandible (Ag) growth is down and out transversally (Popov- ich and Thompson, 1977). For example, a case that is two standard de- viations (SD) narrow in the maxilla and 5 mm wide in the mandible is a difficult combination and worsens because of the differential transverse growth. In this case, the objective would be to make a wide maxilla to match a wide mandible (wide-wide). Males usually are approximately 1.5 to 2 years younger skeletally than their calendar age; females are usually older skeletally than their Calendar age. After sutural closure or significant slowing in maxillary transverse growth (15 years for females and 16 years of age for males), Skeletal expansion mostly has been ineffective. At this age, the expan- Sion is primarily alveolar or dental tipping with little or no basal skeletal change (Vanarsdall, 1999), unless a bone-anchored RPE is used. DeGeorge (2015) reported that with lip bumper (LB) therapy, the growth of the transverse dimension of the mandible can be changed and increased significantly if the LB is used between 20 and 25 months. We evaluated the changes at the level of the mucogingival junction (MGJ), of 26 consecutive patients with pre-treatment age of 9.2 +/- 0.8 and the post-treatment of 12.3 +/- 0.8, treated with a bonded RPE (occlu- Sal and palatal coverage) and LB. The control group consisted of 15 un- treated individuals. A significant increase in the left to right MGJ distance (P<0.001) was found. The mean change at the level of the first molar Was 4.9 mm, second premolar 4.1 mm, first premolar 4.9 mm and ca- nine 3.1 mm. The control group had little to no change. Therefore, the 179 Correction of the Tranverse Dimension younger the patient is and the longer the LB is used, the better the re- sponse to treatment. Vanarsdall and associates (2004) reported a skeletal result of the LB on the basal bone as well. The transverse dimension of the basal structure of the mandible measured at the antegonial notch (Ag-Ag) in- creased relative to double the control. The jaws are more responsive to modification at an early phase of growth and development than at future stages. Proper management of growth and development and con- trol of habits (tongue thrust, low tongue posture) that will worsen as the patient grows are important to avoid secondary effects (e.g., developing an adenoid face). Furthermore, it is possible to redirect the growth in the transverse dimension and create a better occlusal and periodontal environment (Fig. 7). Beginning early treatment with orthopedic appliances (e.g., RPE and LB) permits the clinician to take advantage of muscles, eruption and growth, coordinate the skeletal pattern and develop a broader arch form. Early skeletal correction of the transverse dimension is valuable for managing growth and development, long-term periodontal health, proper occlusal function and stability (Secchi and Wadenya, 2009; De George, 2015). CHANGES OF OTHERSKELETAL CHARACTERISTICS AND AIRWAYS Changes of the basal form cannot be accomplished with wires or brackets (Lundstrom, 1925). Orthodontics alone will move teeth only within the basal structure of the jaws. If a skeletal discrepancy needs to be corrected, orthopedics and/or surgery may be the treatment of choice. Orthopedic maxillary expansion is accomplished by placing trans- versally directed forces in the orthopedic range on the maxilla to accom- plish transverse maxillary expansion. There is increased facial resistance to skeletal expansion with increasing maturity and age. The higher site of resistance is not the midpalatal suture, but the remaining maxillary articulations (Zimring and Isaacson, 1965) increased rigidity of the fa- cial bones (e.g., the zygomatic buttress) and other circummaxillary Su- tures. As the sutures mature, the majority of rapid orthopedic palatal expansion occurs via dental tipping and alveolar bone bending, rather than skeletal movement. RPE may affect structures directly or indirectly 180 Vanarsdalſ and Blasi Figure 7. Early treatment case. The patient was treated with phase I for 20 months With bonded tooth-tissue-borne expander (occlusal and palatal coverage) and lip bumper (LB). A: Initial coronal CBCT cut shows buccal inclination of upper mo- lars. B. After early phase I treatment. CBCT coronal cut reveals properly inclined molars creating a better periodontal environment. The teeth are centered on the alveolar process, where occlusal forces of mastication are received over the long axis of the dentition. related to the maxilla, mandible, nasal cavity, pharyngeal structures, zy- 30matic bone and the pterygoid process of the sphenoid bone (Brodie, 1950). The maxilla is associated with ten bones in the face and head. For this reason, when purely skeletal expansion occurs, these anatomical Structures are affected (Fig. 8). The expansion achieved with RPE is in a vertical, triangular shape. The structures at the level of the expansion jackscrew are affected º º º º - Figure 8. A 16-year-old female patient treated with a bone-borne expander. A: Superimposition of rendered CBCTs before and after expansion on the cranial base. Note the midfacial skeletal expansion of bony structures surrounding the "axilla. B-C Comparison of nasal cavity 3D volume increased from before (84.0 *) to after expansion (99.4 cc). 181 Correction of the Transverse Dimension most and as it progresses vertically, the expansion diminishes. Due to the correlation of anatomical structures with the maxillary bone, a midface skeletal expansion occurs as well (Fig. 8A). The zymogatic bone and the nasal width are expanded among others. The nasal cavity increases in volume as nasal width is expanded, which reduces nasal resistance and improves nasal respiration (Fig. 8B). There have been multiple reports on airways and RPE demonstrating that RPE improves the posterior airway spaces and other skeletal characteristics (Wriedt et al., 2001; Kilig and Oktay, 2008; Haralambidis et al., 2009; Villa et al., 2011). With bone-anchored RPE, skeletal expansion can be achieved in mature patients. However, the benefits of changing the skeletal charac- teristics associated with maxillary expansion while growing and skeletally developing at an early age patient are irreplaceable. EVOLUTION TO BONE-ANCHORED RPE APPLIANCES The midpalatal suture opening by orthopedic expansion was de- scribed first by Angell (1860) and the concept was reintroduced by HaaS (1961, 1965). Orthopedic expansion was successful mainly in children pri- or to suture closure. The most effective skeletal expansion was achieved with a Haas-type bonded appliance (Christie et al., 2010). The Haas-type RPE is a tooth-tissue-borne expander that has acrylic palatal flanges inte- grated into the appliance and has been shown to result favorably in skel- etal expansion with less dental tipping. The Hyrax RPE is a tooth-borne appliance similar in design, but without acrylic palatal coverage and with only the expansion screw and a metal framework. It has been shown to result in more dental tipping and less skeletal expansion (Fig. 5). The oc- clusal-coverage Haas-type bonded appliance (bonded tooth-tissue-borne RPE) is essentially a hybrid of the Haas appliance and a flat-plane occlusal coverage splint. It is bonded to the maxillary teeth and its use is recom- mended in growing patients for a significant skeletal correction. Addition- ally, rapid—as opposed to slow—maxillary expansion is used to maximize skeletal expansion over dental expansion (Hicks, 1978). Oliveira and colleagues (2004) evaluated the morphologic changes of the maxilla, comparing two different types of RPE designs. They evaluated data from a previous prospective, randomized clinical study using PA cephalometric and cast analysis, and compared the HaaS 182 Vanarsdall and Blasi appliance to the Hyrax RPE. Both appliances showed maxillary expansion. However, the Haas appliance had a higher component of true orthopedic movement and the Hyrax appliance had expansion by means of dentoal- Veolar tipping. As a result of the dental tipping side effect and the popular use of temporary anchorage devices (TADs), more than a decade ago we started evaluating the skeletal anchorage Supported appliances in surgically as- sisted rapid palatal expansion (SARPE) cases that had no posterior denti- tion and/or periodontally compromised teeth (Fig. 9A). An evident lack of dental tipping was noted in the upper posterior teeth, as the maxilla was changed with a skeletal anchorage type of expander; bone-borne RPE design was modified to avoid including the dentition into the appliance and its use was expanded to the mature patient. It includes four TADs inserted on the palatal slopes of the maxilla with acrylic palatal coverage, similar to a Haas-type design (Fig. 9B); two TADs per side give a better distribution of forces. This design has been shown to be the choice for ef- ficient treatment of maxillary transverse deficiency (Lee et al., 2014). We reported the difference between a bone-borne and bonded tooth-tissue- borne RPEs used in twin patients with the same skeletal severity, age and gender (Vanarsdall et al., 2012). There was a significant increase in width of the basal bone as a result of the palatal expanders as measured on CBCT imaging. Both appliances demonstrated significant skeletal change; however, the bone-borne RPE achieved significantly more skeletal basal change without dental compensation that did the bonded tooth-tissue- borne appliance (Vanarsdall et al., 2012). Moreover, the bone-borne RPE twin completed orthodontic treatment six months earlier than did the bonded tooth-tissue-borne RPE twin, even with teeth in a better position. Lagravére and associates (2010) reported that bone-anchored maxillary expanders and traditional rapid maxillary expanders (Hyrax) present similar results, though the Hyrax appliance resulted in greater first premolar expansion than the bone-anchored appliance. Both treat- ment modalities showed an increase in crown inclinations and that dental expansion was greater than skeletal expansion. Yet, this study evaluated only dental objectives and focused on dental correction of posterior crossbites. There were no skeletal objectives nor evaluation of the skeletal transverse dimension changes at the basal bone level. Fur- thermore, the design of the bone-borne RPE included only two TADs 183 Correction of the Transverse Dimension - D - E Figure 9. A. One of the first bone-borne expanders used on a periodontally Com- promised patient with missing teeth on the upper right segment. Two TADs were used to support the appliance on the right side (arrows). Note the red patch of atherton mesial to the right center incisor as the expansion increased. B-C: Bone- borne expander modified to avoid including the dental units on the design. Note opening of the suture in a parallel fashion from anterior to posterior. D-E: Hybrid expander anchored on TADs and first molars. The occlusal radiograph shows a triangular shape opening of the suture. From Garib et al., 2008. Reprinted with permission of the Journal of Clinical Orthodontics. when four TADs usually are recommended for a better anchorage and appliance design (Lee et al., 2014). We have reported and compared the treatment response of par tients with similar transverse skeletal severity, gender and age with the most effective orthopedic tooth-tissue-borne expander versus bone- anchored maxillary expander on changes of the basal bone and molaſ teeth of consecutively treated patients (Vanarsdall et al., 2017). TWO groups were evaluated after expansion and compared with CBCT data: a group of eleven patients (11.3 to 17 years) treated by one clinician only with bone-anchored expander (TAD type); and a group of 24 patients (7.8 to 12.8 years; Christie et al., 2010) treated with a bonded tooth- tissue-born expander (bonded type). T-test statistical analysis demon- strated a statistically significant difference (p + 0.05) between the meaſ. of maxillary basal bone change at the first molars of both groups. The percentage of the mean screw expansion associated with the width of 184 Vanarsdall and Blasi the palatal expansion at the first molar was calculated as follows: 40.65% on the bonded RPE group and 65.04% on the TAD RPE. The large differ- ence in the efficiency of the expansion was due to the direct effects of the expansion upon the palate itself and not the surrounding molars of the maxillary arch where the bonded tooth-tissue-borne RPE device general- ly retains. This analysis also is supported Strongly by the large inter-molar tipping angle effect of the bonded RPE compared with the TAD group before and after expansion. The bonded RPE group resulted in a mean of 11.7 SD +/- 3.05° difference versus the near absence of any mean ef- fect 0.2 SD +/- 3.47° difference in the case of the TAD treatment group. A T-test exhibited a highly significant difference (p<0.00001) between the two groups. Furthermore, both groups exhibited midline suture opening in a parallel fashion (Fig. 9C). This was different from the earlier type of expanders, which have been reported to cause openings of the midpala- tal suture in a triangular shape with extended opening on the anterior maxilla area (Garib et al., 2008; Woller et al., 2014; Figs. 9D-E and 10A- B). Expansion efficacy was exhibited in both significant skeletal changes. However, the bone-anchored devices obtained 25% more skeletal bas- al change (MX-Mx) without dental compensation than did the bonded tooth-tissue-borne RPE. Greater maxillary orthopedic expansion was Seen with the bone-anchored versus the bonded tooth-tissue-borne ex- pander and a highly statistically significant difference in molar tipping an- gulation. With the Hass appliance, therefore, 20% of basal bone change from the jack screw activation can be achieved, 41% with the bonded RPE and 65% with the TAD RPE (Fig. 10C-E; Vanarsdall et al., 2017). It is impor- tant to know what an appliance will provide for the skeletal correction. Lin and coworkers (2015) reported similar results. They evalu- ated and compared the effects of a Hyrax expander and a bone-borne expander (similar to our design). The Hyrax group had more buccal tip- ping of the dentition and alveolar process with significant adverse buc- cal dehiscence in the first premolar area. They also concluded that the bone-borne expanders produced greater orthopedic changes and fewer dentoalveolar tipping compared to the Hyrax expander group. Although there have been demonstrated benefits of skeletally an- chored RPE, potential adverse effects may exist. These include reversible microfractures at the level of the nasal bone or cracked nose that could be seen clinically as a bump on the nose; damage to the surrounding 185 Correction of the Transverse Dimension Figure 10. A-B: Hyrax appliance used on a mixed dentition case. The CBCT axial cut reveals a triangular shape expansion more prominent on the anterior part of the maxilla. From Woller et al., 2014. Reprinted with permission of Dental Press Publishing. C-E: There is a need to select the proper rapid palatal expander (RPE) that will provide the skeletal correction needed for the skeletal age of the patient. C. Haas-type appliance provides 20% of basal change. D: Bonded tooth- tissue-borne expander, 41% of basal change. E. Bone-borne, 65% basal change of the mean jackscrew opening at the level of the first permanent molars. From Vanarsdall et al., 2017. Reprinted with permission of Elsevier. tissues due to a failed TAD and/or pain if the RPE impinges on palatal tissues. Skeletal anchorage should permit orthopedic change without the adverse dental changes by applying force directly to the maxillary bone. Its use is indicated for moderate to severe skeletal discrepancies, skeletal mature individuals and patients with missing teeth and/or peri- odontal involved cases (Vanarsdall et al., 2017). Orthopedic expansion can be accomplished in adolescents, even in young adults, with skeletally anchored devices (Fig. 11). Future research is needed to determine the skeletal age limitation of bone-borne RPEs; nevertheless, it is clear that the envelope of treatment has evolved to include older patients (Fig. 12). _- -> Figure 12. Treatment envelope of the transverse skeletal dimension. A. though there is a need of future research to determine the skeletal age limits of the bone-anchored expander, the envelope of treatment has been changed to include adult patients without SARPE. From Vanarsdall et al., 2017. Reprinted with permission of Elsevier. 186 Vandrsdalſ and Blasi Figure 11. A 25-year-old female with history of orthodontic treatment. The pa- tient was treated with upper premolar extractions only to relieve crowding due to a narrow maxilla. A: Three TADs used per side to maximize the skeletal change of the maxillary expansion. B: Rapid palatal expander bone-borne Haas type with acrylic for better support and distribution of forces of expansion. C-D: 3D CBCT confirms purely skeletal expansion with separation of the palatal suture in a par- allel fashion in an adult patient. Treatment Envelope TAD Supported RPE Today Tx: < RPE > <- SARPE —- 1995 AGE: 6 7 8 9 || 0 || || 2 || 3 || 4 || 5 || 6 || 7 || 8 || 9 20 ADULTS Greater Potential Treatment Options 187 Correction of the Transverse Dimension LONG-TERM STABILITY In our view, RPE has less to do with gaining arch perimeter and extraction/non-extraction treatment and more to do with the skeletal correction of the transverse dimension. It generally is accepted by orthodontists that mechanically pushing or pulling the teeth to expand the dental arches is not a stable correction. One of the biggest problems in orthodontics is arch form. Clinicians want to keep that arch form because if it is modified, it can relapse to the original configuration; however, it is important to realize that if it is corrected orthopedically, it does not relapse. Stability of RPE depends partially on the histological activity at the site of the separated suture. Ten Cate and colleagues (1977) described a single layer of active osteoblasts that continued to lay down new bone at the bony margins of the suture. The uniting layers consisted of a large fiber bundle running across the borders of the suture. The response to expansion was osteogenesis and fibrillogenesis, followed by the sutural connective tissue fibroblasts to remodel, which led to regeneration of the suture (Revelo and Fishman, 1994). With growth, the skeletal transverse correction with RPE and LB do not reverse (Vanarsdall et al., 2004; DeGeorge, 2015). In a young patient, when inducing tooth movement (orthopedics, LB) by muscles, eruption and growth, the dentoaveolar widening that occurs provides a broad arch form that is not determined mechanically by the brackets and arch wires. Before any bracket system is used, the wider, natural or broader arch form is established. Other treatment options that do not influence the growth and change of the apical skeletal base (orthopedics/ surgery) are limited to maintain the original arch form of the malocclusion. In these treated cases, satisfactory mandibular alignment may exist in less than 30% of the cases long term (Little et al., 1981). Relapse tendencies after RPE have been reported in the past, but many of the studies are based on intermolar width dental measurements (Mew, 1983). Much of the relapse may be due to expansion achieved with means of dentoalveolar tipping, rather than palatal suture opening. Therefore, it is important to maximize skeletal expansion and minimize dental tipping for long-term stability of the correction. 188 Vanarsdall and Blasi CONCLUSIONS The benefits of correcting a transverse skeletal deficiency include: 1. Improved periodontal health; 2. Dental and skeletal stability of the correction; 3. Dentofacial esthetics—improving buccal corridors; and 4. Improved airway resistance. Its diagnosis must be based on skeletal and not dental components. The earlier the patient is treated, the better the response to treatment. It is important to assure skeletal expansion regarding the appliance selection. With the new skeletally-anchored expanders, the envelope of treatment definitely has changed to include mature patients and avoid certain surgi- cal procedures (e.g., SARPE). Further research is needed to delineate the limits of such expanders. 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Angle Orthod 1965;35:178-186. 193 194 EXTRACTION VERSUS NON-EXTRACTION: LONG-TERM RESEARCH FINDINGS ON ARCH WIDTH AND BUCCAL CORRIDORS Sercan Akyalçin ABSTRACT Arch length deficiency is one of the most common problems with which ortho- dontists have to deal while striving to achieve their treatment objectives. The extent of the space needed makes the clinician decide whether or not to extract teeth. Extracting teeth—mainly all four premolars—has been condemned for Various reasons including its negative effects on the temporomandibular joint (TMJ), facial and smiles esthetics and, more recently, its potential association with sleep disorders. The aim of this chapter is to present a brief perspective of the extraction versus non-extraction debate and further elaborate on the long- term changes in arch width and buccal corridor ratios following orthodontic treatment. Extraction and non-extraction treatment options should not substi- tute for each other. Orthodontic treatment outcome is primarily a result of the mechanotherapy and clinical management of the case. When the two treatment options were compared, there were certain treatment differences between them. However, it was difficult to conclude that orthodontic therapy with extrac- tions resulted in the constriction of the maxillary dental arch and increased the buccal corridor spaces accordingly. Additionally, long-term comparisons of these Variables showed that extraction and non-extraction patients did not differ sig- nificantly at the post-retention period. KEY WORDS: extraction, non-extraction, arch form, smile esthetics INTRODUCTION The primary goal of orthodontic case management is to achieve proper articulation of teeth that ideally are aligned along a functional Occlusal plane with adequate axial and buccolingual inclinations. The Secondary goal is to ensure long-term stability of the final treatment 195 Arch Width and Buccal Corridors outcome. Lack of adequate space in the dental arches is the most Com- mon problem the clinician runs into while striving to achieve these goals. Nature has the ability to deal with the space problem owing to the remodeling processes in the jaws. The increase in dental arch width and length and a coordinated eruption of teeth are natural mechanisms that allow for sufficient space during tooth eruption. The orthodontist's main responsibility is to estimate the extent of the space needed in this dynamic environment. Poorly planned orthodontic cases may result in eruption problems (i.e., commonly observed in the second molar region, cortical bone loss and subsequent periodontal problems along the alveo- lar bone). Upon the resolution of the main problem, a long-term reten- tion plan should be in place to counteract for lifelong changes of the Soft tissues and alveolar bone along with the physiological movement of the teeth. The fundamental decision that needs to be made by the clini- cian is whether there is a need for tooth extractions in the individual's treatment plan. Extracting teeth—mainly all four premolars—has been condemned for various reasons including its negative effects on TMJ, fa- cial and smiles esthetics and, more recently, its potential association with sleep disorders. The orthodontic practice has witnessed dramatic fluc- tuations and trend changes in this regard over the decades (DiBiase and Sandler, 2001). Keim and colleagues (2008) demonstrated that only 18% of orthodontic cases presenting with arch length deficiency are treated with extractions. Today, the number is more or less the same across the United States. The American Board of Orthodontics (2016) still requires one out of six cases submitted for initial certification exam (ICE) to be managed with extractions in all four quadrants. The thought that extraction treatment causes or increases the risk for temporomandibular disorders (TMDs) is disputed highly today. Many studies (Gianelly et al., 1988; Dibbets and van der Weele, 1991; Kundinger et al., 1991; Artun et al., 1992; Kremenak et al., 1992a,b; Luecke and Johnston, 1992) have shown that there is no difference be- tween extraction and non-extraction treatment for the incidence of TMD symptoms, joint sounds and posterior displacement of the joint or man- dible. Dibbets and van der Weele (1991) presented no relationship be- tween the choices of not to extract or to extract either first premolars 196 Akyalçin or any other teeth and the registration of pain, limitation of mouth open- ing, crepitation and radiological signs. Excessive anterior interferences re- Sulting in possible posterior condyle displacement are the result of poor treatment mechanics. When arches are leveled properly and space clo- Sure and overjet reduction are controlled adequately, there is no reason that such interferences should occur (McLaughlin and Bennett, 1995). The outcome of extraction therapy on the final soft tissue profile also has been documented extensively. Most common findings follow- ing extraction treatment were reported as retruded upper and lower lips (Bravo, 1994; Bishara et al., 1995; Cummins et al., 1995), straighter profile (Bravo, 1994; Bishara et al., 1995) and more upright maxillary and man- dibular incisors (Bishara et al., 1995; Kocadereli, 2002). It was reported, however, that the actual percentage of patients who finish orthodontic treatment with extractions of four premolars and excessively flattened and distorted profiles was small (Drobocky and Smith, 1989; Young and Smith, 1993; Bravo, 1994; Bowman and Johnston, 2000). Additionally, Some reports concluded that the mean finished profile for both extrac- tion and non-extraction patients were within the normal and ideal aes- thetic ranges of the parameters studied (Bravo, 1994; Boley et al., 1998; James, 1998). Changes in dentition regarding incisor movement evidently Would bring about changes in the soft tissue profile of extraction patients. In a study that used digital subtraction of pre- and post-treatment cepha- lograms (Akyalçin et al., 2007), upper and lower lip vermillion points and lower lip Sulcus moved backward in the extraction group, whereas the non-extraction group had opposite tendencies. However, comparison of these changes between extraction and non-extraction patients, on aver- age, did not exceed 1 mm. Based on the body of evidence available today, there is no reason to believe that premolar extraction causes undesirable flattening of the facial profile. The soft tissue profile following orthodon- tic treatment is primarily a result of the biomechanical management of the case. The recent claim that extraction treatment leads to obstructive Sleep apnea (OSA) originates from the potential changes in the ana- tomical position of the anterior teeth. Larsen and associates (2015) shed Some light on this thought process as they investigated electronic medi- Cal and dental health records of 5,584 patients. Half of study sample 197 Arch Width and Buccal Corridors included individuals with one missing tooth in each quadrant. They matched the study and control groups using age, body mass index and gender criteria. The incidence of OSA in extraction and non-extraction groups was 10.7% and 9.5%, respectively. Accordingly, no significant dif- ference in the incidence of OSA was found between the two groups. AS a result, the thought that past orthodontic treatment including premo- lar extractions played a significant role in the cause of OSA was not Sup- ported. Although orthodontic treatment is based primarily on correction of the dental relationships, enhancing the dentofacial characteristics of the individual is an inseparable goal. The literature contains noteworthy studies describing the esthetic elements of the dentition and the Sur- rounding soft tissues during smiling that can be evaluated on a three-di. mensional (3D) canvas (Ackerman et al., 1998; Zachrisson, 1998; Johnston et al., 1999; Sarver, 2001; Sarver and Ackerman, 2003a,b). With regard to the esthetics of the Smile, two main characteristics of the smile—arch form and buccal corridor—have gained much attention. It was claimed that some consequences of extraction treatment result in a constriction of dental arches, which would have deleterious effects on the smile (Wit- zig and Spahl, 1987). Since smile is a dynamic facial trait that also needs to be evaluated within the perspective of time (Sarver and Ackerman, 2003a,b), the following section in this chapter will elaborate on our find- ings from long-term investigations. LONG-TERM CHANGES IN ARCH WIDTH AND BUCCAL CORRIDOR RATIOS Narrow and collapsed arch forms may result in dark buccal corri- dors at the corners of the mouth during smiling. Using relatively broader arch forms and modifying the crown torque of cuspids and premolars may offer a solution to this problem (Zachrisson 2001, 2002, 2003). It needs to be kept in mind, however, that the practice of widening and modifying the arch form brings about long-term stability issues. Practic- ing orthodontists are looking for answers as to whether or not premolar extractions would cause any significant constriction in the dental arches and if this would deteriorate over time. On the premise that extraction of four premolars leads to nar- rowing of the dental arch width and decreased fullness of the dentition 198 Akyalçin in the mouth during a smile, Johnson and Smith (1995) evaluated buccal corridor ratios—the relationship of the width of the dentition to the soft tissue by ratios—on smile photographs after extraction and non-extraction treatments. They did not find a predictable relationship between the extraction of premolars and the esthetics of the smile. Gianelly (2003) compared anterior and posterior widths of the dental arch after both extraction and non-extraction therapies. His findings indicated that maxillary arch widths measured between the canines and the second molars were the same after treatment. Because the premolar and molar anteroposterior positions might change dramatically after Orthodontic treatment, another attempt was made by Kim and Gianelly (2003) to address the circumferential effects of tooth movement in the dental arches. In their study, arch widths were measured and compared at a constant arch depth representing the premolar-molar junction. Interestingly, arch widths of both groups measured from the most labial Surfaces of the teeth at a constant depth differed significantly; they were Wider in the extraction sample. Since lateral expansion and buccal torque implementation are not indicated in all patients, it was important to answer the question Whether fixed appliance therapy, incorporating either extraction or non- extraction therapy, had a deleterious effect on the dental arch. It also was important for us to find out whether the treatment effects are maintained Over time. With these questions in mind, a study was designed (Akyalçin et al., 2011) to address the long-term changes in maxillary arch width following orthodontic therapy. The sample group included individuals in permanent dentition With skeletal and dental Class I malocclusion and normal growth pattern. The subjects were 66 patients with Class I crowding who underwent treatment using edgewise mechanics and achieved acceptable post-treatment results. Treatment records were obtained from three time periods: pre-treatment (T1); post-treatment (T2); and at post-retention (T3). Retention was applied with Hawley retainers and the post-retention period was at least three years. The patients Were divided into non-extraction groups (n = 32; 12 males and 20 females) and extraction (n = 34; 14 males and 20 females). The mean ages of the study groups at the beginning of orthodontic treatment Was 14.2 + 3.9 years for the extraction group and 13.8 + 3.2 years for the non-extraction group. Pre-treatment maxillary and mandibular incisor 199 Arch Width and Buccal Corridors irregularity were 4.7 £3.2 mm and 5.8 + 2.7 mm for the extraction group, and 2.0 + 2.1 mm and 2.3 + 2.2 mm for the non-extraction group, respec- tively. The mean treatment and post-retention times were two years, two months and five years, two months for the extraction group; and one year, eleven months and four years, ten months for the non-extraction group, respectively. Measurements were made on the dental models at three sepa- rate locations (anterior, middle and posterior widths), using the incisive papilla and rugae anatomy. This method helped standardize the location at which the arch width measurements were made for all three time pe. riods (Fig. 1). Significant treatment changes"(p < 0.05) were found between the two groups for all variables (Table 1). These changes resulted from in- creases that were observed in the non-extraction group in all three Vari- ables (p < 0.001). In the extraction group, no significant changes were observed between T1 and T2. In the post-retention period, only the poS- terior arch width measurement was different significantly between the two groups (Table 2; p < 0.05). The difference between the two groups originated from the significant decrease in posterior width measurement (p = 0.01) in the non-extraction group between T2 and T3. Clinical significance of the amount of posterior expansion ob- served in the non-extraction group at post-treatment is open to discus- sion. As an interpretation of the findings, a mean change between 1 to 2 mm at the end of orthodontic treatment hardly ever may be detectable by the observer. It was argued that people with normal occlusions and balanced faces also could have narrow arch forms relative to their wide lip extensions (Isiksal et al., 2006). These findings suggest that post-treat- ment and post-retention maxillary arch width, with or without premo- lar extractions, may affect buccal corridor ratios and the esthetics of the smile accordingly, however, not significantly so. Smile is a complex feature to analyze. Since it is not a fixed concept, esthetic prediction of dynamic facial features upon the Com- pletion of the treatment can be a lot more difficult to judge than any other physical processes. Plaster models and panoramic radiographs are not valuable information when judging complex facial features and the smile itself. Ackerman and associates (1998) suggested that not all 200 Akyalçin * * º ºf - Pre-treatment Post-treatment Post-retention Figure 1. Measurements made on images. 1 = anterior width; 2 = middle width; 3 = posterior width; D = distance from the point immediately distal to the incisive papilla to the posterior width recorded for each individual on the pre-treatment image; D = D was used to mark the D’ point in order to calculate the posterior Width for post-treatment and post-retention images. Table 1. Comparison of changes at the end of treatment (T2-T1) between extraction and non-extraction groups. *P × 0.05. DIFF SD | "..." | SD P Anterior arch width 0.32 2.75 2.05 1.76 0.007* Middle arch width 0.44 2.45 1.92 1.64 0.01% Posterior arch width 0.38 2.24 1.37 1.24 0.023* Table 2. Comparison of changes at post-retention (T3-T2) between extraction and non-extraction groups. NS = not significant; *P º 0.05. T- EXTRACTION NON-EXTRACTION VARIABLE P "..." | SD | "..." sp Anterior arch width –0.14 0.94 –0.21 0.83 NS Middle arch width –0.23 0.86 –0.23 0.99 NS Posterior arch width 0.25 0.93 –0.50 0.90 0.004* Orthodontically well-treated patients with excellent occlusal relationships and exemplary plaster models have acceptable esthetics during smiling. It may not be justifiable to conclude that changes in maxillary arch Width would relate directly to the changes in buccal corridors as they also Wanted to analyze the long-term changes in buccal corridor ratios "an orthodontic patient population treated with and without premolar *tractions (Akyalgin et al., 2016). 201 Arch Width and Buccal Corridors The study (Akyalçin et al., 2016) included 28 four first premolar extraction and 25 non-extraction patients. The extraction decision was based on the need for space to resolve crowding and to align the incisors ideally. The average age of the sample group was 12.8 + 1.2 years. The extraction group had a treatment time of 28.2 + 4.2 months, whereas the non-extraction group had a treatment time of 27.3 + 4.0 months. The extraction and non-extraction groups were retained using an upper wraparound Hawley retainer and lower 3-3 bonded retainer for a mean of 4.6 years and 3.7 years, respectively. Post-retention (T3) records were taken at a mean 18.6 + 6.0 years in the extraction group and 16.8 + 5.8 years in the non-extraction group. The frontal smiling photographs of these individuals were digi- tized and measured to calculate three buccal corridor ratios. Since there were two groups and three different time periods, changes in buccal cor- ridors were analyzed with a two-way mixed ANOVA analysis. No signifi- cant group X-time interaction was identified for any of the buccal corridor ratio measurements investigated in the study. This finding demonstrated that extraction and non-extraction patients did not differ in their buccal corridor ratios over the course of treatment and post-retention period. It was shown that orthodontists and lay people rated smiles with small buccal corridors as significantly more attractive than those with large buccal corridors (Martin et al., 2007). Maulik and Nanda (2007) re- vealed that in a group of orthodontically treated and untreated individu- als, most subjects demonstrated a buccal corridor ratio of 89%. Similarly, buccal corridor ratios were around 92-93% in a group of treated cases, which were successful upon the submission to The American Board of Orthodontics’ (ABO) clinical examination (Akyalçin et al., 2014). Addition- ally, studies that focused on the acceptable threshold of this variable in- dicated a significant decrease in the esthetic score when the buccal cor- ridor ratios were altered more than 10% (loi et al., 2009; Zange et al., 2011). In our study, extraction and non-extraction patients had buccal corridor ratios of 94.8% and 97.2%, respectively, at the end of the post- retention period. This finding supported the fact that treatment and time had virtually similar effects on the buccal corridor spaces of the individu- als treated with and without premolar extractions. Detailed findings from this study will be featured in a future article (Akyalçin et al., 2017). 202 Akyalçin CONCLUSIONS The body of current evidence suggests that extraction and non-ex- traction patients have differences at the end of the orthodontic treatment in Comparison with the maxillary arch width measurements. However, extraction treatment did not lead to any decreases in the transverse arch width measurements. Treatment outcome was fairly stable in both extrac- tion and non-extraction patients at the long-term follow-up. Additionally, buccal corridor ratio measurements from digitized photographs revealed Virtually no difference between the extraction and non-extraction patients Over time. Future studies should be planned to evaluate the smile char- acteristics in the transverse plane using 3D photographs and analyses to Confirm the current results and expand our knowledge in this field further. REFERENCES Ackerman JL, Ackerman MB, Bresinger CM, Landis JR. 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Making the premolar extraction smile full and radiant. World J Orthod 2002;3:260-265. Zachrisson BU. Maxillary expansion: Long-term stability and smile esthet- ics. World J Orthod 2001;2:266-272. Zachrisson BU. Premolar extraction and smile esthetics. Am J Orthod Den- tofacial Orthop 2003;124(6):11A-12A. Zange SE, Ramos AL, Cuoghi OA, de Mendonça MR, Suguino R. Percep- tions of laypersons and orthodontists regarding the buccal corridor in long- and short-face individuals. Angle Orthod 2011;81(1):86-90. 206 ORTHODONTIC APPLICATIONS OF COMPUTER-AIDED DESIGN AND COMPUTER-AIDED MANUFACTURING (CAD/CAM) Tung Nguyen ABSTRACT In recent years, the growth of Computer-Aided Design and Computer-Aided Manufacturing (CAD/CAM) technology has been utilized to create individual- ized orthodontic appliances. While technological improvements to orthodontic appliances seem promising, do they truly improve treatment efficiency and/ or treatment quality? The purpose of this chapter is to review currently avail- able orthodontic appliances that incorporate CAD/CAM technology, specifically clear aligners, customized wires and CAD/CAM-fabricated brackets. Clear aligner therapy has seen vast improvements since its inception; however, clinical stud- ies have shown that it is less effective when compared to conventional brackets. Aligners only produce 50-60% of planned tooth movements (e.g., translation, rotation and torque) with 70-80% of clinicians reporting the need for mid-course revisions. Customized archwires are planned from three-dimensional (3D) virtual setups and bent robotically. Studies have shown a decrease in treatment time with the use of customized wires; however, the quality of treatment results often are less favorable. While this technology is fairly accurate for mesial-distal tooth movements, it is less precise for crown tip and root torque. CAD/CAM brack- ets initially were shown to be more effective and efficient when compared to Standard brackets, but a follow-up study showed no difference in the quality of treatment of outcomes. The study also showed the majority of the reduction in treatment time resulting from CAD/CAM brackets may be due to the indirect bonding process rather than the personalized milled slots. KEY WORDS: CAD/CAM appliances, treatment outcomes, effectiveness, efficiency, indirect bonding 2O7 Orthodontic Applications of CAD/CAM INTRODUCTION In a continued effort to develop a true straight wire appliance, orthodontic manufacturers turned to a well-known engineering technol- ogy: Computer-Aided Design and Computer-Aided Manufacturing (CAD/ CAM). CAD/CAM has been a focus of dental research since the 1980s. Traditionally, much of the dental utilization of CAD/CAM technology has been in the prosthodontics field, specifically in the milling of crowns and fixed partial dentures (FPDs; Miyazaki et al., 2009). However, other den- tal specialties have gained an appreciation for the benefits of CAD/CAM, leading to widespread application of the technology. The study by A Mortadi and colleagues (2012) cited orthodontic CAD/CAM applications that now include aids for diagnosis and treatment planning, clear aligner therapies, lingual appliances and titanium Herbst appliances. Customized brackets with patient-specific torque, machine-milled indirect bonding jigs and robotically bent archwires are among the newest CAD/CAM ad- vances in the specialty. The overarching goal of incorporating CAD/CAM technology into the field of orthodontics can be summed up best as “im- proving reproducibility, efficiency and quality of orthodontic treatment" (Müller-Hartwich et al., 2007). In addition to the precise and customized milling of orthodontic appliances, the application of CAD/CAM technology allows the practitio- ner and patient to utilize virtual treatment planning software to identify case objectives and visualize treatment outcomes better. Practitioners are able to evaluate different treatment plans, including extraction ver- sus non-extraction treatment options or substitution versus prosthetic replacement in cases of missing teeth. The end result is improved Com- munication between the practitioner and patient, allowing for more real- istic treatment expectations and an improved informed consent process (Mayhew, 2005; Gracco and Tracey, 2011). Multiple orthodontic systems now are utilizing this technology with success, including labial and lingual fixed appliances, as well as removable clear aligner Systems. CLEAR ALIGNER THERAPY With the goal of offering an esthetic alternative to traditional fixed appliance orthodontic treatment, Align Technology” introduced In- visalign" in 1998 (Kravitz et al., 2009). Utilizing polyvinyl siloxane (PVS) 208 Nguyen impressions or an intra-oral scan, a digital model of the patient's denti- tion is created. The three-dimensional (3D) model then is manipulated by the clinician and Invisalign" technician to create the desired final posi- tion of the teeth. The CAD/CAM process continues as stereolithic (SLA) models corresponding to the planned tooth position are printed at each Stage of treatment and a series of removable polyurethane aligners is fabricated. Each aligner is worn for approximately fourteen days and is programmed to move a single tooth or small group of teeth 0.25 to 0.33 mm (Kravitz et al., 2009). The outcome from clinical research investigating the efficacy of Invisalign" has been variable. Orthodontists using the appliance report that 70-80% of patients require mid-course correction, case refinement or conversion to fixed appliances before the end of treatment (Kravitz et al., 2009). Djeu and colleagues (2005) found that cases treated with Invis- align" scored thirteen points worse than cases treated with traditional fixed appliances when evaluated using the American Board of Orthodon- tics Phase Ill examination criteria. The correction of large anteroposte- rior discrepancies and occlusal contacts were areas where Invisalign" performed the worst. A follow-up study was completed on the sample three years later to evaluate the relapse of patients treated with Invis- align" compared to those treated with fixed appliances. The Invisalign" patients showed worse relapse in overall alignment, specifically maxillary anterior alignment, though patients in both treatment groups showed Some worsening of mandibular anterior alignment in the retention phase (Kuncio et al., 2007). Multiple improvements have been made to address the clini- Cal shortcomings of early iterations of Invisalign", including updated attachment designs, auxiliaries (e.g., Power Ridges and Precision Cuts) and continued modifications to the aligner material (Simon et al., 2014). In 2014, Simon and associates investigated the most current Invisalign" appliance, Specifically looking at translation, rotation and incisor torque expression. The efficacy of the three movements was found to be 59.3%, With the planned velocity and amount of tooth movement having the biggest impact on success. Upper incisor torque was found to be difficult to achieve with aligners particularly, with less than 50% of the planned movement actually achieved (Simon et al., 2014). 209 Orthodontic Applications of CAD/CAM Invisalign" has been shown to be an effective tooth-moving ap- pliance when used to treat cases of mild to moderate difficulty, especially if limited extrusion and anteroposterior movements are required. Patient compliance with aligner wear also is a critical component of treatment success. In addition, clinicians should utilize overcorrection in the treat- ment planning process for difficult tooth movements to improve the fin- ished case outcome. There is still much investigation to be done regard- ing the biomechanics and clinical efficacy of Invisalign", but the future of the appliance appears promising (Kravitz et al., 2009; Simon et al., 2014). CUSTOMIZED WIRES Orametrix” has been working on its unique approach to CAD/ CAM orthodontics since the early 2000s. Similar to other CAD/CAM orthodontic systems, Oraſvietrix*'s SureSmile" provides digital software that the clinician can utilize for diagnosis and treatment planning. The subsequent fabrication of robotically bent archwires is what separates SureSmile" from other customized appliances (Larson et al., 2013). In- terestingly, the SureSmile" system can be used with any conventional orthodontic brackets and bands, with no special consideration during the placement of the appliances. At any time after placement, the Sure Smile" process begins with a scan of the patient's dentition using an in- tra-oral scanner or cone-beam computed tomography (CBCT). The data is used to construct a digital model of the patient's dentition, including the exact bracket type and location on each tooth. A 3D bracket library with the precise manufacturer's dimensions for each bracket is superimposed over the scanned brackets to allow higher precision of slot dimension. The teeth then can be moved digitally to their desired final positions. Linear and angular measurements can be made from the software, in- cluding a Bolton analysis and arch length discrepancy. Oraſvietrix” cur- rently is developing software to segment the maxillary/mandibular bone and roots on CBCT to define biological boundaries for virtual tooth move- ment. Once the clinician approves the digital dental setup, the software calculates the archwire bends needed to translate the dental setup to the patient's teeth, using the precise location of the bracket slot on each indi- vidual tooth. Wire-bending robots fabricate the custom archwires in the material and cross-section specified by the orthodontist (Fig. 1). Research has shown the error in bends and twists with stainless steel archwires to be as accurate as 1° and 0.1 mm (Larson et al., 2013). 210 Figure 1. A virtual setup of the final occlusion is shown. Once the clinician approves the Setup, a wire-bending robot fabricates the archwires in the material and cross- Section specified by the orthodontist. Courtesy: Oral/etrix” Corporation. There are different approaches to using SureSmile" in daily prac- tice. One is to use it as a comprehensive system, using SureSmile" wires from alignment through finishing. Alternatively, the clinician can begin treatment with standard edgewise wires. After the alignment stage is Completed, scans are taken and customized SureSmile" finishing wires are ordered to refine and detail the case (Fig. 2A-C). SureSmile" wires also can be used in limited objective cases. These include cases where Only specific teeth (e.g., incisors) are planned for movement. The custom- zed wires can be designed to be passive in the posterior segment where the occlusion is ideal, and active in the anterior segment where the align- ment is desired (Fig. 2D-F). A robust retrospective study investigating the clinical efficiency of SureSmile" was completed by Sachdeva and coworkers (2012), eval- Lating the treatment records of 9,390 SureSmile" patients and 2,945 Conventional patients. The group found that the SureSmile" cases fin- shed treatment about eight months faster than the conventional pa- tients and had four less treatment visits. Alford and colleagues (2011) found that Suresmile” reduced treatment time by seven months with better ABO scores for alignment and rotations; however, the second or- der root angulation was worse when compared to conventional treat- ºnent. It was interesting to note that the conventional treatment group had a higher ABO Discrepancy Index score, suggesting the conventional §ſoup had more difficult malocclusions pre-treatment than the Sure- Smileſm grOup. 211 Orthodontic Applications of CAD/CAM Figure 2. Customized wires can be used to refine and detail a case (A-C) or to move only specific teeth (D-F). In D-F, a customized wire was used to add distal root tip to the upper right central and lateral incisors, and mesial root tip the up- per left central and lateral incisor. - Larson and associates' study (2013) focused on the effectiveness of the SureSmile" appliance, which involved the superimposition of the post-treatment digital model on the initial virtual treatment plan model using best-fit, surface-based registration. The superimposition allowed comparison of the planned tooth position and the actual case outcome with respect to six dimensions of tooth movement. Mesiodistal and Ver tical tooth positions were found be the most accurate movements with the SureSmile" system, while crown torque, tip and rotation movements were less predictable. Variations in the dimensional accuracy of bracket slots, bone density, root anatomy, occlusal forces and patient compliance were cited as possible causes for the discrepancies between planned and final tooth position. Nevertheless, the SureSmile" system has been shown to be an effective tooth-moving appliance when the initial diagº nosis and treatment plan are established correctly and compensations are built into the treatment plan to overcorrect large tooth movements (Larson et al., 2013). CUSTOMIZED BRACKETS One of the most comprehensive CAD/CAM orthodonticappliances on the market is Ormco's Insignia", which is available in standard and self-ligating applications with optional use of esthetic ceramic brackets. The process begins with a PVS impression or intra-oral scan of the patient's dentition, which is sent to Ormcoe for creation of digital models of the dental arches. A virtual buccal-lingual boundary is constructed from the soft tissue outline of the intra-oral scan. The technicians then 212 Nguyen Complete a virtual setup for ideal archform and occlusion that is sent to the clinician for approval. Utilizing Ormco"'s Insignia"Approver software (Fig. 3), the clinician can manipulate the digital setup to refine the 3D position of individual teeth, adjust the archform, alter the smile arc when needed and detail the dental contacts in final centric occlusion (Gracco and Tracey, 2011). Once the clinician approves the treatment plan and virtual setup, the Insignia" system is reverse engineered in one of several ways, de- pending on the clinician's choice of brackets. If metal twin brackets are Selected, they then are individualized by precision cutting the slots in the milled-in faces, while metal self-ligating brackets are customized by vary- ing the thickness and angulations of the bracket base. The selection of Ceramic twin or self-ligating brackets limits the amount of customization that can be achieved; however, stock brackets that most closely match the torque prescriptions in the Insignia" Approver Software are selected and a custom pad is laser welded to the brackets. Further adjustments to the positioning jigs and archwires allow for a high degree of individualiza- tion for each Insignia" setup (Graco and Tracey, 2011). Custom wires also are included in the system. The size and dimension of the virtual arch- form is milled precisely into metal plates; nickel titanium, stainless steel or beta-titanium wires are fabricated from these plates. The final step of the Insignia" system is delivering the custom- ized brackets precisely in the ideal position on each tooth to maximize the effectiveness of the individualized appliance. Bracket transfer jigs are milled to fit the occlusal surfaces of the teeth, allowing for indirect place- ment of the appliances. This step is crucial to the success of the system Since imprecise bonding of brackets will not produce the planned tooth movement (Fig. 4). The jigs allow for 75% of the bracket pad edges to be exposed during bonding so that the majority of excess composite can be removed prior to polymerization, minimizing composite flash cleanup time after the jigs are removed (Gracco and Tracey, 2011). Weber and coworkers (2013) investigated Insignia", comparing treatment effectiveness and efficiency of the customized appliances to traditional twin appliances. The final outcome differences between the two treatment groups were widespread, with the Insignia" cases show- ing significantly lower ABO scores, a reduced number of archwire ap- pointments and shorter overall treatment times. 213 Orthodontic Applications of CAD/CAM Figure 3. A: A virtual tooth setup is performed by a technician with the brackets placed in the ideal location to achieve the “ultimate straight-wire appliance." B. The clinician can change the position of any teeth using the Insignia" Approver software. C. Brackets are CAD/CAM milled. D: Bonding jigs are fabricated to transfer the bracket to the planned position on the teeth. Courtesy: Ormoo” Corporation. Figure 4. In order for a system like Insignia" to be effective, the bonding jigs must transfer the planned position of the bracket to the teeth precisely. A: planned bracket position. B: Actual bracket position. C: Improper seating the placement jigs could result in first, second and third order errors. A follow-up study by Brown and colleagues (2015) analyzed º orthodontic patients treated with: 1) direct bonded conventional appli- ances; 2) indirect bonded conventional appliances; or 3) indirect bonded 214 Nguyen CAD/CAM appliances. Intuitively, precision-milled appliances combined with digitally planned setup should reduce the effects of human error during bonding and account for anatomical variations present in tooth shape, thereby improving the overall finished case quality. The study found no significant difference in treatment outcomes between the three groups, as measured using the ABO Cast/Radiograph Evaluation scores. Interestingly, the mean ABO score for the direct bonded group was nearly four points lower when compared to the indirect bonded and CAD/CAM groups. Though the difference was not significant statistically, it is sur- prising that the treatment protocol with the least patient customization produced the best result. Since the appliances have subtle differences in design, can true study blinding be obtained with a prospective clini- cal trial? Simply put, operator bias can influence the results of efficiency Studies. Therefore, any studies evaluating efficiency of treatment as an outcome also must assess the quality of the final occlusion. The reduction in total treatment time for the CAD/CAM group was reported by Weber and associates (2011). The total treatment time for the CAD/CAM group was approximately eight months shorter than the direct bonded group, but only three months shorter than the indirect bonded group. The indirect bonded group showed a five-month reduc- tion in treatment time when compared to the direct bonded group, sug- gesting the indirect bonding process potentially had a bigger impact on treatment duration than the customized appliances. When evaluating treatment efficiency, a single measure of treat- ment time is not always adequate; the number of appointments and in- terval between appointments also must be considered. Though overall treatment time varied significantly among the three groups, the interval between appointments was shorter for the CAD/CAM group. In other Words, while the CAD/CAM group finished treatment in fewer months, this could be due to the fact that these patients were seen more fre- quently. Additional investigations of CAD/CAM orthodontic appliances are needed and ideally would require prospective randomized clinical tri- als. An important factor in future studies would include standardization of appointment intervals between different treatment groups to identify potential differences in clinical efficiency better. In addition, adequate Sample sizes, standardized protocols and blinding would minimize biases 215 Orthodontic Applications of CAD/CAM when assessing measures of clinical effectiveness and efficiency. Another area of interest would involve the comparison of CAD/CAM appliances to CAD/CAM archwires to provide more insight as to whether custom- ized brackets or customized wires have a bigger impact on treatment out- COIT) eS. CONCLUSION Significant advances in orthodontic technology have occurred in recent decades, largely due to the incorporation of CAD/CAM technology into the design and fabrication of orthodontic appliances. The clinical evidence to support the efficiency and effectiveness of these appliances is varied, with no single system emerging as clearly superior. Further research into the advantages and disadvantages of the available CAD/ CAM orthodontic appliances is needed to gain a better understanding of the technology and how it should be utilized best. REFERENCES Al Mortadi N, Eggbeer D, Lewis J, Williams RJ. CAD/CAM/AM applications in the manufacture of dental appliances. Am J Orthod Dentofacial Or- thop 2012;142(5):727-733. - Alford TJ, Roberts WE, Hartsfield JK Jr, Eckert GJ, Snyder RJ. Clinical out- comes for patients finished with the SureSmile" method compared with conventional fixed orthodontic therapy. Angle Orthod 2011; 81:383–388. Brown MW, Koroluk L, Ko CC, Zhang K, Chen M, Nguyen T. Effectiveness and efficiency of a CAD/CAM orthodontic bracket system. Am J Or- thod Dentofacial Orthop 2015;148(6):1067-1074. Djeu G, Shelton C, Maganzini A. Outcome assessment of Invisalign and traditional orthodontic treatment compared with the American Board of Orthodontics objective grading system. Am J Orthod Dentofacial Orthop 2005;128(3):292-298. Gracco A, Tracey S. The insignia system of customized orthodontics. J Clin Orthod 2011;45(8):442–451. Kravitz ND, Kusnoto B, BeGole E, Obrez A, Agran B. How well does In- visalign work? A prospective clinical study evaluating the efficacy of 216 Nguyen tooth movement with Invisalign. Am J Orthod Dentofacial Orthop 2009;135(1):27–35. Kuncio D, Maganzini A, Shelton C, Freeman K. Invisalign and traditional orthodontic treatment postretention outcomes compared using the American Board of Orthodontics objective grading system. Angle Or- thod 2007;77(5):864-869. Larson BE, Vaubel C, Grünheid T. Effectiveness of computer-assisted orth- odontic treatment technology to achieve predicted outcomes. Angle Orthod 2013;83(4):557-562. Mayhew MJ. Computer-aided bracket placement for indirect bonding. J Clin Orthod 2005;39(11):653–660. Miyazaki.T, Hotta Y, Kunii J, Kuriyama S, Tamaki Y. A review of dental CAD/ CAM: Current status and future perspectives from 20 years of experi- ence. Dent Mater J 2009;28(1):44-56. Müller-Hartwich R, Präger TM, Jost-Brinkmann PG. SureSmile: CAD/CAM System for orthodontic treatment planning, simulation and fabrica- tion of customized archwires. Int J Comput Dent 2007;10(1):53-62. [In English and German.] Sachdeva RC, Aranha SL, Egan ME, Gross HT, Sachdeva NS, Currier GF, Kadioglu O. Treatment time: SureSmile vs conventional. Orthodontics (Chic.) 2012;13(1):72-85. Simon M, Keilig L, Schwarze J, Jung BA, Bourauel C. Treatment outcome and efficacy of an aligner technique: Regarding incisor torque, premo- lar derotation and molar distalization. BMC Oral Health 2014;14:68. Weber DJ 2nd, Koroluk LD, Phillips C, Nguyen T, Proffit WR. Clinical ef- fectiveness and efficiency of customized vs. conventional preadjusted bracket systems. J Clin Orthod 2013;47(4):261-266. 217 218 EVIDENCE FOR UTILIZING THREE-DIMENSIONAL TECHNOLOGY IN ORTHOGNATHIC SURGERY AND SLEEP APNEA CARE R. Scott Conley ABSTRACT Routine orthognathic surgery for correction of severe malocclusion is relatively recent with the development of predictable intra-oral surgical procedures oc- Curring in the late 1950s. Imaging techniques at the time were limited to two dimensions; Sagittal and vertical. Early surgical treatment planning and predic- tion required several manual (i.e., by hand) cumbersome, time-intensive steps fraught with multiple opportunities for error. In the 1980s, personal computers became available and the first at- tempts at Computerized treatment planning began. Planning remained in two dimensions, but now enabled digital measurements of plane film radiographs. AS technology advanced, further direct computer-based video capture was in- cluded to enable the team to overlay a single lateral photograph onto the lateral Cephalometric radiograph; however, the third dimension remained elusive. As technology continued to evolve and computing power increased, new imaging modalities became available including digital photography, medical computed tomography and more recently, cone-beam computed tomography (CBCT) and laser model scanning. When these seemingly disparate records are merged, the Surgical orthodontic team now can visualize all three planes of space simultane- ously to finally plan patient care in all three dimensions. With the increased treatment planning capabilities, questions remain whether the new tools are better, worse or only equally effective in obtaining predictable and safe surgical outcomes. A critical review of the best available evi- dence behind the classic two- and new three-dimensional (2D and 3D) orthogna- thic Surgery treatment planning approaches will be contrasted to provide an up- date on the current status of combined surgical orthodontic treatment planning. KEY WORDS: cone-beam computed tomography (CBCT), orthognathic surgery, Surgical prediction, sleep apnea, evidence-based dentistry 219 Three-dimensional Technology INTRODUCTION Orthognathic surgery has been performed for over a century with the first procedure performed during the American Civil War (Moloney and Worthington, 1981). Surgeons were limited by the techniques and technology of the day including ether anesthesia, limited pain control, the complete absence of antibiotics and minimal ways to address bleeding— all of which led to mixed results. The first orthognathic procedure was a Success because the stated goal of nasopharyngeal carcinoma removal was accomplished; however, the patient died shortly after due to complications resulting from the surgery. Because of the surgical limitations of the initial attempts, orthognathic surgery was abandoned largely for almost 50 years. In the early 1900s, new attempts at orthognathic surgery were conducted in an attempt to rehabilitate patients with severe facial burns and other handicapping Class Ill malocclusions that could not be resolved by orthodontic care, which was only in its infancy. The updated surgical approaches were crude by today's standards and generally did not combine the expertise of the two specialties of oral and maxillofacial surgery and orthodontics (Blair, 1907). Due to the incomplete understanding of bone healing and surgical sustainability of the jaws, most early attempts focused on mandible procedures with the body ostectomy (Keller and Gandy, 1993), body osteotomy (Blair, 1909) and mandibular anterior subapical (Waſmund, 1934) procedures the most common. Despite the improvements, results remained unpredictable and surgery remained an uncommon treatment approach. The discovery of and subsequent large scale production of antibiotics (Ligon, 2004) enabled surgery of all forms to be conducted more safely by dramatically reducing the risk of infection which led to renewed interest in the development of intra-oral procedures to correct malocclusion. Trauner and Obwegeser (1957) were among the first to report on a predictable new way to correct both mandibular skeletal deficiency and mandibular skeletal excess surgically using a series of cases involving mandibular ramus surgery. The presentation of their technique in the U.S. at Walter Reed Medical Center ushered in the “modern era” of orthognathic surgery. For the next two decades, the majority of complex dentofacial dysplasia cases were treated with 220 Conley mandibular Surgery regardless of a Class II or Class Ill malocclusion (Dal Pont, 1961; Hunsuck, 1968; Epker, 1977). Bell (1969, 1970, 1973) and colleagues (1975) published the bio- logical basis for maxillary surgery following his pioneering microangio- graphic studies on Macaca mulatta monkeys, which conclusively demon- Strated the maxilla now could be moved safely. Nearly a decade passed, however, before the Lefort | osteotomy became popular (Willmar, 1974; Bell et al., 1975) and routinely accepted by major medical insurance, practitioners and patients. With the ability to reposition not only one but both jaws surgically, the peak period of orthognathic surgery began and orthognathic surgery became far more common. During the period between 1980 and the early 2000s, patients and providers experienced a wide range of results with major medical Centers in having the best results and most scholarly activity. Both the Scholarly work and the clinical care generally utilized two-dimensional (2D) treatment planning and plaster based physical models (Bell, 1982, 1986). Since the mid 2000s, new technology including cone-beam com- puted tomography (CBCT; Danforth et al., 2003; Winter et al., 2005), digi- tal photography, direct and/or indirect digital model capture have made it possible to incorporate all three dimensions of patient assessments sim- ply and comprehensively into the surgical plan. The modern dentofacial deformity team now can perform three-dimensional (3D) digital treat- ment planning (Xia et al., 2005; Gateno et al., 2007). As new technology and tools emerge, it is essential to evaluate their utility critically. Effective tools eventually should replace their prede- Cessors, while ineffective new approaches should be abandoned due to their inability to surpass their historically superior techniques. Decisions must be based on the best available evidence which enables the profes- Sion to review and revise its standards of care. This chapter will review the historical 2D surgical treatment planning approach, present the more recently developed 3D approach and contrast their results to enable the practitioner to determine the current status of 3D computer-aided surgi- Cal simulation (CASS). The specialized use of the 3D technique also will be discussed both as a way to assess and treat surgical complications and as a way to assess the impact of Surgery on the airway Space. 221 Three-dimensional Technology HISTORICAL APPROACH TO SURGICAL TREATMENT PLANNING: ANALOG, 2D AND PLASTER The classic approach to orthognathic surgery involves collection of the surgical database or records including the clinical exam, plaster dental models, film-based photographs and film-based lateral cephalo- gram. In some surgical centers, a posterior-anterior film also was included in an attempt to bring in the third dimension, particularly for asymmetric patients (Morrees et al., 1976; Carlotti and George, 1987). The surgeon and the orthodontist would work either independently or preferably in coordination with one another to develop the pre-treatment diagnosis, orthodontic treatment plan and the surgical treatment plan. In general, treatment required approximately nine to twelve months of pre-surgi- cal orthodontic care, Surgery (one or two jaw) and six to nine months of post-surgical orthodontic care. Treatment planning required the team to perform five critical steps: 1. Determine the ideal position of the maxillary denti- tion with particular emphasis on the position of the maxillary central incisor; 2. Determine the ideal position of the mandibular denti- tion with particular emphasis on the position of the maxillary central incisor; 3. Determine the ideal position of the maxilla with re- spect to the cranial base; 4. Determine the ideal position of the mandible with re- spect to both the cranial base and new maxillary posi- tion; and 5. Determine the ideal position of the chin with respect to the cranial base, new maxillary and new mandibu- lar position. To accomplish this, the lateral cephalometric and posterior- anterior (PA) were traced and analyzed to determine how much of an occlusal (dental) and jaw base (skeletal) discrepancy existed. Once known, cephalometric prediction tracings were required to depict the 222 Conley amount of vertical and anterior-posterior (AP) movement of the denti- tion in order to obtain ideally positioned dental arches. The surgeon then could predict on a lateral cephalogram the amount of skeletal movement that was required to position the bony bases ideally in space. Following discussion and agreement by the team, the orthodontist would initiate Care for the patient and periodically obtain progress records to assess readiness for surgery. Immediately pre-surgically, the process was repeated, gener- ally with updated models, photographs, radiographs (lateral and PA, if available), centric relation bite and face-bow registration. Models were mounted on a semi- or fully-adjustable articulator, measured on a stable Erickson model platform, jaw surgery was simulated with model surgery and custom final (and interim if two-jaw surgery was performed) occlusal Splints were created (Ellis et al., 1992). The approach was time intensive, had multiple steps, could only be performed manually and was fraught with potential error (Marchiori et al., 2013). CONTEMPORARY APPROACH: 3D AND DIGITAL MODELS With the advent of the personal computer and its incorporation into clinical practice, attempts were made to move the analog treatment planning approach into the digital realm. As digital photography, digital models, CBCT, 3D stereophotogrammetry and laser facial scans each be- Came available, CASS now became possible. The same five-step approach must be performed, this time following successful merging of the digital database. Digital models, centric relation bite registration and the CBCT must be merged successfully along with a digital scan of the final occlusal Scheme in order to fabricate the custom interim and final splints through 3D rapid prototyping prints (Xia et al., 2005; Gateno et al., 2007). An addi- tional benefit is that the surgeon and orthodontist are no longer required to be in the same room to perform treatment planning, but instead can Share a “Go to Meeting” regardless of physical location. The new technology brings questions regarding the efficiency, Outcome quality, complication rates and whether use of the new technol- Ogy can be used effectively if and when complications occur. New assess- ments (e.g., 3D airway analysis) also can be conducted. 223 Three-dimensional Technology Comparison of the 2D Analog and 3D CASS Approaches Several factors must be considered when comparing the histori- cal plaster and plane film approach with the more recently developed 3D digital approach. While several areas overlap, each factor will be con- sidered separately. A systematic review or meta-analysis would be ideal; however, the majority of the evidence to date is from case reports, case series (retrospective and prospective) with only limited randomized, pro- spective blinded clinical trials, making a critical review more appropriate. Time Efficiency and Cost Using the previously described diagnosis and treatment plan- ning approach—regardless of analog or digital format—the dentofacial team essentially treatment plans the case twice. The primary focus of this chapter will be the peri-surgical timeframe since this is most com- monly when the clinical care team performs the final and entire detailed step-by-step approach with the additional steps of mounting the models and splint fabrication. Time spent planning is important, but so too is the time spent in the actual surgery. Reducing both would enable surgeons to treat more cases—an important element due to the limited number of oral and maxillofacial Surgeons performing orthognathic Surgery. Reduc- ing operative time while maintaining or improving outcomes (if possible) has the additional potential benefit to the patient of reduced time under anesthesia and its associated risks. A recent publication by Schwartz (2014) reported a total of 865 minutes (14:25 hours) for meeting, planning, performing and observ- ing the traditional orthognathic surgery patient. Use of the CASS tech- nique reduced the total time to 805 minutes (13:25 hours) and saved the surgeon and surgical team one hour of time. The authors subdivid- ed the total for each technique into patient visits and operative time. The range of patient visits was similar (seven to twelve visits for the traditional approach versus seven to thirteen for CASS), but the CASS patients averaged a higher number of visits. Operative time was no dif- ferent with both groups undergoing slightly more than four hours of surgical care (250 minutes). Ouestions that remained unanswered in- cluded the experience and expertise with both techniques. It is possible that the length of time required for the two techniques were skewed, 224 Conley particularly because the authors self-report that their surgical team was a new adopter for the CASS technique; they used the traditional ap- proach 90% of the time and the CASS approach only 10% of the time. Their results likely demonstrate their acclimation period to a new ap- proach rather than a similar experience base with both techniques. It also is important to note that the paper reports the results of four Surgeons within one surgical center, so broad application beyond this patient pool studied may not be appropriate. Direct comparison with multiple surgical centers, each of which has equal experience with tra- ditional and CASS technique, would be beneficial to answer the ques- tion of time savings better. Cost analysis of the two approaches is complex (Xia et al., 2006), difficult at this point and cannot be reported fully. A true cost analysis must include the actual costs (e.g., CBCT scanner, digital model scanner, Splint construction, computer technician service fee), as well as other Costs of the operating room, operating room personnel, reimbursement rates and opportunity cost of lost time of planning when other surgical procedures (e.g., third molar extraction) could be performed. Some of these costs can be amortized over time, while others are one time, making the analysis more complicated. Outcomes and Accuracy With a trend toward CASS saving surgeon time, one also must consider outcome. Does the CASS technique provide results equal to, better than, or worse than traditional 2D analog approach? The wide range of surgical outcomes across the various surgical centers make direct Comparison a challenge, but key publications from both the historical and CASS techniques will be compared. 2D Analog Results Anecdotal evidence suggests that surgical outcomes within 2 mm of the desired position can be finished ideally or nearly ideally through post-operative orthodontic manipulation when rigid internal fixation is utilized or orthodontic manipulation combined with callus manipulation when wire osteosynthesis is used. Multiple publications have demonstrated that surgical centers can achieve mean surgical positioning accuracy within 2mm or 3’ (Donatsky et al., 1992, 1997; Semaan 225 Three-dimensional Technology and Goonewardene, 2005). When additional steps such as placing cus- tom location/orientation wires into molar and/or canine brackets are performed during the surgical planning (Bouchard and Landry, 2013), maxillary positioning accuracy can be enhanced; however, these addi- tional steps require increased patient appointment and visits, as well as increased planning time (and cost) and, therefore, rarely are performed. One deficiency of many of the surgical accuracy papers is that publica- tions typically report results from a single surgical center rather than across multiple surgical centers, making broad application of the data challenging. The multi-center surgical outcome assessments show simi- lar findings (Dolce et al., 2000, 2003), but these are major medical cen- ters with experienced surgeons and still may not represent accurately the orthognathic surgery experience of patients in more remote or less experienced centers. To apply information more broadly, Goonewardene examined multiple aspects of surgical accuracy by reviewing the results of two surgical centers (Semaan and Goonewardene, 2005). For simplicity, the data only examined isolated single jaw maxillary osteotomies. Their re- sults demonstrated that both centers achieved a 2 mm mean accuracy of Surgical positioning though the average was misleading; Some patients experienced nearly 4 mm of difference between predicted and actual po- sition, while other patients experienced results nearly identical to what was predicted. The publication found no difference between surgical centers. Finally, the publication explored accuracy by type of maxillary surgical intervention (i.e., was the surgeon more accurate with maxillary inferior positioning, superior positioning or advancement?). Each opera- tion depicted a consistent trend that some patients in each group were positioned with a high degree of accuracy (~0.5 mm) while others were positioned with a high degree of inaccuracy (~3.5 mm) relative to the predicted position of the maxilla. 3D Results Several studies have examined the accuracy of the CASS tech- nique (Xia et al., 2005, 2006, 2007, 2011; Gateno et al., 2007; Hsu et al., 2013; Schwartz, 2014). One early publication reported a < 0.5 mm dif- ference between the predicted and the actual surgical outcome (Tucker et al., 2010). When examining the paper closely, it is significant to note that the study performed a unique and biased retrospective approach. 226 Conley The CASS technique was performed after the actual surgery with the team using the known operative movements taken directly from the operative report and immediate post-operative radiographs; therefore, their highly accurate outcome does not simulate appropriately the actual Clinical treatment planning protocol. Another early report on the accuracy of the CASS technique re- Sults from a pilot study of a small sample of patients who underwent both traditional and CASS planning (Gateno et al., 2007). The investiga- tors performed earlier animal studies of the technique and found it to be accurate, but in their initial attempt to incorporate the technique to humans, they elected to perform both traditional and CASS technique so they would have a traditional approach failsafe should CASS not work, enabling them to complete the operation safely. The pilot study patient pool consisted of the most severe dentofacial deformity patients and Syndromic patients from whom it has been the most challenging to ob- tain accurate results. The pilot study goal was to obtain results that were Within 2 mm or 4” of predicted jaw position. Their results were a suc- cess and demonstrated jaw positions within 0.85 mm and 1.7"; the team Concluded that CASS not only was safe, but also accurate and now could be employed on a broader range and number of patients with dysplasia. Subsequent reports (Xia et al., 2007, 2011; Hsu et al., 2013) used blinded evaluators to compare CASS and traditional surgical outcomes and dem- onstrated higher visual analog scale (VAS) acceptance of the CASS tech- nique over traditional treatment planning. When specific cephalometric/ CBCT landmarks were measured, the CASS technique showed precise jaw positioning with less than 0.64 mm difference in the sagittal plane, 0.81 mm in the vertical plane and 0.44 mm difference in the coronal plane. The Coronal plane results are significant because asymmetry or yaw has been the most challenging aspect for the surgical orthodontic team to quantify, plan and treat, leaving some patients uncorrected or only par- tially corrected instead of obtaining ideal final facial outcomes. One of the elements critical to achieving surgical accuracy remains the surgical splint (Ellis et al., 1992). Whether the case will be treated with traditional, CASS, CAD/CAM or computer naviga- tion, the interim and final splints dictate the position of the respective jaws. To assess the accuracy of the splint itself, a subsequent surgical team examined 30 prospective cases comparing three different splint 227 Three-dimensional Technology fabrication/transfer techniques; CAD/CAM splint from the CASS tech- nique, computer navigation and traditional splint fabrication (Zinser et al., 2013). Each was highly accurate (< 2.0 mm), but the CAD/CAM splint from the CASS technique was the most accurate and positioned the jaw within 0.23 mm, which was followed by computer navigation (< 0.61 mm) and the traditional approach (< 1.1 mm), respectively. While much of the evidence in 3D surgical outcomes to date comes from a limited number of surgical teams, greater numbers of surgical centers are adopting the technology. In the future, prospective multi-center accuracy studies will be possible providing results, which will be applicable more broadly to the orthognathic surgery community. Post-op Ouality Control and Complications Any surgical orthodontic team that has performed a significant amount of orthognathic surgery has experienced one or more surgical complications. It would be ideal if the CASS technique could reduce com- plications by providing the surgeon with enhanced anatomic information so that customized osteotomies can be created to meet the individual anatomic situation best. While no data exists yet on complication rates for CASS versus traditional surgical planning, early reports from 3D surgi- cal planning are beginning to enable the surgeon to perform real-time post-operative quality control and enhanced visualization of their oste- otomies, which may result in enhanced surgical stability. Plooj and col- leagues (2009) reported a wide variety of both location and amount of controlled lingual plate fracture (Hunsuck) of the mandible that occurs during the sagittal split osteotomy (Fig. 1). In evaluating their results, they report that they achieved the desired location and amount of lingual frac- ture in just over 50% of the cases, while experiencing lesser quality but acceptable splits of the proximal and distal segment in another "14%. A smaller group (~33%) experienced lingual plate fracture near the inferior alveolar nerve canal and the classic “bad” split represented in only 2.5% of their cases. Following analysis of their own data, they reported on re- vised surgical techniques (more complete inferior border osteotomy) in future patients that resulted in improved surgical outcome. 228 Conley 1135 deg 1575 Figure 1. Lingual fracture pattern of a representative patient from The University of Michigan Oral and Maxillofacial Surgery Department. Figure courtesy of Dr. Sean Edwards. Complication Management Some surgical patients, despite having appropriate surgical technique, will develop post-operative complications including seg- ment rotation. Figures 2 and 3 demonstrate a patient four months 90St-operatively who was developing an open bite. To assess the poten- tial causes for the complication better, a follow-up CBCT was obtained. Analysis of the pre-, post- and four-month post-operative CBCT demon- Strates adverse proximal and distal segment rotation, which provides the team the ability to counsel the patient on the respective correc- tive measures. Re-operation was offered to address definitively the ob- Served segment rotation, as was a course of post-operative elastic trac- tion from the orthodontic appliances. Though the ideal correction was 229 Three-dimensional Technology D - Figure 2. Intra-oral photos of a Class || mandibular deficient patient. A: Pre-treat- ment. B: Pre-surgical. C: Twelve weeks post-surgery. D: Final occlusion. surgical, the patient selected elastic traction knowing that if it was unsuccessful, she could opt for re-operation later. Following a short course of elastics (eight weeks), the patient obtained ideal overbite that was monitored for another eight weeks without elastics, at which time the patient had the appliances removed and went into retention. She remained stable for two years during the retention period. Figure 4 depicts another fixation complication that can OCCUſ, particularly when bi-cortical rigid internal fixation screws are used. This patient returned to the orthodontic office with recurring oral infections from near both sagittal split sites. The panoramic radiograph appears tº show fixation in close proximity to unerupted teeth, but because it is a 2D representation of a 3D anatomic situation, the panoramic radiograph is not sufficient to determine the exact screw location. CBCT. Was performed and axial views clearly demonstrate bi-cortical screws positioned through tooth roots on both sides. The only definitive treatment is removal and replacement of the fixation screws completely after 230 Conley Figure 3. Superimposed CBCT renderings of the Class II mandibular deficient pa- tient whose intra-oral photos are depicted in Figure 4. The white image is the immediate pre-surgical CBCT rendering. The red image is the twelve-week post- Surgical CBCT image that demonstrates significant rotation of both the proximal and distal segments creating the telltale “V notch” deformity. Successful bony union or early removal of the screws and replacement With mono-cortical screws and plate. Specialized Uses: Role of 3D in Airway Analysis The same 3D technology essential for CASS now also can pro- Wide the potential to evaluate airway changes (Mehra et al., 2001). Sev- eral previous publications have demonstrated that orthognathic surgery, Specifically maxillomandibular advancement, is one of the more suc- Cessful treatments for treating obstructive sleep apnea (OSA, Ogawa et al., 2007; Thompson et al., 2007; Brevi et al., 2011). Many studies have depicted not only airway enlargement, but also airway shape change (Fig. 5; Ogawa et al., 2007; Thompson et al., 2007, Brevi et al., 2011). While 3D imaging techniques are beginning to emerge as a way to vi- Šualize airway changes, it is essential to remember that CBCT has not been validated as a way to distinguish whether the OSA has resolved. The BCT-while illustrative—analyzes the airway in upright and awake pa- tients, limiting its use in this patient population. Attempts are being made 231 Three-dimensional Technology Figure 4. A: Post-operative panoramic radiograph that depicts possible fixation trauma to multiple teeth. B: Axial view CBCT image that depicts actual trauma to the mandibular left second molar. C: Axial view CBCT image that depicts ac- tual trauma to the mandibular right second molar. Periapical radiograph depict ing the fixation trauma following removal of the right (D) and left (E) bi-cortical SCreWS. to correlate the airway change with the gold standard overnight poly Somnogram, but work remains in this area. CONCLUSIONS Easy-to-use, accurate and user-friendly 3D technology im: provements represent a major shift forward not only in the Orthogna: thic Surgery community, but also in related areas (e.g., airway analysis). Further refinement in technique and accuracy, as well as cost reduº tions, in time likely will make 3D technology the standard not only for orthognathic surgery treatment planning, but also many other form? of orthodontic diagnosis and treatment planning. 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A comparison of navigation, Computer-aided designed/computer-aided manufactured splints, and "classic” intermaxillary splints to surgical transfer of virtual orthogna- thic planning. J Oral Maxillofac Surg 2013;71(12):2151.e1-e21. 237 238. UPPER AIRWAY DIMENSIONS AND HYOID BONE POSITION IN SKELETAL CLASS || ADOLESCENTS TREATED WITH FUNCTIONAL APPLIANCES: WHAT IS THE CBCT EVIDENCEP Thikriat S. Al-Jewair, Jeremy Abdul, Sawsan Tabbaa, Edwin Chang ABSTRACT OBJECTIVES: To determine the effects of functional appliance treatment for Class ll skeletal malocclusion on upper airway dimensions and hyoid bone position using cone-beam computed tomography (CBCT). METHODS: Four electronic databases were used to search for articles published until March 2016. A search of grey literature and manual search of the references of retrieved articles also were conducted. Two independent reviewers screened the articles for inclusion based on pre-set criteria. The primary outcome measures were short- and long- term changes in upper airway dimensions, linear and angular measurements of hyoid bone position. The secondary outcomes were improvement in sleep quality, subjective daytime sleepiness and sleep-related quality of life. Meta- analyses were conducted using random-effects models. RESULTS: Six longitudinal studies were included. One used removable and the rest used fixed orthopedic appliances. Two of the studies were medium quality and four were low quality. Meta-analyses of two studies revealed an increase in the oropharyngeal volume by 2.89 cm3 (MD = 2.89; 95% CI, 1.46, 4.33; P = < 0.0001) in the functional appliances group over controls. Transverse and anteroposterior (A-P) dimensions of the oropharynx also increased significantly, favoring the functional appliance groups. Two studies found significant anterior positioning of the hyoid bone with functional appliances compared to controls, while one did not. CONCLUSIONS: There is limited evidence that suggests short-term improvement in upper airway Volume, transverse and A-P dimensions with the use of functional appliances for Class Il correction in adolescent patients. Evidence on the effects on hyoid bone position is inconclusive. Future high quality studies are warranted. KEY WORDS: functional appliance, Class Il malocclusion, cone-beam CT (CBCT), pharyngeal airway, systematic review 239 Upper Airway Dimensions INTRODUCTION Skeletal Class Il division I with mild to moderate retrognathic mandible (deficient mandible) in adolescent orthodontic patients is one of the most common forms of Class Il malocclusion. Almost 33% of the United States' population exhibits Class Il malocclusion (Proffit et al., 1998). Mandibular retrognathia is treated with functional orthodontic appliances placed by the orthodontist; the treatment is effective mostly during the peak of growth spurt in the adolescence stage (Pancherz and Hägg, 1985; Malmgren et al., 1987). Treatment during this stage permits tooth movements, dentoalveolar changes and skeletal modifications to be achieved (Proffit and Tulloch, 2002) and eventually results in maloc- clusion normalization and favorable facial esthetics. Functional orthodontic appliances can be fixed (e.g., Herbst) or removable (e.g., Bionator); tooth-borne (e.g., Mandibular Anterior Re- positioning Appliance [MARA]) or tissue-borne (e.g., Frankel); compliant (e.g., Activator) or non-compliant (e.g., MARA); and rigid (e.g., Herbst) or non-rigid (e.g., Forsus Fatigue Resistant Device (FFRD]). These appliances move the mandible forward, along with the associated hyoid bone and muscles. This anterior movement in theory is expected to create more space for the upper airway by increasing its dimensions (Restrepo et al., 2011; Schütz et al., 2011). The unique shape and location of the hyoid bone helps balancing the head during upright position. The hyoid bone is a four-sided U-shaped structure that has no bony articulation and is located below the mandible anterior to the neck. Only muscles and ligaments attach the hyoid bone to the cranium, pharynx and mandible. The hyoid bone is important for tongue movement during chewing, talking and swallowing. Previous re- search studying the correlation between various types of malocclusion and hyoid bone position resulted in conflicting conclusions (Adamidis and Spyropoulos, 1992; Jena and Duggal, 2011; Jose et al., 2014). The upper airway is a dynamic soft tissue, which has plasticity and could adapt to the surrounding space. Functional orthodontic appliances are expected to have a direct effect on mandibular posture and, subsequently, the airway dimensions. However, whether functional appliances increase the dimensions or not is a debated topic in the litera- ture (Li et al., 2014; Bavbek et al., 2015), along with the correlation be- 240 Al-Jewair et al. tween the hyoid bone position and airway dimension (Lowe, 2000; Jiang, 2016; Tarkar et al., 2016). The cone-beam computed tomography (CBCT) imaging tech- nique was developed in the late 1970s and became known in the field of dentistry in 1995, at first for dental implants and then developed to cover other fields of dentistry, including orthodontics (Kau et al., 2005). At the present time, three-dimensional (3D) CBCT is used increasingly in orth- Odontic practices to obtain patients' initial, progress and final treatment records since it includes all required radiographs in one scan and provides a wealth of information about the skeletal and surrounding soft tissues, including the topic of this chapter, the upper airway (Jaju and Jaju, 2014). The anticipated change in upper airway dimensions with repo- Sitioning of the hyoid bone has significant clinical implications. To deter- mine the best evidence-based clinical recommendations, a systematic review and meta-analysis of research findings is necessary. The overall purpose of this chapter is to review systematically the available literature on adolescents with mandibular deficient Class | division I malocclusion that were treated with functional orthodontic appliances. Specifically, the objective of this chapter is to determine the pooled treatment effects of functional orthodontic appliances on upper airway dimensions and hyoid bone position using CBCT. MATERIALS AND METHODS Study Inclusion/Exclusion Criteria The ‘PICO' question was whether functional appliances for the Correction of Class Il division 1 malocclusion in adolescent orthodontic patients cause a short- or long-term change in upper airway dimensions and hyoid bone position (Table 1). Only prospective or retrospective stud- ies on humans were considered for inclusion. The primary outcome mea- Sures were short- or long-term changes in upper airway height, width, Volume, minimum cross-section area, and linear and angular measure- ments of hyoid bone position. The secondary outcomes were improve- ment in sleep quality, subjective daytime sleepiness and sleep-related quality of life. Studies were excluded if they were case reports, case series, reviews, abstracts, conference proceedings, patients who had previous 241 Table 1. Inclusion criteria for studies. Population intervention Control Outcomes Types of Studies - Adolescent boys and girls | - Patients who received - Untreated - Primary outcomes: - Randomized controlled ages 9-17 removable or fixed controls Measurements of clinical trials - Class Il division 1 functional appliances with - Treated without naso- oro-and hypo- - Prospective or malocclusion or without functional pharyngeal airway retrospective - Class II skeletal (ANB > 4 concurrent fixed appliances dimensions and hyoid longitudinal studies degrees) with orthodontic treatment - Historical bone position using retrognathic mandible e & controls CBCT; before and (SNB & 78 degrees) - Functional appliance after treatment Angle Class II molar maintained for at least six 4-º months relationship (end-to-end - Secondary outcomes: or full cusp) - Overjet & 10 mm - Before, during or past pubertal growth spurt Sleep quality, daytime sleepiness and sleep related quality of life § Al-Jewair et al. Orthodontic treatment, extraction treatment, history of adenotonsil- lectomy, craniofacial anomalies, sleep-disordered breathing and airway measurements using 2-dimensional (2D) lateral cephalograms. Data Sources Four electronic databases (PubMed, Medline, Embase, CINHAL) were searched for articles in any language from the database's concep- tion until March 3, 2016. A mix of medical subject headings and keywords were used depending on the database. The MeSH/keywords were: “func- tional appliance,” “orthodontic appliance,” “cone beam,” “cone beam CT,” "CBCT,” “airway,” “hyoid bone,” “airway dimension,” “Class Il division I” and “Class Il malocclusion.” OpenGrey database was searched for grey lit- erature. Theses, dissertations and reference lists of retrieved articles also were searched. Two independent reviewers conducted all searches and Study appraisals, and disagreements were resolved with discussion. Ar- ticles then were assessed for quality using the Cochrane Collaboration's tool for assessing risk of bias (Higgins et al., 2008). The criteria evalu- ated were: random sequence generation, allocation concealment, blind- ing of outcome assessors, completeness of outcome data, evaluation of Selective reporting and other sources of bias. If a criterion was fulfilled, it received two points; if it was unclear, it received one point; and if not fulfilled, it received no points. The quality of a study was considered low if it received 1-4 points, medium if it received 5-8 points and high if it received 9-12 points. PA (ſ Statistical Analysis Meta-analyses were conducted for the continuous outcomes re- ported in the studies that had: 1) presented treatment changes in both the functional appliance and control groups; or 2) presented pre- and post-treatment measurements that would allow calculation of changes. The means and standard deviations of the changes in oropharyngeal vol- ume, transverse and anteroposterior (A-P) dimensions for the functional appliance and control groups were obtained from each study. Review Manager Software (Version 5.2.10, Cochrane Collaboration, Canada) was used to analyze the data (Review Manager, 2012). The effect size was Calculated using weighted mean difference (MD), 95% confidence inter- Val (Cl) and a 5% significance level. The inverse variance random-effects model was used to combine the studies. Heterogeneity between the 243 Upper Airway Dimensions studies was assessed using the Cochrane test (P< 0.1 was considered significant) and the I* Statistic (Higgins et al., 2003). I* cut-offs of 25%, 50% and 75% were used to define low, moderate or high heterogene- ity between the studies (Higgins et al., 2003). Orophayngeal volume was measured in cubic centimeters (cm3) and transverse and A-P dimensions in millimeters (mm). Sensitivity and publication bias analyses were not conducted due to the small number of studies. RESULTS A total of 313 articles were retrieved and screened for eligibil- ity (Fig. 1). After exclusion by title and abstract, fifteen full-text articles were evaluated; nine were excluded either because they used 2D lateral cephalograms or were of different study design (Table 1, supplementary data). A total of six studies (Dillehay, 2013; Erbas and Kocadereli, 2014; Iwasaki et al., 2014; Li et al., 2014; Rizk et al., 2016; Temani et al., 2016) were included in this review (Table 2). Four studies (Dillehay, 2013; Iwa- saki et al., 2014; Li et al., 2014; Rizk et al., 2016) were retrospective lon- gitudinal in nature and two (Erbas and Kocadereli, 2014; Temani et al., 2016) were prospective. The total sample sizes in these studies ranged from 25 to 93 subjects. The mean (+standard deviation) chronological ages at baseline ranged from 11.1 (+1.1) to 13.5 (+3.5) years old. The types of functional appliances studied were fixed in five studies, FFRD (Temani et al., 2016), MARA (Dillehay, 2013; Risz et al., 2016), Xbow (Erbas and Kocadereli, 2014) and Herbst (Iwasaki et al., 2014) and re- movable in one (Twin-Block; Li et al., 2014). The fixed-functional appli- ances were used concurrently with edgewise-fixed appliances in all stud- ies (Dillehay, 2013; Iwasaki et al., 2014; Rizk et al., 2016; Temani et al., 2016) except for one study (Erbas and Kocadereli, 2014), in which only the Xbow appliance was inserted after a phase of maxillary expansion. Four of the studies (Dillehay, 2013; Iwasaki et al., 2014; Li et al., 2014; Rizket al., 2016) used a separate control group, while two did not (Erbaş and Kocadereli, 2014; Temani et al., 2016). The mean treatment timing with the functional appliances ranged from 6.0 to 13.7 (+1.5) months. 244 Al-Jewair et al. ſº Records identified through database Additional records identified £ searching through other sources g (Embase: 29, CINAHL: 46; MEDLINE: 230; (n = 5) 5 Pubmed: 329) 5 (n = 633) E \- y -N Records after duplicates removed (n = 313) bº) ! fe 'E Q9 Q9 § Records screened y (n = 35 after title exclusion) h. Records excluded (n= 15 after abstract exclusion) (n = 278 by title) *—” (n= 20 by abstract) 2–N y Full-text articles assessed Full-text articles excluded £ for eligibility hº (n = 9) F (n = 15) sº nº ! *—” Studies included in qualitative synthesis (n = 6) * ! g TJ Studies included in E quantitative synthesis (n = 2) *— Figure 1. PRISMA flow diagram. Table 1. List of excluded studies and reasons for exclusion. Reasons for Reference tº exclusion Graber, 1978 Grim, 1995 Ozbek et al., 1998 Performed using 2D Gao et al., 2003 lateral hal Yassei et al., 2007, 2012 ateral Cepnalograms Yassei and Soroush, 2008 Bavbek et al., 2015 Abstract Li, 2009 (type of study excluded) 245 Table 2. Summary of the studies that met the inclusion criteria. Abbreviations; F = female; M = males; SD = standard deviation; MARA = mandibular anterior repositioning appliance; CBCT = cone beam computer tomography; FMA = Frankfort-mandibular plane angle; AP = anteroposterior; C3 = third cervical vertebrae; |PS = inferior pharyngeal space; MPS = middle pharyngeal space; SPS = superior pharyngeal space; AD2-H = upper adenoid thickness; defined as the soft tissue thickness at the posterior nasopharynx wall through the PNS-H line (H, Hormion); PNS-AD2 = upper airway thickness; distance between the PNS and the nearest adenoid tissue measured through a perpendicular line to Sella-Ba from PNS; PNS-AD1 = lower airway thickness; distance between the PNS and the nearest adenoid tissue measured through the PNS-Ba line (AD1); AD1-Ba = lower adenoid thickness; defined as the soft tissue thickness at the posterior nasopharynx wall through the PNS-Ba line; RA = retropalatal airway; OA = oropharyngeal airway; LA = laryngopharyngeal airway. initial mean initial Mean Total Type of Number of age + SD of Number and mean age treatment treatment/ Authors functional functional treatment type of +SD of time with observatio CBCT outcome measures - | appliance group untreated controls functional | timing appliance subjects (years/ controls (years/ appliance in t º, months) months) (months) (months) 30 Temani Forsus Fatigue Post- Volume of oropharynx, et al., Resistance F/M ratio: 13.50 + 3,50 6 6 functional hypopharynx and total 2016 Device (Fixed) NS * appliance (pre- and post-treatment) 73 untreated º Standard ceph 20 skeletal Class . Rizk et al., MARA |l subjects Not 10.6 postºed (via CBCT) volume of w 11.7: 1.75 g 27.4 * oropharynx, AP and 2016 (Fixed) F/M ratio: specified appliances 13/7 Matched by transverse oropharynx CVM stage dimension, AP hyoid bone position Volume of nasopharynx, 30 untreated oropharynx and subjects hypopharynx, mean cross- 30 F/M ratio: Post Sectional area, hyoid bone Li et al., Twin-Block ſº 11.72 + 13.67 + - to C3, hyoid to C3-Menton 2014 (Removable) F/M ratio: 11.57 it 0.94 || 17/13 0.86 13.67 + 1.51 1.51 . line 17/13 e Matched by Mandible advancement, age, sex and AP and lateral airway development dimension and ioteral to AP ratio # Table 2 continued Initial mean Initial Mean Total Twpe of Number of age +SD of Number and mean age treatment treatment/ - . functional treatment type of + SD of time with CBCT Authors functional - tº- observatio Outcome measures sppliance appliance group untreated controls functional n time timing p - subjects (years/ controls (years/ appliance ths months) months) (months) (months) Standard ceph measurements Erbas and 25 Post- (vio CBCT), airway volurne, Kocadereli, Xbow (Fixed) F/M ratio: 11.1 : 1.1 6 6 functional vertical, horizontal and AP 2014 14/11 g appliance lengths, IPS, MPS, SPS, AD2-H, PNS-AO2. PNS-AD1, and AD1-82 20 skeletal Class I subjects treated without functional Standard ceph measurements 24 appliances Treatment . CBCT), hyoid º: h º (Edgewise group: 42 - Istances, airway length, ºn4. Herbst (Fixed) F/M ratio: 11.64 : 0.94 . *...* 12.3 = 4.2 º: volume, and 13/11 F/M ratio: 11/9 Control minimum cross sectional area, group: 40.8 depths, width:5 and volume of Matched by RA, OA, LA sex, age and FMA and skeletal age 32 skeletal Class 11 subjects without 38 functional standard ceph measurements Dillehay, MARA 12.1.197 | * 12.14 : Not rea nºse (vocac), nasopheryngeal 2013 (Fixed) F/M ratio: ge sº tº e (Edgewise 1.97 specified 26.4 spºnse, ºrway, otopharyngeal airway 15/23 appliance • (superior and inferior), airway Class Il elastics area and volume only) º F/M ratio: 19/13 § Upper Airway Dimensions The outcomes measured included the naso- oro- and hypo-pha- ryngeal volume, airway height, and transverse dimensions, minimum cross-section area, anteroposterior and vertical hyoid bone position. The settings used in the CBCT devices are depicted in Table 3. The types of CBCT scanners varied among the studies. The scanning time was 8.9 seconds in two studies (Li et al., 2014; Rizk et al., 2016), 17 sec- onds in the third (Iwasaki et al., 2014), but was not reported in the rest. Methodological quality assessment of the studies showed that two were medium quality (Iwasaki et al., 2014; Rizket al., 2016) while the rest were low quality (Dillehay, 2013; Erbas and Kocadereli, 2014; Li et al., 2014; Temani et al., 2016; Table 4). The effects of functional appliances on the upper airway varied among the studies. In five studies (Erbas and Kocadereli, 2014; Iwasaki et al., 2014; Li et al., 2014; Rizk et al., 2016; Temani et al., 2016), there were statistically significant (P<0.05) increases in oropharyngeal volume in the functional appliances groups over their respective treatment pe- riods. In the sixth study (Dillehay, 2013), the mean inferior oropharynx significantly decreased in volume with the use of MARA. The greatest amount of change in oropharyngeal volume among the six studies was in that of Rizk and associates (2016) at 5537.4 mm” over 27.4 months, with a mean treatment time with MARA of 10.6 months. The smallest change was present in the study by Dillehay (2013), with a reported superior oro- pharyngeal volume difference of 574.7 mm”. In the studies conducted by Rizk and coworkers (2016), Iwasaki and colleagues (2014) and Li and associates (2014), there was a significant increase in oropharyngeal volume after the use of functional appliances as compared to the controls. On the contrary, Dillehay (2013) found a significantly smaller oropharyngeal volume with MARA compared to the edgewise control group. Iwasaki and coworkers (2014) also measured the volume at the laryngophayrnx and at the retropalatal area. The volume increased at both sites in the functional appliance group over the controls, but this finding was significant statistically only for the laryngophayrngeal volume (P = 0.021). With regard to the transverse and A-P dimensions of the orophar- ynx, there was a statistically significant increase in the studies by Rizk and associates (2016), Li and coworkers (2014), Iwasaki and colleagues (2014) 248 Table 3. Settings in CBCT devices. *3D-Doctor (Able Software Corporation, Lexington, MA); Dolphin 3D (Dolphin imaging and Management Solutions, Chatsworth, CA); Mimics (Version 16.0, Materialise Interactive Medical Imaging, Leuven, Belgium); Ouick Ceph Studio (Ouick Ceph System, San Diego, CA); TTK-SNAP 2.2.0 (www.itksnap.org); INTAGE Volume Editor (Cybernet, Tokyo, Japan). Scan Slice Scanned Anatomic Head So ſe Voltage/ Tongue Mandibular to Authors Scanner MA time thickness || Voxel size volume region posture positi ition ſnº SUITC (sec) (mm) dimensions scanned reference scans” Temani Carestream 0.09 mm Oropharynx, et al., 2016 CS9300 voxel h harvn 3D-Doctor al., resolution ypopharynx º º Natural Held breath 9 Rizk et al., i-CAT 120kVpſ as 0.3 mm Hyoid bone head without centric Dolphin 3D 2016 18.45 mAs Oropharynx tº ~ * - Occlusion position swallowing Nasopharynx, In Contact oropharynx, with anterior - - Li et al., Kavo Dental 120 kVp/5 0.30 mm hypopharynx, Natural palate Maximum Mimics 8.9 0.4 mm voxel head $ - e Version 2014 GmbH mA & mandible, - - - without intercuspation resolution - position º 16.0 hyoid bone touching and vertebra anterior teeth Oropharyngeal volume, length Quick Erbas and of oropharynx Natural Held breath - Ceph Kocadereli, º . . 19x24 and AP and head without º Studio and 2014 º lateral position $wallowing 9 |TK-SNAP retroglossal 2.2.0 aſed Retropalatal, Frankfort Imagnosis g tº oropharyngeal horizontal Hekd breath VE and Iwasaki * | Bokv/2mA 17 and plane without INTAGE et al., 2014 3030 * laryngophar- parallel to swallowing Volume yngeal airway the floor Editor Nasopharynx, e Dillehay, Next oropharynx, * Dolphin 3D Generation 0.4 mm - Version 2013 total airway i-CAT 11.5 volume § Table 4. Risk of bias summary. Quality” was defined as low (1-4 scores), medium (scores 5-8) or high (9-12 scores). Score categories: 2 points for “Yes,” 1 point for “Unclear” and zero point for “No." Blinding | Incomplete Free of Free of Adequate * g Stud S(2CU, Allocation of OutCOme selective other Scor Ouality” y quence concealment outcome data OutCOme SOUIſ CºS (e uality generation gº * assessors evaluated reporting of bias Temani et al., 2016 No NO No Yes No No 2 Low Rizket al., 2016 No NO Unclear Yes Yes NO 5 Medium Li et al., 2014 No No NO Yes Yes No 4 Low Erbas and Kocadereli, 2014 No No No Yes Yes NO 4 Low Iwasaki et al., 2014 Yes No No Yes Yes No 6 Medium Dillehay, 2013 No NO No Yes No No 2 Low § Al-Jewair et al. and Erbas and Kocadereli (2014); however, Dillehay (2013) concluded that there were no significant changes in these dimensions. In terms of hyoid bone position, there was statistically significant anterior movement with functional appliances over controls in the stud- ies by Li and associates (2014) and Rizk and coworkers (2016). Yet, Iwasa- ki and colleagues (2014) found no significant change in hyoid bone posi- tion (P = 0.418). Li and coworkers (2014) reported a statistically signficant increase in the minimum cross sectional area at the orophayrnx with the use of Twin-Block compared to controls (P = 0.010). The two medium quality studies (Iwasaki et al., 2014; Rizk et al., 2016) were the only studies that have presented changes in oropharyn- geal dimensions for the treatment and control groups (pre- and post- treatment; Table 5). Meta-analyses of these studies revealed favorable effects on airway dimensions of functional appliances over controls. The oropharyngeal volume increased by 2.89 cm° in the functional appli- ances groups over the controls (MD = 2.89; 95% Cl, 1.46, 4.33; chi square test, 0.27; 1df; P = 0.60; I* = 0%; test for overall effect, Z = 3.94 and P = < 0.0001; Fig. 2). Similarly, statistically significant increases were noted in the transverse (MD = 3.95; 95% CI, 2.18, 5.71; chi square test, 0.01; 1df; P = 0.93; I2 = 0%; test for overall effect, Z = 4.38 and P = < 0.0001) and A-P dimensions (MD = 2.97; 95% CI, 2.00, 3.93; chi square test, 0.01; 1df; P = 0.92; I2 = 0%; test for overall effect, Z = 6.02 and P = < 0.00001) of the Oropharynx favoring the functional appliance groups (Figs. 3 and 4). DISCUSSION This systematic review included six longitudinal studies that evaluated the upper airway dimensions and hyoid bone position in skel- etal Class II adolescents treated with functional appliances. Only airway Changes determined from CBCT were included as this imaging technique Can provide accurately volumetric measurements in three dimensions: the height, width and diameter for the upper airway as compared to 2D Cephalograms (Aboudara et al., 2009). Only two studies (Iwasaki et al., 2014; Rizk et al., 2016) were in- cluded in the quantitative analysis of the short-term outcomes of func- tional appliances on airway dimensions. The two other controlled stud- ies either did not present baseline, post-treatment or change data 251 Table 5. Changes in oropharyngeal volume/dimensions between the functional appliance and control groups in the medium quality studies. Pre-treatment Post-treatment Change Variable Authors Functional Controls Functional Controls Functional Control Pvalue mean tSD mean tSD mean tSD mean +SD mean tSD mean tSD - Ranges (based on Rizk 9081.90 + CVM stage) from 14619.27: Not reported 5537.38 + 2220,4770 + 0.005 Oropharyngeal et al., 2016 3406.15 7884.2 + 2361.54 to 5534.69 p 4849.72815 1310.07942 tº volume (mm”) 11649,7 t 1080.03 Iwasaki 3591.5 + 8591.7 it 7321.2 + 5000.2 + 2451.6 it et al., 2014 1660.7 4869.5 + 2276.8 4117.8 2927.5 3675.6 2878.7 0.015 Ranges (based on Rizk 21.19 + CVM stage) from 4.795 + 0.8063 + oropharyngeal | ..., 2016 4.15 20.2 + 6.04 to 25.99:421 | Not reported .sº 1.03516 0.000 transverse tº- 22.95 + 2.18 dimension (mm) Iwasaki 19.82 + et al., 2014 6.50T 21.59t 7.54 27.54+ 7.77 25.51 + 6.89 7.72 + 5.29 3.92 + 6.85 0.044 Ranges (based on Rizk CVM stage) from 1.835 + -1.1043 + oropharyngeal | .2016 || 7.24:2:21 6.45 + 1.79 to 9.08:2.52 | Not reported . 0.83776 0.000 A-P dimension Eº 8.66 + 2.32 (mm) Iwasaki 10.59 + __*- et al., 2014 3.617 12.11 + 2.46 14.75 + 3.61 13.22 + 3.20 4.16+ 3.59 1.11 + 2.81 0.004 § Al-Jewair et al. Mean Difference Mean Difference Study or Subgroup Weight IV, Random, 95% CI Year IV, Random, 95% Cl Rizk et al. 44.9% 3.32 [l. 17, 5.46] 2015 — H Iwasaki et al. S5.1% 2.55 (0.61, 4.49] 2014 — H Total (95% CI) 100.0% 2.89 [1.46, 4.33] <> Heterogeneity: Tau” = 0.00; Chi’ = 0.27, df = 1 (P = 0.60); I* = 0% H # l —h Test for overall effect: Z = 3.94 (P º 0.0001) – 10 –5 0 S 10 Favours [control] Favours [functional app) Figure 2. Forest plots for changes in oropharyngeal volume in functional appli- ances versus controls. Mean Difference Study or Subgroup Weight IV, Random, 95% CI Year Mean Difference IV, Random, 95% Cl Rizk et al. 76.9% 3.99 [1.98, 6.00] 2015 Iwasaki et al. 23.1% 3.80 (0.13, 7.47] 2014 Total (95% CI) 100.0% 3.95 [2.18, 5.71] t— Heterogeneity: Tau = 0.00; Chi’ = 0.01, df = 1 (P = 0.93); I* = 0% -10 Test for overall effect, Z = 4.38 (P & 0.0001) — H —º- C T –5 O 10 Favours [control] Favours [functional appl Figure 3. Forest plots for changes in oropharyngal transverse dimensions of func- tional appliances versus controls. Mean Difference Mean Difference Study or Subgroup Weight IV, Random, 95% CI Year IV, Random, 95% Cl Rizk et al. 73.9% 2.94 (1.82, 4.06] 2015 — H Iwasaki et al. 26.1% 3.05 (1.16, 4.94] 2014 –-º- Total (95% CI) 100.0% 2.97 [2.00, 3.93] <> Heterogeneity, Tag' -0.00. Chº - 0.01, df = 1 (P - 0.92); P = 0x H: º 0 ; 16 Test for overall effect: Z = 6.02 (P º 0.00001) Favours [control] Favours [functional app) Figure 4. Forest plots for changes in oropharyngal A-P dimensions of functional appliances versus controls. for the control groups (Dillehay, 2013; Li et al., 2014), therefore, prohibit- ing the inclusion of those studies into the meta-analysis. The meta-analysis showed that the oropharyngeal volume in- Creased significantly by 2.89 cm° in the functional appliances group com- pared to the controls, as well as the transverse and A-P airway dimen- Sions, which increased by 3.95 and 2.97 mm, respectively. Previous stud- ies (Kyung et al., 2005; Zhao et al., 2008) that assessed the effects of man- dibular advancing devices (MAD) in patients diagnosed with obstructive Sleep apnea (OSA) found an increase in the pharyngeal airway, but this increase was more in the transverse dimension than in the A-P dimen- Sion. This is similar to the findings in this meta-analysis. The mechanisms by which airway dimensions change after functional appliances still are not clear. However, it has been suggested that the anterior positioning of the mandible and hyoid bone result in the anterior movement of the 253 Upper Airway Dimensions pharyngeal muscles and the tongue which subsequently increases the airway size (Zhao et al., 2008). The studies included within this review were of medium or low quality due to the inherent weaknesses in their methodologies. The sam- ples in the functional appliance groups were neither random nor con- secutive in all studies, except for one (Iwasaki et al., 2014) that used con- secutive recruitment of subjects. This potential selection bias may have inflated the results and threatened their validity. All six studies used a separate control group except for two (Er- bas and Kocadereli, 2014; Temani et al., 2016). Airway length, volume, cross-section area and soft tissue thickness grow significantly during ado- lescence until 20 years of age then slow down until age 50, when a sig- nificant decrease starts to occur (Schendel et al., 2012). Therefore, it is considerably important to rule out normal growth changes when evaluat- ing effects of interventions by comparing the results to a matched control group. Of the four studies that used controls, three (Erbas and Kocadere- li, 2014; Iwasaki et al., 2014; Rizket al., 2016) matched the treatment and control groups by Skeletal age. Iwasaki and associates (2014) used a skeletal Class sample that was treated with fixed edgewise appliances as their concurrent control group. This group may not be comparable with the Class Il functional ap- pliance group. The craniofacial growth pattern and the anteroposterior jaw relationship can have a significant effect on the airway size (Iwasaki et al., 2009; Zheng et al., 2014). Kim and coworkers (2010) compared the airway dimensions between skeletal Class I and Il adolescent boys and girls and found significantly larger mean total airway volume in the Class | subjects compared to their Class || counterparts. The minimum cross- section area and volumetric measurements for each airway section, how- ever, were not different significantly between the groups. Iwasaki and colleagues (2014) reported significantly larger oropharyngeal volume in the Class I control group compared to the Class || Herbst subjects at baseline, but post-treatment, the Herbst group had significantly larger oro- and laryngopharyngeal dimensions compared to the Class I controls. Conley and colleagues (2014) argued that craniofacial morphology on its own cannot describe variation in upper airway dimensions and other fac- tors (e.g., body mass index, height and posture) need to be considered. 254 Al-Jewair et al. It is not known if the samples in the included studies were obese or not. Obesity has been established as a major risk factor for sleep-disordered breathing, particularly OSA (Bixler et al., 2016). Gender differences were not accounted for in any of the stud- ies. Males have been shown to have larger airways (Jiang et al., 2015). Rizk and associates (2016) and Erbas and Kocadereli (2014) both included Subjects that had received maxillary expansion prior to functional appli- ance insertion. On the contrary, Iwazaki and coworkers (2014) excluded this group. Previous studies have confirmed a significant effect of rapid maxillary expansion (RME) on the nasopharyngeal dimensions’ (Zhao et al., 2010; Zen and Gao, 2013; El and Palomo, 2014), but the findings are inconsistent for the effects of RME on the oro- and hypopharynx. Most current CBCT machines employ the same projection geom- etry, which should be accurate dimensionally. However, volumetric mea- Surements can differ significantly between software programs. El and Palomo (2010) found the volumetric measurements to be reliable within the same software program after a two-week washout period, but signifi- Cant differences existed between the programs. Another study suggested that Mimics, Dolphin2D, TK-Snap and OsiriX may be more accurate than InVivo Dental and Ondemand 3D (Weissheimer et al., 2012). Given that five different programs were used between the six studies included in the present review, this may have introduced additional heterogeneity to the reported results. Another potential variable to consider is how linear measure- ments and minimal cross-sectional areas were derived. Since CBCT view- ers allow image reformatting in any plane, the cross-sectional area and linear dimensions of the airway can change readily by virtue of reorient- ing the image plane. Even if the image planes were not altered, these measurements likely will be different depending on how the patient's head was positioned during image acquisition. “Natural head positions” is not defined clearly and it is unclear if the exact same head position was used in both the pre- and post-treatment scans in the two compara- tive groups, which may have increased the risk of bias further. Moreover, two of the included studies (Dillehay, 2013; Temani et al., 2016) did not report if the head posture, tongue positioning or mandibular occlusion were standardized during the scans in the treatment and control groups. 255 Upper Airway Dimensions The scanning time, kVp, and mA settings all can affect the resul- tant image quality. In particular, the CBCT scanning times in the included studies ranged from 8.9 to 17.0 seconds. With increased exposure time, the image volume is more susceptible to motion artifacts. This is particu- larly true in the pediatric population, as children and adolescents often find it difficult to remain still during the duration of image acquisition. If motion artifacts are present, the ability to delineate the borders between soft tissue and airway clearly may be compromised. Differences in how the boundaries of the naso-, oro- and hy- popharynx are defined existed among the included studies or were not specified. Also, if the patient swallowed during image acquisition or inad- vertently activated his/her suprahyoid muscles, the hyoid bone may be moved superiorly; this could lead to differences in the volumetric mea- surement of the oropharynx. Lastly, there currently is no clear consensus on the 3D definition of the regional airway boundaries. All included studies evaluated the short-term effects of func- tional appliances on upper airway dimensions and no study was identi- fied on the long-term effect. Relapse in mandibular advancement after functional orthopedic treatment has been noted previously (Bock et al., 2016); it is not clear how this would affect the pharyngeal airway dimen- sions. Future high-quality experimental studies are warranted to evaluate the short- and long-term effects of functional appliances for Class || cor- rection on upper airway dimensions and other sleep-related outcomes. CONCLUSIONS There is limited evidence that suggests short-term improvement in upper airway volume, transverse and A-P dimensions with the use of functional appliances for Class Il correction in adolescent patients. Evi- dence on the change in hyoid bone position is inconclusive. Future high- quality studies are warranted. REFERENCES Aboudara C, Nielsen I, Huang JC, Maki K, Miller AJ, Hatcher D. Compari- son of airway space with conventional lateral headfilms and 3 dimen- sional reconstruction from cone-beam computed tomography. 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Three-dimensional evaluation of upper airway in patients with different anteroposterior skeletal patterns. Orthod Craniofac Res 2014;17(1):38-48. 261 262 ANECDOTE, EXPERTISE AND EVIDENCE: APPLYING NEW KNOWLEDGE TO EVERYDAY ORTHODONTICS: CAN 3D PHOTOGRAMMETRY REPLACE CEPHALOMETRICSP Mohamed I. Masoud ABSTRACT With the introduction of cephalometric radiography by Broadbent (1931) and the cascade of research that followed, cephalometrics became the cornerstone of orthodontic diagnosis and practically a standard of care for the specialty. As We enter a new age of radiation hygiene forbidding the routine use of ionizing radiation and requiring a cost-benefit analysis for every radiographic exposure (Atchinson et al., 1992; Ruf, 2005; Remedios and McCoubrie, 2007; Isaacson et al., 2008; Turpin, 2008; American Academy of Oral and Maxillofacial Radiology, 2013), we need to ask ourselves important questions like: What should standard- of-care orthodontic records include? Is a cephalometric radiograph really neces- Sary to diagnose and treatment plan orthodontic cases? Why does the entire Cranium need to be exposed? Is there an alternative non-radiographic imaging method that can provide the necessary information? Is there an alternative to the cranial base that can be used as a reference for measuring discrepancies and Changes? This chapter attempts to answer some of these questions by proposing a method for orthodontic diagnosis that depends on dentofacial photogrammetry instead of cephalometric radiography and uses the eyes as a reference instead of the cranial base. Adult male and female reference values are presented and tested on an orthodontic population. CONCLUSIONS: 1. Most diagnostic decisions have fair agreement within and between the traditional and photogrammetry methods. 2. Important treatment planning decisions (extractions, surgery) had Substantial agreement between the traditional and photogrammetry methods. 3. The majority of users (83%) agreed that cases with Class I malocclusions +25% Cusp with crowding or spacing can be diagnosed and planned without a cepha- lometric radiograph. KEY WORDS: treatment planning, 3D imaging, orthodontic diagnosis, orthodontic records, cephalometrics, photogrammetry 263 3D Photogrammetry INTRODUCTION: THE RISE AND FALL OF CEPHALOMETRIC RADIOGRAPHY Broadbent's research (1931) on the Bolton Brush Sample Con- cluded that cranial base landmarks like Sella Turcica (S) were stable and could be used to quantify discrepancies and growth. Since then, various cephalometric analyses and reference values have been developed uti- lizing different parts of the the cranial base as references for their mea- surements (Tweed, 1946; Downs, 1948; Steiner, 1953; McNamara, 1984). Although the cranial base is relatively stable over time, researchers dem- onstrated that individual variations in the position of Sella and the length of the cranial base can result in inaccurate diagnostic conclusions (Jacob- son, 1975; Moorrees et al., 1976; Lundström et al., 1995). Moorrees and colleagues (1976) developed a visual analysis using a grid system that uti- lized natural head position (NHP) as its reference plane instead of a refer- ence plane dependent on cranial base landmarks (Fig. 1). The Moorrees Mesh Analysis still involved a lateral cephalometric radiograph exposing the entire cranium and centering the grid around Nasion which has been shown to undergo significant growth during puberty (Björk, 1966; Moor- rees et al., 1976). However, using an extra-cranial reference plane was a significant departure from traditional techniques which opened the door for potential non-radiographic approaches to orthodontic diagno- sis. Even orthodontists who do not use the Mesh Analysis often will rec- ognize a high or low Sella and correct for it. The correction often involves measuring the angle between Sella to Nasion (SN) and the true horizontal and comparing it to the 7"average. If it deviates from that average, an imaginary Sella is used that is in the correct orientation to the true hori- zontal, which questions the reason for exposing the cranial base in the first place. Research has shown that a cephalometric radiograph does not impact actual orthodontic decision making (Nijkamp et al., 2008; De- vereux et al., 2011). Moreover, radiographic exposure guidelines prohibit the routine use of any ionizing radiation without careful evaluation of how the exposure will benefit the health of the patient. This has resulted in the prohibition of cephalometric radiographs after the completion of orthodontic treatment (Atchinson et al., 1992; Ruf, 2005; Remedios and McCoubrie, 2007; Isaacson et al., 2008; Turpin, 2008; American Academy of Oral and Maxillofacial Radiology, 2013). A systematic review recently concluded that cephalometric radiographs should not be part of routine 264 Masoud Figure 1. Moorrees Mesh Analysis with a distorted grid show- ing bimaxillary dentoalveolar protrusion with an increased lower anterior face height and a steep mandibular plane. Orthodontic records and that “the minimum record set required for orth- Odontic diagnosis and treatment planning could not be defined" (Rischen et al., 2013). This puts orthodontists in a compromising position without the ability to document treatment changes and makes it difficult for the spe- Cialty to define its standards of care clearly. Over the last couple of de- Cades, technology has had a huge impact on almost every aspect of life, but orthodontists still diagnose cases the way they did a half century ago. Even proponents of cone-beam computer tomography (CBCT) often end Up Converting those images into cephalometric radiographs, measuring SNA and SNB, and comparing their patients to traditional standards se- lected by orthodontists (Halazonetis, 2012). Peck and Peck (1970) com- Pared those standards to cephalometric measurements obtained from People acknowledged by the public for being attractive and concluded that the public prefers fuller, more protrusive dentofacial patterns than 265 3D Photogrammetry traditional cephalometric standards permit (Lundström et al., 1995). The public is rather consistent regarding what it considers attractive with high agreement across different racial and ethnic backgrounds (Cunningham, 1986; Cunningham et al., 1995; Rhodes et al., 2001; Kohl, 2006; Sforza et al., 2009). Research has shown that the greater number of faces in- cluded in a computer-generated composite image, the more attractive the face becomes as each feature becomes more average in size (Buss, 2003). A random sample of over 1,200 participants showed that people found mixed-race faces to be more attractive over those originating from only one race (Lewis, 2010). As populations become more mobile, tra- ditional “norms” become much less relevant. Many major U.S. cities no longer have Caucasian majorities (U.S. Census, 2010), 80% of the popula- tion of Mexico now is considered multi-racial (Silva-Zolezzi et al., 2009), most North Africans have mixed ancestry, 50% of black Caribbeans in the U.K. have white partners (Twine, 2011) and many Southeast Asian popu- lations cannot be classified using traditional racial categories. These re- alities become important in deciding the standards to which patients are compared. Rapid changes in technology, society and regulations all have created a need to explore new approaches to the way we diagnose and plan orthodontic patients. THREE-DIMENSIONAL (3D) DENTOFACIAL PHOTOGRAMMETRY USING THE EYES AS A REFERENCE 3D dental models have been accepted widely as an alternative to traditional study models (Whetten et al., 2006) and can be taken in color potentially to replace intra-oral photographs. Although landmarking and measurements using 3D facial images have been validated (Plooijet al., 2009; Kochel et al., 2010a,b), the technology has been viewed by the pro- fession as a toy more than a serious diagnostic tool. The primary reason for that is the absence of a standardized comprehensive analysis with a stable reference that allows orthodontists to relate the teeth to the face and compare a patient to a standard. Combining 3D facial and dental im- aging has been reported in the literature, but it has been used mostly in conjunction with cone-beam imaging (Rosati et al., 2010). The eyes have been shown to experience less than 2 mm of growth between the ages offive and nineteen. Since they are visible with- out radiographic exposure, they were combined with NHP as references 266 Masoud to evaluate the position and orientation of different dentofacial struc- tures (MacLachlan and Howland, 2002; Dijkstal et al., 2012). The primary objectives of this project were to: 1. Standardize a non-radiographic technique with ex- tra-cranial references to be used for the diagnosis of orthodontic problems and evaluate progress and out- comes (Masoud et al., in press); 2. Develop male and female reference values for the method (Masoud et al., in press); and 3. Test the method on an orthodontic population and Compare diagnosis and treatment planning outcomes to traditional records (Manousprasit et al., in press). THE METHOD Patients were positioned in NHP by having the patient look at him/herself in a mirror. A 3D facial photograph was taken with the lips relaxed and repeated with a full smile. Drying the teeth with gauze or air Was important since saliva causes light reflection and an irregular dental Surface on the 3D image, which can make dental superimposition chal- lenging. Taking a third facial image with cheek retractors can make drying the teeth easier, which allows more accurate indexing of the smiling im- age to the teeth. Any 3D facial scanner can be used for this application. We used the Vectra M3 imaging system (Canfield Scientific, Fairfield, NJ), but we have had similar results using Canfield's more affordable hand- held model (Vectra H1) and Motion View's Facial Insight scanner (Motion View Software, LLC, Hixson, TN). We did not have access to a 3DMD unit, but it would be expected to work just as well. Any 3D dental imaging System can be used to capture the teeth including using a desktop scan- ner to digitize traditional impressions. Bite registrations were imported and could be taken with a leaf gage if the patient has a CR-CO shift. All facial and dental components were imported into Facial Insight 3D (Mo- tion View Software, LLC, Hixson, TN) for digitization and superimposi- tion. The central incisors, canines, first premolars and first molars were landmarked as described Huanca and associates (2013) and Andrews (1989). The long axis of each incisor was determined by extending a line from the central of the incisal edge, canine tip or center of occlusal 267 3D Photogrammetry surface to a point midway between the labial and gingival intersections of the FACC line (Taylor, 1969; Carlsson and Rönnerman, 1973; Andrews, 1989; Srinivasan et al., 2013). The bite registration was used to relate the maxillary and mandibular arches. Automatic dental landmark rec- ognition was found to be useful, but often needed to be checked and modified (Fig. 2A). The face was landmarked as described by Farkas and coworkers (1986) and Plooij and associates (2009). If the jawline was not visible clearly, the mandibular plane was palpated and marked with an eye liner before the facial images were taken. The teeth and smiling pho- tograph were indexed by Superimposing the incisal and gingival embra- sure points, which were visible on both images (Fig. 2B). The smiling and non-smiling facial images were indexed by superimposing on the pupils and the brow ridges (Fig. 2C). The smiling picture of the face then can be removed and the image with the lips relaxed transparent to view the relationship between the teeth and the lips (Fig. 2D). The MC plane was defined as a coronal plane perpendicular to true horizontal contacting the pupil points. This was used to as a reference for measuring linear and angular Sagittal relationships of the dental and facial structures (Figs. 3A and 4). On a lateral cephalogram, the base of the alar curvature coincides with the anterior nasal spine so the right and left alar curvature points were used along with soft tissue A point as indicators of maxillary skeletal position on the 3D facial image. Soft tissue B point and soft tissue pogo- nion were used to estimate the skeletal position of the mandible. Angular and linear measurements were used to relate the maxilla and mandible to each other and to the MC plane determined by the position of the eyes (Fig. 4). Linear and angular measurements were used similarly to related the upper and lower incisors to the MC plane. In addition, the lower inci- sors were related to the soft tissue mandibular plane. The MA plane was defined as an axial plane parallel to NHP going through the pupils (Fig. 3B). It was used as a reference for determining the vertical orientation and position of the dentofacial structures (Fig. 5). The occlusal plane and the mandibular plane were measured relative to the MA plane. The right and left soft tissue gonion points were marked at the beginning of the gonial curvatures instead of the middle of the go- nial angle since the beginning of the curvature could be located more 268 Masoud Figure 2. A: The upper and and lower teeth were digitized using automatic land- mark recognition, then interdigitated using the bite registration. B: The inter- digitated teeth were indexed to the smiling 3D photograph of the face using the incisal and gingival embrasure points that can be identified on views. C. The 3D facial smiling image and image of the face at rest were indexed by superimposing On the pupils, the inner canthus and the brow ridges. D: The smiling image of the face can be removed and relaxed image can be made transparent to relate the teeth to the lips at rest. From Masoud et al., in press. Consistently. They were used along with soft tissue menton to create a mandibular plane. The distances from the soft tissue gonion points and Soft tissue menton to the MA plane were used to measure posterior and anterior face heights, respectively. The vertical relationships of the upper teeth were determined by measuring their vertical distance from the MA plane and stomion. The lower teeth also were related vertically to the mandibular plane. 269 3D Photogrammetry Figure 3. A: MC plane defined as a coronal plane perpendicular to true horizontal and touching pupil points. B: MA plane defined as an axial plane parallel to NHP passing through the pupils. C. MS plane defined as a sagittal plane perpendicu- lar to true horizontal passing through a point midway between the pupils. From Masoud et al., in press. Figure 4. Angular and linear sagittal measurements using the MC plane as a reference. From Masoud et al., in press. 270 Masoud Figure 5. Vertical measurements relative to the MA plane and the mandibular plane. From Masoud et al., in press. The MS plane was defined as a midsagittal plane perpendicular to NHP passing through a point midway between the pupils (Fig. 3C). Soft tissue pogonion, the right and left soft tissue zygomas and the right and left soft tissue gonion points were related to the MS plane to evaluate Symmetry. The upper and lower midlines, as well as the inclination and position of the right and left canines and molars, were related to the MS plane (Fig. 6). Incisors, canines and molars also were evaluated vertically and transversely relative to the lips upon smiling. 271 3D Photogrammetry Figure 6. Transverse dentofacial measurements relative to the MS plane. From Masoud et al., in press. THE STANDARD AND ITS USE One hundred eighty female and 200 male models between the age of 18 and 35 were screened for near ideal occlusion defined by the presence of all the teeth excluding the third molars, within 2 mm of Class molars and canines, overjet and overbite between 1.5 to 3.0 mm, less than 3.0 mm of crowding or spacing and no crossbites. Orthodontic residents were involved in screening the occlusions, but had no role in selecting the faces to be included. Sixty female models and 64 male models met the inclusion criteria and had black and white facial photographs at rest and smiling (Fig. 7). The photographs were shown to lay people with no mediº cal or dental background to be evaluated for attractiveness on a visual 272 Masoud Figure 7. Sample screened model images shown to lay people for evaluation. From Masoud et al., in press. analogue scale and whether or not they were considered “acceptable.” Thirty-four females and 30 males were considered acceptable by over 60% of the evaluators and had an average visual analogue scale score greater than 5.8. That group was invited to have the records described in the methods section above taken. A total of nine models failed to show for their imaging sessions and five models (four females and one male) Were excluded upon closer examination of their teeth. The final sample that made up the standard included 24 females and 25 males. Although all the female models and 17 of the male models identified themselves as Caucasians, the majority of them had one parent that was considered African, Hispanic or Mediterranean with only nine of the female mod- els considering themselves pure Caucasians. Of the eight male models that considered themselves non-Caucasian, three identified themselves as Asian, two as Hispanic, two as African American and one as Indian (Subcontinent). The mean model age was 20.94/-2.8 years for the female models and 25.4+/-4.01 for the male models. Inter- and intra-examiner reliability was tested for landmarking and indexing the different components. The Intra-class Correlation Coef- ficient (ICC) was greater than 0.8 for all the measurements, even when a Completely different facial photograph of the same patient was indexed. A Procrustes Analyses was used to eliminate size, positional and ſotational differences between the different subjects and produce an av- erage male and female dentofacial template that can be overlaid on a patient to visualize and quantify dentofacial discrepancies (Fig. 8). The male and female means and standard deviations were calculated for each 273 3D Photogrammetry d -50 Figure 8. Female standard dentofacial image with landmarks generated by averaging the selected female models after eliminating size, rotational and positional differences. From Masoud et al., in press. of the measurements mentioned in the methods section and a paired T. test was used to identify significant differences between the males and females (Table 1). Male faces had significantly greater vertical and trans- verse dimensions. Sagittal chin projection was greater in males, but the differences were not significant statistically. Both males and females had soft tissue pogonion approximately 0.5 mm anterior to the alar curvatuſ? and 8.5 mm posterior to subnasale. This demonstrates that the public prefers faces that are not as prognathic as orthodontic and orthognathic standards would suggest (Arnett et al., 1999). With the exception of the tip of the occlusal plane, which was significantly steeper in females than males, none of the facial angular measurements or ratios were signifi- cantly different between genders. Males had more proclined maxillary 274 i Table 1. Male and fernales means, standard deviations and gender differences. Significance set at 0.05 (Masoud et al., in press). P Male Male female soft tissue go to soft tissue Me Description of Measurement Code Unit Mean SD Mean Female SD Value Sig Maxillary apical base. SAPMCP deg | 21.42 || 3.8 21.05 || 4.19398221 0.75 NS soft tissue A to MC Maxillary sagittal lip position to MC $5MCP mn 24.04 4.12 21.23 4.336416552 0.02 S Maxillary vertical position, SnMA mm || 48.32 || 2.92 || 43.70 || 2.294.223212 || 0.00 | S subnasale to MA Upper lip length, subnasale to stomion STUSN mm 23.33 2.02 20.12 2.165716904 O.00 S Occlusal plane angleto MA OCC-MA deg 7.32 3.6 11.85 6.242710474 O.00 S FMaxillary cant, occlusal pian to MS MaxCant deg Q.13 1.86 -0.59 0.968582466 0.10 NS Maxillary right first molar width, UR6MP- MP cusp to MS MS mrm 25.02 1.95 23.13 1.935.910638 O.00 S Maxillary left molar width, UL6MP- MP cusp to MS MS mrm 23.15 2.32 22.01 1.50859.2719 0.05 S Maxillary right canine width, UR3-MS mm | 16.47 | 1.83 || 15.26 1.341270218 || 0.01 || S cusp to MS Maxillary etcanine width, UL3-MS mm 15.92 | 1.95 || 14.69 | 1.300434,431 || 0.01 || S cusp tip to MS | Mandibular apical base angle, SBP-MC deg | 7.91 2.55 || 5.94 5.007541848 || 0.09 | NS soft tissue 8 to MC. Mandibularip position. li-MC mm 20.15 3.53 17.98 || 4.60382.2431 0.07 || NS lubrale inferioris to MC Chin position, soft tissue Pg to MC pg-MC mm. 14.84 3.63 12.78 5.073669294 0.11 NS Anterior face height Stme-MA || mm | 120.46 || 4.26 || 106.73 || 4.734158022 || 0.00 | S soft tissue menton to MA Posterior face height average right and PFH mm 87.5 5.94 | 78.85 5.675613674 || 0.00 | S left soft tissue gonion to MA * I Mandibular plane angle, right and left MP-MA deg 26.7 || 3.94 || 25.12 || 7.15377.548 || 0.34 NS § Table 1 continued. Right facial width, r-M mm. 8.09 4. .24 .574 º right soft tissue gonion to MS stgor-MS 5 39 52.2 2,574.388031 || 0.00 | S Right facial width, 5tgol-MS mm 56.18 || 4-28 || 52.54 || 3.3207241.22 || 0. right soft tissue gonion to MS tg 00 S chingeviation, Chin-MS mm 1.27 || 0.97 || 1.17 0.875720821 || 0.71 || NS soft tissue pogonion to MS Mandibular right first molar width LR6-MS mm 23.38 2.01 || 21.62 | 1.696280618 0.00 | S from the central fossa to MS | º Mandibular left first molar width LL6-MS mm 21.36 2.51 | 20.67 | 1.6165.65513 || 0.26 | NS | from the central fossa to MS Mandibular right canine width LR3-MS mm 13 1.97 || 11.80 | 1.298.135508 || 0.02 || S from the cusp tip to MS Mandibularletcanine width LL3-MS mm | 12.42 2.07 || 11.64 | 1.365720864 0.13 | NS from the cusp tip to MS Apkal base angle rom the eyes to soft SAP-SBP deg | 13.38 2.56 13.06 | 1.953071717 | 0.62 | NS tissue points A and 8 & intermaxillary angle from the eyes to ArP-Pogſ’ deg 5.63 3.06 || 6.16 3.852085615 || 0.59 || NS the alar base and pogonion Lower face height, Sn-Strne mm | 72.13 || 3.34 || 63.03 || 3.46483,1149 || 0-00 || S subnasale to soft tissue menton Maxillary incisal edge to MC UR1|-MC mm 10.44 || 4.74 8.51 4.114181906 || 0.14 || NS Maxillary incisors long access to MC UR1LA-MC deg 20.1 7.36 15.62 8.562313777 0.06 NS Mandibular incisal edge to MC irli-MC mm. 8.04 || 4.66 || 6.25 3.713275806 || 0.14 || NS R * > Mandibular Incisors long access to MC º:º deg 27.32 9.56 31.18 6.118593356 0.00 S Lower incisor long access to soft tissue LR11A-MP deg | 81.27 5.88 81.38 4.588969683 || 0.00 S mandibular plane Upper incisal display at rest measured UR1Stsrest || mm O.87 2.58 3.03 1.45098767 O.00 S to stomion § i Table 1 continued. Maxillary anterioralveolar height Antálv mm 21.64 || 2.49 || 19.61 2.003442644 || 0.00 | S central incisal edge to MA Maxillary posterior alveolar height, Post Alv || “mm | 19.09 || 3.09 | 16.11 || 3.126182443 || 0.00 | S first molar MP cusp to MA Mandibular anterior alveolar height, LAntAlv mm 48.07 || 3.04 || 40.66 || 2.836690222 || 0.00 | S kower incisal edge to MP Mandibular posterior alveolar height, LPostAlv || mm | 38.18 || 3.32 || 32.45 || 3,342553047 || 0.00 || S kower first molar MP cusp to MP Maxillary inter-canine distance UR3C- mm | 36.37 | 1.72 || 33.66 2.00272.3101 || 0.00 || S from cusp tip to cusp tip UR3C Mandibularintercanine distance ||3c-Ir:3c | mm 27.82 | 1.51 || 25.48 || 1.304206614 || 0.00 || S from cusp tip to cusp tip Maxillary first molar width from MP urónp- mm. 42.2 3.09 39.70 2.523081241 0.00 S cusp to MP cusp ulbmp Mandibular first molar width from ||6c-iróc | mm || 43.06 || 2.91 | 40.66 || 2.540272973 || 0.00 || S central fossa to central fossa Upper right first molar long axis to MS UR6LA-MS deg 7.9 5.12 5.89 6.093.50236 0.00 S Upper left first molar long axis to MS UL6LA-MS deg 9.79 6.21 5.79 6.044654828 0.00 S Lower right first molar long axis to MS LR6LA- MS deg -16.12 6.02 -13.01 6.79481.2586 0.00 S Lower left first molar long axis to MS LL6LA-MS deg -12.38 7.18 -15.24 6.18494.1024 0.14 NS § 3D Photogrammetry incisors and more retroclined mandibular incisors relative to the MC plane, but this was not significant statistically. Individual size and shape variations are difficult to take into ac- count using an analysis like this to compare a patient to the the stan- dard. A more suitable way of evaluating a patient would be to use a tem- plate analysis that eliminates size, positional and rotational differences between the standard; the patient's dentofacial image then generates directional arrows from the patient's facial and dental landmarks to the standard’s corresponding landmarks (Fig. 9). The differences also can be expressed in a table listing the differences between the X, Y and Z coordi- nates of the patient and the standard. VALIDATION ON ORTHODONTIC PATIENTS The standard described above was tested on a group of 20 con- secutive post-pubertal orthodontic patients (> than CS4) with no missing teeth other than third molars. Standard orthodontic records were taken including traditional study models, extra- and intra-oral photographs, panoramic radiographs and cephalometric radiographs. Each patient also had 3D dentofacial images taken as described in the methods section above. The 20 cases were diagnosed and treatment planned by twelve orthodontistic evaluators (six orthodontic faculty, two orthodontists and four orthodontists that completed more than eighteen months of their residency) using a multiple-choice form. Each orthodontic evaluator di- agnosed and treatment planned all 20 cases over three sessions. During the first session, each orthodontist diagnosed and planned ten out of the 20 cases with the traditional records and the remaining ten cases with the 3D photogrammetry records and a panoramic radiograph. At least four weeks later, the ten cases that previously were planned with traditional records now were planned with the the 3D records and vice versa. At this point, each case had been evaluated by each evaluator uS- ing both methods. At least four weeks after that session, each evaluator re-planned four random cases (two with standard records and two with the 3D records) to assess evaluator consistency within each method. Table 2 reports orthodontic evaluator diagnostic and treatment planning agreement within and between the two methods. The percent- age of agreement and the Kappa values are reported for each question. A Kappa measurement below 0.2 indicates slight agreement, between 278 Masoud Figure 9. Sample dentofacial images of a patient with directional arrows pointing from the patient's landmarks to the landmarks of the standard after scaling and eliminating rotational and positional differences. 0.2 to 0.4 indicates fair agreement, between 0.4 to 0.6 indicates moder- ate agreement and above 0.6 indicates substantial agreement (Viera and Garrett, 2005). The traditional records had overall higher intra-method diagnostic agreement, especially when determining the mandibular po- Sition, mandibular incisor position and mandibular incisor inclination. The 3D records had better intra-method agreement when determining the lo- Cation of the maxilla, the location of the maxillary incisors, the divergency and the presence of asymmetries. Detecting asymmetries with the 3D records was the only parameter that had 100% agreement and a non- applicable Kappa. Most of the diagnostic parameters had fair agreement between the two methods; however, the skeletal relationship question had moderate inter-method agreement, although the traditional records had higher intra-method diagnostic agreement that did not translate into higher treatment planning agreement, especially when it came to the goal for the position of the lower incisors. Most important treatment planning questions (e.g., the decision to extract and the need for surgery) had substantial intra-method agreement for the 3D photogrammetry re- Cords and moderate to substantial agreement between the two methods. 279 3D Photogrammetry Table 2. Diagnostic and treatment planning agreement between and within the 2D and 3D treatment planning methods. From Manousprasit et al., in press. Re- printed with permission of Elsevier. 2D-3D 2D-2D 3D-3D º Kappa º Kappa º Kappa Agreement Agreement Agreement Incisor inclination-maxilla 49.58 0.206 75 0.522 70-83 0.408 Incisor inclination-mandible 53.33 0.285 91.57 0.345 70-83 0.483. Incisor position-maxilla 49.17 0.135 79.17 0.532 33.33. 0.718 Incisor position-mandible 50.42 0.248 79.17 0.513 62.5 0.353 Maxilla position 62.92. 0.289 58.33 0.151 62.5 0.2 Mandible position 42.5 0.076 87.5 0.783 75 0.5 Skeletal relationship 70-83 0.548 87.5 0.793 83.33 0.578 Mandibular plane 52.5 0.23 . G6.67 0.314 70-83 0.425 Lower face height 58.75 Q.325 45.83 0.158 55.57 0.347 Chin position 56.25 0.287 79.17 0.555 52.5 0.357 Facial asymmetry 76.67 0.381 87.5 0.333 100 N/A Will extractions be required? 30.42 0.578 79.17 0.524. 83.33. 0.554 ... ." 50 || 0.353 54.17 || 0.251 || 52.5 || 0.27 ...*..." 59.58 0.341 41.67 0.125 54.17 0.221 Will surgery be required? 87.5 0.533. 62.5 0.25 91.17 0.812 ..., one year) 77.08 0.457 55.57 0.22 79.17 0.555 Average % agreement 66.43 75.27 72.92 T After the orthodontic evaluators completed their diagnosis and treatment planning sessions, they were asked to complete a usability questionnaire describing their experience using the 3D photogrammetry method (Table 3). When asked whether or not they felt a cephalometric radiograph was necessary in conjunction with the 3D records, 91.7% of them said it was only necessary in some of the cases. 83.3% of evaluators felt that cases with a Class occlusion +/-25% cusp and crowding or Spact ing can be diagnosed and planned accurately with the 3D records with: out a lateral cephalometric radiograph. 100% of the evaluators felt that a cephalometric radiograph was necessary to diagnose accurately and treatment plan surgical cases and cases with a full cusp Class III relation: ship. Although the evaluators were unfamiliar with the 3D photograſſ- metry method after receiving only a short tutorial before using it, 50% of 280 Masoud Table 3. Subjective evaluation of the 3D method by orthodontists and orthodon- tic residents. From Manousprasit et al., in press. Reprinted with permission of Elsevier. Sometimes NO (%) (%) Do you feel that a lateral cephalogram was 91.7 8.3 necessary when using the 3D records? wºuleeneº Yes (%) | No (%) - Class 1 +1.5 mm with crowding or spacing? 16.7 83.3 - End on Class || +1.5 mm? 66.7 33.3 - Full cusp Class || +1.5 mm? 83.3 16.7 - End on Class || +1.5 mm? 100 O - Deep bite cases? 58.3 41.7 - Open bite cases? 91.7 8.3 - Surgical cases? 100 O the evaluators did not feel any less confident with their treatment plans using the 3D photogrammetry records. MOVING FORWARD This method is currently in its infancy. Changing regulations and available technology are expected to be the driving force behind further research in the area. With handheld 3D facial cameras now available for under $10,000 and the availability of colored intra-oral Scanners, dentofacial photogrammetry likely will replace traditional Colored photography and traditional study models. The author and Other researchers currently are working on correlating cephalometric and photogrammetric corresponding measurements, developing age- and race-specific reference values, and validating the method on an adolescent orthodontic population. Our current data suggests that 3D dentofacial photogrammetry in conjunction with a panoramic radiograph can eliminate the need for a Cephalometric radiograph in cases with crowding or spacing and a near Class I occlusion. As exposure values of ultra-low dose cone-beam images 281 3D Photogrammetry limited to the upper and lower arches approach those of panoramic ra- diographs, eventually they may replace them altogether. The CBCT im- ages of the arches can be indexed to the 3D dentofacial photogramme- try images and similarly related to the eyes without exposing the crania base. This would provide substantially more information about the roots and apical bone than a panoramic radiograph and could potentially ex- pand the range of cases that can be planned with this method. CONCLUSIONS 1. Inter- and intra-examiner ICC were greater than 0.8 for both landmarking and indexing. 2. Males had significantly greater vertical and transverse dimensions and non-significantly greater chin projec- tion. 3. Males had longer, more protrusive upper lips along with steeper occlusal planes and more lingually in- clined lower teeth. 4. Most diagnostic decisions have fair agreement within and between the traditional and photogrammetry methods. 5. Important treatment planning decisions (extractions, surgery) had substantial agreement between the tra- ditional and photogrammetry methods. 6. The majority of users (83%) agreed that cases with Class 1 malocclusions +25% cusp crowding or spacing can be diagnosed and planned without a cephalomet- ric radiograph. 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SameShima ABSTRACT This chapter summarizes the current knowledge of how and why external apical root resorption (EARR) occurs and how the clinical orthodontist manages root resorption at the initial, mid- and post-treatment stages, by answering ten Commonly asked questions: 1 Which patients are at the greatest risk? Can I move teeth with really short roots? What happens if I move a root that is still growing? What happens if I move a tooth with endo? How do I manage patients at risk? What do I do if I see EARR at progress? What do I do if I see EARR at the end? What is invasive cervical root resorption? Can EARR be detected without radiographs? What happens to resorbed roots long term? 1 0. KEY words: external apical root resorption, orthodontic tooth movement, risk factors, clinical management, long-term consequences INTRODUCTION Resorption of the root surface when forces are applied to the tooth crown is a well-established side effect of clinical orthodontics. Clinical management of orthodontic root resorption begins with an un- derstanding of the etiology. As teeth are moved, the root surface is re- Sorbed and repaired constantly. This is documented well in the literature and there generally is no negative outcome. However, the root apex can demonstrate an exception to this benign pattern, where apical resorption 287 Orthodontic Root Resorption may lead to a pathological process of destruction that is progressive and irreversible. This chapter provides a review of current literature with the aim of addressing several clinically relevant questions about orthodontic root resorption. EVIDENCE-BASED ANSWERS TO IMPORTANT CLINICAL OUESTIONS ABOUT ROOT RESORPTION Which patients are at the greatest risk for orthodontic root re- sorption? Many clinical papers have been written about what is properly termed “external apical root resorption” (EARR). There are a few system- atic reviews and many reasonably well-executed retrospective studies and interesting case reports from which there is a general consensus on risk factors (Sameshima and Sinclair, 2001a; Segal et al., 2004; Weltman et al., 2010; Roscoe et al., 2015; Sharab et al., 2015). Severe EARR usu- ally is defined as greater than 3 to 4 mm (or a third of the root) and is relatively rare; this rarity causes problems in designing and conducting a proper clinical study. Risk factors can be divided into diagnostic and treatment factors. The main diagnostic risk factor is genetic predisposi- tion (Harris et al., 1997; Al-Qawasmi et al., 2003; Sharab et al., 2015). What does this mean to the clinician? It means that if a patient had sig- nificant EARR, then his/her siblings are at higher risk. The orthodontist also would be wise to advise the patient of higher risk if a parent had a positive history for significant EARR. Evidence indicates that there is a gene or family of genes that, unfortunately, remain to be discovered. For example, Harris and associates (1997) found significantly higher suscep- tibility among siblings using heritability estimates. More recently, Sharab and colleagues (2015) showed that the presence of specific genotypes for the markers P2RX7 SNP rs208294 were associated significantly with EARR in an orthodontic patient study sample. The most commonly resorbed tooth is the maxillary lateral incisor, followed by maxillary central incisors, maxillary canines, mandibular canines and mandibular incisors. In larger retrospective studies, the mean EARR for maxillary lateral incisors was 1.5 mm (Sameshima and Sinclair, 2001a). Several papers have reported increased risk for abnormal or odd root shape, particularly dilacerations; however, the systematic reviews do not support this (Segal et al., 2004; Weltman et al., 2010; Roscoe et al., 2015). Other factors (e.g., type of malocclusion, presence of decalcification, crown root ratio) also are not considered risk factors (Weltman et al., 2010). Historically, girls were 288 SameShima thought to have more EARR than boys, but the evidence strongly sug- gests that sex is not a factor (Weltman et al., 2010). Age no longer is con- sidered a significant risk factor for EARR (Weltman et al., 2010). Anterior openbite as a risk factor remains debatable (Harris and Butler, 1992; Mo- tokawa et al., 2013), most likely because the treatment methods used are more of the determining factor than the condition itself. Increased over- jet also is associated with EARR (Sameshima and Sinclair, 2001a). There is Some evidence that certain ethnic groups are at higher risk (Sameshima and Sinclair, 2001a). History of trauma may be factor and predisposing medical conditions and rare syndromes (e.g., familial expansile osteoly- sis; Mitchell et al., 1990) are associated with EARR. Asthma (McNab et al., 1999) and endocrine problems (Newman, 1975) have been associated with increased EARR, but there is a lack of strong evidence. Many hypothesized treatment risk factors have been found not to be true and the percentage of treatment factors is now thought to be less than 20%. The most significant treatment risk factor is treatment duration or extended treatment time (Weltman et al., 2010). The over- whelming majority of studies have shown this to be a significant risk fac- tor; in practice, long treatment is relative and the cases that take signifi- Cantly longer than the average time for that type of case in that practice will be at higher risk. Equally important as a risk factor is the amount of apical displacement (Weltman et al., 2010). There is a direct relationship between the distance a root apex is moved (in all three planes of space, but especially horizontal distal displacement) and EARR. Skeletal anchor- age has allowed the clinician to do absolute intrusion of 4 mm or greater and there is increasing evidence that these teeth will show higher than average EARR (Liou and Chang, 2010; Heravi et al., 2011). A number of retrospective studies have shown a direct association with extractions and EARR, but this probably is related to apical displacement, as is over- jet correction (Sameshima and Sinclair, 2001b). Suspected but difficult to prove treatment factors are wearing elastics and oral habits. If clear align- ers move the apex, normal patterns and prevalence of EARR will be ob- Served (Brezniak and Wasserstein, 2008). There is no evidence to support that appliance type (e.g. self-ligation; Jacobs et al., 2014) or treatment philosophy can decrease risk. There is insufficient evidence to determine if the various methods of tooth acceleration affect the risk of EARR. Can I move teeth with really short roots? There is no evidence that teeth with short roots are at higher risk. Sameshima and Sinclair 289 Orthodontic Root Resorption (2001a) found a positive association between amount of EARR and root length, but this has not been confirmed by other studies. It is vitally im- portant to distinguish a patient with one or two teeth with relatively short roots from a patient who has “short root anomaly.” Fortunately, this syndrome is extremely rare, but there are case reports demonstrat- ing a much higher risk of EARR (e.g., Puranik et al., 2015). What happens if I move a root that is still growing? A tooth that has not achieved its full length will have an immature apex. This seems to have a protective effect against EARR (Mavragani et al., 2002). What happens if I move an endodontically treated tooth? Suc- cessfully endodontically treated teeth seem to have a decreased risk (loannidou-Marathiotou et al., 2013). Teeth with undiagnosed fractures or compromised pulps can be moved orthodontically, but other types of resorption can occur (Hamilton and Gutmann, 1999). How do I manage patients at risk for root resorption? Recogniz- ing the diagnostic and treatment risk factors is paramount, but good clinical management also requires excellent pre-treatment and progress radiographs. Ouality periapical radiographs are preferred over panoram- ic radiographs (Sameshima and Asgarifar, 2001). For patients who are at risk, the amount of apical displacement should be considered when es- tablishing treatment goals, particularly incisor torque. Treatment length must be monitored closely. Additionally, management should include an informed patient regarding the risks and the possibility that treatment goals cannot be met. What do I do if I see EARR at progress evaluation? It is recom- mended that progress radiographs be taken at one year or soon after significant tooth movement has commenced in the teeth at risk. If prog- ress films show active EARR of greater than 2 mm, the orthodontist must decide whether or not to proceed with movement of the afflicted teeth. This decision will be based upon how close to finishing the case is and how much apical displacement is necessary to achieve the desired outcome. Usually if the amount of tooth movement is minimal and the case is close to finishing, the clinician can proceed. However, if greater movements are required (e.g., torque or space closure), then the recom- mended strategy is to halt treatment for a minimum of four months. Four months is the length of the human bone remodeling cycle (Roberts et al., 1990); for a month or so, osteoclast activity slowly abates, followed by a 290 SameShima three-month period of osteoblast recruitment and bone formation. Hence, after four months, the lamina dura, PDL and cementum biological- ly return to a pre-orthodontic tooth movement state. It has been shown that resuming treatment is without increased risk. The clinician must ensure that the patient and the patient's general dentist are informed fully about the reason for the delay and prognosis for completing the treatment. There presently is no pharmaceutical intervention that can help prevent EARR because as stated previously, root resorption is part of normal Orthodontic tooth movement. What do I do if I see EARR at the end of treatment? Post-treat- ment radiographs should be taken to assess root resorption; obviously, if progress radiographs showed EARR, then further progress radiographs may be beneficial. Regardless of the amount of EARR, the orthodontist must inform the patient and the patient's general dentist immediately. Fortunately, EARR ceases when active forces are halted. There is no evi- dence that EARR continues with passive retention, either fixed or remov- able. What is invasive cervical root resorption? A relatively rare type of root resorption called invasive cervical root resorption is well known to the endodontist, but is not as well known to the orthodontist. This type of root resorption is insidious and it usually is not detectable until it is too late to save the tooth. Orthodontists should be aware of this type of root resorption because in the few observational studies reported in the lit- erature, orthodontics and trauma are the two most commonly reported associated factors. The interested reader is encouraged to read the semi- nal article by Heithersay (1999). Can EARR be detected without X-rays? The current standard for assessing root length in clinical practice is good quality periapical radio- graphs. Digital panoramic radiographs (PANs) also may be acceptable for initial assessment, however, periapicals are best if risk factors are pres- ent (Sameshima and Asgarifar, 2001). CBCT images can provide detailed three-dimensional (3D) views of the root if the appropriate software is utilized (Kapila et al., 2011). For example, recent findings from 3D im- ages have shown that EARR occurs on the surfaces facing the direction of tooth movement (Prero, 2014). These 3D images also can show pre-exist- ing resorption on maxillary lateral incisors that are not visible on PANs or periapicals. Valid attempts have been made to assess markers in saliva or gingival crevicular fluid as non-ionizing methods to detect EARR early, but 291 Orthodontic Root Resorption no practical tools have emerged from these findings (George and Evans, 2009; Ramos Sde et al., 2011; Yoshizawa et al., 2013). What happens to resorbed roots in the long term? This question may be the most important one. Fortunately, there is good evidence from retrospective studies and case reports showing that there is no increased risk for tooth loss with good periodontal and occlusal health, even with severe EARR. Like all teeth with mobility at debonding, teeth with EARR will “firm up" over time. There have been reports in the literature de- scribing patients with significant EARR recalled 25 years later with stable outcomes (Remington et al., 1989; Savage and Kokich, 2002; Jönsson et al., 2007; Marques et al., 2011). There simply is no justification to replace a tooth with a short root with a dental implant, regardless of cause. CONCLUSIONS In summary, EARR is considered an unavoidable risk of orthodon- tic tooth movement. The broad spectrum of magnitude of EARR statisti- cally means that there will be teeth that unpredictably incur severe EARR. This is supported by the fact that severe EARR is relatively uncommon. 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Frazier-Bowers ABSTRACT Dental ankylosis is a histological definition for a condition that often is indistin- guishable clinically from other eruption disorders. Confusion between ankylosis and other eruption disorders, specifically Primary Failure of Eruption (PFE) can result in an inaccurate diagnosis and inappropriate orthodontic management. The current understanding of tooth eruption is surprisingly poor, as is our knowl- edge of many of the conditions in which this process is impaired. Dental ankylo- SiS is illustrative of the gaps in our current knowledge of tooth eruption and its related pathology. In this chapter, we review dental ankylosis as a distinct pathology com- pared to PFE and other eruption disorders. More specifically, we explore and delineate the factors known to be involved in ankylosis from a clinical, histologi- cal and molecular perspective using human and animal models. We purport that future studies that compare dental ankylosis with other eruption disorders (e.g., PFE) at a molecular and genetic level will make it possible to establish whether these conditions are distinct and unrelated completely or part of a wider spec- trum of aberrant physiology. Furthermore, a greater understanding of the differ- ences and similarities between distinct eruption disorder, as well as the mecha- nisms that give rise to them, will lead to improved diagnosis in terms of sensi- tivity and accuracy, resulting in better-informed clinical decisions and improved outcomes for all patients. KEY WORDS: ankylosis, primary failure of eruption, infra-occluded tooth, emergence TOOTH ERUPTION AND ERUPTION DISORDERS Tooth eruption is the developmental process behind the move- ment of a dental unit from the crypt where it forms, across the bone of 297 Tooth Eruption Disorders the jaws and into the oral cavity, toward its place across a functional oc- cluding counterpart (Suri et al., 2004). Some clinicians use the term erup- tion to refer to the appearance of a tooth in the oral cavity, but a more accurate term for this developmental milestone is emergence or moment of eruption. It has been noted that using the terms eruption and emer- gence interchangeably is sub-optimal as it does not preserve their more specific and separate meanings (Suri et al., 2004), while pointing out that tooth eruption in the true sense of the word is without a doubt a complex process, involving many tissues and cell types that are coordinated with precision and specificity in time and space. The downside of this com- plexity, however, is that it presents many elements and mechanisms that have the potential to go awry. A functional occlusion may not be main- tained without proper eruption of the teeth, which is why this process is an area of study of utmost importance not only to orthodontics, but also to all of dentistry. Based on population studies, there are expected timelines for teeth both to erupt and emerge during human growth and development, either from a perspective of chronological age or from the viewpoint of cell and tissue development. Many different conditions and phenomena have the potential to cause a deviation from the expected timelines in tooth eruption, but in spite of their extensive study, the nature of the forces behind dental eruption is still a controversial topic. Furthermore, the variety of conditions that may result in delayed tooth eruption is vast indeed and ranges from systemic conditions that affect all of the denti- tion and even other organ systems as well to localized elements that af- fect only one dental unit at a time. Conditions that affect the eruption of all teeth can affect their development, size, shape, structure and color when they are syndromic; such is the case with dentinogenesis imper- fecta, amelogenesis imperfecta and dentinal dysplasia. Compared to the general population, malnutrition, Downs Syndrome and hypopituitarism also can result in teeth having shorter roots than expected when they erupt (Suri et al., 2004). Our tacit understanding of localized elements that can result in physical obstruction of dental eruption include super- numerary teeth, tumors of either odontogenic or non-odontogenic ori- gin, cysts, Scar tissue, Secondary trauma or Surgical procedures and gin- gival fibromatosis. The current understanding of tooth eruption still is surprisingly poor, as is our knowledge of many of the conditions in which this process is impaired (Suri et al., 2004). Dental ankylosis is an illustra- 298 Senties-Ramirez and Frazier-Bowers tive example of the gaps in our current knowledge regarding to tooth eruption and its related pathology. Dental ankylosis is a phenomenon that was described early in the literature when Noyes (1932) referred to primary teeth that appeared to be "sinking into the tissues.” Normal and healthy teeth are in a state of Continual eruption and any cessation of this movement can be considered abnormal (Biederman, 1962). In ankylosis, the cementum of the affected tooth becomes fused with alveolar bone (Bert et al., 2012). A tooth may become ankylosed along any part of its root (Biederman, 1956). As teeth adjacent to one that is ankylosed retain their eruption potential and keep erupting over time, the ankylosed tooth progressively becomes apical to the plane of occlusion, giving the appearance of “sinking into bone” (Sil- ver, 1951). Not only can ankylosis lead to a tooth that is infra-occluded, but it also can be detrimental to the development of the alveolar process (Silver, 1951). Although this condition was observed in many patients in the early 20th century, limitations in the diagnostic aides and laboratory techniques of those days narrowed the scope and depth of studies that Could be carried out in an attempt to elucidate its causes and pathological process. Early research on dental ankylosis provided better information on its incidence and clinical presentation, while theories on its etiology were more speculative in nature. ANKYLOSIS: A DIAGNOSTIC CHALLENGE One of the complications in gathering data during clinical studies of dental ankylosis is that the condition can be challenging to detect and diagnose correctly compared to other causes of delayed tooth eruption (Frazier-Bowers et al., 2010). The methods most relied upon by dental professionals to diagnose this condition in a clinical setting are percus- Sion and mobility tests, as well as radiographic examination (Andreasen, 1975). Ankylosed teeth are thought to lack any mobility due to the fusion of their root surface with the surrounding bone and to produce a clear and high-pitched noise, which in healthy teeth would be dampened by the periodontal ligament (PDL; Bertl et al., 2012). The percussion, mobil- ity and radiographic methods, however, provide no histological assess- ment of the relationship between the root surface of a tooth and its sur- rounding bone. Andersson and colleagues (1984) contrasted these three Widely-used clinical methods with a subsequent histological analysis in a 299 Tooth Eruption Disorders monkey animal model by examining incisors that were extracted and re- planted experimentally. They found that in order for a tooth to present abnormal mobility and sound on tapping consistently, ankylosis must affect more than 20% of its root surface. These abnormal results were observed approximately 50% of the time in teeth that have an affected root surface that is between 10–20% of the total; teeth with an affected surface of less than 10% of the total showed no clinical difference with unaffected teeth. Diagnosis of dental ankylosis based on radiological evaluations can be even more problematic. When ankylosis is present at the buccal or lingual surfaces of the dental root, it is not evident radiologically; it can be detected by that method only if it is present on the proximal surfaces of the tooth, giving rise to many false negatives (Andersson et al., 1984). Furthermore, it has been observed that a thin layer of bone on the root surface can be linked to the surrounding alveolar bone by thin trabeculae and give the appearance of a PDL in a radiograph, which contributes to false negatives even when the condition affects proximal root surfaces (Andersson et al., 1984). Resonance frequency analysis (RFA) has been proposed as a new diagnostic tool for dental ankylosis (Bertl et al., 2012). This technique is used most often as a measure of stability in dental implants by measur- ing the implant-to-bone interface based on resonance frequencies during oscillations exerted into the implant and bone contact point (Meredith et al., 1996; Turkyilmaz et al., 2006; Bertl et al., 2012). Although initial studies suggest that RFA might provide greater sensitivity than more tra- ditional methods in the diagnosis of dental ankylosis, more testing will have to take place before it is implemented widely. The practicality and economic feasibility of using this technique and the equipment it requires in a private orthodontic office is not clear yet throughout the literature. For a conclusive diagnosis of dental ankylosis, histological examination of a specimen removed from the oral cavity remains the diagnostic gold standard. ANKYLOSIS: INCIDENCE AND CLINICAL PRESENTATION Despite the diagnostic challenge that dental ankylosis repre- sents, reports in the literature in the mid 1950s described the growing knowledge regarding the epidemiological factors of this condition in its 300 Senties-Ramirez and Frazier-Bowers different clinical presentations. Biederman (1956) identified the prima- ry second molar as the dental unit that was affected most often, even though the condition could be observed in both permanent and decidu- ous dentition. His work illustrated that dental ankylosis was a selective Condition with regard to its onset during dental development and the lo- cation of the dental units it affected. By comparing 119 patients who pre- sented with two ankylosed deciduous second molars each, he statistically determined that the clinical presentation of dental ankylosis followed a discreet pattern that was not random. Further, it was shown that the con- dition occurred in the teeth of the mandible more than 2x as frequently as the teeth of the maxillary arch and that more than 90% of the affected teeth were either first or second primary molars. This body of work also laid an early foundation toward elucidat- ing the pathophysiology of dental ankylosis through his observation that the condition being present in one dental unit did not correlate with its occluding Counterpart being affected as well, thus undermining the early theory that dental ankylosis was caused by traumatic or heavy occlusal forces (Biederman, 1956). As an alternative theory, it was postulated that dental ankylosis probably was caused by “some metabolic disturbance of a local character.” This theory was expanded six years later to contrast dental ankylosis with the natural dental eruption process and character- ize it as pathology (Biederman, 1962). Ankylosed teeth were contrasted with impacted teeth by pointing out how the latter retain their eruption potential and can continue to progress into the oral cavity and occlusal plane once mechanical obstructions are removed from their eruption path, while ankylosed teeth do not have an eruption potential any longer and will not emerge into the oral cavity or occlusal plane once mechani- cal obstacles are cleared from their path. The body of literature available by that time confirmed his earlier observations that dental ankylosis was Specific with respect to its location in the oral cavity, with nearly all af- fected teeth being primary or permanent molars and mandibular teeth being represented more than 2x as often as maxillary teeth. Additionally, this phenomenon appeared to be specific with respect to time of onset Since deciduous teeth were represented over permanent teeth by a ratio greater than 10:1. Two different presentations have been reported in the roots of teeth with dental ankylosis (Andersson et al., 1984). In some cases, resorption 301 Tooth Eruption Disorders of cementum and dentin was observed, while there was direct deposi- tion of bone on top of cementum in the root of the ankylosed tooth in others. This group also gathered enough sources and evidence to report that ankylosis was observed as a common complication of avulsed per- manent teeth that were replanted, while Kurol (1981) reported that a familial tendency in the pattern of ankylosis of primary molars could be demonstrated. Although the epidemiology and clinical presentation of dental ankylosis has been documented well in the literature, the exact patholog- ic mechanism that gives rise to this condition remains elusive. Advances in elucidating its pathological process are discussed next. ETIOLOGY OF ANKYLOSIS: ANIMAL STUDIES Although theories have been offered to explain the biologic pro- cess that leads to dental ankylosis, its mechanism has never been dem- onstrated (Biederman, 1962; Andersson et al., 1984). Dental ankylosis, being the fusion of the tooth cementum with bone, may not occur as long as the PDL of the tooth is intact (Regezi et al., 2008). Biederman (1956) was among the first to speculate that ankylosis could be caused ei- ther by an incompletely developed PDL or by its partial local ossification. He further hypothesized that a disturbed local metabolism would cause an alteration of the periodontal membrane and lead to the fusion of the surrounding bone with the tooth's cementum by way of lysis of the mem- brane. His work also showed that dental ankylosis was not likely to have a systemic cause, since the dental units all were not affected equally, nor did the condition present itself at the same rate throughout dental devel- opment. During the middle of the 20th century, Biederman reported that traumatic occlusal forces might be a causative factor for ankylosis, but he observed that most of the time, the affected teeth were not in occlusion with each other in patients who displayed multiple ankylosed teeth. Fur- thermore, he pointed out that although molars are subjected to greater occlusal forces and suffer from ankylosis at a greater rate than other types of dental units, the occlusal forces in an adult's permanent dentition are much greater than those that deciduous teeth experience in a primary or mixed dentition patient. The fact that dental ankylosis occurs in pri- mary molars at 10x the rate of permanent molars suggests that traumat- ic occlusal forces are not a significant etiologic factor (Biederman, 1962). 302 Senties-Ramirez and Frazier-Bowers An alternative hypothesis that has been offered is that a congeni- tal or genetic gap in the periodontal membrane of some patients not only may lead to dental ankylosis (Biederman, 1962), but also would account for the familial tendency in its development as reported by Kurol (1981). Sharawy and coworkers (1968) implicated genetic factors in addition to environmental insults when describing and analyzing dental ankylosis that was produced experimentally using a rat animal model. Biederman's theory of “arrhythmic metabolism” (1962) postulat- ed that as a tooth erupts, there are alternate phases of local resorption and deposition of bone on one side of the PDL and of cementum on the other side, which allows for adjustment of Sharpey fibers along the root Surface while the PDL remains intact. Under normal circumstances, the PDL disappears after the roots of a deciduous tooth are resorbed, but if the PDL disappears or is not continuous any longer before root resorp- tion, then cementum and bone can come into contact, leading to dental ankylosis. ETIOLOGY OF DENTAL ANKYLOSIS USING ANIMAL MODELS Further inroads toward the elucidation of the pathophysiology of dental ankylosis resulted from a primate (monkey) model where an- kylosis was re-created experimentally through dental extractions and re-implantations (Andersson et al., 1984). After carrying out histological examinations, they further subdivided dental ankylosis into two distinct Categories: the majority in which ankylosis had been preceded by resorp- tion of both cementum and dentine, and no cementum was found at the ankylosed site; and a smaller subset in which apposition of bone on the Cemental surface had occurred without previous resorption of the ce- mentum. They found the latter type to be more common along the apical part of the root surface. Rubin and colleagues (1984) also employed a monkey animal model in order to stimulate dental ankylosis experimen- tally in deciduous teeth. In their study, five different methods were used in an attempt to create dental ankylosis in four separate animal subjects: 1. One had its PDL surgically exposed and injured with a periodontal curette (mechanical periodontal trauma); 2. A second had one tooth subjected to chemical trauma (using phenol) at the PDL following surgical exposure, 303 Tooth Eruption Disorders while a second tooth was denuded of its PDL at the distal root using a dental bur; 3. A third received a stainless steel Crown that would contact the opposing tooth prematurely; and 4. The final subject had a tooth luxated with forceps. Follow-up histological analysis revealed that the three animals that underwent periodontal trauma, root trauma and hyperocclusion showed no evidence of dental ankylosis; wound repair resulted in new bone that still was separated from the root cementum by a thin PDL. The subject that had its tooth luxated was the only one to display histologic evidence of true ankylosis, making the case against occlusion or damage to parts of the PDL as possible etiologic factors (Rubin et al., 1984). More recently, Fujiyama and associates (2004) were able to pro- duce dental ankylosis experimentally in the rat by transecting the inferior alveolar nerve (IAN); this procedure resulted in dentoalveolar ankylosis and a decrease in width of periodontal spaces. Their findings revealed that malassez epithelium (ME) is imbedded in the PDL predominantly along the coronal root surface; after denervation, it was observed that its distribution decreasds within one week post-surgically. This reduction in ME precedes dental ankylosis along the coronal root surface by a mar- gin of approximately six weeks. No degenerative changes were reported along the apical PDL region, which is innervated densely by the IAN, sug- gesting that it is not the denervation that directly results in ankylosis, but the decrease in ME, which must have a role in maintaining the periodon- tal space, preventing alveolar bone fragments from migrating into the ce- mentum surface. Further, they postulated that the ME and cementoblasts secrete molecules to inhibit osteogenesis in the periodontal space, which suggests that the ME plays an inhibitory role in the appearance of osteo- clasts and odontoclasts in this anatomical region. They also implicated the ME in the formation of acellular cementum through epithelium to mesenchyme interactions and it is hypothesized that its absence results in lesser cementum formation, which leads to root resorption. In the ex- periments described above, the ME recovered by regeneration after the surgical denervation and the reduced periodontal spaces increased in width once again. These experiments also revealed that the ME is located predominantly on the coronal end of the PDL, which means that other mechanisms that are understood less well must play a role in maintaining 304 Senties-Ramirez and Frazier-Bowers the width of the periodontal space toward the apical end of the root Surface. Taken together, these reports make the case for a multitude of possible etiological processes resulting in dental ankylosis and/or re- placement resorption, with a compromise of the inhibitory effect of the ME playing a role in the coronal end of the root surface, while other unidentified mechanisms predominate in the apical end (Fujiyama et al., 2004). THE POSSIBLE ROLE OF GENETIC FACTORS |N DENTAL ANKYLOSIS Earlier in this chapter, we discussed how some data in eruption Studies support the secretion by cementum and the inhibitory factors of ME that prevent dental ankylosis and/or replacement resorption along the dental root surface. Muthukuru (2003) described how the tissues of the PDL also contain progenitor cells that are capable of forming bone, ce- mentum and PDL connective tissue matrix, as well as endogenous growth factors that facilitate tissue homeostasis. Some of those endogenous growth factors are bone morphogenetic proteins (BMPs), molecules that facilitate periodontal bone regeneration, but also have been implicated in causing ankylosis and root resorption. BMPs are a group of approxi- mately 20 distinct proteins belonging to the superfamily of transforming growth factor-3 (TGF-3). They play critical parts in cardiac, neural and Cartilage development and one of their main functions is to induce plu- ripotent cells to commit to the osteoblastic lineage and form new bone. Because of their ability to stimulate intramembranous bone formation, BMPs are of interest in periodontal bone regeneration (Kobayashi et al., 1999); research has shown, however, that their use could result in tooth ankylosis and root resorption (King and Hughes, 1999). There is evidence in the literature that BMPs induce apoptosis in progenitor cells (Muthu- kuru, 2013). Specifically, the progenitor cells of the PDL were found to be 10x more cytotoxic when exposed to BMP-2 compared to osteoblasts. It was postulated further that disruption of PDL homeostasis by BMP- induced apoptosis could play a role in dental ankylosis. Together with BMP-2, other members of this cytokine family (e.g., BMP-4 and BMP-6) have been reported to have high osteoinductive potential, influencing regeneration and healing of bone (Sakou, 1998; Shen et al., 2004), bone formation (Kugimiya et al., 2005; Wan and Cao, 2005) and odontogen- esis (Botchkarev, 2003; ProCuest, 2016). The precise roles that these 305 Tooth Eruption Disorders cytokines may or may not play during dental ankylosis are an active area of research where much remains to be learned. The receptor activator of nuclear factor-kappa-3 (RANK) is a membrane-bound receptor that has been identified in many tissues of the human body (e.g., muscle, liver, brain, kidney, lung and trabecular bone; Anderson et al., 1997). RANK is activated by binding to RANK-li- gand, also known as RANKL and osteoclast differentiation factor, resulting in osteoclastic differentiation and activation (Lacey et al., 1998). Some authors have proposed that altered expression of RANKL may be related to or even play a key role in root resorption during orthodontic tooth movement (Boyle et al., 2003). Additionally, mice with a compromised RANKL gene have been shown to have severe osteopetrosis and defects in tooth eruption by Kong and associates (1999). Finally, although the precise etiology of dental ankylosis within the larger spectrum of erup- tion disorders remains unclear, the involvement of BMPs and RANKL in the homeostasis and remodeling of bone, as well as their possible link to dental root resorption, make them ideal subjects to study in order to confirm or rule out their relevance in the etiology of dental ankylosis. PRIMARY FAILURE OF ERUPTION AND ITS POSSIBLE RELATION TO DENTAL ANKYLOSIS Primary failure of eruption (PFE) was first described in the litera- ture by Proffit and Vig (1981) and its subcategories have been character- ized since in the literature (Rhoads et al., 2013). These subcategories, or types, are defined in terms of timing of onset and presentation. Type PFE is characterized by a progressive posterior open bite. In Type | PFE, all teeth distal to the most mesial infra-occluded tooth are affected and do not erupt into occlusion. Type || PFE, on the other hand, displays greater eruption as compared to Type I, yet it still is inadequate for the more dis- tal teeth (e.g., second molars; Rhoads et al., 2013). Clinical signs common to PFE and ankylosis include supracrestal position of the affected teeth and involvement of the first permanent molar (Rhoads et al., 2013). Although they reported that teeth with PFE present with anomalies in their eruption mechanism, they do not display fusion of cementum to bone, as is the case in ankylosis. Furthermore, this group also reported observations that in ankylosis, the affected tooth is confined to only one dental arch, while in PFE, 74% of the patients are 306 Senties-Ramirez and Frazier-Bowers affected in both arches. The above studies also have discussed that with- out knowledge of prior trauma, treatment history of the tooth, damage to the PDL, or genetic mutations, PFE and ankylosis might be indistin- guishable clinically (Figs. 1 and 2). PFE has been described as predominantly affecting posterior teeth. Moreover, the defect in eruption caused by PFE manifests as a lat- eral open bite and the teeth affected by it did not respond to orthodon- tic treatment. Studies by this same group have shown that some cases of eruption failure as caused by a genetic mutation. Specifically, genetic mutations in one gene, PTH1R, have been associated with PFE and 10- 40% of cases have a familial component (Rhoads et al., 2013). Those genetic mutations identified include, but are not limited to, missense, Substitution and intron-skipping mutations (Decker et al., 2008; Frazier- Bowers et al., 2010, 2014). A mutation was identified that revealed PFE in the deciduous dentition (Rhoads et al., 2013). Although a mutation in PTH1R confirms a diagnosis of PFE, a lack of it is not definitive in ruling out this diagnosis, as PFE is believed to be caused by more than one gene since PFE cases were identified without a causative mutation in PTH1R (Frazier- Bowers et al., 2010). Recent genotype:phenotype studies revealed that the hallmark features of PFE that provide a definitive diagnosis include: 1. Involvement of the first permanent molar; 2. Supracrestal presentation of the affected teeth; and 3. A posterior lateral open bite. Provided that other alternative causes for it are ruled out (e.g., mechani- cal failure of eruption or skeletal discrepancies), these diagnostic crite- ria serve as a definitive clinical rubric. Other clinical hallmarks associated with a mutation in PTH1R are involvement of the second premolar and the second molar, multiple adjacent teeth affected, supracrestal presen- tation of the infra-occluded teeth, bilateral presentation, involvement of teeth in both the maxilla and the mandible, frequent Class Ill maloc- clusion and a high prevalence of concurrent dental anomalies (Frazier- Bowers et al., 2007). Definitive diagnosis of PFE currently is made through the identi- fication of a mutation in the PTH1R gene, which has been shown to be Consistent largely with the diagnosis of PFE based on clinical parameters. Gaining a deeper understanding of the relationship between ankylosis and PFE has the potential to impact the treatment decision process in 307 Tooth Eruption Disorders TYPE I Ankylosis Primary failure of eruption (PFE) TYPE II Figure 1. Graphical representation of PFE and ankylosis. Both PFE and ankylosis involve an infra-occluded tooth or infra-occluded teeth, but Type || PFE is char- acterized by a tooth distal to the affected first molar that has a greater eruption potential than the affected first molar. Both present P F E De nt a | "..." An kylosis Cancause isolated evidence - "..., ofteeth mobile in º Cementum IS with continuous Socket during fused to bone archwire Suſgeſy • Cause is not ..". * Genetic defect s known toºth might lead likely – proven in to ankylosis SOſſie C2S6S Figure 2. A Venn diagram summary shows the overlap of PFE and ankylosis. orthodontics. Ankylosis can be treated successfully by extraction of the ankylosed tooth and subsequent orthodontic movement of all other teeth. This is in contrast to patients suffering from PFE, who have moſt 308 Senties-Ramirez and Frazier-Bowers limited treatment options at their disposal, including small segmental Osteotomies and prosthetic restorations of the occlusion. For a patient suffering from PFE, orthodontic treatment with a continuous archwire results in exacerbation of the lateral open bite by intrusion of the adja- cent teeth and, frequently, ankylosis of the affected teeth—regardless of whether or not the most affected of them—are extracted (Frazier-Bowers et al., 2010). Unlike cases of ankylosis, no treatment or limited esthetic treatment often is the best option for patients suffering from PFE. Cases of PFE that are misdiagnosed and treated with a continuous archwire can lead to an inferior occlusal end result, leaving the patient in worse con- dition compared to the start of treatment. Investigating the clinical and molecular differences or similarities between dental ankylosis and PFE Will form the basis of future genetic tests that will improve the diagnosis and clinical management of the two conditions. CONCLUSIONS Dental ankylosis has been reported in the scientific literature Since the early 20th century. The clinical presentation and epidemiology of this phenomenon were documented and characterized early on de- Spite the difficulties in diagnosis and given similarities to other cases of delayed tooth eruption. Such diagnostic difficulties persist currently and even with advances in genetics, radiology and other imaging techniques, dental professionals are forced to rely on methods that present limited Sensitivity and significant subjectivity. New approaches to diagnose the Condition are being explored, but they still are in the nascent stages of development conceptually and technically. Advances in biochemistry and molecular biology have led to the elucidation of many physiological pathways with regard to metabolism, remodeling and repair in the tissues of the alveolar bone, PDL and dental root surface. Progress in these areas provides multiple opportunities of investigation for the possible factors that play a role in the pathological process leading to dental ankylosis, a condition whose etiology is not un- derstood completely to this day. By comparing dental ankylosis with other eruption disorders (e.g., PFE) at a molecular and genetic level, it will be possible to establish Whether these conditions are distinct and unrelated completely or part of a wider spectrum of aberrant physiology. 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Biochem Biophys Res Commun 2005;328(3):651-657. p 313 314 THE TRUTH ABOUT WHITE SPOT LESIONS: ETIOLOGY, PREVENTION AND MANAGEMENT Eser Tüfekçi and Steven J. Lindauer ABSTRACT Enamel demineralization around fixed appliances is a common sequela associ- ated with orthodontic treatment. In the presence of fixed appliances, there is an increase in the number of plaque retention sites and it becomes more difficult to maintain optimal oral hygiene. Therefore, in non-compliant patients, these lesions may form as early as four weeks after bonding. The first clinical sign of enamel caries is white spot lesions (WSL), which if left untreated, may progress to cavitations. Therefore, the early diagnosis, prevention and treatment of de- mineralization is extremely important to minimize the occurrence of these le- Sions. The first line of defense in the prevention of white spots is to address the risks factors including diet and poor oral hygiene habits. Additionally, topical fluoride delivery agents in the form of varnishes and sealants may be beneficial in patients with high caries risk. If the prevention is unsuccessful and white spots are present on tooth surfaces, the esthetics may be improved with the applica- tion of microabrasion or resin infiltrant. The purpose of this chapter is to review the etiology, prevalence, prevention and post-orthodontic management of white Spot lesions. KEY WORDS: demineralization, fluoride, white spots, microabrasion, resin infiltrant INTRODUCTION The development of white spot lesions (WSLs) is a significant risk associated with orthodontic treatment in patients with poor oral hygiene. Despite the modern technology in biomaterials, prevention of deminer- alization continues to pose a great challenge to clinicians. The presence of these unaesthetic lesions may affect orthodontic treatment outcomes adversely and in some cases, WSLs may need further intervention by general dentists (Fig. 1). White spots are incipient carious lesions that 315 White Spot Lesions Figure 1. Orthodontic patient with white spot lesions (WSLs) at the end of orth- odontic treatment. The white, opaque appearance is due to the differences be: tween the light refractive index of demineralized enamel and sound enamel. develop around brackets and bands, usually near the gingival margin, due to prolonged plaque retention. In the presence of fixed appliances, it is difficult for orthodontic patients to brush and floss efficiently. In addi- tion, brackets, bands, wires and other attachments increase the number of plaque retention sites on tooth surfaces (@gaard et al., 1988a; Richter et al., 2011). Maintaining good oral hygiene during orthodontic treatment is an important factor for the prevention of WSLs. Fixed appliances in- evitably lead to the accumulation of food debris on the tooth surfaces that may turn into biofilm over time. Previous studies have shown an in- crease in the levels of acidogenic bacteria such as S. mutans in dental plaque shortly after the introduction of orthodontic appliances (Rose- bloom and Tinanoff, 1991; Lovrov et al., 2007; Tüfekçi et al., 2008). When fermentable carbohydrates are present, the pH of the plaque may drop to critical levels due to the production of the acid byproducts. Around a pH of 4.5, the demineralization process will be initiated and if the Sa: liva pH levels are sustained at these levels for a long time, carious le: sions will develop within four weeks after the bonding appointment. A WSL is the first visible sign of enamel demineralization (Žgaard et al., 1988a). These initial carious lesions are observed as subsurface ename porosities that are manifested as white opacities (Fejerskov et al., 2008). 316 Tüfekçi and Lindauer Unfortunately, if left untreated, these lesions may progress rapidly and, in Some cases, may cause cavitations on the tooth surfaces that will require restorative intervention by dentists. Since WSLS may develop during the initial months of orthodontic treatment, it is extremely important for the clinician to recognize the patients at risk early enough so that preventive measures can be taken. The prevalence of WSLS in orthodontic patients is reported to be between 23–97% (Gorelick et al., 1982; Boersma et al., 2005; Tüfekçi et al., 2011). The wide range in prevalence is attributed mainly to the differ- ences in the duration of the studies and the assessment method used. Chapman and colleagues (2010) reported that the incidence of having at least one WSL on the labial surface of the maxillary anterior teeth was 36%. In their study, the incidence of white spots in orthodontic patients was found to be 38 and 46% after six and twelve months, respectively. Furthermore, it was determined that the incidence of WSLs stayed stable for the remainder of the Orthodontic treatment. PREVENTION OF DEMINERALIZATION The most important preventive measure to reduce the develop- ment of WSLS is to implement good oral hygiene measures. Overwhelm- ing evidence supports the anti-cariogenic effect of topical fluorides. The efficacy of fluoride regimens in reducing caries during orthodontic treat- ment is documented well (Geiger et al., 1992; Benson et al., 2004, 2013). Therefore, the first line of defense against WSLs consists of brushing and rinsing with a fluoride-containing toothpaste and mouth rinse. Based on a systematic review, Benson and coworkers (2013) concluded that there was evidence to support the daily use of sodium fluoride mouth rinses and bonding of fixed appliances with glass ionomer cements, which were effective in reducing the occurrence and severity of WSLs. For example, fluoride mouth rinses with 0.05% sodium fluoride previously have been shown to reduce demineralization significantly under orthodontic bands. However, the effectiveness of preventive measures administering fluoride topically in the form of toothpaste and mouth rinse is limited because of unpredictable compliance (Geiger et al., 1992; Bishara and Ostby, 2008; ten Cate, 2013). Therefore, other fluoride delivery systems (e.g., fluoride Warnishes and sealants that do not depend on patient cooperation) may be used in non-compliant patients. * , 317 White Spot Lesions Of the current fluoride products on the market, varnishes are easy to use and do not depend on patient cooperation. Numerous stud- ies have shown that the application of fluoride varnishes can be effective in minimizing demineralization in orthodontic patients (Stecksén-Blicks et al., 2007; Farhadian et al., 2008; Benson et al., 2013; Weyant et al., 2013). Stecksén-Blicks and associates' study (2007) compared the ap- plication of a fluoride varnish every six weeks to a non-fluoride placebo varnish. In this double-blind clinical study, the regular application of the fluoride varnish every six weeks resulted in a 70% decrease in the for- mation of WSLs in patients who underwent six months of orthodontic therapy. Farhadian and colleagues' study (2008) concluded that at the end of three months of fixed appliances therapy, teeth treated with the experimental varnish exhibited a 40% decrease in lesion depth when compared to control teeth. Based on a systematic review, Benson and coworkers (2013) indicated that there is moderate evidence that fluoride varnish applied every six weeks during orthodontic treatment is effective in reducing demineralization; however, they cautioned clinicians that this finding was based on a single study. To date, the routine application of fluoride varnish seems to be an effective preventive measure to avoid WSL development in orthodontic practice. Another measure to prevent demineralization is the application of a fluoride-containing sealant to enamel surfaces prior to bracket bond- ing. Fluoride resin sealants with a high-filler content (>38%) such as Pro Seal” and Opal" Seal" have been found to be effective in minimizing the development of WSLs by providing a physical barrier that is resistant to mechanical wear (Buren et al., 2008; Van Bebber et al., 2011; Tüfekçi et al., 2014). In addition, the fluoride release from the sealant into the oral environment is thought to provide an anti-cariogenic effect. However, the amount of fluoride released from these sealants is highest on the first day, Sharply decreases on the second day and gradually decreases to un- detectable levels by the end of three months (Basdra et al., 1996). There- fore, the protective effect of these sealants may be attributed mainly to the physical barrier that they provide on tooth surfaces around brackets (Benham et al., 2009). Opal" Seal" is marketed as a fluoride releasing bonding primer with a superior fluoride recharging ability (Schemehorn, 2008, 2009). In the study by Farah and associates (2013), Opal" Seal" was shown to exhibit the ability to be recharged with fluoride ions from acidulated 318 Tüfekçi and Lindauer phosphate fluoride gel; however, the amount of released fluoride ions decreased drastically over a six-week period. Therefore, the fluoride ion rechargeability of Opal" Seal" remains questionable. The preventive ef- fect of Opal" Seal", which lasts up to three months, was demonstrated in a clinical study by Tüfekçi and coworkers (2014); however, there was no statistically significant difference in the incidence of WSLs between the teeth treated with Opal" Seal" and control teeth beyond this time point. In addition, the amount of sealant retention was determined to be around 50% at three months. The study by Knösel and colleagues (2015) found the amount of sealant retention to decrease over time, therefore the reapplication of Opal" Seal" at three month intervals was recom- mended throughout orthodontic treatment. In Booth's study (2015), where a more sophisticated measurement system was utilized, the amount of sealant retention was as high as 70-80% at the end of three months. Based on these findings, regular application of Opal" Seal" throughout orthodontic treatment—preferably every three months—is required to achieve a protective effect. In addition to fluoride gels, varnishes and sealants, casein phos- phopeptide-amorphous calcium phosphate (CPP-ACP) also has been proposed for use in high-risk orthodontic patients for its anti-cariogenic properties. CPP-ACP is a milk-derived product that is claimed to prevent caries and remineralize enamel (Elsayad et al., 2009; Somasundaram et al., 2013; Duraisamy et al., 2015). In the in vitro study by Duraisamy and associates (2015), a demineralization inhibitory effect was observed when CPP-ACP was used in conjunction with fluoride varnish; the lesion depth on enamel surfaces was less when compared to fluoride varnish or CPP application alone. The synergistic effect of the use of CPP-ACP with fluo- ride has been reported to decrease demineralization and increase rem- ineralization (Elsayad et al., 2009; Duraisamy et al., 2015). It was thought that the formation of stabilized amorphous calcium fluoride phosphate resulted in the increase of fluoride ions incorporated into plaque togeth- er with the increase in concentration of calcium and phosphate ions. In the orthodontic literature, while in vitro studies suggest a significant reduction in lesion depth on enamel surfaces treated with CPP-ACP paste (Somasundaram et al., 2013; Duraisamy et al., 2015), the Study by Sitthisettapong and colleagues (2012) does not support the ef- ficacy of this product in minimizing demineralization. They reported that 319 White Spot Lesions there was no significant added effect in preventing caries in the primary dentition of pre-school children. Future studies are needed to draw a de- finitive conclusion. In summary, there is no doubt that topical fluorides have an im- portant place in everyday orthodontic practice. Preventive protocols in- clude fluoride toothpaste, mouth rinse, gel and varnish. Based on the level of evidence following a systematic review, the American Dental AS- sociation (2013) compiled an executive summary outline providing rec- ommendations on the use of topical fluorides (Table 1). Although the recommendations were for the general patient population, they could be beneficial for high-risk orthodontic patients 6 to 18 years of age as well. Specifically, the professional application of 2.26% fluoride varnish or 1.23% fluoride gel (APF) for four minutes, at least every three to six months, was recommended as measures effective in preventing caries in patients 6 to 18 years of age. In addition, the use of 0.09% fluoride mouth rinse, at least weekly, was the recommended home-use topical fluoride agent for the same age group. It should be kept in mind, however, that the effectiveness of fluoride mouth rinses depends heavily on patient compliance; therefore, the professional application of high concentration fluoride gel and varnish should be the choice of topical agents used for high risk and non-compliant patients. POST-ORTHODONTIC MANAGEMENT OF WSLS If WSLs are present after the removal of orthodontic appliances, patients need to be informed and the most conservative approaches need to be taken. In general, there will be an improvement in the esthet- ics as the size of WSLs tends to decrease over the first six months follow- ing the debonding appointment. Although high concentration fluorides are used to prevent demineralization, their application immediately after debanding and debonding procedures is not recommended. Øgaard and associates (1988b) caution clinicians against treating WSLs with fluoride during the first several months after the removal of fixed appliances. Oth- erwise, the application of high concentration fluoride will remineralize the most superficial layer of enamel, but leave the deeper enamel crys- tals unaffected. At the end of orthodontic treatment, allowing remineralization gradually (or slowly) by saliva or low concentration fluoride toothpaste 320 Tüfekçi and Lindauer Table 1. Clinical recommendations for use of professionally applied or prescrip- tion-strength, home-use topical fluorides for caries prevention in patients at el- evated risk of developing caries. *APF = acidulated phosphate fluoride. Repro- duced from Weyant et al., 2013 with permission from Elsevier. Strength of recommendations: Each recommendation is based on the best available evidence. The level of evidence available to support each recommendation may differ. O Strong O In Favor O Weak O Expert Opinion O Expert Opinion O Against For Against Evidence Evidence Evidence suggests Evidence is lacking: Evidence is lacking: Evidence suggests not stronghy favors implementing this the kevel of certainty the level of certainty implementing this supports providing this intervention only is knw. Expert opinion is kw. Expert opinion intervention or providing intervention after alternatives guides this suggests not impkementing discontinuing ineffective this have been recommendation this intervention procedures intervention considered Age Group or Professionally Applied Topical Fluoride Agent Prescription-Strength, Home-Use Topical Dentition Fluoride Agent Affected Younger Than 2.26% fluoride varnish at least every three to six 6 Years months O In Favor 6-18 Years 2.26% fluoride varnish at least every three to six 0.09% fluoride mouthrinse at least weekly months O In Favor O In Favor OR OR 1.23% fluoride (APF") gel for four minutes at least 0.5% fluoride gel or paste twice daily every three to six months O In Favor O Expert Opinion For Older Than 2.26% fluoride varnish at least every three to six 0.09% fluoride mouthrinse at least weekly 18 Years months O Expert Opinion For O Expert Opinion For OR OR 1.23% fluoride (APP) gel for four minutes at least 0.5% fluoride gel or paste twice daily every three to six months O Expert Opinion For O Expert Opinion For Adult Root 2.26% fluoride varnish at least every three to six 0.09%fluoride mouthrinse at least weekly Caries months O Expert Opinion For O Expert Opinion For OR OR 1.23% fluoride (APF") gel for four minutes at least 0.5% fluoride gel or paste twice daily every three to six months O Expert Opinion For O Expert Opinion For is the recommended course to take. The healing effect of low levels of fluoride ions in saliva also was reported by ten Cate and Featherstone (1991). According to these authors (1991, 2013), even sub-ppm levels of available fluoride ions have been shown to be effective to initiate remineralization and to inhibit demineralization of enamel and dentin. In van der Veen and coworkers' study (2007), patients who had devel- oped WSLs during orthodontic treatment were followed for six months after the removal of brackets. About 20% of the lesions showed some im- provement after six weeks and a further regression in size was observed 321 White Spot Lesions six months following debonding. The majority of the lesions (50%) re- mained stable and approximately 1% needed restoration. Studies on the effects of post-orthodontic application of CPP-ACP to WSLs report conflicting results. For example, while Akin and Basciftci (2012) concluded that CPP-ACP is more beneficial than fluoride rinse for post-orthodontic remineralization, Huang and associates (2013) conduct- ed a randomized controlled trial and found that there was no difference in the effectiveness of MI Paste Plus and standard oral hygiene for im- provement of the appearance of WSLs. Therefore, with little information and lack of evidence in the literature, it can be concluded that the ben- efits of CPP-ACP are yet to be proven. Another method for improving the esthetics of WSLs after the removal of fixed appliances is the performance of microabrasion. This technique consists of repeated applications of a slurry of pumice and 18% hydrochloric acid (Croll, 1989). The success of microabrasion in improving the cosmetic appearance of post-orthodontic lesions is attributed main- ly to the removal of discolored and unhealthy enamel (Murphy et al., 2007; Pliska et al., 2012). According to several in vitro studies (Croll, 1989; Murphy et al., 2007; Akin and Basciftci, 2012; Pliska et al., 2012), micro- abrasion is found to reduce visible enamel demineralization significantly. However, the success of microabrasion depends on the lesion depth; it is possible to improve the esthetics of post-orthodontic lesions if the le- sions are less than 0.3 mm in depth. As another method to improve the appearance of white spots, resin infiltration is the application of low viscosity resin onto the po- rous enamel surface. Resin infiltration is a novel, minimally-invasive ap- proach for masking post-orthodontic lesions (Glazer, 2009). The white appearance of the demineralized enamel results due to the difference in the light refraction index of porous enamel (n = 1.0–1.33) compared to healthy enamel (n = 1.62). Demineralized tooth surfaces, therefore, ap- pear as white, opaque lesions. Following resin infiltration, the voids are filled with this material rather than air or water. The procedure results in a refractive index (n = 1.52) that is similar to that of healthy enamel and the lesion is no longer white in appearance (Glazer, 2009). Despite limited data on the efficacy of the resin infiltration technique, both in vitro and in vivo studies report successful masking of post-orthodontic lesions (Eckstein et al., 2015; Hallgren et al., 2016; Leland et al., 2016). 322 Tüfekçi and Lindauer Furthermore, studies on the color stability of the resin infiltrant suggest that it is stable for twelve months after application (Eckstein et al., 2015; Hallgren et al., 2016; Leland et al., 2016). Although lesions treated with resin infiltrant are shown to be more susceptible to discoloration than the surrounding sound enamel, prophylaxis is able to reverse the staining (Hallgren et al., 2016; Leland et al., 2016). 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Longitudinal development of caries lesions after orthodontic treatment evaluated by quantitative light-induced fluorescence. Am J Orthod Dentofacial Orthop 2007; 131(2):223-238. Weyant RJ, Tracy SL, Anselmo TT, Beltrán-Aguilar ED, Donly KJ, Frese WA, Hujoel PP, lafolla T, Kohn W. Kumar J, Levy SM, Tinanoff N, Wright JT, Zero D, Aravamudhan K, Frantsve-Hawley J, Meyer DM; American Den- tal Association Council on Scientific Affairs Expert Panel on Topical Flu- oride Caries Preventive Agents. Topical fluoride for caries prevention: Executive summary of the updated clinical recommendations and sup- porting systematic review. J Am Dent Assoc 2013;144(11):1279–1291. 327 328 VICARIOUS LEARNING IN ORTHODONTICS: VALUE OR VALUELESSP Kelton T. Stewart ABSTRACT Vicarious learning can be defined as that which is experienced by watching, hearing about or reading about someone else, rather than by doing something yourself. Though this subject area is not discussed and researched heavily in the orthodontic literature, it is a ubiquitous learning modality within orthodontics. Vicarious learning can take many forms; however, the impact and ultimate value associated with this form of learning varies widely. By understanding better how vicarious learning influences knowledge acquisition and professional develop- ment within our profession, orthodontic professionals can filter what information they incorporate through this learning modality more selectively and ultimately determine what information they use to guide their individual professional de- velopment, as well as the overall enhancement of the orthodontic profession. KEY WORDS: vicarious learning, orthodontic education, knowledge acquisition, professional development, orthodontics INTRODUCTION The word vicarious is rooted in the Latin language and originated around 1630 from the term vicărius, which means substitute, equivalent to, interchange or alternation (dictionary.com, 2016). In contemporary language, the Merriam-Webster dictionary (2016) defines vicarious as experienced by watching, hearing about or reading about someone else, rather than by doing something yourself. The Oxford Dictionary (2016) provides a more simplistic definition of vicarious, citing that it refers to acting or doing for another. Vicarious learning—the act of learning through the experiences of another (Hoover and Giambatista, 2009)—is a fundamental part of the human learning experience and constitutes a 329 Vicarious Learning significant portion of the information humans acquire. In the late 1960s, work on vicarious learning focused primarily around pathways to fear. This research hypothesized that individuals could acquire fear of an animal, object or situation vicariously by observing another's fear of it (Rachman, 1968; Bandura, 1969). Vicarious learning was proposed as one of the possible pathways by which fears could be developed (Rach- man, 1977). With continued psychology-based research on the subject of vicarious learning, additional ideas and studies began to emerge that focused on utilizing vicarious learning to influence a person's behavior (Bektas et al., 2010) and alter student's learning abilities (Orsini et al., 2016). As with many health-based professions, orthodontics seems to utilize vicarious learning—at various levels—to advance learning and understanding among its members. The purpose of this chapter is to explore the concept of vicarious learning, discuss the impact it has on orthodontics and evaluate the potential value the orthodontic profession obtains through numerous vicarious learning Sources. HISTORY OF VICARIOUS LEARNING The concept of vicarious learning has been studied in countless settings for numerous decades. Contemporary thoughts on vicarious learning can be traced back to the Social Learning Theory developed by Canadian psychologist, Dr. Albert Bandura. Bandura's theory postulates that learning is a cognitive process that occurs in a social context (Grusec, 1992). A key component of the Social Learning Theory is that learning can occur by observing the consequences of behavior, initially coined vicari- ous reinforcement. Over time, Bandura expanded and renamed his origi- nal theory to the Social Cognitive Theory. Bandura's decision to revise his original theory was meant to stress the significant role that cognition plays in conceding and performing behaviors (Bandura, 1986). As with his earlier theory, a core pillar of his Social Cognitive Theory was that knowledge acquisition or learning by an individual occurs by observing others, with the surrounding setting, behavior and cognition as main fac- tors. Bandura's work has influenced the direction of several professional fields greatly including psychology, marketing, mass media, public health and education (Miller, 2005; Ahmed, 2009). Intuitively, one might expect there to be a significant connection between vicarious learning and education, particularly health professions 330 Stewart education. Learning by or through others is a hallmark of the health professions educational process, especially in fields like nursing, medi- cine, dentistry and orthodontics. Aspiring healthcare professionals ob- tain immense knowledge about their potential profession by observing the conduct and actions of more advanced peers, as well as their fac- ulty members. Skills and behaviors as simple as how to greet a patient to more challenging tasks (e.g., conducting effective communication with numerous other healthcare professionals during the management of an interdisciplinary case) all are gained through vicarious learning. Such a ubiquitous teaching modality typically is studied heavily and Supported by decades of investigation and research. The nursing profession has Studied the impact of vicarious learning for more than a half century; however, if one were to conduct a literature search using the keywords "vicarious learning” AND “nursing” in either PubMed or Web of Science, a total of only 14 articles would be identified. Though fewer than the numbers that one might expect, the presence of these articles do indi- cate that the nursing profession understands the importance of vicarious learning within their field and has sought to investigate how its impact can be maximized. The articles from the search appear to fall into one of two major categories: 1) studies evaluating how vicarious learning influ- ences nursing student knowledge acquisition; and 2) studies evaluating how nurses use vicarious learning to impact patient behavior in a clinical Setting. From evaluating how video clips can enhance nursing education (Herman, 2006) to how vicarious learning can influence self-efficacy and a patient’s ability to overcome psychological barriers to physical activity (Lee et al., 2008), the nursing profession has made great strides in utiliz- ing this learning modality to elevate their profession and the service they provide to their students and patients. VICARIOUS LEARNING IN DENTISTRY AND ORTHODONTICS What have been the efforts of the dental and orthodontic pro- fessions on assessing and applying vicarious learning to enhance their respective professions? Astonishingly, conducting a query in the same da- tabases with the keywords “vicarious learning” AND “dentistry” yields no results. Likewise, a query with the keywords “vicarious learning” AND “or- thodontics” in the aforementioned databases also yields no returns. How should one interpret the complete paucity of publications and/or other 331 Vicarious Learning literary works on this subject within the dental profession? One assump- tion may be that there is no relevance or impact of vicarious learning on our profession—that even with the ubiquitous nature of vicarious learning, it is a valueless process as indicated by the results of a Scientific inquiry. However, based on a review of current dental and orthodontic curricula, as well as the systems used to promote continued professional development within our profession, the author argues for a different con- clusion. The current lack of dental and orthodontic literature published on the subject of vicarious learning is not indicative of its importance or influence within our profession; rather, it simply represents an area of unexplored professional and educational investigation and research opportunity. Often, topics in orthodontics lie dormant with little inter- est and/or research activity until some event incites activity in the topic. Things such as technological advances, changes in federal funding initia- tives or modifications to accreditation standards often will stimulate new interest in topics that previously had seen little or no interest at all. With an increasing focus on student indebtedness and the efficiency of insti- tutions of higher education, the educational system may begin to place an increased emphasis on evaluating how health professional students are trained and what teaching modalities are most effective and cost ef- ficient. With such a shift, it is only a matter of time before more research is conducted and disseminated regarding several educational teaching Strategies, including vicarious learning. As we move forward and discuss how vicarious learning impacts orthodontics, it is important that we have a clear working definition. Within the context of the orthodontic profession, we will define vicarious learning as the review and acquisition of non-self-generated information for professional development. Based on this definition, the author con- tends that vicarious learning, both planned and unplanned, constitutes a key foundational component of orthodontic education. The professional knowledgebase of orthodontics, particularly the portion presented in orthodontic residency programs around the world, is the continued cul- mination of numerous individuals for well over a century. Orthodontics is so extensive and interrelated with other subjects that it would be impos- sible for individuals to teach themselves all the components necessary to manage their patients properly. Bandura (1989) noted that learning would be limited extremely if individuals learned only through personal 332 Stewart experiences. It is by assessing and integrating the work conducted by oth- er individuals that we are able to gain quickly the fundamental knowledge necessary to manage patients safely and effectively in a clinical setting. Table 1 depicts some of the many forms of vicarious learning that one might encounter at different stages of an orthodontic career. While the list is not all encompassing, it does highlight the significant role that vicarious learning plays during and after formal orthodontic training. Many forms of vicarious learning (e.g., the assessment of peer-reviewed journals and instructional videos depicting the completion of numer- ous clinical procedures) are useful information sources both during and after a formal orthodontic education process. The key point with each of these forms of vicarious learning is that another professional gener- ates the information assessed by the learner. There are exceptions that should be noted. One such example would be a clinician who begins to manage patients under his/her own supervision. The knowledge that the individual gains during independent patient care now is self-generated, rather than non-self-generated, and thus is no longer considered a form of vicarious learning. The same thought process could be applied to an in- dividual conducting original research on a topic in his/her own lab. While this individual might utilize techniques previously acquired in another researcher's lab, the new information obtained would be self-generated and again is not considered a form of vicarious learning. While examples such as these do exist, the author contends that the vast majority of initial learning in the orthodontic profession comes from some source of vicarious learning. Based on the presented information, it would appear that vicarious learning is indeed a pervasive learning modality that pos- sesses value for its learner. But the question now becomes: are all forms of vicarious learning the same? ASSESSING THE VALUE OF VICARIOUS LEARNING As with most forms of acquired information, the level of value ascribed to vicarious learning is determined by multiple factors. Elements such as the source from which the information is derived, the review pro- cess through which the information was assessed, if applicable, and the immediate or long-term applicability of the information are just a few of the considerations one must make when evaluating the usefulness of a 333 Vicarious Learning Table 1. Examples of orthodontic vicarious learning. Vicarious learning during formal orthodontic training Textbooks Peer-reviewed journal articles Faculty-guided clinical experiences Departmental case reviews Instructional videos Webinars Vicarious learning after formal orthodontic training Textbooks Peer-reviewed journal articles Study clubs ". Mini-residency programs Regional/national/international meetings Instructional videos Webinars vicarious learning source. Even by considering only these three factors, it becomes clear that not all forms of vicarious learning are equal. This Con- cept is similar to the hierarchy of evidence used to guide evidence-based clinical care of patients (Fig. 1). The concept underlying the hierarchy of evidence suggests that some forms of research provide a stronger level of evidence toward clinical decision making than others (Guyatt et al., 1995). As an example, it is not that the information gleaned from a Case series is not useful for an inquiring clinician seeking to perform evidence- based orthodontics, but that the information would be of lesser value than information obtained from a randomized controlled trial on the same subject. Both forms of information would provide helpful informa- tion, but because of the rigor and utilized study design associated with a randomized controlled trial, the perceived and potential level of Support- ing information obtained with it would be of more value. Such a System has to be developed yet to assess the perceived and/or actual value of different vicarious learning sources. This additional deficiency makes it difficult to categorize vicarious learning and subsequently select forms that yield a higher learning return. 334 Stewart Meta shalyses &systematic controlled trials Cohort studies Figure 1. Hierarchy of evidence (Guyatt et al., 2015). To initiate some method of delineation between different types of vicarious learning, the author proposes the use of a simple three-tiered hierarchy system (low, medium and high) to assess the value of vicarious learning sources (Fig. 2). This scale ranks each source of vicarious learn- ing on two primary factors: 1) the source of the information; and 2) the Context within which the information is disseminated. While a multitude of vicarious learning sources exist, three specific sources will be used to demonstrate how the assessment scale can be utilized. Peer-reviewed Orthodontic journals, “expert" presentations and company-sponsored presentations are three common forms of vicarious learning and will be the examples reviewed in the following sections. Along with the place- ment of these forms of learning on the hierarchy scale, the strengths and potential weakness of these forms of vicarious learning also will be dis- Cussed. Within orthodontics, one of the most commonly used forms of Vicarious learning is the orthodontic literature, specifically peer-reviewed journal articles. When assessed with respect to the provided ranking hi- erarchy, the author submits that peer-reviewed articles provide a high level of value and as such, lie in the highest portion of the vicarious learn- ing scale. The orthodontic profession has spent considerable time devel- oping multi-phased, critical assessment processes to review or evaluate Scientific works prior to publication. The American Journal of Orthodon- tics and Dentofacial Orthopedics (AJODO) and the Angle Orthodontists 335 Vicarious Learning * Medium Figure 2. Hierarchy of orthodontic vicarious learning sources. Vicarious learning delineation criteria: 1. Source of the vicarious learning information; 2. Context within which the vicarious learning information is disseminated. (AO) are two of the strongest and heavily reviewed literary sources in the orthodontic profession. One metric used to assess the influence of a journal is its impact factor, which is a measure of the frequency by which an average article in a journal is cited over a certain time period (NIEHS, 1995). While the 2014 impact factors for these two orthodontic journals are relatively low—AJODO: 1.382, AO: 1.225, compared to other more notable journals, Science: 33.611, Nature: 41.456 (Greenhalgh, 1997)- the information that they contain often represents the most accurate and contemporary material that an individual can use to guide his/her clini- cal and research activities. Furthermore, the processes through which published articles are selected are evolving and improving continuously. It is the combination of current information and a rigorous acceptance process that makes peer-reviewed journal articles perhaps the most valu- able of all forms of vicarious learning. There are cautions that must be considered, however, when re- viewing the literature. First, while all peer-reviewed articles undergo a high level of scrutiny prior to publication, these processes are not without fault. Periodically, articles are published that contain deficiencies in their methodology and/or yield biased results, which make it difficult for read: ers to interpret and apply the study's findings easily and meaningfully. To avoid utilizing articles that contain these limitations, readers should de- velop a certain degree of confidence and sophistication when reviewing 336 Stewart the literature. Tools are available to help individuals assess the informa- tion that they read in journal articles more critically. Dr. Trisha Greenhalgh (1997), a British professor of primary healthcare and practicing general practitioner, has written a number of articles that help individuals expand their ability to identify quality articles, decipher the material in those ar- ticles and then establish meaningful conclusions about the material. Other tools also are available to help individuals evaluate the lit- erature systematically. One such example is an article review checklist developed by Dr. Peter Buschang, Professor in Orthodontics at the Texas A&M University, Baylor College of Dentistry (Fig. 3). His checklist assesses the strength of journal articles quantitatively by having the reader assess Certain components of the article critically and then assign a numerical Score based on a pre-established scale. This tool can be helpful for identi- fying key components within an article quickly and providing an objective Score that a reader can use to assess the overall strength of an article, es- pecially readers who are less experienced with literature review. Another more significant problem that should be considered when reviewing the literature is not with the journals themselves, but with the journal in- formation users. Individuals engaging in vicarious learning through peer- reviewed articles must protect themselves from injudicious utilization of the literature. Many times, readers review the literature not to seek the truth, but to confirm their own biases and preconceived notions. When this occurs, a reader will select and embrace material that supports his/ her current stance or understanding on a topic, while ignoring or refut- ing material that opposes his/her position. This is a dangerous approach toward professional development: it can lead to radically warped profes- Sional perspectives and ultimately create clinical or research processes that are ineffective or even harmful. Even with these potential cautions, peer-reviewed journals remain one of the highest and most fruitful forms of vicarious learning that an individual can experience. “Expert” presentations are another common form of vicarious learning utilized in orthodontics. This type of learning is one of the prima- ry educational mechanisms observed at national meetings, study clubs and even guest lecturers in university settings. These forms of presenta- tions typically include the dissemination of information from individuals more experienced or knowledgeable than the recipient(s). 337 Vicarious Learning Total point count | Title Authors - Journal 1. Was the problem stated and substantiated? Yes (1) No (0) 2. Were the research aims specified? Yes (1) No (0) 3. External Validity: Sample characteristics 8. A. Can we generalize the results; was there random sampling? Yes_(1) No L(0) B. Was the sample focused? Yes (1) No (0) C. Was the sample size adequate? ~25 (0) 225 (1) Construct validity A. Were the outcome (dependent) measures operationally defined? Yes_(1) No (0) B. Was the intervention (independent) measures adequately defined? Yes_(1) No L (0) Experimental design/Internal validity A. Control: Prospective (2) Retrospective (1) * B. Repeated measures: Cross-sectional (1) Longitudinal (2) C. What type of study was it? Causal (3) Relational (2) Descriptive (1) Literature review/expert opinion (0) D. What was the research design? case series (0), cross-sectional (1); Case-control (2), Cohort_(3), RCT (4);Self-controlled trial (4) E. Bias (accuracy of the results): The study needs to provide you with enough information about its design to assess the following: a. Within subject control? Yes (3) No (0) b. Selection bias controlled? (randomized allocation): Yes_(3) No (0) c. Operator/procedural bias controlled? (blinded): Yes_(1) No (0) d. Detection bias controlled? (blinded) Yes_(1) No (0) F. Reliability (precision of the results): (1) Selection/rejection criteria used to limit sources of variation? Very much (2) Somewhat (1) None (0) (2) Procedure(s)/operators(s) standardized? Yes_(1) No (0) (3) Examiners standardized/calibrated (inter- & intra-examiner reliability)? Yes_(1) No_(0) Statistical treatment/Conclusion validity A. Variables. Qualitative (1) Quantitative (2) B. Are descriptive statistics provided? Yes (1) No (0) C. Are the statistical comparisons appropriate? Yes_(1) No (0) Conclusions A. Do they match the stated purpose? Yes (1) No (0) B. Are they supported by the results? Yes_(1) No (0) Comments: Figure 3. Objective article review checklist (Buschang and Seale, 2016). Reprint- ed with permission of Linus Publications. Based on the previously established selection criteria, this form of vicarious learning usually carries a medium level of value. Expert 338 Stewart speakers usually possess a sufficient body of knowledge and an unbiased agenda, resulting in the distribution of knowledge for the betterment of their audience without complicating personal motives. However, a pre- senter's ability to disseminate his/her knowledge, as well as the actual breadth of his/her knowledge, can influence his/her overall effectiveness greatly as a speaker. When using expert presentations as a source of vicarious learn- ing, learners again must consider several potential problems that could impact their learning. The first possible limitation one must consider is the knowledge source utilized by the speaker. Periodically, expert speak- ers will elect to include and utilize information/evidence obtained only from their particular clinic or laboratory, while ignoring information from external sources. In this instance, it is possible that the presenter is pro- viding a partial viewpoint on a Subject and could produce a biased opinion for the audience. Learners must ensure that an expert presenter is provid- ing as broad an information base as possible or at least acknowledge that they might need to acquire additional information on a topic. Another likely concern with expert presentations is the utilization of outdated in- formation. Occasionally, expert speakers will re-package old information for new presentations over an extended period. When this occurs, the information disseminated may become less useful for addressing newly existing problems. Learners again must be conscientious about whether the information being presented is current and/or applicable to contem- porary issues. One final caution about “expert” presentations is recogniz- ing the true intent of a presenter. Unfortunately, not all expert presenters possess an unbiased agenda. When presenters have a financial stake or other conflicting interest in the information that the learners acquire, this mode of vicarious learning can become compromised and result in a low degree of value. When a potential bias or conflict is identified, learners must consider critically the usefulness of the information being dissemi- nated, a point that will be discussed further in the next section. Company-sponsored presentations are informational sessions hosted by a particular company on materials, techniques or subjects of interest to the sponsoring company. Events such as university-based lunch-n-learns, company summit meetings and company technique courses all are examples of company-sponsored presentations. This form 339 Vicarious Learning of learning also includes company-sponsored “expert” speakers, indi- viduals who speak about a company's product or technique on behalf of the company. This form of vicarious learning generally is considered to be of low value because of a critical issue: no matter the format, an inherent concern about the presentation's intent always exists. While companies provide many forms of support to the orthodontic profession (e.g., donations to universities and funding for technology advancement programs), they still function and exist as for-profit entities; as such, their primary goal is the selling of goods and services to individuals for a profit. Due to this fact, a natural conflict of interest exists because the informa- tion shared during company-sponsored presentations almost always is intended to validate the purchase of goods and/or services by clinicians. It must be emphasized that this conflict of interest does not make a com- pany representative or company sponsored “expert” speaker less knowl- edgeable about certain products or materials, neither does it make him/ her less capable of providing important information about recent events within the profession. It does, however, render that person incapable of providing clinicians with objective guidance on how best to manage their patients. When obtaining information from this source of vicarious learn- ing, all professionals should exercise extreme prejudice while receiving, reviewing and possibly utilizing their information. It is the ultimate re- sponsibility of each individual professional to ensure that he/she is using the most appropriate and evidence-based materials and techniques dur- ing the clinical management of patients. With the presented examples, it has been shown that not all vi- carious learning sources possess the same level of value. It is possible to distinguish between these forms of learning by using a simple hierarchy scale that delineates sources containing high value from those containing medium or low value. Where a particular learning source will fall in this hierarchy is based on numerous factors both within and outside of the learner's control. Until more sophisticated and useful processes are es- tablished to help distinguish different forms of vicarious learning, it is the primary role of the learner to assess the potential value and applicability of these sources for themselves. CONCLUSIONS Vicarious learning is an understudied yet pervasive and pow- erful modality of knowledge acquisition in orthodontics. The value of 340 Stewart information obtained through this modality of learning can vary widely based on the source, method of delivery and intent of the information provider. Orthodontic professionals always should exercise a sufficient degree of criticism when evaluating whether information from this mode of learning will be useful in the enhancement of their individual profes- Sional development, as well as the overall elevation of our profession. ACKNOWLEDGEMENTS I would like to thank Dr. Sunil Kapila and the organizing commit- tee of the 43rd Annual Moyers Symposium and 41st Annual International Conference on Craniofacial Research for the opportunity to participate in this program and share this information. I also would like to thank Dr. Peter Buschang for the conceptualization of the review checklist depicted in this chapter. REFERENCES Ahmed A. 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