º -- --- - --- ºffl ºffl - E::::::::::::: ºffl ºffl ºffl - ----------- ------------ --- -- --- - ------------ ---------> ---------- - ºffl -------- ######################## ºffl --~~~~ ----------- º --- º:::::::::: --------- º: º #º ----------- º: - ################# ºffl ºfflº ------------ --~~~~ ºffli ºffli --------- - º ##################### ºffli --- - - ºffl - -------- º:::::::::::::::Hº: ºffl ##########################::::::::::::::::::: - -------- -- --- --- - # É ºffl ==== -- - --- ºffli Effl º: ºffl --- º: =:# --- ------- ºffl - -º-º-º-º-º: - ºffl º: --- º: º - º:ºffl ## º ------ ---------- ºffl - --- SURGICAL ENHANCEMENT OF ORTHODONTIC TREATMENT This volume includes the proceedings of the Thirty-Sixth Annual Moyers Symposium February 28 and March 1, 2009 Ann Arbor, Michigan Editors James A. McNamara, Jr. Sunil D. Kapila Associate Editor Kristin Y. Van Riper Volume 47 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 ©2010 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 Surgical Enhancement of Orthodontic Treatment Volume 47 ISSN 0.162 7279 ISBN 0-929921-00-3 ISBN 0-929921-43-7 No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the Editor-in- Chief of the Craniofacial Growth Series or designate. CONTRIBUTORS AIRTON O. ARRUDA, Clinical Assistant Professor, Department of Orthodontics and Pediatric Dentistry, University of Michigan School of Dentistry, Ann Arbor, MI. TIZIANO BACCETTI, Research Professor, Department of Orthodontics, The University of Florence, Florence, Italy; Thomas M. Graber Visiting Scholar, Department of Orthodontics and Pediatric Dentistry, School of Dentistry, The University of Michigan, Ann Arbor, MI. SCOTT M. BEHNAN, private practice of orthodontics, Birmingham, MI. SONG CHEN, Associate Professor, Department of Orthodontics, Sichuan University West China College of Stomatology, Chengdu, Sichuan, China. R. SCOTT CONLEY, Clinical Associate Professor, Department of Orthodontics and Pediatric Dentistry, University of Michigan School of Dentistry, Ann Arbor, MI. PIERPAOLO CORTELLINI, Lecturer, Department of Orthodontics, The University of Florence, Italy. LOUIS E. COSTA II, Director, Southeastern Facial Plastic/Cosmetic Surgery Center, Charleston, SC; Clinical Professor of Facial Plastic and Reconstructive Surgery, Medical University of South Carolina, Charleston, SC. DAVID A. COVELL, JR., Associate Professor and Chair, Department of Orthodontics, Oregon Health & Science University, Portland, OR. SEAN P. EDWARDS, Assistant Professor and Residency Program Director, Oral and Maxillofacial Surgery, University of Michigan, Ann Arbor, MI; Chief, Pediatric Maxillofacial Surgery, C.S. Mott Children’s Hospital, University of Michigan Health System, Ann Arbor, MI. TAREK EL-BIALY, Associate Professor of Orthodontics and Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada. LORENZO FRANCHI, Research Professor, Department of Orthodontics, The University of Florence, Florence, Italy; Thomas M. Graber Visiting Scholar, Department of Orthodontics and Pediatric Dentistry, School of Dentistry, The University of Michigan. Ann Arbor. MI. - CARLOS GONZALEZ-CABEZAS, Director, Oral Health Research Institute, School of Dentistry, Indiana University, Indianapolis, IN; Director of Master’s Program, Preventive and Community Dentistry, School of Dentistry, Indiana University, Indianapolis, IN; Associate Professor, School of Dentistry, Indiana University, Bloomington, IN. JOHN J. GRAEBER, Private Practice, East Hanover, NJ; Visiting Lecturer, Certified Dental Laser Educator, University of Medicine and Dentistry of New Jersey, East Hanover, NJ. VERONICA GIUNTINI, Research Associate, Department of Orthodontics, The University of Florence, Florence, Italy. CHESTER S. HANDELMAN, Clinical Associate Professor, Orthodontic Department, Dental School, University of Illinois, Chicago, IL. sº JAMES K. HARTSFIELD, JR., Professor and E. Preston Hicks Endowed Chair in Orthodontics and Oral Health Research, University of Kentucky College of Dentistry, Lexington, KY; Adjunct Professor of Orthodontics and Oral Facial Genetics, Indiana University School of Dentistry, Bloomington, IN; Adjunct Professor of Medical and Molecular Genetics, Indiana University School of Medicine, Bloomington, IN. DAVID M. KIM, Assistant Professor, Department of Oral Medicine, Infection and Immunity, Division of Periodontics, Harvard School of Dental Medicine, Boston, MA. NOLEN LEVINE, Clinical Associate Professor, Orthodontic Department, Dental School, University of Illinois, Chicago, IL. ZI-JUN LIU, Department of Orthodontics, School of Dentistry, University of Washington, Seattle, WA. RAVINDRA NANDA, Head of the Division of Orthodontics and Department of Craniofacial Sciences, School of Dental Medicine, University of Connecticut, Farmington, CT. YANA NEDVETSKY, Clinical Associate Professor, Orthodontic Department, Dental School, University of Illinois, Chicago, IL. MYRON NEVINS, Clinical Associate Professor, Department of Oral Medicine, Infection and Immunity, Division of Periodontics, Harvard School of Dental Medicine, Boston, MA. MATHILDE C. PETERS, Professor, Department of Cariology, School of Dentistry, The University of Michigan, Ann Arbor, MI. GIOVANPAOLO PINI PRATO, Professor and Chair, Department of Periodontology, The University of Florence, Italy. AMY E. RICHTER, private practice of orthodontics, Buffalo, NY. DAVID M. SARVER, private practice of orthodontics, Vestavia Hills, AL; Adjunct Professor, University of North Carolina, Department of Orthodontics, Chapel Hill, NC. STEPHEN A. SCHENDEL, Professor Emeritus of Surgery, Stanford University Medical Center, Palo Alto, CA. LAUREN M. SIGLER, Research Assistant, Department of Orthodontics and Pediatric Dentistry, School of Dentistry, The University of Michigan, Ann Arbor. WOOSUNG SOHN, Assistant Professor, Department of Cariology, School of Dentistry, The University of Michigan, Ann Arbor, MI. FLAVIO URIBE, Program Director, Division of Orthodontics, Department of Craniofacial Sciences, School of Dental Medicine, University of Connecticut, Farmington, CT. ANDREA VANGELISTI, Research Fellow, Department of Orthodontics, The University of Florence, Italy. CARLOS VILLEGAS, Assistant Professor, Department of Orthodontics and Maxillofacial Surgery, University of CES, Medellin, Colombia. ROGER WISE, Private practice of periodontics and orthodontics, Swampscott, MA; Lecturer, Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA. JING ZHOU, Assistant Professor, College of Dental Medicine, Medical University of South Carolina, Charleston, SC. PREFACE The development of more sophisticated technology and the refinement of surgical techniques have led to an ever increasing array of surgical protocols that can be used to enhance orthodontic treatment outcomes. Such technologies include the use of the diode laser by the orthodontist for re-contouring the gingival and mucosal soft tissue to more extensive interventions such as guided tissue and bone regeneration and the sinus lift prior to implant placement provided by other specialty disciplines. Similarly, facial plastic and reconstructive surgery has shown a development of surgical and non-surgical protocols for improving the soft and hard tissues of the face, both of the routine orthodontic patient and of those individuals with major facial imbalances. A final type of patient, the severity of whose breathing problem now is being addressed more aggressively both surgically and non-surgically, is the obstructive sleep apnea sufferer. Current and emerging protocols for the management of these and other related problems were considered by an interdisciplinary group of expert clinicians during the 36th Annual Moyers Symposium, which was held in Rackham Auditorium on The University of Michigan campus on Saturday, February 28th and Sunday, March 1, 2009. As in previous years, the Symposium honored the late Dr. Robert E. Moyers, 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 School of Dentistry and the Center for Human Growth and Development. In addition, the 35th International Annual Conference on Craniofacial Research (the so-called “Presymposium”) was held on the Friday before the Symposium (February 27th) in the Amphitheater on the fourth floor of the Horace H. Rackham School of Graduate Studies. The Presymposium Conference featured papers relevant to orthodontics and craniofacial biology that were presented by an international group of investigators. Many of the papers dealt with the general theme of the Moyers Symposium; these topic-related papers are included within this Volume as well. Kris Van Riper was the “go-to” person involved in the day-to-day preparation of this volume. As Associate Editor of the Craniofacial Growth Series, she facilitated the publication of this book through her interactions with the authors, editing, manipulating a variety of figure formats and formatting the entire layout of the book. We thank Kris all of her hard work in producing this volume in a timely manner. We also thank Lauren Sigler, our research assistant and now freshman dental student at the University of Michigan, for her help in preparing this Volume. As Chair of the Department of Orthodontics and Pediatric Dentistry, Dr. Sunil D. Kapila has provided the financial resources to underwrite partially the publication of this book; he also served as co- editor. We also recognize Dr. Twila Tardif, the new Director of the Center for Human Growth and Development, for the continued financial and moral support of the Moyers Symposium provided by the Center. We have been fortunate to work with the Staff from the Office of Continuing ". Dental Education for organizing and running the Presymposium and Symposium. We thank Michelle Jones, Debbie Montague and Karel Barton for running both meetings in such a smooth and efficient fashion. Finally, we thank the participants of the Symposium and Presymposium and those that buy the volumes of the Craniofacial Growth Series, without whose support none of this would exist. All Volumes still in print are available online (www.needhampress.com) or by phone (734.668.6666). James A. McNamara DDS MS PhD Ann Arbor, Michigan November, 2009 FRIENDS OF THE SYMPOSIUM Gary E. Hall Thomas A. Herberger Hyeon-Shik Hwang Robert J. Isaacson ‘John O. Nord William Patchak Alwyn Wong TABLE OF CONTENTS Contributors Preface Friends of the Symposium Augmenting and Improving Esthetics through Surgical Intervention David M. Sarver Surgical Management of the Facial Soft and Hard Tissues to Enhance Facial Esthetics' Louis E. Costa II Computer-assisted Craniomaxillofacial Surgery Sean P. Edwards Laser Sharp Orthodontics John J. Graeber Treatment Resolutions for Periodontally Compromised Mandibular Molars Myron Nevins, David M. Kim Mucogingival Interceptive Surgery of Bucally Erupted Premolars in Patients Scheduled for Orthodontic Treatment Tiziano Baccetti, Pierpaolo Cortellini, Andrea Vangelisti, Giovanpaolo Pini Prato Orthodontic Treatment Options for Periodontally Compromised Patients Roger Wise, David M. Kim The Orthodontist’s Role in Dental Implant Site Maintenance and Development Chester S. Handelman, Yana Nedvetsky, Nolen Levine The Airway: Assessment of the Patient with Obstructive Sleep Apnea Stephen A. Schendel The Face of Obstructive Sleep Apnea R. Scott Conley 33 51 85 101 125 149 175 203 231 Evaluation of Finishing and Surgical Enhancement Procedures in Orthodontic Patients Relative to Changes Due to Aging: A Review Veronica Giuntini, Tiziano Baccetti, Lauren M. Sigler, Lorenzo Franchi The Importance of Analyzing Specific Genetic Factors in Facial Growth for Diagnosis and Treatment Planning James K. Hartsfield, Jr., Jing Zhou, Song Chen Effects of Surgical Tongue Volume Reduction: Outcome Measures on Function and Growth Zi-Jun Liu Recent Insights into Tooth Eruption and Future Prospects for Treating Unerupted Teeth David A. Covell, Jr. Surgically Enhancing the Speed of Tooth Movement: Can We Alter the Biology? Flavio Uribe, Carlos Villegas, Ravindra Nanda Clinical Applications of Therapeutic Ultrasound in Craniofacial Repair and Replacement Tarek El-Bialy White-Spot Lesions in Orthodontics: A Drawback of the Specialty Airton O. Arruda, Scott M. Behnan, Amy E. Richter, Mathilde C. Peters, Woosung Sohn, Carlos González- 253 267 283 309 323 345 367 Cabezas AUGMENTING AND IMPROVING ESTHETICS THROUGH SURGICAL INTERVENTION David M. Sarver ABSTRACT The term augmentation is defined as “the process by which the stages that al- ready have established treatment is accelerated or potentiated by deliberate and artificial means.” The term improvement describes “the process of making or becoming better.” This chapter reflects our experiences and subsequent tech- niques developed in the surgical arena that have had significant impact on our diagnostic perceptions and overall approach to orthodontic treatment. The clas- sical cascade of orthodontic treatment planning includes the definition of the functional goals of Angle classification, overbite and overjet. Today, we have added the esthetic components of macroesthetics (the face), miniesthetics (the smile) and microesthetics (esthetic characteristics of the teeth). This expansion of orthodontic diagnosis opens up many opportunities for treatment options that often are not considered. Numerous hard and soft tissue surgeries are available to enhance the esthetic outcome of orthodontic treatment on both “normal pa- tients” and orthognathic patients. The term augmentation is defined as “the process by which the stages that already have established treatment is accelerated or potenti- ated by deliberate and artificial means.” The term improvement is de- fined as “the process of making or becoming better.” The background leading to this chapter has been a result of our experiences and tech- niques developed in the surgical arena since 1985, which has had signifi- cant impact on our diagnostic perceptions and overall approach to ortho- dontic treatment. The classical cascade of orthodontic treatment planning includes the definition of the functional goals of Angle classification, overbite and overjet. In today’s diagnostic schemes, we have added the esthetic com- ponents of macroesthetics (the face), miniesthetics (the smile) and mi- croesthetics (esthetic characteristics of the teeth). This expansion of or- thodontic diagnosis opens up many opportunities for treatment options that often are not considered. Augmenting and Improving Esthetics The principles of contemporary treatment planning are featured by direct clinical measurement. In contrast to diagnosis based on cepha- lometric measurements, direct clinical measurement is recommended in order to gather data on patients not attainable through model analysis and cephalometric radiography (Proffit et al., 2007). The most prominent example is that of the smile, which has important components such as incisor at rest (an assessment of age characteristics of the Smile) and Smile characteristics. As general guidelines: 1. Proportions are recommended over linear measure- mentS: 2. Cephalometrics now is deemphasized as a diagnostic tool; and 3. Treatment goals are designed in four dimensions, in- cluding not only the previously described macro-, mini- and microesthetic elements of treatment, but also in the fourth dimension—time. The characteristics of the aging face and the aging smile are important criteria in treatment planning both adolescent and adult cases. SURGICAL ENHANCEMENT OF MACROESTHETIC FEATURES Figure 1 represents our suggested landmark identification for fa- cial assessment (Sarver and Jacobson, 2007). While it appears to be a daunting task to evaluate all of these relationships, as in many parts of orthodontic diagnosis, the process can be facilitated by digitization of these points. Then computer analysis can be initiated much as commonly is performed during conventional cephalometric analysis. What is impor- tant to note is that none of these measurements has great meaning in lin- ear terms, but they help us establish proportional relationships of the face in both vertical and transverse relationships. Figure 2 represents ideal nasal shape and the artistic elements that include dorsal width and form; there is no measurement for how wide the bridge of the nose should be, but its relationship with the alar width and the eyebrows is an artistic element as pictured (Anderson and Rees, 1986). Assessment of the esthetic nasal tip only requires the appli- cation of an artistic eye to determine what is appropriate. One useful guideline includes the concept that the base of the nose should have a Sarver FACIAL LANDMARKS Soft tissue nasion O Inner canthus outer canthus C Zygomatic width C. Mid-dorsum Nasal tip O Alar base O Columella C. Mid-philtrum | Philtral tubercle C. Outer commissure O Gonial width O Labiomental sulcus O Midsymphysis O Trichion Figure 1. Facial landmarks suggested as a guide for assessing facial proportion- ality. “gull in flight” appearance (illustrated) and the ideal alar width should be the same as the intercanthal distance. Numerous hard and soft tissue surgeries are available to enhance the esthetic Outcome of Orthodontic treatment on both “normal” and Or- thognathic patients. These procedures include: Orthognathic surgery; Genioplasty; Rhinoplasty; Submentoplasty; Cheiloplasty (lip surgery); Blepharoplasty (eyelid surgery); and Rhytidectomy (facelift). Augmenting and Improving Esthetics Nasal form Artistic elements Figure 2. The elements of ideal nasal form include alar base width, dorsum width and the artistic features such as the continuity of the nose into the eye- brows. Any of these procedures may be considered in an overall treatment plan, more so for the adult patient than the adolescent patient. Knowledge of these procedures can become an important part of the treatment planning process, however, if the overall treatment goals include maximizing fa- cial appearance. The following patient illustrates that principle. This 12-year-old patient (Fig. 3) presented with a slightly short lower facial height and severe lip incompetence. The chief concern of both the dental referrer and the patient’s parents was improvement of his mild Class II malocclusion (Fig. 4). The initial determination of the pa- tient’s Angle classification of occlusion makes other attributes secon- dary. We suggest that the clinician consider adopting the viewpoint that orthodontic evaluation begins from the outside and works its way in. The patient’s profile was convex, which was not surprising with the Class II malocclusion (Fig. 5). Our initial clinical impression included: Sarver Figure 3. This 12-year-old patient’s facial propor- tions were characterized by short lower facial height and severe lip incompetence. Figure 4. Initial intraoral images with a Class II malocclusion. Augmenting and Improving Esthetics Figure 5. The patient’s profile was convex and the treatment decision process must include soft tissue changes anticipated with growth. - The maxilla appears to be procumbent; There appears to be a component of maxillary dental protrusion: the acute nasolabial angle is associated with maxillary dental protrusion; and, 3. The mandible also appears deficient potentially exacerbated by chin deficiency. Obviously, the patient’s profile may represent a combination of all these features (Fig. 6). Traditionally, we would use cephalometric analysis to help determine what the problems are. In today’s era of the “soft tissue paradigm,” however, the characteristics of facial maturation are impor- tant to keep in mind as the treatment planning process progresses (Sarver, 1997). From the perspective of many orthodontists, this patient would be considered bialveolar protrusive because of the lip fullness, lip incompe- tence and acute nasolabial angle. Many treatment options can be consid- ered for Class II correction. Each of these options should be evaluated in Sarver Crani al Maxilla |MX derºtoalveolus Md. dertoalveolus Mandible cºin Figure 6. Proffit’s schematic representation of an- teroposterior dentofacial relations. In this illustration, the chin itself should be considered as a separate component of the dentofacial structure. light of both the soft tissue response to the recommended dental/skeletal movements and expected maturational changes. The treatment options include: 1. 2. Extraction of the four premolars to reduce protrusion and correct the Class II dental relationship; - Extraction of maxillary first premolars to correct the Class II canine relationship and reduce overjet; Orthodontic alignment coupled with Class II elastics; and Orthodontic alignment coupled with some form of growth modification. Ultimately, how is the best treatment option decided? We rec- ommend that this decision not be paternalistic in nature (“the doctor knows best”) but rather through an interactive consultation with the par- ents outlining their choices and what soft tissue outcome would be ex- pected. In our practice, this consultation is facilitated through the use of digital imaging modification. While in the child it is not a prediction, but Augmenting and Improving Esthetics it serves as an excellent communication tool in discussing with the fam- ily what is expected with further growth and response to treatment. Figure 7 represents the final outcome that was made without tooth extraction since at age twelve we would expect dramatic soft tissue changes such as nasal growth, particularly in males (Subtelny, 1959, 1961; Fishman, 1969; Mauchamp and Sassouni, 1973; Chaconas and Bartroff, 1975; Meng et al., 1988; Genecov et al., 1990; Nanda et al., 1990; Buschang et al., 1993; Formby et al., 1994; Prahl-Andersen et al., 1995; Bishara et al., 1998; Hoffelder et al., 2007), an increase in phil- trum height (thus diminishing lip incompetence; Dickens et al., 2002) and reduced lip thickness. Figure 8 shows the final facial outcome from the frontal view. While some lip strain is still evident in the chin area, the philtrum height and lip incompetence have improved greatly, as expected. The profile at fifteen years of age (Fig. 9) reflects the expected nasal growth and lip changes. The change in nasolabial angle is a function of downward and forward growth of the nose and nasal tip along with reduction of maxil- lary lip thickness (Behrents, 1985). In the end, lip balance is excellent but the chin still is deficient. To achieve macroesthetic goals, therefore, an advancement genioplasty is recommended to complete the esthetic goals discussed in the original consultation. The final result is seen in Figure 10. Figure 7. The final intraoral relations. - Figure 9. The final profile (age 15) demonstrates the expected nasal growth and lip changes. The nasal tip is lower, there is more nasal projection and the lips are less prominent – all a result of normal soft tissue maturational changes. Sarver Figure 8. The final frontal view distinguished by bet- ter lip competence and philtrum height. Augmenting and Improving Esthetics Figure 10. At age 16, chim augmentation via inferior border osteotomy resulted in a balanced profile. Orthodontists are familiar with and comfortable recommending to their patients chin augmentation via inferior border osteotomy of the mandible; soft tissue surgery for esthetic enhancement is not discussed often with patients (Proffit et al., 2002; Sarver, 2004; Sarver and Rousso, 2004a,b; Sarver and Yanosky, 2005b). The patient shown in Figure 11 was a 40-year-old male who sought improvement both of his malocclu- sion and his smile. After 26 months of orthodontic treatment, his appli- ances were removed, resulting in nice alignment of his teeth and im- proved smile (Fig. 12). Having completed the mission of obtaining a bet- ter smile, the patient asked if anything else might enhance his appearance- 10 Sarver Figure 11. This 40-year-old male sought improve- ment of both his malocclusion and his smile. Figure 12. After orthodontic treatment, the result was nice alignment of his teeth and an improved smile. | 1 Augmenting and Improving Esthetics He liked his smile, but recognized that the aging process had resulted in hooding of his upper eyelids and fatherniation of the lower lids, what he termed “bags under his eyes” (Fig. 13). Most bags under the eyes are the result of accumulated fat in the eye; this happens when the septum sur- rounding the eyeball weakens, causing the outer layer of fat within the socket to sink forward, literally resulting in “bags” under the eyes. Pa- tients usually complain that others think they are tired when they are not. Blepharoplasty of the upper lids is treated surgically by removing excess skin. The surgical treatment of the lower eye area is designed to remove excess fat, skin and muscle around the eyes. The patient was referred to a facial plastic surgeon who performed an upper and lower blepharoplasty (eyelid surgery), resulting in significant improvement and revitalization of his esthetic presentation (Fig. 14). This enhanced appearance is an appropriate part of orthodontic discussion for the adult patient. SURGICAL ENHANCEMENT OF MINIESTHETIC FEATURES There are many features considered in attaining an ideal smile in orthodontic treatment. Our analysis and treatment of miniesthetic presen- tation is a synthesis of many different philosophies and theories of smile esthetics, but many of these attributes have been tested for the lay per- son’s perception of an ideal smile and studies appear to be validating many of the concepts. The quantitative elements of an attractive smile can be summarized as: 1. Vertical elements: comprised of the amount of gingi- Val display on Smile, gingival margins matched with the upper lip on smile and incomplete display of the anterior teeth on smile; 2. The amount upper incisor shows at rest (to give a hint as to the aging potential of a smile); Crown height; . 4. Buccal corridor as measured from the outermost den- tal component to the inner commissure; and 5. Artistic elements include assessment of the smile arc — consonant, flat and reverse. 3 As orthodontists, we think about resting lip morphology during the esthetic assessment of our patients but probably do not give it enough credit as an important esthetic element. For example, people clearly iden- 12 Sarver ºn and ºuston of a Start of treatment Figure 13. A common aging characteristic of the eyes includes “hood- ing” of the upper lids and fat accumulation around the lower part of the eyes. This picture demonstrates his eyes before and after a few years. Note the area of the pupil that becomes covered by the upper lid. Figure 14. After upper and lower lid blepharoplasty, the patient had a much more “rested” appearance. 13 Augmenting and Improving Esthetics tify full, “pouting” lips as attractive in females and thin lips with dimin- ished Vermilion as associated with aged patients. The lips should be dia- mond shaped with a clearly formed “M” at the vermilion border, also called the Cupid’s bow. In the ideal resting lip arrangement, the philtrum height generally is coincident with philtrum height, but there are accept- able variations to a degree; it also is impossible to put a standard number on how much differential is not acceptable to the patient. So what does this discussion of lip morphology have to do with the orthodontist? Lip incompetence often is ascribed to dental protrusion and while this sometimes is the case, it certainly is not the only reason. Vertical maxillary excess is another frequently recognized etiology of lips incompetence for the simple reason that the skeleton is longer than the face. A soft tissue attribute that often is not on the differential list is the short philtrum, likely because we do not think there is much we can do about it. The short philtrum is associated with lip incompetence and/or excessive gingival display on smile. The patient in Figure 15 sought consultation from her dentist for a veneer on the maxillary right central incisor. In discussing her goals of treatment, she voiced her desire to pursue a career in broadcasting. The dentist wisely backed up and looked at her entire resting and smile relations, noting that her frontal resting lip relationship was characterized by a short philtrum and lip in- competence. On smile, she showed some slightly excessive gingival dis- play, but certainly not enough for a LeFort I osteotomy. Her profile reflected a low nasal tip and slight nasal projection (Fig. 16). After discussing all these concerns with the patient, the dentist referred her to us for consultation regarding her philtrum height. While we recommended a V-Y cheiloplasty, in our experience, this correction is best performed with a rhinoplasty. The theory is that “deskeletoniza- tion” of the nose facilitates the V-Y procedure. Figure 17 illustrates the technique of the incision resembling a LeFort incision, with vertical mat- tress sutures placed in an orientation designed to redirect tissue inferi- orly. 14 Sarver Figure 15. This adult patient had lip incompetence secondary to her short philtrum. Figure 16. Her profile reflected a low nasal tip and slight nasal projection. 15 Augmenting and Improving Esthetics Figure 17. One of the techniques for surgically improving upper lip length is the V-Y cheiloplasty where the upper lip can be lengthened with horizontal and vertical incisions as shown here. After rhinoplasty and V-Y cheiloplasty, our patient achieved lip competence and better definition of the cupid’s bow of her upper lip with improved resting lip posture (Fig. 18). The profile change was signifi- cant, and considerable improvement in upper lip length and projection also was achieved (Fig. 19). 16 Sarver Figure 19. The profile reflected improvement in up- per lip length and projection, as well as improved na- sal esthetics. - Figure 18. After combined rhinoplasty and V-Y cheiloplasty, lip competence was achieved as well as better definition of the cupid’s bow of her upper lip and improved resting lip posture. 17 Augmenting and Improving Esthetics V-Y cheiloplasty can be performed as an isolated procedure, but also may be performed simultaneously in orthognathic surgery. This 22- year-old female (Fig. 20) presented with a chief complaint of a gummy smile. At rest, she had severe lip incompetence secondary to both vertical maxillary excess and a short philtrum height. The potential etiologies of the gummy Smiles include: 1. Vertical maxillary excess; Upright maxillary incisors; Short philtrum; Short crown height; and Hypermobile smile. This patient had a long lower facial height consistent with vertical maxillary excess, but the gingival display was exacerbated by the very short philtrum height. Her profile also was rather retrognathic (Fig. 21); her treat- ment plan was designed for orthodontic alignment of her teeth in preparation for surgical maxillary impaction via LeFort 1 maxillary osteotomy combined with advancement of the maxilla, mandible and the inferior border of the mandible for chin augmentation. Coupled with the hard tissue surgery, rhinoplasty combined with V-Y cheiloplasty was recommended in order to facilitate lip lengthening. The final images reflect the desired facial outcome with a shorter lower facial height increased lower facial projection (Fig. 22), improved philtrum length and profile (Fig. 23). | 8 Sarver Figure 21. Her profile was very retrognathic, and the orthodontic/surgical plan included maxillary impac- tion, mandibular advancement and advancement gen- ioplasty. Adjunctive soft tissue surgery included rhinoplasty and V-Y cheiloplasty. - Figure 20. This 22-year-old female had a long lower facial third with vertical maxillary excess. The skeletal relationship alone could result in lip incompe- tence, but she has the additional problem of a very short philtrum. 19 Augmenting and Improving Esthetics Figure 22. After completion of treatment, the patient had improved resting lips relations, with a decreased lower facial height and improved philtrum height permitting her to bring her lips together. SURGICAL ENHANCEMENT OF MICROESTHETIC FEATURES The ideal microesthetic features of inferior teeth include appro- priate height/width ratio, Zenith placement, gingival and incisal embra- sure form in terms of soft tissue, gingival shape and contour. Gingival shape refers to the two-dimensional anatomy of the gingival margin, while gingival contour refers to the three-dimensional gingival anatomy of the gingival margin (Fig. 24; Sarver, 2004). In the past six years, we have incorporated the use of diode la- sers in our practice for soft tissue contouring (Sarver and Yanosky, 2005a,b; Sarver, 2006). Almost all orthodontists feel comfortable “dust- ing off” the incisal edges of anterior teeth when finishing a case, but most of us are not to the point of looking at the gingival tissues the same way. In addition to the use of the diode laser, radiosurgery (Miles, 2007) and conventional scalpel approaches also are reasonable approaches. We have found two major applications of diode lasers in our practice. The first application is esthetic enhancement and the second is what we term “treatment management,” which includes oral hygiene is- 20 Sarver Figure 23. Her profile has improved dramatically. sues and unerupted teeth. Esthetic enhancement includes such procedures as crown lengthening for gingival display, bracket placement, improving height/width ratio, shape management and improvement of contour es- thetic issues. We will cover some examples in the rest of this chapter. Shape Management Ideal zenith placement (Fig. 25) is defined by its relationship to the long axis of the tooth, with the apex of gingival shape being placed slightly distal to the long axis of the maxillary central and canines, while coincident with each other in the lateral incisor. The patient in Figure 26 had finished orthodontic treatment and had undergone esthetic periodon- tal crown lengthening. The final outcome was characterized by very point- 21 Augmenting and Improving Esthetics Incisal contour Figure 24. Gingival shape refers to the two-dimensional anat- omy of the gingival margin, while gingival contour refers to the three-dimensional gingival anatomy of the gingival margin. edgingival shape, not the symmetrical and rounded shape that is consid- ered ideal. With the diode laser, the gingival shape was contoured to more ideal, resulting in a better smile presentation (Fig. 27). Hypertrophic Tissue at the Debonding Appointment This 11-year-old girl was treated for her Class II malocclusion over a two-year period (Fig. 28). On the day of appliance removal, her smile was moderately gummy due to hypertrophic gingival tissues (Fig. 29); she and her mother, while excited that her braces were off, were some- 22 Sarver Fººths Figure 25. Ideal gingival Zenith placement is slightly distal the long axis of the tooth on maxillary centrals and canines and coincident on the laterals. Figure 26. This patient had undergone periodontal crown lengthening after orthodontic treatment. Her gingival shape was narrow and pointed rather than rounded and symmetrical, with large interdental papilla. what disappointed in the Smile. As much as we try to encourage proper oral hygiene, this tissue response is not uncharacteristic of many of our Orthodontic patients. Not only were there esthetic issues, but also hygiene issues as well. Because the hypertrophic gingival tissues resulted in nu- merous pseudopockets, which would be difficult to clean, soft tissue re- covery would require much effort on the part of the patient and her den- tist. 23 Augmenting and Improving Esthetics Figure 27. With the diode laser, the shape and contours were reshaped to a better esthetic outcome. Figure 28. This patient was treated for a Class II malocclusion. On the day of appliance removal, her gummy Smile was slightly disappointing to her and her mother. We decided to re-contour the gingival margins with a diode laser in order to eliminate the pseudopockets and gain crown length (Fig. 30). Note the amount of gingival encroachment that was present after appli- ance removal as compared to the immediate post-operative appearance. This procedure not only improves access for proper hygiene, but because the diode laser sterilizes as it ablates the inflamed tissue, the healing process also is accelerated. An improved smile was an immediate benefit 24 Sarver Figure 29. Like many orthodontic patients who are unable to manage excellent hygiene in treatment, her gingival tissues were moderately inflamed and hyper- trophic. This condition was not just an esthetic issue, but a gingival health issue as well. Figure 30. The gingival margins were recontoured with a diode laser in order to eliminate the pseudopockets and gain crown length. (Fig. 31) as was the elimination of inflamed tissue and pocket depth. The tissue discoloration normally takes one to two days to resolve. One week after the debonding and laser procedure, the patient has a beautiful smile with healthy gingival contours (Figs. 32 and 33). 25 Augmenting and Improving Esthetics Figure 31. Immediately after the procedure, in spite of mild tissue discoloration, her smile was improved significantly and was approved by her and her mother. 26 Sarver Figure 33. The gingival condition was improved significantly and oral hygiene very manageable. Augmenting and Improving Smile Design in Treatment This 12-year-old patient (Fig. 34) had blocked-out maxillary ca- nines and treatment was directed toward making space for these teeth and bringing them down into alignment orthodontically. As a result of the extrusion on the canines, an opposite mechanical response occurred; the centrals and lateral were intruded, leaving her with a flat smile arc (Fig. 35). Assessing her Smile before finishing, it was noted that not only did she now have a flat smile arc, but the height/width ratios of the lat- eral incisors also were unfavorable, with a 1:1 ratio as compared to the ideal of 8:10. At this point, we decided to reset brackets on the incisors in or- der to extrude the four incisors for a better smile arc and incisor display. After removal of the incisor brackets, the maxillary lateral incisors were lengthened with the diode laser (Fig. 36) to attain a better height/width ratio and to allow us to reposition the lateral brackets more superiorly for their extrusion as well as to provide more space between the bracket and - Figure 32. One week later, the patient displayed a beautiful and healthy smile. 27 Augmenting and Improving Esthetics Figure 34. This patient sought treatment for blocked-out ca- nines. Figure 35. As the canines were brought down, some intrusion of the incisors was noted, resulting in decreased incisor display and a flat smile arc. The lateral incisors also were short. Figure 36. Before resetting brackets to extrude the incisors to improve the smile arc and incisor display, the lateral incisors were lengthened with a diode laser. 28 Sarver Figure 37. The resulting smile displayed all of the incisors and a consonant smile arc. the gingival margin to avoid cleaning issues. The final smile demon- strated a consonant smile arc and excellent balance of tooth display and appropriate microesthetic characteristics (Fig. 37). CONCLUSION The understanding of soft tissue dynamics is an important com- ponent of contemporary orthodontic treatment planning. The incorpora- tion of adjunctive soft tissue surgical procedures can range from rela- tively simple gingival contouring to rhinoplasty and blepharoplasty. Recognition and implementation of all the factors that might work in the patients favor can be of great benefit to patient and doctors alike. REFERENCES Anderson JR, Rees W.R. Rhinoplasty. Emphasizing the External Ap- proach. New York. Thieme Inc., 1986. Behrents RG. Growth in the Aging Craniofacial Skeleton. Monograph 17, Craniofacial Growth Series, Center for Human Growth and De- velopment, The University of Michigan, Ann Arbor, 1985. Bishara SE, Jakobsen JR, Hession TJ, Treder JE. Soft tissue profile changes from 5 to 45 years of age. Am J Orthod Dentofacial Orthop 1998; 114:698–706. Buschang PH, De La Cruz R, Viazis AD, Demirjian A. Longitudinal shape changes of the nasal dorsum. Am J Orthod Dentofacial Orthop 1993; 104:539-543. 29 Augmenting and Improving Esthetics Chaconas SJ, Bartroff JD. Prediction of normal soft tissue facial changes. Angle Orthod 1975;45:12-25. Dickens S, Sarver DM, Proffit WR. The dynamics of the maxillary inci- sor and the upper lip: A cross-sectional study of resting and smile hard tissue characteristics. World J Orthod 2002:3:313–320. Fishman LS. A longitudinal cephalometric study of the normal cranio- facial profile, utilizing a proportional analysis of skeletal, soft tissue, and dental Structures. Int Dent J 1969; 19:35 l–379. Formby WA, Nanda RS, Currier GF. Longitudinal changes in the adult facial profile. Am J Orthod Dentofacial Orthop 1994; 105:464–476. Genecov J, Sinclair P, Dechow P. Development of nose and soft tissue profile. Angle Orthod 1990;60:191-198. Hoffelder LB, Lima EMS, Martinelli FL, Bolognese AM. Soft-tissue changes during facial growth in skeletal Class II individuals. Am J Orthod Dentofacial Orthop 2007;131:490–495. Mauchamp O, Sassouni V. Growth and prediction of the skeletal and soft tissue profiles. Am J Orthod 1973;64:83-94. Meng HP, Goorhuis J, Kapila S, Nanda RS. Growth changes in the nasal profile from 7 to 18 years of age. Am J Orthod Dentofacial Orthop 1988;94:317-326. Miles PG. Electrosurgery: An alternative to laser surgery in orthodontics. J Clin Orthod 2007;41:222-223. - Nanda RS, Meng H, Kapila S, Goorhuis J. Growth changes in the soft tissue facial profile. Angle Orthod 1990;60:177-190. Prahl-Andersen B, Ligthelm-Bakker AS, Wattel E, Nanda R. Adolescent growth changes in soft tissue profile. Am J Orthod Dentofacial Or- thop 1995;107:476-483. Proffit WR, Fields HW Jr, Sarver DM. Contemporary Orthodontics. 4th ed. St Louis: Mosby 2007. Proffit WR, White RP, Sarver DM. Contemporary Treatment of Dento- facial Deformity. St Louis: Mosby 2002. Sarver DM. Esthetic Orthodontics and Orthognathic Surgery. St Louis: Mosby 1997. Sarver DM. Principles of cosmetic dentistry in orthodontics: Part 1. Shape and proportionality of anterior teeth. Am J Orthod Dentofacial Orthop 2004;126:749-753. 30 Sarver Sarver DM. The use of the 810 nm diode laser: Soft tissue management and orthodontic applications of innovative technology. Pract Proced Aesthet Dent 2006; 18:S7-S13. Sarver DM, Jacobson RS. The aesthetic dentofacial analysis. In: Patel PK, ed. Clinics in Plastic Surgery. St Louis: Elsevier Inc., 2007:34: 369-394. Sarver DM, Rousso DR. Facial plastic surgical procedures combined with orthodontic/orthognathic procedures. Am J Orthod Dentofacial Orthop 2004a: 126:305-307. Sarver DM, Rousso DR. Surgical procedures to improve esthetics in cases where orthognathic surgery is not an option. Am J Orthod Dentofacial Orthop 2004b;127:299-301. Sarver DM, Yanosky MR. Principles of cosmetic dentistry in orthodon- tics. Part 2. Soft tissue laser technology and cosmetic gingival con- touring. Am J Orthod Dentofacial Orthop 2005a;127:85–90. Sarver DM, Yanosky MR. Principles of cosmetic dentistry in orthodon- tics. Part 3. Laser treatments for tooth eruption and soft tissue prob- lems. Am J Orthod Dentofacial Orthop 2005b;127:262-264. Subtelny JD. A longitudinal study of soft tissue facial structures and their profile characteristics defined in relation to underlying skeletal struc- tures. Am J Orthod 1959;45:381-507. Subtelny J. The soft tissue profile, growth and treatment changes. Angle Orthod 1961:31:105-122. 31 32 SURGICAL MANAGEMENT OF THE FACIAL SOFT AND HARD TISSUES TO ENHANCE FACIAL ESTHETICS Louis E. Costa II I am convinced that nothing has so marked an influence on the direction of one's mind as his or her appearance, and not the appearance itself, so much, as the conviction that it is attractive or unattractive.... Leo Tolstoy, Childhood ABSTRACT Historically, the legacy of orthodontic diagnosis and treatment has been predi- cated upon dento-osseous relationships consistent with the Angle Paradigm. The prerequisite was ideal dental occlusion that dictated “nature’s intended ideal form.” Over the past decade the ideal has shifted. The fact that facial appearance plays a role in the quality of one’s life has been confirmed through behavioral, scientific research. The ‘ideal” now has become the pursuit of optimal esthetics with a stable, functional occlusion. This cognizance is driven as much by the patient as the treatment planning professional. Inherent to contemporary, com- prehensive dentofacial treatment plans is an understanding of the various options that can reconcile safely and predictably both objectives: appearance and occlu- sion. In the past, dental form and position frequently have been utilized to pro- vide contour and soft tissue support when the facial drape would have best been treated with non dento-osseous modalities. Indeed, many of the surgical proce- dures now available in the treatment armamentarium are less invasive with bet- ter long-term, stable esthetic outcomes than the traditional means and methods. Such is the case with soft tissue procedures that can supplant bimaxillary, or- thognathic surgery. Whether the goal is achieving more esthetically pleasing facial form or rejuvenation, it is incumbent upon the orthodontist to be familiar with the indications as well as limitations of these soft tissue treatment alterna- tives. Outcomes-based evidence supports the soft tissue paradigm in treatment planning and patients are beginning to mandate it. Many esthetic scholars in recent years have espoused the value of appearance in determining the quality of one’s life. One of the earliest and most insightful was Dr. Ronald Goldstein. In his book, Change Your Smile (1997), he emphasized the importance of looking at the face as an 33 Enhancing Facial Esthetics esthetic unit. He, as well as many behavioral and clinical psychologists, has recognized that the perioral anatomy and other facial features are integral to establishing an esthetically pleasing smile. Two chapters in his book are noteworthy: A New Smile. Your Key to Success and The Role of Facial Plastic Surgery in Enhancing Your Smile (Goldstein, 1997). Much research has affirmed the correlation between positive emotional feedback and a predisposition to success with overall facial form and attractiveness (Adams, 1977; Adams et al., 1978; Berscheid, 1981; Langlois et al., 1987; Flanary, 1992). Flanary (1992), in her as- sessment of the psychology of appearance and the psychological impact of the surgical alteration of the face, was quick to point out that Freud’s quip, “anatomy is destiny,” has become all the more objective and appre- ciated in view of contemporary research. She stated, “Beautiful people are thought to be good, independent, sexually responsive, sociable, kind, sensitive, strong, assertive and successful.” According to her, beautiful people are perceived to have a higher quality of life and enhanced self- concept. This observation is corroborated by other studies and supports the justification for the pursuit of an attractive smile (Adams, 1977). Re- search findings further indicate that the perception of facial beauty is in- nate (Slater et al., 1998) and universal regardless of race or culture (Jones and Hill, 1993). Neurophysiological investigations have found that the subcortical areas of the brain produce a sense of well-being and euphoria when the observers are stimulated by an attractive face (Breiter et al., 2001). LeSage’s definition of beauty (personal communication, 2007), “the inherent quality in an object that is pleasing to the eye or mind,” addresses the quintessential issue: how can we best facilitate a patient’s facial form in a way that is “pleasing” to him/her and to the ob- Server? No one is better prepared or positioned than the orthodontist to address the esthetic treatment planning requirements for patients that have come to realize the association between their appearance and qual- ity of life. Sarver stated (1998), “the final decision of treatment is a syn- thesis of what the patient wants, what can be reasonably expected in treatment, and what interdisciplinary treatment may be required to attain the desired facial goals.” In this era of treating the soft tissue paradigm, as advocated by Ackerman and colleagues (1999), patients expect a comprehensive con- 34 Costa sideration of their esthetic goals. As Moss’ functional matrix theory maintains (1997), the interdependence between form and function is all the more relevant when one considers the craniofacial skeleton in the context of esthetics. Indeed, when treatment alternatives include maxillo- facial surgery, the distinction between cosmetic and functional goals be- comes blurred. Cosmetic surgery by convention implies taking normal form and improving its esthetic appeal. Reconstructive surgery typically is intended to remedy abnormal form or function towards normal. The treatment of craniofacial deformities melds the two. The treatment uniformly is intended to establish a healthy relationship be- tween the cranial base and the masticatory skeleton and, in so doing, provides a more esthetically pleasing facial drape. Such is the case in the patient with Class II skeletal deformity, e.g., vertical maxillary excess and severe mandibular retrusion with microgenia. The treatment demon- strated in Figure 1 includes a LeFort I osteotomy with impaction, bilat- eral sagittal split osteotomies with mandibular advancement and chin augmentation with rhinoplasty. The patient mistakenly assumed that her proptotic eyes were responsible for her esthetic dissatisfaction. The cor- rect diagnosis was Class II skeletal deformity requiring relatively inva- sive procedures to obtain the optimal result. As in all forms of medical and dental treatment, there must be a justified risk/benefit ratio. A fundamental tenet in surgical treatment planning is to offer the most conservative, least invasive alternative that sustains a healthy, stable occlusion and optimizes esthetics. Too often the orthodontist and/or maxillofacial surgeon falls victim to, “if you have a hammer, everything is a nail.” A reasonable less-invasive alternative for the patient with a “gummy Smile,” but otherwise is satisfied with his/her facial form, is the coronal repositioned vestibuloplasty (Perenack, 2005). This conservative soft tissue procedure can be performed under local anesthesia with reduced risks and more expedient recovery. With proper patient selection, results can be gratifying when considering the osseous Surgical option (Fig. 2). * In patients with microgenia, the best treatment may be alloplastic chin augmentation, which spares the patient the need for a ramus or symphyseal osteotomy. The assumption is that there is a stable functional occlusion and the absence of internal joint derangement. The surgical literature indicates that the incidence of complications, including paras- thesia, infections and gingival recession is less with the extraoral place- ment of biocompatible implants, than with osteotomies performed for advancement (Godin et al., 2003). Furthermore, when the mentalisraphe is 35 Enhancing Facial Esthetics Figure 1. A Treatment with LeFort impaction, bilateral sagittal split osteotomies with ad- vancement and ad- vancement genioplasty. B: Frontal views, before (left) and after (right) results. C: Profile views, before (left) and after (right) results. not detached, the incidence of chin drop and prolonged edema is reduced significantly. 36 Costa Figure 2. A: Outline of excision (left), surgical bed following excision (middle) and immediately after wound closure (right). B. Frontal before (left) and after (right) coronal positioning vestibuloplasty. It has been the empirical observation of this author that the pro- Cumbent lip roll and lip incompetence also is facilitated by this approach to horizontal advancement at pogonion (Fig. 3). The same advantages of minimal invasiveness can be realized with alloplastic augmentation of the midface for the treatment of malar hypoplasia (Fig. 4). Often the combination of these less invasive alternatives, e.g., upper lip caudal ad- Vancement along with chin and cheek augmentation using alloplastic im- plants, can offer the patient a reasonable outcome, alleviating the need for bimaxillary orthognathic surgery (Hackney et al., 1988: Fig. 5). Ret- rospective studies have indicated that the stability of augmentation utiliz- ing implants is as good, and in certain instances exceeds that obtained With orthognathic surgery. The patient shown in Figure 5 is five years post-operative, having had simultaneous cheek and chin augmentation With upper lip lengthening. 37 Enhancing Facial Esthetics Figure 3. A. Oblique view before (left) and after (right) alloplastic chin implant with improved lip position. B. Profile view before (left) and af. ter (right) alloplastic chin implant with improved lip position. - 38 Costa Figure 5. A. Frontal before (left) and after (right) double V-Y closure lip advancement with chin im- plant. B. Profile before (left) and after (right) double V-Y closure lip advancement with chin implant. Establishment of a sharp cervio-mental angle and a distinct infe- rior border of the mandible is a valuable esthetic attribute. The treatment is predicated upon the cause of the ill-defined chin/neck relationship. If the diagnosis primarily is excessive, pre-platysmal adipose tissue, a safe, predictable modality of treatment is sub-mandibular anterior cervical liposuction. The redundant adipose tissue is removed through an incon- spicuous 3 mm incision placed in the inferior mental crease. The suction- * Figure 4. Oblique before (left) and after (right) transoral, bilateral alloplastic cheek implants. 39 Enhancing Facial Esthetics assisted lipectomy is performed along the inferior border of the mandible in the pre-platysmal muscle plane and may extend over the anterior tri- angle of the neck (Fig. 6). It often is used as an adjunct to mandibular or chin advancement. The newfound interest in enhancement of the lips through aug- mentation has been facilitated by the introduction of hypoallergenic fill- ers. The most common approach is sub-mucosal, extra-muscular injec- tions with hyaluronic acid in the form of Restylane”, Perlane" or Juved- erm” (hyaluronic acid). These materials typically have a clinical duration of six to twelve months. The lips attain a maximum size and mass at 16 years of age in females and 18 in males (Sarver, 1998). With age, there is a progressive atrophy of the sub-mucosal fat and, to a lesser extent, the orbicularis oris muscle. Treatment objectives may include replacement or enhancement beyond the typical tooth/lip projection (Fig. 7). The proce- dure generally takes less than 30 minutes and is performed with buccal vestibular infiltration of local anesthetic. A longer lasting option is placed surgically acellular dermal matrix, Alloderm”. Despite what we may think as dentists, the nose, not the teeth, is the most salient feature of the human face. Indeed, an obtrusive nose may deprive the patient of what otherwise might be an attractive esthetic baseline (Nouraei et al., 2009). The most common nasal deformities are size disparity, whether frontal or profile, relative to the patient’s bi-malar width and vertical facial height (Tardy, 1997). Reduction rhinoplasties are directed toward establishing an appropriate proportional balance and symmetry. A straight dorsum with a distinct tip defining point and a slightly obtuse nasolabial angle are appealing nasal features universally. The tip generally should measure one-third the width of the nasal base (Figs. 8-10). One of the most popular forms of esthetic surgery is directed to- ward rejuvenation, that is, surgery to reduce the signs and Stigmata of aging. The dynamic morphologic change of the craniofacial skeleton with time is well documented (Behrents, 1985; Pessa et al., 1999). Though some of the adverse esthetic effects associated with the senile course can be treated through skeletal augmentation, the majority of re- juvenating measures are directed toward the incurred soft tissue changes. An age-related feature of the lips is the development of a perioral rhytides or vertical wrinkles. The primary etiology for this condition is a 40 Costa Figure 6. A. Oblique before (left) and after (right) full-face liposuction. B. Pro- file before (left) and after (right) full-face liposuction. progressive decrease in the random order of collagen fibrils in the pe- rioral dermis. Effective treatment requires the re-orientation of these or- dered fibrils into a more random cross-hatched state, thereby diminishing the overlying epithelial folds (Fig. 11). 41 Enhancing Facial Esthetics E. Figure 7. A. Oblique before (left) and after (right) Alloderm lip aug- mentation. B. Frontal before (left) and after (right) Alloderm lip aug- mentation. 42 Costa Figure 9. Profile before (left) and after (right) after rhinoplasty with de- projection. Figure 10. Oblique before (left) and after (right) rhinoplasty with tip width reduction. * Figure 8. Profile before (left) and after (right) reduction rhinoplasty with tip rotation. 43 Enhancing Facial Esthetics Figure 11. Before (left) and after (right) dermabrasion for wrinkle re- duction. One of the most effective treatments involves the careful abla- tion of the epithelium and the superficial dermis through mechanical re- surfacing in the form of dermabrasion. A rotating diamond fraise can be applied under careful control in such a way as to reduce the level of the skin in the region of the wrinkles. The ablation is carried through the epi- thelium into the superficial layers of the papillary dermis. Re- epithelialization takes place in approximately 72 hours, though erythema may persist for weeks. Typically the patient can apply makeup in seven to ten days and return to reasonably normal social activities. The depth of treatment is limited by the thickness of the underlying dermis. In addition, as a consequence of age, redundancy of tissue devel- ops in the upper eyelids, puffiness in the lower eyelids due to pseudo-fat herniation and laxity in the lower portions of the face. In the periocular region, there is a loss of visibility of the upper eyelid pre-tarsal tissue. The infra-brow tissue begins to hood the pre-tarsal lid causing a tired appearance and, in the extreme, blocking superior and lateral gaze. The excessive tissue actually can come to rest on the lashes, causing a visor effect (Fig. 12). In the lower lids, there can be concomitant wrinkling with pseudo-fat herniation producing lower eyelid “bags” and festooning. Treatment in the form of blepharoplasty involves the meticulous surgical removal of the redundant skin and fat. The incisions are fashioned care- fully in order to rest in inconspicuous natural skin folds. Bruising and swelling usually resolve in one to two weeks; however, the patient can resume fairly normal activity under the cover of sunglasses within 24 to 48 hours. Pain usually is non-existent. The workhorse procedure for facial rejuvenation is the facelift or facial rhytidectomy. The universal consistency for facial aging is the downward and forward migration of the midfacial, perioral and neck tis- 44 Costa Figure 12. Before (left) and after (right) upper and lower blepharoplasty (eyelifts). Sues. This displacement of tissues is the result of an attenuation of the Suspensory system of the face and neck. This system is referred to as the Superficial musculo-apponeurotic system (S.M.A.S.). The drift manifests as deepening of the nasolabial folds, dropped oral commissures, mario- nette lines extending from the commissures to the inferior border of the mandible, jowling as a result of ptotic buccal fat pads and the develop- ment of a double chin or platysmal banding, referred to as the “turkey gobble.” The most effective treatment for this state requires the restora- tion of these tissues to their more youthful position (Fig. 13). “Effective” treatment has several mandates. The restoration must be natural and void of surgical stigmata. The results must have duration of effect and longev- ity that justifies the process. Lastly, the recovery must be reasonable in terms of discomfort and return to normal social and vocational activities. These assurances are technique sensitive and dependent not only on the Surgical expertise of the doctor, but also on his/her sense of art. Unfortunately, some surgeons have a creative rather than restora- tive motivation. In these instances, the patients may lose their individual- ity and assume an appearance unlike that of an earlier age of the patient. The most common expectation is for patients to look rested and the best they can at any particular age. Typically the face, cheeks, jowl and neck- lift provides a ten- to fifteen-year natural rejuvenation. The surgery usu- ally is performed on an outpatient basis under intravenous sedation with minimal if any dressings required after the first post-operative day. Though discomfort afterward is common, frank pain is unusual. Swelling 45 Enhancing Facial Esthetics Figure 13. Before (left) and after (right) facelift with restoration of perioral tis- sues to more youthful positions. presents in the midface and bruising generally is limited to the neck area. The vast majority of patients feel comfortable in public after approxi- mately two weeks convalescence. There is no age limitation for healthy patients, though typically the earlier the procedure is performed after the patient has noticed distracting changes, the better. Paradoxically, the ear- lier the process is addressed, the better the longevity of the result. Early intervention also has the advantage of less invasive procedures, quicker convalescence and a less obvious change with the same gratifying results (Fig. 14). The role that appearance plays in a patient’s life can be positive. The extent to which a person desires to enhance his or her appearance is a matter of personal motivation and self-realization. It helps neither the healthcare professional nor the patient to deny the fact that enhanced physical appearance can play a viable role in one’s life. The continuum before us is one that spans the range from Straight teeth with appropriate arch form to the composite of facial features that establish the esthetic Smile. 46 Costa Figure 14, A. Before (left) and after (right) facelift in male patient with restoration of well-defined jawline. B. Before (left) and after (right) facelift in female patient with restoration of cheeks and neckline. CONCLUSION The extent to which a patient may be motivated to consider sur- gical options is embodied within the micro- vs. macro-esthetic spectrum. We can best serve these patients when we endeavor to understand their motivation and extent to which appearance plays a role in their self- Concept as it relates to quality of life. It is our responsibility to direct them toward those modalities of treatment most likely to satisfy their expectations. However, the patient ultimately will decide and he/she should not be limited by a lack of understanding of contemporary alter- natives. 47 Enhancing Facial Esthetics REFERENCES Ackerman JL, Proffit WR, Sarver DM. The emerging soft tissue para- digm in orthodontic diagnosis and treatment planning. Clin Orthod Res 1999:2:49-52. Adams G. Physical attractiveness research: Toward a developmental psychology of beauty. Human Development 1977:20:217-239. Adams G, Crossman S. Physical Attractiveness: A Cultural Imperative. Rosalyn Heights, NY: Libra Publishing 1978. Behrents RG. An Atlas of Growth in the Aging Craniofacial Skeleton. Monograph 17, Craniofacial Growth Series, Center for Human Growth and Development, The University of Michigan, Ann Arbor, 1985. Bercheid E. An overview of the psychological effects of physical attrac- tiveness. In: Lucker GW, Ribbens KA, McNamara JA Jr, eds. Psy- chological Aspects of Facial Form. Monograph 11, Craniofacial Growth Series, Department of Orthodontics and Pediatric Dentistry and Center for Human Growth and Development, The University of Michigan, Ann Arbor, 1981. Breiter H, Aharon I, Eteoff N. Beautiful faces have variable reward value: fMRT and behavioral evidence. Neuron 2001:32:537–551. Flanary C. The psychology of appearance and the psychological impact of surgical alteration of the face. In: Bell W., ed. Modern Practice in Orthognathic and Reconstructive Surgery. Vol 1. Philadelphia; WB Saunders Co., 1992:2–21. - Godin M, Costa L, Romo T, Truswell W, Wang T, Williams E. Gore- Tex chin implants: A review of 324 cases. Arch Facial Plast Surg 2003;5:224-227. Goldstein R. Change Your Smile. 3rd ed. Carol Stream: Quintessence Publishing Co. Inc., 1997. Hackney F, Nishioka G, Sickles JV. Frontal soft tissue morphology with double V-Y closure. J Oral Maxillofac Surg 1988:46:850-855. Jones D, Hill K. Criteria for facial attractiveness in five populations. Human Nature 1993;4:271-296. Langlois JH, Roggman LA, Casey RJ, Ritter JM, Rieser-Danner LA, Jenkins VY. Infant preferences for attractive faces: Rudiments of a stereotype? Dev Psychol 1987:23:363-369. LeSage B. Annual ADA Meeting. San Francisco 2007; personal commu- nication. 48 Costa Moss ML. The functional matrix hypothesis revisited. Part 1. The role of mechanotransduction. Am J Orthod Dentofacial Orthop 1997; 112:8- | 1. Nouraei R, Pulido M, Saleh H. Impact of rhinoplasty on objective meas- urement and psychophysical appearance of facial symmetry. Arch Fa- cial Plast Surg 2009:11:198-202. Peranack J. Treatment options to optimize display of the anterior dental esthetics in the patient with the aged lip. J Oral Maxillofac Surg 2005;63; 1634–1641. Pessa J, Zadoo V, Yuan C, Ayedelotte J. Concertina effect and facial aging: Nonlinear aspects of youthfulness and skeletal remodeling, and why, perhaps, infants have jowls. Plast Reconstr Surg 1999; 103:635- 644. Sarver DM. Skeletal and soft-tissue facial changes in youths, adoles- cents, and adults. In: Rudolph P, ed. Esthetic Orthodontics and Or- thognathic Surgery. St Louis: Mosby Year Book Inc., 1998: 136-138. Slater A, Vonderschulenberg C, Brown R, Badenoch M, Butterworth G, Parsons S, Samuels C. Newborn infants prefer attractive faces. Infant Behav Dev 1998:21:345-354. Tardy M. Patient evaluation and preparation. In: Rhinoplasty: The Art and the Science. Vol 1. Philadelphia: WB Saunders Co., 1998: 126- 187. 49 50 COMPUTER-ASSISTED CRANIOMAXILLOFACIAL SURGERY Sean P. Edwards ABSTRACT Continuous quality improvement has been a mantra in healthcare for many years Surgeons always are looking not only to improve the quality of their results, but also the consistency with which these results are achieved. To this end, new technology is being incorporated into or replacing traditional diagnostics and treatment planning. The knowledge gleaned from this technology is being taken to the operating room, augmenting conventional Surgical techniques and improv- ing the surgeon’s eye. Interest in the application of these technologies has been broad throughout all fields of surgery and dentistry, but now has arrived with vigor to craniomaxillofacial surgery. This chapter reviews some of the general concepts and techniques of computer-assisted craniomaxillofacial surgery, along with its potential benefits and limitations. How often should our results be what we planned? No surgeon is perfect all the time, yet surgery is a results-driven discipline. To this end, surgeons have turned to technology to improve not only their outcomes, but also how often they achieve high quality results. Computer-assisted surgery (CAS) is really an umbrella term used to describe all forms of surgery planning and/or execution that in- corporate various forms of advanced imaging, software, analysis and planning and in some cases, rapid prototyping technology, robotics and image guidance systems. While these may represent the current state of affairs, innovation is progressing at a rapid rate and new forms of tech- nology will continue to be incorporated and evaluated for their value in improving the operations we do on a daily basis. Critics of these new methods often point to the increased direct costs that may result from these technologies. While the direct costs of an operation may be increased, the overall cost of care may be reduced. Decreased operative time, blood loss, complications and the need for re- operative surgery are all potential cost-saving benefits. Minimally inva- sive, or at least less invasive, approaches also may result from improved 51 Computer-Assisted Surgery planning and visualization. Minimally invasive procedures can decrease hospitalization and recovery time, thus reducing morbidity and indirect costs of care. Such procedures also may increase the time spent preparing for a case. That said, the value of planning is not lost on the orthodontist or the oral and maxillofacial surgeon. Each performs model surgery, prepares diagnostic set-ups, makes splints, reviews clinical photographs and per- forms cephalometric analyses for cases. The value of this time invest- ment has been recognized for several decades as critical to achieving consistent, high quality results. Because the newer methods are not stan- dardized, little effort has been directed at evaluating the benefits of CAS in terms of cost and treatment time. An evaluation of the value of prepa- ration time ultimately will be needed before these techniques ever be- come standard of care. Interest in this field is broad. In addition to craniomaxillofacial surgery, this technology has been incorporated into orthodontics, radia- tion oncology, neurosurgery, sinus Surgery, joint replacement Surgery, spine surgery and dental implantology. The acceleration in CAS interest is due to the increased availability of lower cost, low radiation imaging technology and powerful, commercially available software packages that allow a surgeon, without sophisticated computer expertise, to visualize and simulate operations. Rapid prototyping and stereolithography be- came commonplace in the late 1990s; this technology has been married with the software planning serving to push the technology further for- ward. IMAGING While virtually any imaging system can be incorporated into CAS treatment schemes, cone-beam computed tomography (CBCT) and conventional multi-slice computed tomography are the workhorse imag- ing modalities in craniomaxillofacial CAS. Skeletal surgery is particu- larly well suited to CAS. The skeleton is easy to image well with com- puted tomography and, given its inflexible nature, represents an invariant data set that can be manipulated in the virtual environment. CBCT is a medical imaging system that uses a cone shaped X- ray beam centered on a two-dimensional (2D) detector (Fig. 1). The source-detector complex makes one rotation around the patient analo- gous to a panoramic radiograph. These systems have found broad use in medicine and dentistry in the fields of radiation oncology, interventional 52 Edwards Figure 1. In-office CBCT scanner (EWOO Master 3DS). Note the non-intimidating profile that is compa- rable to a conventional panoramic machine. This ma- chine has a minimal footprint and is incorporated into the office environment easily. radiology, otolaryngology, implantology, orthodontics and craniomaxil- lofacial surgery. Dedicated scanners for the oral and maxillofacial region Were introduced in the late 1990s; since then, there has been an explosion of interest in the imaging technique and applications to which it might be applied. Image quality in most instance lags behind conventional multi- slice scanners but is more than adequate for its intended need (Fig. 2). Since their initial introduction, it seems two general classes of *anners have emerged based on size of their field of view. Scanners With a smaller field of view, on the order of 13 cm or smaller, lend them- 53 Computer-Assisted Surgery Figure 2. Typical image quality of a large field of view CBCT. Quality of skeletal detail is more than adequate for diagnostic and treatment planning purposes. selves well to implant dentistry and other dentoalveolar applications such as impacted teeth. Those scanners with broader fields of view, greater than 13 cm and up to 21 cm, allow the clinician to image the entire face. These larger data sets permit evaluation of a facial deformity, allow the generation of cephalograms, airway analysis and complex craniomaxillo- facial Surgery planning. The CBCT scanners are relatively inexpensive when compared to conventional multi-slice scanners and as such, many are purchased and situated in the surgeon’s clinic under his/her control. This proximity offers a better degree of control over how the images are acquired. Since most surgeons have a dental lab situated in or close to their clinic, this also allows the surgeon to fabricate guides for template-based surgery or even dental splints for surgical navigation. Having a dental radiology technician acquiring the imaging data is useful in that they already are 54 Edwards familiar with preparing the patient for panoramic radiographs and cepha- lograms. As a result, concepts such as natural head position, Frankfort horizontal, centric relation and resting lip posture are not foreign to the technologist taking the images, simplifying the process and improving the data set acquired. Quality control in such an arrangement also is eas- ier to maintain. As computer processors improve in their power, so does the time taken to acquire these scans. A full head scan generally can be performed in under a minute, sometimes in less than 20 seconds, with roughly the same amount of time taken to process the data for image display. From a workflow perspective, this efficiency permits these systems to be inte- grated into busy practices rapidly without suffering any significant loss in productivity. Moreover, by saving a revisit after the image is obtained prior to presenting an operative plan to a patient, clinic time may be re- duced in the end. As a result, these scanners quickly are being incorpo- rated in oral and maxillofacial surgery and orthodontic offices across the globe. Dosimetry is one of the biggest advantages of the cone-beam technology. The dose reduction is due, in part, to the fact that the image is acquired in a single sweep instead of multiple slices and because only images of the skeleton are acquired. Actual doses vary based on machine and scan specifications. Larger fields of view and higher resolution scans (smaller Voxel size) result in higher doses. The radiation source can de- liver a continuous beam or it may pulse the radiation, further lowering the dose. Doses for full head scans range from 69 to 560 microSv. This dosage range compares favorably with the 860-2000 microSV for a con- ventional head CT scan (Ludlow, 2008; Roberts et al., 2009; Suomalainen et al., 2009). This dosage still is a significant increase over conventional dental radiography at four to 43 times the dose of a conven- tional panoramic radiograph and should not be seen as a substitute for these films when they are adequate (Ludlow et al., 2006; Ludlow, 2008). ENHANCED 3D DIAGNOSTICS To correct a deformity accurately, a surgeon first must be able to identify and quantify all the different components of a deformity. Using orthognathic surgery as an example, midline discrepancies are measured easily. Cants are somewhat more difficult to measure and yaw deformi- ties that result in asymmetric buccal corridors are much more difficult to quantify. Differences in the height of the mandibular body and ramus 55 Computer-Assisted Surgery also are not measured easily with clinical means or with conventional 2D radiographic techniques (Fig. 3). A three-dimensional (3D) data set ob- tained from a CT scan overcomes many of these difficulties. Figure 3. Young adolescent with hemimandibular hyperplasia and facial asymmetry. The midline dis- crepancy is obvious and easy to measure. The differ- ence in the height of the inferior border of the mandi- ble is more difficult to quantify, as is the yaw/rotat- ional deformity of the jaws. Several software packages have been developed to display in CT data sets for this type of analysis. Typically, images are reconstructed in axial, sagittal and coronal planes along with 3D views of the patient (Figs. 4 and 5). First, all aspects of a patient’s skeletal detail can be ex- amined, permitting a qualitative assessment of a deformity. This data set includes the soft tissue mask that may be viewed in the context of the skel- – Figure 5. A. Virtual skull is aligned according to sagittal, coronal and axial planes to orient the head for analysis. A natural head posture registration could be used as well. B. Three-dimensional reconstruction of CT data permits 3D analysis to help the surgeon understand and quantify a complex deformity. 56 Edwards º Figure 4. CT data reconstructed to sº axial, coronal and Sagittal planes along With a 3D view of the head. 57 Computer-Assisted Surgery etal deformity. Furthermore, 2D and 3D stereophotogrammetry may be fused with the CT data set easily, creating a lifelike, virtual patient model Most of these commercially available software packages also generate lateral cephalograms and panoramic radiographs easily. These films re- main useful because clinicians are comfortable viewing anatomy pre- sented this way, but they ignore some of the potential advantages of such a 3D data set. The reader is referred to a thorough overview of 3D cepha- lometry by Swennen and colleagues (2009). Despite there being standard landmarks and planes described, a deformity can be quantified from virtually any orthogonal plane that the surgeon deems helpful in terms of formulating an operative plan. These measurements can extend to virtually any portion of the face including the supraglottic airway. Maxillomandibular surgery has the potential to impact a patient’s airway and thereby create or correct sleep-disordered breathing. As our understanding of the relationship between maxillo- mandibular surgery and the airway improves, we eventually may be able to incorporate airway analyses and diagnostics as a routine part of Sur- gery planning. The next step in the evolution of the treatment planning software and its utility with respect to CAS was the development of segmentation tools. Segmenting, analogous to creating an osteotomy, is a way to Se- quester portions of a patient’s anatomy. The cutting planes for this func- tion are arbitrary and user-defined in most instances. Segmentation can be used to define anatomical units, such as the airway or a tumor, or to simulate typical operations such a LeFort I osteotomy. With an osteot- omy, the bones on either side of the cut, each its own separate data set, can be repositioned according to the developed treatment plan, soft tissue changes simulated and the adequacy of the treatment plan can be as- sessed (Fig. 6). TACTILE MODELS Tactile model technology, or rapid prototyping (RP), became relatively commonplace in craniomaxillofacial surgery in the late 1990s. These models became familiar immediately and were recognized as valuable diagnostic adjuncts to orthodontists and oral and maxillofacial surgeons who had been working with stone dental models for decades. This model technology gave the surgeon a full view of a patient’s skele- tal deformity; it could be used to quantify the deformity and plan a patient’s 58 Edwards Figure 6. Cutting planes are established and the data segmen- tation accomplished to simulate a LeFort I osteotomy, sagittal split of the mandible and asymmetric, sliding genioplasty. Operation (Figs. 7 and 8). Osteotomies could be simulated and templates Created to help transfer the desired treatment plan to the operating room. These models initially were limited by cost and the availability of means to fabricate them. RP printers now are more commonplace, which eliminates one hurdle to their routine use. Many hospitals have purchased the systems, engineering departments at most universities have the technology and several companies now offer the service as well. This technology involves several steps, beginning with data file conversion. Because RP was used primarily in the automotive and aero- Space industry for design and prototyping, it originally was not con- ceived to work with medical imaging data, CT scans and magnetic reso- nance imaging (MRI) scans are stored in Digital Imaging and Communi- cations in Medicine (DICOM) format and must be converted to an STL file format for use in RP. In essence, the universal file format for imag- ing, DICOM, is converted to the universal file format for RP, STL (Christensen, 2007). 59 Computer-Assisted Surgery - - Figure 7. Stereolithographic model of a complex asymmetry associated with type III hemifacial mi- crosomia. The quality of these data, which will determine the quality of the model produced, is dependent primarily on the quality of the imaging data. Because CT scans give the best images of skeletal structures, this type of scan is the primary modality used to fabricate patient specific tactile models. High resolution, thin slice CT scans acquired without mo- tion artifact and distortion produce the best images and thereby the best models. Metal from dental restorations or fixation devices will produce streak artifacts that will affect the quality of every step of this process negatively. Thin bones, such as the anterior wall of the maxillary sinus and the walls of the orbit, often are missed and poorly represented in 3D 60 Edwards Figure 8. Sterolithographic model of an adolescent severely affected with cherubism. Measurements can be taken from this model to plan and establish goals for the remodeling procedures. data sets and so are not well represented in 3D models without signifi- cant image processing. This limitation is important because it directly impacts a surgeon’s ability to use these models for planning surgery in these regions. There are steps and software packages available to process imaging data to improve the quality of scan and reduce the impact of these issues on scan data, but the effort can be laborious. Several methods exist to produce these models, each with their advantages and disadvantages. In essence, each of these methods con- Verts a series of axial images slices into 2D layers of some material that is layered upon itself to make a model (Christensen, 2007). Stereolithography (SLA) is the method best known to most sur- geons and dentists. These models are translucent, key anatomical struc- 61 Computer-Assisted Surgery tures can be inspected and even colorized and studied for their relevance to the desired treatment plan. They are produced from a vat of liquid polymer that is photopolymerized a layer at a time. Selective application of additional UV energy colorizes the polymer red in desired areas. Typically, teeth and the inferior alveolar nerve are treated in this fashion. Time and relatively high cost are the biggest drawbacks to this technique. It takes between 10 and 30 hours to produce such a model, depending on the size needed. These models, when made from high quality CT scans, are accurate; they are produced at a 1:1 size ratio, so planning also can be accurate (Christensen, 2007). Other methods produce opaque models. Three-dimensional printing is analogous to inkjet printing with layers of a powder fused to- gether with a liquid binder. This method yields opaque models but is fast and relatively inexpensive. One drawback is that these models are rela- tively fragile. Fused deposition modeling (FDM) involves the extrusion of a melted plastic in layered fashion to create a model. These models are opaque and take a great deal of time to produce but they are strong. Se- lective laser sintering (SLS) uses a CO2 laser to sinter or fuse a given material one layer at a time into a model. This method is flexible in terms of the materials that can be used; nylon is most common (Christensen, 2007). In the future, custom titanium devices could be produced by this method. Resorbable, patient-specific anatomic constructs made of poly- caprolactone (PCL) for tissue-engineering applications also have been produced with SLS (Smith et al., 2007). COMPUTER-ASSISTED SURGERY CONCEPTS In the broadest possible sense, CAS of the craniomaxillofacial skeleton exists in two forms: image-guided surgery and template-based Surgery. Image-guided surgery (Figs. 9 and 10), also known as naviga- tional Surgery, uses imaging data as a road map for the operating surgeon It is analogous to the global positioning systems (GPS) becoming ubiqui- tous in modern automobiles. The techniques pair well with minimally invasive approaches and operations where broad exposure cannot be achieved, such as the deep orbits. The surgeon uses various forms of probes to locate or guide instruments and correlates this position with the patient’s anatomy in real time on a computer screen displaying the pa- tient’s imaging data in all three planes of space. Image guidance has been 62 Edwards Figure 9. Surgical navigation is analogous to a GPS system in automobiles. The navigation tower consists of a camera and a monitor. The camera registers the position of the patient and the navigation probe and displays the position of the probe on the monitor. - adopted widely by sinus surgeons and neurosurgeons to help them navi- gate the deeper structures of the head without broad surgical exposure. In craniomaxillofacial surgery, it has found use in orbital trauma. FCConstruction and tumor extirpation, especially that of the skull base. For 63 Computer-Assisted Surgery C. Figure 10. A. At the beginning of a case, landmarks on a patient are registered to corresponding landmarks on their CT data set. To maintain this linkage, a system to track movement of the patient is required. In this case, the Medtronic Stealth System uses a headband with four fiducial markers. Changes in the position of the patient’s head are reflected in positional changes in the markers that are tracked by the camera. B and C: Instruments and probes with a similar fiducial system are tracked by the camera to display progress on the patients CT scan. routine use in reconstructive surgery, however, the techniques are un- wieldy, which has limited their broader application. Improvements in intra-operative imaging systems will increase its value to the CMF sur- geon because current systems do not reflect any anatomical changes as a result of surgery. The “road map” in these cases is invariant and only as current as the pre-operative CT scan. Accuracy has been a concern with these approaches but likely will be overcome as technology improves. Template-based surgery is a more familiar paradigm for cranio- maxillofacial surgeons. Templates routinely are used for orthognathic surgery, dental implant placement and even for alveoloplasty. Incorpora- tion of improved imaging, diagnostics and segmentation that leads to template generation is little more than a straightforward and logical ex- tension of current practice. 64 Edwards The general workflow is shown in Figure 11. While these en- hanced diagnostics are valuable, templates are the key to translating this enhanced treatment planning to the operating room. The potential forms for the template are limited only by the imagination of the surgeon and engineer. They can be rapid prototyped guides for cutting osteotomies and repositioning bones, can be customized models on which fixation plates are adapted, may be traditional style orthognathic occlusal wafers and even can be custom-made, implantable prostheses. Data acquisition º Data export to Treatment CBCT - - Multislice CT **") Dalamanipulation MRI - - Surface scans . Segmentation Q- Models urg|Case . º Impressions Maxilim 3. On Template Design and Simplant Distraction Generation Soft tissue change - simulation Tactile model Prebent plate Vector guide Cutting guide Custom implant Figure 11. CAS workflow. RECONSTRUCTIVE SURGERY Unilateral defects, both traumatic and oncologic, as well as asymmetries lend themselves well to CAS techniques. A mirror image of the unaffected side can be created and superimposed on the affected area. Segmenting the deformed portion of a patient’s anatomy and replacing it With a mirror image of the opposite side creates the surgical objective. This technique has been well described for orbital trauma (Metzger et al., 2006, 2007; Schramm et al. 2009). The difference between the two images can be used to quantify the deformity and help plan the reconstructive operation. It also can be used to fashion a variety of templates. For example, a tactile model made of the reconstructed mandible can be used to adapt a reconstruction plate to which a bone graft will be fixed. Because the plate is adapted to the Surgical objective, the bone graft or bone flap form will be exactly as 65 Computer-Assisted Surgery desired. This planning has the potential to take into account not just fa- cial form, but also the eventual dental rehabilitation if the jaws are a part of the intended reconstruction. The following case demonstrates, in step- by-step fashion, the creation of a customized tactile model that was used to design the reconstruction in a situation where the normal reference points and planes were abrogated by the tumor (Figs. 12-18). Bilateral and midline defects are more of a challenge in this re- gard because the opposite side cannot be used to determine the treatment objective. A treatment objective can be created virtually though using anatomic standards to create the desired structures that then can be used Figure 12. Axial view of large desmoid tumor in four-year-old male. -> Figure 14. A 3D view with deformed mandibular half segmented. B. De- formed half removed. C. Mirrored left mandible aligned to replace the deformed right hemimandible. D. Comparison of stereolithographic models of new man- dible and deformed mandible. The new mandible model becomes the surgical objective and the template to guide the reconstructive process. 66 Edwards | D Mirrored Mandible Preop Mandible 67 Computer-Assisted Surgery - Figure 15. Reconstruction plate is adapted to the new mandible. It then is steril- ized and taken to the operating room to guide the reconstruction. Figure 16. Tumor is resected. 68 Edwards Figure 17. A. Specimen. B: Plate fixed to residual mandible and rib grafts then are fixed to the plate. Figure 18. A. Closure with resulting good symmetry and form of the new mandible after a 3% mandibulectomy. B: Frontal view at closure. 69 Computer-Assisted Surgery to generate a template. The following case of a self-inflected gunshot wound resulted in a large composite tissue defect of the anterior mandi- ble. In this instance, data sets from the mandibles of other patients were “tried in virtually until one with the appropriate intergonial width and chin projection was found. The virtual construct of the desired mandible was aligned such that the alveolar ridges would be positioned appropri- ately for future implant rehabilitation. A tactile model then was made of the “reconstructed” mandible such that a plate could then be adapted to shape the reconstruction. Similar strategies have been devised for orbital reconstruction where both orbits are deformed (Metzger et al., 2006; Figs 19–22). Figure 19. Anterior mandibular defect due to gunshot wound. 70 Edwards Figure 20. A 3D data sets of the mandibular defect. On the right is a frontal View of the treatment objective. This composite image was developed by taking Stock mandibular CT scan images and finding one that matched the desired go- nial width and chin projection. B. Lateral view of pre-operative condition and treatment objective. 71 Computer-Assisted Surgery Figure 21. A. This treatment objective data set is used to fabricate a stereolitho- graphic model that then can be used to adapt a reconstruction plate and bone flap and approximate our virtual treatment objective. B: Plate adapted to the custom- ized model. 72 Edwards DISTRACTION OSTEOGENESIS Distraction osteogenesis is a powerful technique for the elonga- tion of bones without the need for bone grafting. The process involves gradual elongation of the bony callus that forms at the site of an osteot- omy. The force to create this movement then can be applied either inter- nally or externally. An external system, which sits eternal to the patient’s face and interfaces with the bones by way of rigid pins or wires, offers the surgeon maximum control over the direction of bone movement and offers the potential for changes in the vector of movement, as warranted by the clinical situation. While favored for this element of control, these external devices are not well accepted by patients and parents because they are unwieldy and must be worn 24 hours per day for several months during the phases of active treatment and consolidation of the newly generated bone. To illustrate the point further, this protocol is analogous to hav- ing a patient wear a protraction facemask all day for several months. As a result, many clinicians have turned to buried devices where the only hardware visible is an activation arm that emerges intra-orally or in the upper cervical region. These devices generally are univector in that the vector of movement is set and relatively immutable once it is installed at the time of surgery. Thus, the quality of the result achieved will be de- pendent on the ability of the surgeon to place the device with the proper orientation in all three planes of space to achieve the desired result. Es- tablishing the correct orientation is even more important when bilateral devices are being placed. Convergence of the distraction vectors of de- vices on either side of the mandible will lead to excessive lateral condy- lar torque. - In the maxilla and upper facial skeleton, where the posterior elements are fixed, improper vector orientation can lead to device bind- ing and ultimately failure. If the devices are not parallel in the vertical planes, this malalignment also can lead to cants, open bites and other untoward iatrogenic deformities (Fig. 23). <- Figure 22. Free fibula osteocutaneous flap osteotomized to adapt intimately to the plate achieving the treatment objective. 73 Computer-Assisted Surgery Figure 23. Maxillary distraction case planned using buried dis- tractors. Devices are selected virtually. Parrallelism is assured as is the angle of declination to achieve vertical lengthening of the maxilla while Sagittal lengthening is ongoing. Accurate device placement and thereby distraction vector deter- mination is not an easy task when the anatomy is abnormal due to the underlying deformity or previous surgery. Furthermore, because man- dibular devices in toddlers often are placed through a transcervical ap- proach, the surgeon seeks to limit the incision length to avoid an un- sightly scar. Computer-based planning systems now exist that permit a Sur- geon to perform the operation virtually. Many benefits result from this process. For example, a multitude of devices may be “tried in virtually 74 Edwards until one of appropriate size and form is selected. It may be positioned so as to avoid injury to developing tooth buds and other Vital structures such as the inferior alveolar nerve, with both the osteotomy and screw place- ment. The distraction process then can be simulated and the reciprocal Soft tissue changes predicted. This simulation also permits the surgeon to select a distractor with an activation arm of appropriate length. The following case demonstrates the application of the technique in a child with Treacher Collins syndrome (Figs. 24–30). ORTHOGNATHIC SURGERY Orthognathic surgery is one area of maxillofacial surgery already subject to extensive pre-operative planning. A single jaw surgical plan requires that the opposing arch be adequate in position, width and sym- metry and as such generally yields predictable, satisfactory results with- out extensive planning. Two-jaw surgery, which involves surgically re- positioning the maxilla and mandible in three planes of space, is a more difficult undertaking. Again, at the risk of stating the obvious, the deci- Sion to embark upon two-jaw surgery is predicated on neither jaw being Satisfactory in position, form or symmetry. This type of surgery is a rela- tively difficult undertaking when one considers the sub-millimetric preci- sion required to achieve a satisfactory result. To this end, pre-operative planning for a double jaw case is much more involved. The pre-operative planning of a single jaw case consists of a review of photographic records and cephalometric analysis with surgical prediction tracings, followed by the fabrication of a single interocclusal splint to guide the establishment of the final, desired occlu- sion. The time spent will vary; it generally is less than one hour for an experienced surgeon. Pre-operative planning for two-jaw cases usually involves im- pressions, centric records, a facebow relation, a series of clinical meas- urements and a mounting on a semi-adjustable articulator. Surgery then is simulated on the articulated casts using a model block to register the desired changes. This protocol includes multiple steps and small errors at each can accumulate. There are components of a deformity, such as a yaw deformity, that are difficult to quantify with traditional diagnostic records and are difficult, therefore, to correct accurately. Several hours typically are spent gathering these records and completing the treatment planning for such a case. Given the labor involved and potential for error, it seems obvious that surgeons would look to incorporate technology that 75 Computer-Assisted Surgery Figure 24. Four-year-old male with Treacher Collins Syndrome and se- were obstructive sleep apnea. He has undergone distraction at 11 months of age. His mandibular anatomy is markedly abnormal. Figure 25. CT data are acquired and analytical stage is begun. 76 Edwards Distractor E. Placement Figure 26. A. Buried, single vector distraction device is chosen and positioned to achieve the desired result. B. A vector transfer guide (in red) then is designed Virtually. The design of this guide is such that it can be positioned easily on the native mandible and will adapt well to the contours of the distractor. It is de- signed purposefully to be larger than will be used in the operating room. This permits customizing the guide further as the operative situation dictates. Figure 27. A model and transfer guide are fabricated using rapid prototyping technol- ogy. The mandibular model allows the distractor to be adapt- ed for a precise fit while the vector trans- fer guide ensures the desired orientation. 77 Computer-Assisted Surgery Figure 28. A. The mandible is exposed and the template seated. B. The dis- tractor is seated in the template, replicating the treatment objective. C. Dis- traction is accomplished having avoided injury to developing tooth buds. Figure 29. Pre-distraction lateral view. 78 Edwards Figure 30. post-distraction lateral view. 79 Computer-Assisted Surgery *— Figure 31 (previous page). A: Complex asymmetric deformity that would be difficult to quantify from traditional 2D imaging modalities. B: 3D view of the same patient. potentially could reduce the time spent in pre-operative planning and simultaneously improve surgical outcomes (Fig. 31). Several schemes have been devised for computer-assisted or- thognathic surgery (Xia et al., 2001; Mischkowski et al., 2006; Uechi et al., 2006; Fushiima et al., 2007; Metzger et al., 2008; Olszewski et al., 2008; Swennen et al., 2009), yet none have found their way into the mainstream for a few reasons. First, establishing a final occlusion is a precise maneuver, with corrections of a fraction of a millimeter having a significant impact on the final outcome. Most surgeons are used to the tactile feedback that comes from hand articulating stone casts to get a sense of the pre-surgical orthodontic setup. Second, enamoplasty occa- sionally is performed to improve a pre-surgical setup; this procedure could not be performed reliably in the virtual environment and then be replicated in the operating room. Third, collision detection is a software property wherein contact between two virtual objects, in this case, teeth, would not allow them to pass through each other. This methodology is an essential property in terms of developing a final occlusion and is a prop- erty poorly developed in current software packages. As a result, the fabri- cation of surgical splints virtually for a final occlusion is not yet routine. The final splint notwithstanding, the intermediate splint is the site where the true benefit of this technology could be realized. CT scans allow for a true 3D evaluation of a given deformity and permit 3D cepha- lometric analysis such that asymmetries can be quantified better. Yaw deformities, which are notoriously difficult to measure clinically, now can be measured accurately in all three planes of space. This method of measurement allows a maxilla to be centered in the face, as desired. An intermediate splint can be made to reposition the maxilla at this point. Collision detection is not relevant here, nor is the tactile appreciation of a Setup. 80 Edwards This methodology could eliminate the error and labor of the most time consuming part of these cases – the intermediate splint. Difficulties arise when a maxilla must be segmented. This segmentation is based on the final occlusion and, as stated previously, because of the non-tactile nature of the planning and the lack of collision detection, segmentation is difficult to accomplish. These techniques are coming slowly into clinical practice, but much work remains to be done to demonstrate consistent accuracy prior to them becoming routine. The general workflow for such an orthognathic case using com- mercially available systems is as follows (Swennen et al., 2009). A 3D data set is acquired with a CT scanner, which may be either a CBCT or conventional multi-slice scanner. This scan and data set must encompass all relevant anatomy for analysis and surgical simulation and will pre- clude the use of some limited field of view CBCT scanners. A set of models is scanned either with the CT scanner or a surface scanner. These image sets (i.e., the CT scan and the stone models) are fused to yield a relatively scatter-free image set for cephalometric analysis and surgical simulation. A Cartesian coordinate system is established in essence to define a natural head posture and serve as reference for aberrations in symmetry and form (Swennen and Hausamen, 2006). Alternatively, a registration of natural head posture can be incorporated into the treatment plan, as described by Xia and Teichgraeber (2005). The anatomy can be sur- veyed, the deformity quantified and a surgical plan devised to correct it. This plan is affected by segmenting the skeleton as would be ac- complished intra-operatively (Fig. 32). After the jaw is segmented and repositioned, an intermediate splint is created virtually and becomes its own data set. This intermediate split then is rapid prototyped and can be taken to the operating room to carry out the surgical plan. Several algo- rithms have been proposed for developing a final occlusion in the virtual environment but, as mentioned previously, all have some limitations. Conventional stone models would be used to develop a final occlusion and then a final surgical splint could be made by conventional means. Again, the real potential here is elimination of multiple laborious steps in Surgical splint fabrication and reducing the potential for error that can accumulate over the several steps of model surgery. 81 Computer-Assisted Surgery Figure 32. Surgical treatment objective developed by segmenting and repositioning the mandible, chin and maxilla. Most studies have shown model surgery to be generally accurate at a submillimetric level. It is likely that asymmetric cases, especially those with cants and yaw deformities, will suffer poorer levels of accu- racy with conventional means and thereby fare better in this new para- digm. Even if the results are equivocal in terms of accuracy, this is a technology that will interest surgeons because of the resultant time sav- ings in a climate of diminishing reimbursement for this type of surgery. CONCLUSIONS Advances in computer-based treatment planning continue to de- velop rapidly and offer many advantages to patients and surgeons alike. Incorporation of these technologies at this stage is far from being pre- scriptive and standardized and, as such, much remains to be done to compare the different techniques, their outcomes and cost effectiveness. 82 Edwards REFERENCES Christensen, A. Tactile surgical planning using patient-specific anatomic models. In: Bell WH, Guerro CA, eds. Distraction Osteogenesis of the Facial Skeleton. Hamilton: BC Decker 2007:99-113. Fushima K, Kobayaski M., Konishi H, Minagichi K, Fukuchi T. Real- time orthognathic surgical simulation using a mandibular motion tracking system. Comput Aided Surg 2007; 12:91-104. Ludlow JB, Davies-Ludlow LE, Brooks SL, Howerton WB. Dosimetry of 3 CBCT devices for oral and maxillofacial radiology: CB Mer- curay, NewTom 3G and i-CAT. Dentomaxillofac Radiol 2006:35: 219–226. Ludlow JB, Ivanovic M. Comparitive dosimetry of dental CBCT devices and a 64-slice CT for oral and maxillofacial radiology. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008:106:106-114. Metzger MC, Hohlweg-Majert B, Schwarz U, Teschner M, Hammer B, Schmelzeisen R. Manufacturing splints for orthognathic surgery using a three-dimensional printer. Oral Surg Oral Med Oral Pathol Oral Ra- diol Endod 2008; 105:e1-7. Metzger MC, Schon R, Weyer N, Rafii A, Gellrich NC, Schmelzeisen R, Strong BE. Anatomical 3-dimensional pre-bent titanium implant for orbital floor fractures. Ophthalmology 2006; 113:1863-1868. Metzger MC, Schon R, Zizelmann C, Weyer N, Gutwald R, Schmel- zeisen R. Semiautomatic procedure for individual preforming of tita- nium meshes for orbital fractures. Plast Reconstr Surg 2007; 119:969– 976. . Mischkowski RA, Zinser MJ, Kubler AC, Krug B, Seifert U, Zoller JE. Application of an augmented reality tool for maxillary positioning in orthognathic surgery: A feasibility study. J Craniomaxillofac Surg 2006:34:478-483. Olszewski R, Villamil MB, Trevisan DG, Nedel LP, Freitas CM, Rey- chler H, Macq B. Towards an integrated system for planning and as- sisting maxillofacial orthognathic surgery. Comput Methods Pro- grams Biomed 2008;91:13–21. Roberts JA, Drage NA, Davies J, Thomas D.W. Effective dose from cone beam CT examinations in dentistry. Br J Radiol 2009;82:35-40. Schramm A, Suarez-Cunqueiro MM, Rucker M, Kokemueller H, Bor- mann KH, Metzger MC, Gellrich NC. Computer-assisted therapy in 83 Computer-Assisted Surgery orbital and mid-facial reconstructions. Int J Med Robot 2009;5:111- 124. Smith MH, Flanagan CL, Kemppainen JM, Sack JA, Chung H, Das S, Hollister SJ, Feinberg SE. Computed tomography-based tissue engi- neering scaffolds in craniomaxillofacial surgery. Int J Med Robot 2007;3:207-216. Suomalainen A, Kiljunen T, Kaser Y, Peltola J, Kortesniemi M. Dosime- try and image quality of our dental cone beam computed tomography scanners compared with multi-slice computed tomography scanners. Dentomaxillofac Radiol 2009:38:367-378. Swennen GR, Mollemans W, De Clercq C, Abeloos J, Lamoral P, Lip- pens F, Neyt N, Casselman J, Schutyser F. A cone-beam computed tomography triple scan procedure to obtain a three-dimensional aug- mented virtual skull model appropriate for orthognathic surgery plan- ning. J Craniofac Surg 2009:20:297-307. Swennen GRJ, Schutyser FAC, Hausamen JE. Three Dimensional Cephalometry. Berlin: Springer 2006. Uechi J, Okayama M, Shibata T, Muguruma T, Hayashi K, Endo K, Mizoguchi I. A novel method for the 3-dimensional simulation of or- thognathic surgery by using a multimodal image-fusion technique. Am J Orthod Dentofacial Orthop 2006;130:786-798. Xia JJ, Gateno J, Teichgraeber JF. Three-dimensional computer-aided surgical simulation for maxillofacial surgery. Atlas Oral Maxillofac Surg Clin North Am 2005;13:25-39. Xia J, Ip HH, Samman N, Wong HT, Gateno J, Wang D, Yeung RW, Kot CS, Tideman H. Three-dimensional virtual reality surgical plan- ning and soft-tissue prediction for orthognathic surgery. IEEE Trans Inf Technol Biomed 2001;5:97-107. 84 LASER SHARP ORTHODONTICS John J. Graeber ABSTRACT The diode laser is one of the wavelengths found in the near infrared range of invisible thermal radiation band of the electromagnetic spectrum. The 810 nm wavelength is absorbed by oral tissues that contain the chromophore melanin and/or the molecule oxyhemoglobin. Diode lasers are available from various manufacturers at a relatively low cost, are small in footprint size, easy to operate and will incise oral tissues without bleeding. They are not absorbed by any commonly used dental materials. When used in contact, irradiated tissue is va- porized. Out of contact, these wavelengths can affect tissue therapeutically without surface changes. Diode lasers are useful for performing a wide variety of ancillary pro- cedures in orthodontic treatment. Within the framework of case preparation, procedures they are useful in clinical crown lengthening, operulectomy, frenec- tomy and exposure of temporary anchorage devices. Diode lasers usually are used at low power settings that often only require the use of topical anesthetics. One of the most beneficial treatments in orthodontics is the ability to uncover teeth that are slow to erupt, enabling orthodontic practitioners to shorten treat- ment times. Having the ability to alter the gingival heights can aid in bracket placement into more ideal positions. Tissue encroachment into orthodontic ap- pliances also can be managed better by the orthodontic practitioner. Bloodless incisions aid in controlling the operative field by creating ideal dry environment for appliance bonding. Lasers treatment of aberrant frenula can be far less invasive than tradi- tional techniques. Diode lasers are particularly useful in treating herpetic and aphthous lesions non-invasively. Transseptal fiberotomy technique is simplified and enhanced by the delayed healing of the wound. Post-treatment gingival hy- perplasia removal is enhanced with a fiberoptically delivered infrared diode la- ser that is not absorbed by tooth structure. Technically difficult procedures such as the tongue-tie release are performed much more easily by lasers due to the hemostatic effects. - A number of different laser devices have become available to or— thodontic practitioners since the first FDA approval of an Nd:YAG laser 85 Laser Sharp Orthodontics specifically for use in dentistry in 1990. The early dental lasers were not only large in size but also were highly expensive instruments in the $50,000 price range. Other disadvantages of this wavelength (1064 Nanometers [nm]) included absorption by certain metals (Watanabe and Baba, 2007). As a result of these disadvantages, few of these units were sold to orthodontic providers. WHY DIODE LASERS2 In 1996, a new type of laser was approved by the FDA, the 810 nm diode or semiconductor laser. Advantages over the initially approved wavelength (Nd:YAG; Fig. 1) included small size, simple controls and a vastly reduced acquisition cost. Since introduction, diode lasers have en- joyed unprecedented acceptance by the dental profession, with market penetration surpassing 15% of the North American dental office market (Goff, 2009). Other advantages over earlier systems included safe use around restorative materials including stainless steel and titanium, be- cause this wavelength is not absorbed by these materials when used at the low power levels normally used on oral soft tissues. As the field of orthodontics began to attract more adult patients, the need became apparent that a certain degree of case finishing of soft tissue was both desired if not demanded by the more aesthetically con- scious patient. Early recognition of this need was made by Sarver and Yanosky (2005a,b; Sarver, 2006). In addition, early treatment philosophy and techniques sometimes require altering tissue to facilitate eruption to shorten treatment times (Tunison et al., 2008). Further refinements and technical advancement in dental lasers since 1996 have added Erbium, the all-tissue laser, as well as a number of additional wavelengths of diode lasers (910, 940, 980 and 1064 nm). Figure 1 depicts these various wavelengths in the near, mid and far infra- red zones of the electromagnetic energy spectrum. The key to selection of the most appropriate laser wavelength for a particular procedure lies in understanding which wavelength will be absorbed, for example, by gin- gival tissue. Gingiva has coloration primarily due to the variable composition of the pigment melanin. The 810 nm wavelength is absorbed most highly into melanin-containing tissues; therefore, diode lasers will vaporize gin- gival tissues efficiently. In addition, due to the presence of the oxyhemo- globin (Hb) in red blood cells, the diode laser is capable of causing co- agulation within small vessels, allowing virtually bloodless incisions. 86 Graeber Currently Available Dental Laser Wavelengths on the Electromagnetic Spectrum Invisible ºn Radiation Visible Invisible Radiation X-Rays UltraViolet Near infrared Mid Infrared, Far Infrared 400 - 700mm ºº º 2000mm 3000mm AGaas 1064 m L- *" / ºn "Nºvae / Bºas gº. |- º 1340mm 2940nm 10600mm 555mm Inºsaas º: Visible LLLT - 330mm 2730mm Invisible LLLT Other diodes, 940, 1064mm Figure 1. Available dental laser wavelengths. (Courtesy of Dr. Donald Coluzzi, Academy of Laser Dentistry.) The Nd:YAG (1064 nm) has similar absorption characteristics in soft oral tissues as the diode family of lasers, but it is somewhat less co- agulative due to the pulsed wave mode of the beam. Diode lasers are more coagulative because they generally are operated in the continuous Wave mode. By contrast, Erbium wavelengths, while capable of creating inci- Sions in soft tissue because the primary chromophore is water (present in Over 90% of soft tissue) exhibits limited capability of sufficiently deep coagulation to produce necessary hemostasis for bonding techniques (Fig. 2). With the far infrared laser, CO, is so highly absorbed by hy- droxyappetite that it is contraindicated for use in close proximity to tooth Structure and bone without extreme caution. Diode lasers have several distinct advantages over other dental laser devices; the first is cost. Usually the cost of a diode laser is but a mere fraction of Nd:YAG type lasers ($10,000-14,000 vs. $40,000- 80,000). The primary reason for the lower price lies in the cost of com- Ponents. Diode laser energy is produced by tiny wafers of relatively in- ºpensive semiconductors as opposed to rare-earth elements such as Er- bium or Neodymium. 87 Laser Sharp Orthodontics Wavelength (microns) 1.0 Melamin - E Sº Nº. - |- º º S- CD O C - º - C. E- C º C º Diode Nd:YAG Er:YAG CO2 810-1064. 1064 2.940 10600 Figure 2. Approximate absorption curves of oral tissue compounds. (Courtesy of the Academy of Laser Dentistry.) Diode lasers are small and lightweight (Fig. 3). They range from handheld to smaller-than-a-toaster countertop models; most are between two and five pounds in weight. The universal delivery system is a thin fiberoptic cable and dentist-friendly shaped handpiece. Most models have simple controls: power (as expressed in watts) up or down, continu- ous operation or pulsed energy and are used for surgery in a narrow range of power levels from 0.8 to 1.5 watts for most procedures. These rather simple controls facilitate ease of operation as well as shorter learning curves for the new laser practitioner. Under most cir- cumstances, they offer complete hemostasis while efficiently ablating or vaporizing. Unlike electrosurgical devices that have been used for many decades in dentistry, the diodes have no known medical contraindica- tions. Histologically (Fig. 4), diode lasers can create incisions that ex- hibit little overheating of tissue and lateral thermal damage while creat- ing a thin layer of coagulated tissue and little post-operative edema and resulting pain. One disadvantage is that laser incisions will lose some volume of tissue as opposed to blade incisions that essentially divide tis- sue with virtually no loss in volume. 88 Graeber Figure 3. Some currently available diode laser models. A. Diodent 980 nm (Hoya ConBio, Fremont, CA). B: Odyssey 810 nm (IvoclarWivadent, Amherst, NY). C. EZlase, Biolase, 810 nm (San Clemente, CA). D. Kavo GENTLEray 980 nm (Kavo, Lake Zurich, Switzerland). Figure 4. Laser interaction with soft tissue. Incision occurs at contact. (Courtesy of the Academy of Laser Dentistry.) CASE PREPARATION PROCEDURES - Many procedures are available that a properly trained orthodon- tic practitioner should be able to add to his or her treatment options. 89 Laser Sharp Orthodontics Among the possible procedures included are soft tissue crown lengthen- ing (gingivectomy/gingivoplasty) for proper bracket positioning and eruption assistance procedures such as operculectomy and frenectomy (Figs. 5 and 6). Figure 5. Second molar soft tissue impaction exposure using 810 nm diode laser at 1.0 watts with continuous wave. A. Before exposure. B. After occlusal expo- sure. C. After occlusal and buccal exposure. D. Bracket placement. Figure 6. Simple operculectomy required by premature loss of primary incisor. 810 nm diode laser 0.7 watt, continuous wave. A. Prior to exposure. B. After CXDOSure. 90 Graeber When primary teeth are lost prematurely, fibrous changes in overlying tissue often can prevent normal eruption. This change may lead to crowding or impaction of permanent successor teeth. While con- troversial in the pediatric community, proper eruption sequence of the permanent dentition is desirable in normal growth and development (Kochhar and Richardson, 1998). In the erupting tooth, there is no firm attachment of the periodontal fibers until the 3 mm biologic width has been formed by achieving full eruption. Therefore, buccal tissue can be removed from the partially erupted tooth without damage to any yet-to- be-formed attachment apparatus (Fig. 7). Figure 7. Soft tissue impaction of right maxillary canine. A: Expo- sure by 810 nm at 1.0 watts and continuous wave. B. After heal- ing. C: Full eruption. All soft tissue impactions need to be distinguished from hard tis- Sue So that the appropriate wavelengths or conventional measures are available at the time of surgery. This differentiation may be accom- plished by probing anesthetized tissue with a sharp explorer and after evaluating appropriate imaging options. Temporary anchorage devices (TADS) have made a huge impact On Orthodontic anchorage techniques. Many TAD manufacturers suggest using tissue punches or rotary devices to remove overlying soft tissue to CXpose alveolar bone of the actual sites. This mechanical site preparation 9 | Laser Sharp Orthodontics Figure 8. Palatal impaction in- volving only soft tissue (1.2 watts, continuous wave, 810 nm diode laser). can cause undesirable inflammatory responses, wider than necessary openings and post-operative pain. Most of the unnecessary trauma can be reduced if the site is prepared by an appropriate wavelength laser exci- sion. A diode laser is safe to use in appropriate fluences (i.e., energy, pulsing, fiber size, time of treatment) over and in intimate contact with bone. Once TADs are placed, hypertrophic tissue can be managed easily with a diode laser if it impedes functioning of the attachment. With early treatment of the primary or mixed dentition, it occa- sionally is necessary to perform a frenectomy (Figs. 9 and 10) in manag- ing and treating diastemas. The diode laser should be considered the wavelength of choice with regard to hemostasis, post-operative pain and lack of tissue regrowth. - Figure 10. Seven-year-old patient with labial frenum problem. A Pre- treatment. B. One-week post-operative. C. One-year post-operative. D. Five- year post-operative (1.0 watt, continuous wave, 810 nm diode laser). 92 Graeber Figure 9. Seven-year-old patient with diastema caused by high and thick maxillary labial frenum (0.7 watt, continuous wave, 810 nm. diode laser). 93 Laser Sharp Orthodontics CASE MANAGEMENT A number of clinical issues occur during active orthodontic treatment for which a diode laser can be utilized to better manage and speed treatment. Control of hemorrhagic granulomatous tissue or hyper- plasia will facilitate bonding/rebonding. Orthodontic appliances can cause both ulcerations of the mucosa and hyperplasia leading to fibroma formation. Other iatrogenic lesions such as traumatic and aphthous lesions (Fig. 11) can become extremely uncomfortable for orthodontic patients. Herpetic outbreaks (Fig. 12) also can make it difficult to treat patients at a given visit, resulting in lost ap- pointment time. While the herpes virus resides within the fifth cranial nerve trunk, occasional outbreaks usually result from localized trauma of the lower lip, potentially caused by orthodontic appliances. These localized lesions easily can be rendered symptomless utilizing the diode dental laser in a non-focused, non-contact mode. When used in non-contact mode, near infrared lasers penetrate through the epithelium and up to 4 mm into the underlying connective tissue, as shown in Figure 13. The coagulative state in the connective tissue has a quieting effect on irritated nerve endings, while there is believed to be a virucidal effect from the direct action of the infrared photonic beam. Figure 11. Aphthous ulcer. 94 - - E. - - Figure 12. Management of herpetic lesion. A. Herpes labialis, day 7. Bullae have opened. B. Immediately post-operative. Raw lesion coagulated. (Courtesy of the Academy of Laser Dentistry.) Figure 13. Histological section of non-contact deep coagula- tion with near infrared wavelength. (Courtesy of the Academy of Laser Dentistry.) It has been reported in personal communications and by direct observation that future herpetic outbreaks do not reappear in the same location. Most often, the lesions are symptom free within minutes and Will advance to end stage within 24 hours after treatment. CASE FINISHING BENEFITS OF DIODE LASERS Many soft tissue procedures can be employed in finishing fixed appliance therapy. Among them are management of hyperplasia, uneven gingival levels and excessive tissue bulk. Mucogingival issues such as frenectomy and lack of attached gingiva as well as necessary transeptal fiberotomy after rotational correction also can be performed. 95 Laser Sharp Orthodontics Among the frequent causes of gingival hyperplasia are a lack of adequate home care as well as the phenomena of tissue fill-in under fixed appliance components. While much of this gingival overgrowth can sub- side after appliances have been removed, it does not always correct itself back to normal pre-treatment contours. With increasing patient esthetic expectations both in the adolescent and adult patient populations, there is a need for immediate correction of these conditions following appliance removal. Arranging appropriate surgical referrals may not be timely or meet patient expectations of treatment responsibility. The orthodontic practitioner then, with a bloodless and often needleless laser procedure, can correct these post-treatment negative outcomes quickly and pain- lessly with vastly shortened healing courses (Figs. 14-16). As oral mucosa is traumatized with fixed appliances chronically, the tissue may react by forming a fibrous tumor or fibroma (Fig. 17). This lesion is found most commonly on cheek mucosa or on the lateral border of the tongue. This lesion is removed easily by way of a diode laser by dissecting through the loose connective tissue between the dense fibrous tissue of the lesion and underlying musculature. Figure 14. Minor correction of post-treatment uneven zenith shapes, maxillary central incisors. A. Before laser treatment. B. Af- ter laser treatment. C. Two years post-treatment. 96 Graeber Figure 15. The reduction of papil- lary hyperplasia with a diode la- ser. A. Before laser treatment. B: After laser treatment. C. Three weeks post-treatment. Figure 16. Transeptal fiberotomy. (Courtesy of the Academy of Laser Dentistry.) 97 Laser Sharp Orthodontics Figure 17. Fibroma from trau- matic occlusion. A. Pre-treatment. B: Post-laser therapy. C. After healing. Patients who exhibit poor oral hygiene often may produce ede- matous gingival conditions (Fig. 18). Diode lasers can be utilized in con- trolling hemorrhage from these tissues. ANESTHETIC OPTIONS While the use of conventional injectable local anesthetics gener- ally is not a part of normal orthodontic treatment routines, the inclusion of some of the surgical options will require anesthesia. For the excision of thick tissue or when the incision will penetrate deep into connective tissue, injected local anesthetic agents will be necessary. Whenever the lesions are purely in the epithelial layers or involve thin tissues, however, topical agents can be adequate for intraoperative pain control. Conven- tional topical agents (e.g., 20% Benzocaine") often are inadequate for these minor surgical procedures. Newer formulations will penetrate mu- cosa more efficiently or eutectic mixtures of local anesthetics com- pounded by local pharmacists by practitioner prescription. TRAINING OPTIONS The introduction of the diode laser to the dental profession has facilitated a simplification of many oral and periodontal surgical tech- niques. Operation of these devices is relatively straightforward compared 98 Graeber ment. to many of the older laser wavelengths. The prudent orthodontic practi- tioner would be well advised to seek additional training in both the con- Ventional surgical modalities described in this chapter as well as in spe- cific laser device training. A significant number of continuing educa- tional opportunities in oral and periodontal surgery are available. Most laser manufacturers offer device specific training opportu- nities for their equipment in single and multiple day hands-on experi- ences. Internet-based education also is available. In addition, the Acad- emy of Laser Dentistry offers laser training in multiple wavelengths at major national and regional meetings as well as at its annual international meeting. Certification at the Standard and Advanced Proficiency levels is offered by the Academy of Laser Dentistry for practitioners, hygienists and laser safety officers. PRACTICE MANAGEMENT CONSIDERATIONS Many orthodontic practitioners are interested in adding lasers to their treatment regimens for the purpose of enhancing the speed of treat- ment by uncovering late erupting teeth or by soft tissue crown lengthen- ing for ideal bracket positioning. By themselves, these laser techniques Will permit shorter treatment times, but it will be difficult to measure re- turn on investment for this expenditure directly. There are, however, many opportunities to add revenue to the practice by providing laser procedures on a fee-for-service basis. If this were the case, it would be appropriate to add suitable lan- guage to the orthodontic contract used by most orthodontic practitioners. Further, including a menu of surgical services available with a fee listing is an ethical way to inform patients of possible additional charges that are Outside of the normal orthodontic range of services. 99 Laser Sharp Orthodontics CONCLUSION The development of the diode laser offers the opportunity for or- thodontic practitioners to shorten treatment times for their patients. The laser also may be employed to enhance aesthetic outcomes of orthodontic treatment in a simplified manner. If desirable, diode lasers can add reve- nue to the orthodontic practice by offering a wider variety of services for its patients. REFERENCES Goff S. Purchasing trends survey 2009. Dental Practice Report: www.dentalproductsreport.com. Karu, T. The science of low power laser therapy. Amsterdam: Gordon and Breach, 1998. Kochhar R, Richardson A. The chronology and sequence of eruption of human permanent teeth in Northern Ireland. Int J Paediatr Dent 1998; 8:243–52. Sarver DM. The use of the 810 nm diode laser: Soft tissue management and orthodontic applications of innovative technology. Pract Proced Aesthet Dent 2006;18:S7-13. Sarver DM, Yanosky MR. Principles of cosmetic dentistry in orthodon- tics. Part 2. Soft tissue laser technology and cosmetic gingival con- touring. Am J Orthod Dentofacial Orthop 2005a;127:85-90. Sarver DM, Yanosky MR. Principles of cosmetic dentistry in orthodon- tics. Part 3. Laser treatments for tooth eruption and soft tissue prob- lems. Am J Orthod Dentofacial Orthop 2005b;127:262-264. Tunison W, Flores-Mir C, El Badrawy H, Nassar U, El-Bialy T. Dental arch space changes following premature loss of primary first molars: A systematic review. Pediatr Dent 2008:30:297-302. 100 TREATMENT RESOLUTIONS FOR PERIODONTALLY COMPROMISED MANDIBULAR MOLARS Myron Nevins and David M. Kim ABSTRACT The treatment of multi-rooted teeth demonstrating interradicular loss of the pe- riodontium continues to present a significant challenge to the therapist. Many proposals have addressed this dilemma, but until recently none has satisfied the definition of success of periodontal regeneration as stated by the American Academy of Periodontology. Such regeneration requires the formation of new cementum, bone and periodontal ligament on a root surface previously exposed to disease in the human model. New information produced by treating angular defects with a variety of materials has been applied to the treatment of Class II defects in mandibular molars. The application of the principles of tissue engi- neering with purified growth factors appears to have increased the likelihood of achieving this elusive goal greatly when treating a problem that is found in a significant percentage of periodontal patients. Platelet-derived growth factor is a natural biologic molecule that regulates key cellular events including chemo- taxis of progenitor cells, proliferation of the cells and intercellular matrix pro- duction. It also is proangiogenic and aids the stimulation of neovas-cularization at the regenerative site. It is necessary to be aware that not all defects can be treated successfully, and the need to correct problems posed by the extraction of periodontally compromised teeth and their replacement with osseointegrated implants is present. Contemporary periodontics has witnessed the previously un- precedented predictability of dental implant therapy and periodontal re- generation. The clinician, therefore, is empowered to provide definitive Solutions for periodontally compromised patients that lead to a collision of concepts and the need to make a clinical decision. Our focus is on the treatment of compromised mandibular mo- lars where tooth structure will not be the determinant for treatment. The prime dictating factors will be interproximal intrabony pockets and fur- cation invasion. When is the tooth treatable with an improved, favorable 101 Periodontally Compromised Molars prognosis and when would the patient be better served with implant treatment? The parameters to consider in addition to predictability are cost, pain and comfort of the treatment as well as possible confounding variables (i.e., smoking, diabetes, medications). Mandibular molar intraradicular areas generally are described by the horizontal degree of invasion of inflammatory disease as follows (Fig 1; Ricchetti, 1982): 1. Class I recipient invasion of the furcation limited to 3 mm horizontal loss; 2. Class II – deeper loss of attachment than a Class I, but not a Class III; and I loſ II liq III Figure 1. Cross-sectional and frontal-sectional drawings of mandibular molar, demonstrating pocket configuration and bone loss generally seen with each classification of furcation involvement (Ricchetti, 1982; re- printed with permission from Quintessence Publishing Co., Inc.). 102 Nevins and Kim 3. Tooth loss of periodontal attachment from the buccal to the lingual. Since all periodontal treatment regimes are predicated on a result that is cleansable by the patient and hygienist, a minimal probing depth is preferred. Recent publications demonstrate the presence of periodontal pathogens, the red complex bacteria, almost entirely in probing depths greater than 5 mm (Levy et al., 1999, 2002). Recognition of a Class I furcation invasion should result in an appropriate solution to prevent it from extending into a Class II, which is much more difficult to treat. Non-surgical treatment may be appropriate, but must be monitored real- istically so that Class I furcation invasions that are non-responders to this regimen should be treated by surgical flap entry with or without osteo- plasty to accomplish a minimal sulcus that facilitates dental hygiene. Several treatment approaches have indicated that periodontal regenera- tion of Class II furcal invasion is an attainable goal and needs to be con- sidered. They include barrier membranes with and without grafting mate- rials, coronal repositioning of the flap and the use of tissue engineering. It is necessary to remember that the definition of periodontal regenera- tion is histologic and requires new bone, a new PDL and new cementum on a root surface previously exposed to disease in the human model (Garrett, 1996). Significant excitement accompanied early reports of success with barrier membranes alone for the treatment of human Class II furca- tion invasion, but with clinical cases, many clinicians were unable to rep- licate the results, possibly because the technique was not user friendly (Pontoriero et al., 1988; Lekovic et al., 1989; Yukna et al., 2001). The combination of a barrier membrane with demineralized bone allograft and root chemotherapy provided enhanced success (Schallhorn and McClain, 1988; McClain and Schallhorn, 1993). Recent results also have been encouraging (Bowers et al., 2003). The use of coronally repositioned flap and root chemotherapy was proposed to promote connective tissue attachment to the root and, thus, reduce probing depth and provide a cleansable gingival sulcus (Garrett et al., 1990). Re-examination of the patient population after Some years proved to be disappointing (Haney et al., 1997). A need to provide human clinical evidence of periodontal regen- eration was provided as a result of 28 consecutive Class II furcation treatments, 25 of which were successful (Camelo et al., 2000). Eleven were reopened after one year and appeared significantly improved; one 103 Periodontally Compromised Molars tooth was removed en bloc at a later time to access the histologic result. This tooth remained stable in the presence of a significant buccal Class II furcation and an extensive intrabony defect on the distal surface of the distal root (Fig. 2A). Buccal and lingual flaps were elevated, granulation tissue enucleated and root debridement accomplished with mechanical instrumentation (Fig. 2B). Additional decontamination occurred with a slurry of tetracycline for decontamination (Fig. 2C). Autogenous bone was harvested from the posterior mandible and particle size was reduced with a bone mill. The defects then were filled with the bone graft and covered with a reinforced resorbable membrane. A periodontal dressing protected the area for two weeks and the patient received supragingival plaque removal on a monthly basis for one year. Radiographic observa- tion at that time appeared to suggest radiographic regeneration and surgi- cal reentry demonstrated clinical regeneration (Fig. 2D,E). This proce- dure, although satisfying the proof of principle, is time consuming, costly and requires a high degree, of surgical skills to accomplish. This tooth was removed later en bloc for histologic analysis (Fig. 2F). Traditional approaches for this tooth would result in extraction, bone regeneration and implant treatment or a fixed bridge as reachable goals with a predict- able prognosis. A paradigm change would recognize the value of a growth factor in combination with an osteconductive matrix to treat a Class II furcation invasion. Growth factors, such as platelet-derived growth factor BB (PDGF-BB), are natural biological molecules that mediate and regulate key cellular events (Heldin et al., 1998; Rosenkranz and Kazlauskas, 1999; Heldin, 2004; Cooke et al., 2006; Nevins et al., 2008). The wound healing response is activated when PDGF is released locally during clot- ting by alpha granules of the blood platelets at the site of soft and hard tissue injury (Lynch et al., 1999, 2008). Once released from the platelets, PDGF binds to cell surface receptors to promote rapid cellular migration (chemotaxis) and proliferation (mitogenesis; Lynch et al., 1999; Lynch 2008). In addition, PDGF-BB is pro-angiogenic in that it acts in synergy with endogenous vascular epithelial growth factor (VEGF) to stimulate neovascularization at the defect site (Sato et al., 1993; Bouletreau et al., 2002; Guo et al., 2003). Thus, the dynamic healing nature of PDGF-BB has a potential to stimulate multiple wound healing cascades to promote the regeneration of the periodontium (Fig. 3; Hollinger et al., 2008). Pu- rified recombinant human PDGF-BB (rhPDGF-BB), in combination with various matrices, underwent a series of rigorous and extensive pre- clinical and clinical investigations to test its safety and efficacy (regen- 104 Nevins and Kim Figure 2. A. A significant Class II furcation defect has compromised this man- dibular molar. B: Full-thickness flaps with sulcular and vertical releasing inci- Sions are designed to provide visibility and access. C. Meticulous root prepara- tion has been performed and the root has been treated with tetracycline paste for four minutes. All granulomatous tissue is removed and decortications are used to achieve bleeding from the bony defect. Autogenous bone harvested from the tuberosity was grafted into the Class II furcation and osseous defect. A titanium- reinforced membrane was placed to cover the interproximal area and furcation. D. The area is reopened after one year to evaluate the result. The defect shows evidence of clinical regeneration but requires minor osteoplasty to refine the interproximal bone between these molars. E. Radiograph of the defect one year post-treatment. F. The surgical block section reveals new cementum (NC), new bone (NB) and a functional new periodontal ligament (NPDL). No root resorp- tion or ankylosis is evident and the junctional epithelium (JE) ends before en- Croaching on the furcation (toluidine blue-basic fuschin stain; Camelo et al., 2000; reprinted with permission from Quintessence Publishing Co., Inc.). 105 Periodontally Compromised Molars E F Figure 3. A. The growth factor-enhanced matrix incorporates rhPDGF-BB in a tissue-specific scaffold material such as bone autograft, allograft or synthetic fl- TCP granules. This mixture is packed in a periodontal bone defect. B. rhPDGF- 106 Nevins and Kim eration of bone, cementum and PDL; Lynch et al., 1989, 1991; Matsuda et al., 1992; Rutherford et al., 1992; Wang et al., 1994; Giannobile et al., 1994, 1996; Cho et al., 1995; Green et al., 1997; Howell et al., 1997; Yu et al., 1997; Haase et al., 1998; Mumford et al., 2001; Camelo et al., 2003; Nevins et al., 2003b, 2005, 2007; Ojima et al., 2003; Papadopou- los et al., 2003; McGuire et al., 2006; Sarment et al., 2006; Ridgway et al., 2008). The first pre-clinical study conducted by Lynch reported in- creased cellular activity with new bone, cementum and PDL formation when treating naturally occurring periodontal defects in beagle dogs with rhpDGF-BB (Lynch et al., 1989, 1991; Matsuda et al., 1992). Numerous pre-clinical and clinical studies followed that provided evidence for the mechanism of action of this vital growth factor (Lynch et al., 2008). Howell conducted the first promising clinical trial with a combination of rhPDGF-BB/rhſ GF-I to treat intraosseous defects (Howell et al., 1997). Recent clinical trials combining rhPDGF-BB with compatible matrices indicate that the application of 0.3 to 5.0 mg/ml of rhPDGF-BB with ei- ther allograft or ſ-tricalcium phosphate (ſ-TCP) prove to be efficacious (Camelo et al., 2003; Nevins et al., 2003b, 2005, 2007; McGuire et al., 2006; Ridgway et al., 2008). RhpDGF-BB currently is available to pur- chase in a package of 0.3 mg/ml gel formulation and ſ-TCP, a biocom- patible osteo-conductive, synthetic scaffold (GEM 21S", Osteohealth Co. USA). Periodontal therapies aimed at regenerating the lost or damaged periodontium have relied for many years on nonviable, osteoconductive matrices (Bowers et al., 1989). Even though they have been effective clinically in some cases (e.g., deep intrabony contained defects), they have not been predictable in the wide variety of bone defects (e.g., less contained one or two wall defects) encountered routinely by the practi- tioner (Camelo et al., 2003). In addition, there may be differences with respect to their regenerative capacity from a histologic point of view (Nevins et al., 2007). The proof of principle confirmation of true perio- dontal regeneration requires evidence garnered from human histologic documentation (Bowers et al., 1989a,b,c, 1991; Reynolds and Bowers *— (Figure 3 Continued) BB is released directly into the site over time. C. rhPDGF-BB helps recruit and stimulate bone- and ligament-forming cells. D and E. Bone and periodontal ligament regenerate and mature. F. Restoration of normal bone structure and tooth function (Lynch et al., 2008; reprinted with permission from Quintessence Publishing Co., Inc.). 107 Periodontally Compromised Molars 1996; Nevins et al., 2000, 2003a; Camelo et al., 2001). It is unreasonable to obtain histologic evidence for all treated cases, so clinicians rely on clinical, radiographic and sometimes surgical re-entry of treated clinical cases to determine the efficacy of the regenerative treatment (Caton, 1997; Machtei, 1997; Carranza et al., 2006). This approach is acceptable if previous studies with the material have fulfilled the definition of periodontal regeneration. One of the greatest challenges in the field of periodontics contin- ues to be the treatment of multi-rooted teeth demonstrating furcation in- vasion due to anatomic characteristics that make treatment difficult and unpredictable with current therapies (Camelo et al., 2003). Although there have been reports of "clinical success" in the treatment of Class II furcations, the first clear histologic demonstrations of periodontal regen- eration (new bone, PDL and cementum) in human Class II furcation de- fects were published by Camelo and coworkers (2003; Fig. 4). The prin- ciples of tissue engineering were applied using a purified growth factor together with demineralized freeze-dried bone allograft (DFDBA) to stimulate a regenerative response (Camelo et al., 2003). Tooth crown 108 Nevins and Kim To date, no one has provided this level of evidence for the treat- ment of Class III furcations (Pontoriero and Lindhe, 1995). It is prudent, therefore, to stop the problem at the Class II level. Class III furcations offer three possible treatments: 1. Maintenance as is: 2. Root re-section (Carnevale et al., 1991, 1997); and 3. Extraction before excessive bone loss and implant treatment is impaired. Contemporary periodontal regeneration for infrabony pockets in- creasingly has become predictable with the advent of new products. Bowers and coworkers' infrabony study (1989a,b,c) demonstrated perio- dontal regeneration with human histologic analysis using DFDBA. Since then, other regenerative products including xenografts with and with- <- Figure 4. A: A periodontal probe reveals a 5 mm, primarily horizontal Class II furcation invasion on the lingual aspect of a mandibular molar. Root condi- tioning for decontamination was accomplished with tetracycline paste, which was applied for four minutes and rinsed with saline. B: rhPDGF has been ap- plied to the root surface. The allograft was hydrated with the rhPDGF and packed into the defect. C. Histologic section of the molar (Fig. 4A), obtained nine months after treatment with rhPDGF mixed with allograft, shows complete periodontal regeneration within furcation. New bone (NB) formed in continuity with original bone and new periodontal ligament is indistinguishable from origi- nal periodontal ligament apical to the original defect. Periodontal ligament fibers are perpendicular, traversing between new cementum (NC) and bone (toluidine blue-basic fuschin stain; original magnification X6.3). D: Higher magnification of boxed coronal area (Fig. 4C). Complete fill of the original defect area, with NB, periodontal ligament (PDL) and new cementum (NC), is present. NB is equal in density to the original alveolar bone. There is no epithelial downgrowth into the furcation (long junctional epithelium), although no membrane was used (toluidine blue-basic fuschin stain; original magnification X6). Tooth root = TR. E: Higher magnification of the boxed root notch area (Fig. 4C), showing TR, newly regenerated bone (NB), new PDL and NC. The PDL is well organized and its fibers are perpendicular and tangential between the NC and NB. The new PDL is the same width as the original PDL and contains abundant blood vessels (BV; toluidine blue-basic fuschin stain; original magnification X25). Old bone = OB; (arrow) base of calculus notch. Note the difference of cemental thickness where the arrow indicates the union of acellular and new cellular cementum (Camelo et al., 2003; reprinted with permission from Quintessence Publishing Co., Inc.). 109 Periodontally Compromised Molars out barrier membranes have Satisfied the definition of periodontal regen- eration with human histology (Camelo et al., 1998, 2001: Nevins et al., 2003a). The regeneration of periodontium lost to inflammatory disease has been accomplished with the utilization of biologically active media- tors matched with appropriate matrices. Human histological studies on intrabony defect lesions have been conduced to demonstrate the robust and substantial periodontal regeneration obtained with the rhpDGF-BB- based therapy (Nevins et al., 2003b, 2005). The defects or experimental teeth were treated with DFDBA that had been hydrated by rhpDGF-BB and the teeth were removed en bloc for histological analyses (Nevins et al., 2003b). The clinical result revealed substantial improvements in ver- tical and horizontal probing depths as well as attachment levels over base- line levels for all sites treated with rhpDGF-BB. → Figure 5. A: Pre-operative photograph of the maxillary right canine with a 15 mm probe in place. B: Intra-operative view of the maxillary incisors and canine. The base of calculus is marked (*). C. Following reflection of a full-thickness flap and root debridement, 6 mm one-wall defects are visible on the mesial and distal aspects of the canine. There is a base of only 1 mm, offering incomplete containment for the protection of a blood clot. The horizontal line represents the maximum vertical level of bone. D: Post-surgical radiograph of the site with rhPDGF-BB in the bone allograft, taken nine months post-treatment. The notches (arrows) were placed at the time of surgery at the apical extent of the calculus. E. Histologic section of the canine taken nine months post-treatment with rhPDGF-BB mixed with bone allograft. Regeneration of clinically new attachment apparatus is evident. New bone (NB) is coronal to the level of old bone (OB) and the notches. The solid line demarcates the original bone from NB A physiologic periodontal ligament (PDL) clearly is evident coronal to the notches (N) and adjacent NB (toluidine blue-basic fuschin stain; original magni- fication X2.5). New cementum = NC. F. Higher magnification of the boxed area in Figure 5E. Regeneration of attachment structures, including a thin layer of NC, adjacent new PDL and NB, is evident. New blood vessel formation also is apparent. The new bone is a dense construct of lamellar and woven bone and appears to be undergoing normal remodeling. The new PDL is well organized with bundles of collagen fibers coursing perpendicularly from the new bone to the root surface (toludine blue-basic fuschin stain; original magnification X25). Alveolar crest = AC (Nevins et al., 2003a; reprinted with permission from Quin- tessence Publishing Co., Inc.). 110 Nevins and Kim Histological analyses revealed robust periodontal regeneration in rhPDGF-treated sites with significant amounts of new bone, cementum and PDL, and attachment level improvement for intrabony defects (Fig. 5). | || Periodontally Compromised Molars Once the proof of principle study was completed, it was neces- sary to conduct a randomized controlled trial to establish predictability of this treatment modality. A large, multi-center, randomized controlled blinded human clinical trial evaluating the safety and efficacy of rh PDGF-BB in combination with particulate B-TCP for the treatment of | 12 Nevins and Kim <- Figure 6. A: Initial pretreatment radiograph. B: The distal surface of the man- dibular right canine has probing depths of 8 to 9 mm. C. The baseline osseous defect on the mandibular canine indicates a significant loss of periodontal at- tachment and the prognosis is questionable. The osseous lesion is deep and pri- marily uncontained. Meticulous debridement and root instrumentation have been completed. D: The defect has been filled with a scaffold of ſº-TCP mixed with rhPDGF-BB. E. The flaps are coated to cover the surgical site. F: Healing at three days. Note the rapidity of maturation of the soft tissues. G. Appearance of the defect on reopening to correct a small residual osseous discrepancy, one year post-surgery. H. Radiographic appearance at one year. I. Five-year post-surgical radiograph (Nevins et al., 2008; reprinted with permission from Dr. Marc Nevins and Quintessence Publishing Co., Inc.). intrabony periodontal defects was conducted (Nevins et al., 2005). RhPDGF-BB-based therapy has demonstrated an increased clinical at- tachment, an increased linear radiographic bone growth and significantly decreased pocket depth (Fig. 6). To demonstrate the sustainability of the achieved results from this clinical trial, repre-sentative cases have been selected for the long-term clinical and radiographic review (at least 24 months; McGuire et al., 2006). These selected cases illustrated that the results obtained during the initial six months period (i.e., CAL, percent bone fill and linear bone growth) remained stable and steady for at least 24 months post-surgery (McGuire et al., 2006). These studies superim- posed on previous proof of principle studies with human histology pro- vide the predictive confirmation important to patient treatment decisions. There are frequent occasions, however, when the first and/or second mandibular molars are missing or damaged beyond treatment; osseointegration provides a safe and efficacious answer for tooth re- placement. Successful results have been recorded in the 95th percentile in this region of the dentition when there is sufficient bone to accommo- date implants (Nevins and Langer, 1993). It is necessary to make a three- dimensional radiograph to accurately assess bone volume and density in addition to the position of the inferior alveolar nerve before initiating a mandibular molar treatment plan. A small height of bone above the canal may guide the discerning clinician toward periodontal regeneration and/or root resection followed by restorative dentistry. The state of repair of tooth structure, the length of clinical roots (that portion of the tooth embedded in bone), pre-existing endodontics and the patient health pro- file all help in determining the appropriate course of treatment. 113 Periodontally Compromised Molars If the first and second molars are in place but have Class III fur- cations and present with long roots, root resection is a predictable alter- native (Fig. 7A, B, Carnevale et al., 1991). If the tooth structure is intact, the removal of the mesial roots allows for a fixed restoration with small edentulous spans (Fig. 7 C, D). If the roots are too short and narrow, the level of difficulty increases and the prognosis decreases. Thus, there are individual considerations for each patient that when collated, direct treatment. There are many cases when a mandibular first molar is missing or must be extracted. The healed localized edentulous ridge offers an interesting mathematical problem. The mesial-distal width of the missing tooth is 11 mm, too small for two implants and too large for one centrally placed implant (Fig. 8A). The buccal-lingual width may be too narrow for a wide body implant, but a 4 mm diameter will fit nicely. If it is placed in a central position, there will be 3.5 mm embrasures proximally on either side and food retention will be encountered. If it is placed in the position of the distal root and a 2 mm embrasure is allowed mesial to the second molar, a 4 or 5 mm cantilever will extend mesially (Fig. 8B, C: Nevins, 1998b). This can be cleansed easily with dental tape. The mesial buccal cusp of the maxillary molar will articulate in the central fossa of the restoration in centric relation and forces will be transmitted through the long axis of the implant (Fig. 8D,E). The tooth should disarticulate in occlusal excursions. The two most difficult challenges for mandibular molar implants are a lack of bone vertically over the inferior alveolar nerve and a thin, knife-like edentulous ridge. The lack of vertical height can be addressed with multiple short implants placed strategically to avoid the inferior al- veolar nerve (Deporter et al., 2001), can be expanded vertically with dis- traction osteogenesis, by Vertical block grafting in some instances or with a particulate bone placed around partially submerged implants with the assembly covered with barrier membranes (Tinti et al., 1996; Simion et al., 1998). A recent publication demonstrates the use of rhPDGF-BB and a Bio-Oss" block graft to gain significant vertical bone height around implants without a barrier membrane (Simion et al., 2006). The thin edentulous ridge traditionally is expanded horizontally with a cortico-cancellous block that is harvested intra- or extra-orally (Triplett and Schow, 1998). It is common for the patient to be more un- comfortable at the harvest site than at the treatment site. 114 Nevins and Kim Figure 7. A and B. In 1973, the patient presented with a complete (Class III) furcation invasion of the mandibular first molar and a clinical Class II furcation invasion of the Second molar. The presence of the external oblique ridge, as well as the thickness of the cortex, precludes a definitive diagnosis of furcation involvement on the second molar. Clinical diagnosis is of clinical importance. C. Seven-year observation after the mesial roots were sectioned and the prosthesis was constructed using the distal roots. D. Result 24 years after surgical and prosthetic care (Nevins and Cappetta, 1998c, reprinted with permission from Quintessence Publishing Co., Inc.). Another approach is to expand the narrow ridge by bone splitting With a piezoelectric knife along the superior border and then placing a verti- cal bone incision mesially, so as to release the buccal bone plate and fill the area between the buccal and lingual plates with allograft or xenograft (Ver- cellotti, 2000). It is not easy to split narrow mandibular posterior bone ridge because it is so cortical in nature. It is wise to make a vertical bone incision and to use a very fine cutting instrument that can make a fine bone incision. This structure then is covered with a non-resorbable membrane and the buc- cal and lingual flaps advanced to ensure complete soft tissue coverage. 115 Periodontally Compromised Molars Figure 8. A Treatment planning for implant placement in this edentulous space may be difficult. The mesiodistal dimension of the missing first molar does not permit the inser- tion of two implants with appropriate interproximal spaces. B. The implant has been placed in the position of the distal root. C. Radiograph taken following loading of the implant. D. Final restoration of first molar with a cantilevered prosthesis. E. Radio- graphic evidence of crestal bone level maintenance for 14 years (Nevins, 1998b; re- printed with permission from Quintessence Publishing Co., Inc.). | | 6 Nevins and Kim Once again, rhpDGF-BB is used to hydrolyze the grafting material and over the membrane to promote soft tissue healing. It also is recommended that the grafting be performed at the time of extraction to preserve and/or expand the volume of bone before re- sorption occurs (Vercellotti, 2000; Nevins et al., 2006). It is omnipotent that primary flap closure be accomplished to ensure the possibility of SUlCCCSS. In the final analysis, the decision as to providing periodontal re- generation or extraction followed by an osteogenic procedure and a staged implant is multifaceted when treating the compromised mandibu- lar molar area. 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J Perio- dontol 1994;65:429–436. 124 MUCOGINGIVAL INTERCEPTIVE SURGERY OF BUCCALLY ERUPTED PREMOLARS IN PATIENTS SCHEDULED FOR ORTHODONTIC TREATMENT Tiziano Baccetti, Pierpaolo Cortellini, Andrea Vangelisti, Giovanpaolo Pini Prato ABSTRACT Rationale: When a permanent tooth erupts on the buccal or the lingual aspect of the alveolar ridge (ectopic eruption), it entraps and destroys the keratinized tis- sue between its cusps and the corresponding primary tooth. The lack of kerati- nized tissue caused by ectopic eruption can be viewed as a potential risk for gin- gival recession in buccally erupted premolars due to the possibility of an accu- mulation of plaque and/or traumatic tooth brushing during subsequent orthodon- tic treatment. The goal of mucogingival interceptive therapy in patients with buccally erupting teeth scheduled for orthodontics is to prevent the ectopic per- manent tooth from developing the periodontal lesion in its most incipient stage. Procedures have been proposed that utilize the tissue entrapped between the erupting tooth and the deciduous tooth for donor material to create a satisfactory width of the gingiva for the permanent tooth. Aim: The aim of the two longitu- dinal clinical studies presented here is a follow-up evaluation of keratinized tis- Sue width of buccally erupted premolars after mucogingival interceptive surgery (MIS) and orthodontic treatment. Results and Conclusions: Technical aspects of MIS change according to the distance between the buccally erupting tooth and the mucogingival line. Contraindications for MIS are represented by inflamma- tion and lack of attachment of the entrapped gingival. MIS is effective in saving the entrapped gingiva, with an adequate amount of keratinized tissue still present at two- and ten-year follow-up evaluations after fixed appliance therapy. The physiological site of tooth eruption is the center of the al- veolar ridge. This pattern of eruption usually results in an ideal soft tis- sue and osseous anatomy (Hall, 1977). When the permanent tooth erupts on the buccal or the lingual aspect of the alveolar ridge (ectopic erup- tion), it entraps and destroys the keratinized tissue between its cusps and the corresponding primary tooth (Fig. 1). Some modifications of the pe- 125 Mucogingival Interceptive Surgery Figure 1. Gingival tissue entrapped between deciduous molar and buccally erupting premolar. riodontium may be observed after completion of the eruption. There of. ten is a reduction in the height and the width of the cortical alveolar bone and in the amount of keratinized tissue on the side of the deviation (Bowers, 1963; Maynard and Ochbseinben, 1975; Hall, 1977; Artun et al., 1986). Bone dehiscence can be observed as well (Parfitt and Mjör, 1964). These alterations in the periodontium of the permanent tooth may facilitate gingival recession during subsequent orthodontic treatment to align the ectopically erupted tooth, when tooth brushing often either is impaired or traumatic (Pini Prato et al., 2000a,b). 126 Baccetti et al. Several clinical conditions have been considered as causes of ec- topic eruption of permanent teeth (McDonald and Avery, 1983), includ- ing: 1. Abnormal tooth size or shape; 2. Arch length inadequacy; 3. Arch length loss due to interproximal caries of pri- mary molars, ectopic eruption of first permanent mo- lars, delayed eruption after loss or primary teeth, or premature loss of primary teeth; 4. Over-retained primary teeth; 5. Ankylosed primary molars; 6. Presence of supernumerary teeth; and/or 7. Premature occlusal contacts. Beside these conditions, there is experimental evidence that the deep caries in primary molars alters the timing and pattern of eruption of the corresponding permanent teeth in dogs (Aida, 1984). A few studies (Lauterstein et al., 1962; McCormick and Filostrat, 1967; Valderhaug, 1974) suggest that aberrant or accelerated eruption of the permanent teeth, tooth deflections, impactions and rotations may result from in- fected primary teeth in human subjects. Pini Prato and coworkers (2001) demonstrated that deep caries with pulpal involvement could be a factor associated with deviations of the eruption pattern. As stated above, buccally erupting teeth tend to show reduced dimensions of the gingival in that the abnormal eruption of the perma- nent tooth restricts or eliminates the keratinized tissue between the erupt- ing cusp and the deciduous tooth (Agudio et al., 1985). The lack of keratinized tissue caused by ectopic eruption can be viewed as a potential risk for gingival recession in buccally erupted premolars due to the pos- sibility of an accumulation of plaque and/or traumatic tooth brushing during subsequent orthodontic treatment (Wennström, 1996). Recession of marginal tissue may occur, in fact, during ortho- dontic therapy, as shown by both clinical and experimental studies (Maynard and Ochbsenbein, 1975; Boyd, 1978; Coatoam et al., 1981; Steiner et al., 1981; Hall, 1988). Fixed orthodontic appliances make oral hygiene more difficult, thus allowing plaque accumulation. A thin gingi- Val may serve as a locus minoris resistentiae for developing gingival re- cessions in the presence of bacterial plaque (Wennström, 1987; Wenn- ström et al., 1987). The placement of an orthodontic band in a subgingi- Val position (or a bracket close to the gingival margin) in those sites with 127 Mucogingival Interceptive Surgery minimal or no keratinized gingiva may, in the presence of subgingival plaque, favor the apical displacement of soft tissue margins (Ericsson and Lindhe, 1984). Orthodontic appliances also alter tooth brushing technique, which may become more traumatic for the gingival tissue. Evidence also has shown that, regardless of the level of oral hygiene, there is a shift in the subgingival microflora soon after the placement of an orthodontic band or bracket to a periopathogenetic population with increases in anaerobic rods (Atack et al., 1996). Moreover, orthodontic movement of the tooth in the proper arch position will not create additional keratinized tissue (Maynard and Ochbsenbein, 1975; Busschop et al., 1985). At the completion of the therapy, teeth having no keratinized tissue prior to orthodontic treatment remain in the same condition (Coatoam et al., 1981). Creeping of the gingival margin in coronal direction was observed in only a few cases after orthodontic treatment (Boyd, 1978; Dorfman, 1978), especially in the presence of optimal plaque control (Cozzani et al., 1997). Increases in gingival width were recorded in association with extrusion of lower incisors in monkeys (Batenhorst, 1974). The goal of mucogingival interceptive therapy in patients with buccally erupting teeth scheduled for orthodontics is to prevent the ec- topic permanent tooth from developing the periodontal lesion in its most incipient stage. Procedures have been proposed that utilize the tissue en- trapped between the erupting tooth and the deciduous tooth for donor material to create a satisfactory width of the gingiva for the permanent tooth (Agudio et al., 1985; Pini Prato et al., 1993, 1995). The aim of the two longitudinal clinical studies described here is to present the results of a follow-up evaluation of keratinized tissue width of buccally erupted premolars after mucogingival interceptive therapy and orthodontic treatment. A SEVEN-YEAR LONGITUDINAL STUDY Materials and Methods Study Population. A sample of 38 subjects, ages 10 to 13 years, was examined. The subjects had been referred to private practices due to buccal eruption of premolars. Informed consent for therapy was obtained from all the patients and their parents. The investigation was conducted in agreement with the Helsinki Declaration on experimentation involving human subjects. 128 Baccetti et al. Entry Criteria. In order to enter the clinical study, examined sub- jects presented with a buccally erupting premolar on one side of the den- tal arch (test site) and a normally erupting premolar on the contralateral side of the dental arch (control site). Additional criteria for case selection were as follows: 1. The deciduous tooth corresponding to the buccally erupting premolar had to be present on the test site; 2. The gingiva entrapped between the cusp of the erupt- ing premolar and the crown of the deciduous tooth had to be healthy, thick, without any signs of inflam- mation, in the presence of a shallow crevice; and, 3. The probe inserted into the sulcus did not pass api- cally to the entrapped gingiva. Nine subjects were excluded from the study due to the lack of one or more of the inclusionary criteria. All of the remaining 29 subjects (17 females, 12 males) required orthodontic treatment for the reposition- ing of buccally erupting premolars. Surgical Technique. The aim of mucogingival therapy on test sites was to move entrapped keratinized tissue apically to the buccally erupting premolar. Plaque was removed from the deciduous tooth and from the erupting permanent tooth by means of a rubber cup with cleansing paste prior to intervention. After local anesthesia, gingival tissue along with its epithelial lining in immediate contact with the buccally erupting tooth was removed completely. Three different techniques have been described for the mucogin- gival interceptive treatment of buccally erupting premolars, depending on the distance from the donor site (entrapped gingiva) to the recipient site (area located apically to the erupting permanent tooth; Agudio et al., 1985; Pini Prato et al., 1993, 1995): 1. Double pedicle flap (DPF; Fig. 2). This flap is indi- cated when the tip of the cusp of the permanent tooth erupts in the keratinized tissue close to the mucogin- gival junction. An intrasulcular incision is performed extending to the gingival crevice of the adjacent teeth. An incision parallel to the long axis of the tooth al- lows for the elevation of the entrapped gingiva as a full thickness flap, which is moved apically to the 129 Mucogingival Interceptive Surgery erupting cusp. Two horizontal gingival pedicles pro- vide sufficient blood supply to the flap (Fig. 3). 2. Apically positioned flap (APF: Fig. 4). When the cusp of the permanent tooth is erupting in the alveolar mucosa slightly apical to the mucogingival junction, it is not possible to move the entrapped gingiva api- cally to the erupting cusp as a DPF. An intrasulcular incision is performed in correspondence with only the deciduous tooth. Two lateral releasing incisions are made which extend apically to the mucogingival junction and a full-partial thickness flap is elevated which also includes the entrapped gingiva (Fig. 5). 3. Free gingival graft (FGG; Fig. 6). When the cusp is erupting in the alveolar mucosa apically to the mu- cogingival junction, an APF is not practical because of overextended releasing incisions. The entrapped gingiva then is removed completely and used as an epithelialized connective tissue graft (Fig. 7). After the surgical procedures, the previous deepithelialized lac- eration was sutured. The recipient area, apically to the erupting tooth, was prepared by eliminating muscular fibers, if any. The underlying pe- riosteum was left on the donor site. Flaps or grafts were sutured in their proper position by means of subperiosteal silk sutures and the deciduous tooth was extracted. No surgical dressing was applied. - - - - - - - - Figure 2. Double pedicle flap (DPF); schematic diagram. 130 Baccetti et al. Figure 3. A. Buccal eruption of an upper second premolar. The entrapped gin- giva is healthy. The probe shows 1 mm of sulcus depth. B. After deepitheliza- tion of the soft tissue laceration around the erupting cusp, an incision parallel to the long axis of the tooth is performed to raise a double pedicle flap (DPF). C. The flap is sutured apically to the erupting cusp. D. Seven years subsequent to | 3 | Mucogingival Interceptive Surgery (Figure 3 Continued) surgery and five years after the end of orthodontic treat- ment, the second premolar presents an adequate amount of keratinized tissue. Figure 4. Apically positioned flap (APF), SC ematic diagram. -> Figure 5. A. Buccal eruption of a lower second premolar. The entrapped gin- gival is attached to the root of the deciduous tooth. B. An APF is performed. C. Seven years subsequent to surgery and five years after the end of orthodontic treatment, the second premolar presents with an adequate amount of keratinized tissue. 132 Baccetti et al. Mucogingival Interceptive Surgery Figure 7. A. The upper first premolar is erupting buccally in a horizontal posi- tion. B. The entrapped gingiva is used as a free gingival graft (FGG) and sutured perpendicularly to its original position. C: Healing is complete two years after the end of the orthodontic treatment. The previously entrapped gingival is in its original horizontal position. Post-surgical Care. An anti-inflammatory drug (nimeSulide) was prescribed for three days. Sutures were removed after one week. Two weeks after surgery, all patients were instructed to resume mechanical tooth cleaning of the treated areas using a soft toothbrush. Orthodontic Treatment. Orthodontic treatment by means of edgewise technique was started three months after surgery. The duration of orthodontic therapy ranged from 14 months to two years. 134 Baccetti et al. Follow-up. Patients were recalled for monthly professional tooth cleaning during the orthodontic treatment and every six months during the follow-up period. Follow-up periodontal evaluation of both test and control sites in treated patients was carried out three months, two years and seven years Subsequent to mucogingival surgical intervention. Data Collection. The following measurements were recorded: 1. Pre-operative (baseline) measurements. These measurements were performed with a manual pres- sure-sensitive periodontal probe on the deciduous tooth of the test site and on the normally erupted pre- molar of the control site. Measures were rounded to the nearest 0.5 mm. In the test site, probing depth (PDO), bleeding on probing (BOPo; Ainamo and Bay; 1975) and the amount of keratinized tissue (KTo) were recorded on the buccal aspect of the deciduous molar. KTo was measured as the extension of en- trapped gingiva between the gingival margin of the deciduous tooth and the erupting cusp in the test site. In the control site, the above-mentioned measure- ments were recorded on the buccal aspect of the nor- mally erupted premolar. KTo was measured as the dis- tance from the gingival margin to the mucogingival junction. Plaque index (Plo; O’Leary et al., 1972) also was recorded. 2. Post-operative and follow-up measurements. The following measurements were collected on the pre- molars three months, two years and seven years sub- sequent to surgery: probing depth (PD, PD2, PD3); and amount of keratinized tissue (KT1, KT2, KT3), measured as the distance from the gingival margin to the mucogingival junction in both sites and presence of gingival recession (Reci, Recz, Recº). Statistical Analysis. A comparison was performed by means of Student t test for independent samples (P º 0.05) on the amount of keratinized tissue between the test site and the control site in the 29 sub- jects before mucogingival treatment (KTo) and three months (KT), two years (KT2) and seven years (KT3) subsequent to mucogingival treat- ment. An analysis of variance with post hoc test for multiple compari- 135 Mucogingival Interceptive Surgery sons (P º 0.01) was carried out to test the significance of the compari- sons among KTo, KT1, KT, and KT3 within the three surgical techniques. In order to test the influence of initial periodontal measurements on the post-operative width of gingiva, multiple linear regression analy- sis was carried out with the amount of keratinized tissue three months after mucogingival interceptive treatment (KT) as the dependent vari- able, and parameters before treatment (KT), PDO, Plo, BOPO) as inde- pendent variables. All statistical computations were performed with a computer sta- tistical software program. RESULTS Buccally erupting teeth were represented by first upper premo- lars in 14 patients, by first lower premolars in six patients, by second up- per premolars in five patients and by second lower premolars in four pa- tients. According to the indications for the different surgical techniques, eight patients underwent DPFs, ten APFs and 11 FGGs. The immediate and post-operative period was uneventful for all patients. There were no complaints of swelling or pain. The results of the comparisons of the amount of keratinized tis- sue between the test site and the control site (KT0, KT1, KT2, KT3) are reported in Table 1. Table 2 shows the results of the analysis of variance that tested the amount of keratinized tissue at the four examined times within each group of patients treated with a specific surgical procedure. No significant differences were noted between the amount of keratinized tissue in the control and test sites at any time interval in ei- ther Table I or Table II. Mean values for probing depth before surgery (PDO) were 1.3 mm for the test site and 1.4 mm for the control site. Mean Values for PD were 0.9 mm and 1.3 mm for the test site and the control site, respec- tively. Mean values for PD, were 1.1 mm for the test site and 1.4 mm for 136 Baccetti et al. Table I. Amount of keratinized tissue (mm) before treatment and at three post- operative observations. KTo was measured on the deciduous tooth at the test site and on the permanent tooth at the control site. KT through KT3 were measured on the permanent tooth in both the test and control sites. ns = not significant. Amount of No Test site Control Student’s keratinized tissue CaSCS Mean + SD site t test (KT; mm) Mean + SD t p KTo (baseline) 29 3.2 1 0.77 3.60 0.54 0.426 ns KT (after three months) 29 2.97 ().90 3.75 0.61 0.831 ns KT2 (after two years) 29 2.99 0.86 3.70 0.59 0.756 nS KT3 (after seven years) 29 3.01 1.07 3.90 0.88 0.741 ns Table II. Comparison of the amount of keratinized tissue (mm) at different time periods. ns = not significant. Surgical No KTo KTI KT2 KT3 ANOVA technique | cases Mean + SD Mean + SD Mean + SD Mean + SD F p Double pedicle 8 3.19 ().46 3.06 0.56 3.07 0.55 3.25 0.53 0.521 ns flap Apically positioned 10 2.87 0.70 2.82 0.93 2.83 0.93 2.75 1.06 0.337 nS flap Free gingival 11 3.82 0.72 3.18 1.06 3.17 1.07 3.32 1.33 0.658 ns graft . the control site, while seven years subsequent to surgery (PD3), both test and control sites exhibited a mean probing depth of 1.3 mm. None of the examined cases showed gingival recession three months subsequent to surgery. One patient treated with an APF devel- oped an apical shift of the gingival margin on the first upper premolar in the test site after two years. After seven years, the same tooth (test site) showed a 1 mm recession. A similar 1 mm recession was recorded on the contralateral premolar (control site) at the same time period. 137 Mucogingival Interceptive Surgery Multiple regression analysis demonstrated significant associa- tions between the amount of keratinized tissue three months after surgery (KTI) and pre-surgical measurements for keratinized tissue width (KTo), probing depth (PDO) and bleeding on probing (BOP0). DISCUSSION The findings of the present study demonstrate that mucogingival interceptive therapy in patients with buccally erupting teeth is successful in saving the keratinized tissue entrapped between the erupting tooth and the deciduous tooth, maintaining a satisfactory width of the gingiva for the permanent tooth. The amount of keratinized tissue three months, two years and seven years subsequent to mucogingival treatment on the sites exhibiting buccally erupting premolars is not significantly smaller than on the control sites where premolars erupted normally. Surgical intercep- tive procedures, therefore, appear to be indicated in subjects with buc- cally erupting teeth scheduled for orthodontic treatment. It has been shown, in fact, that orthodontic therapy with fixed appliances may lead to gingival recessions due to poor oral hygiene and traumatic tooth brushing in the presence of an insufficient amount of gingiva (Wenn- ström, 1996). The entrapped gingiva must be of adequate width and thickness to allow for the surgical procedure. It is of paramount importance that the entrapped gingival tissue be attached via healthy connective fibers to the cementum of the deciduous tooth. Consequently, the probe should indi- cate a shallow sulcus and should not reach the soft tissue laceration due to the erupting cusp of the permanent tooth (Fig. 3A). On the other hand, if the probe inserted in the pocket of the deciduous tooth reaches the gin- gival laceration, the procedure is contraindicated. Multiple Linear Regression Analysis to Test the Influence of Initial Periodontal Parameters on the Amount of Keratinized Tissue Three Months after Surgery (KT) Mucogingival interceptive surgery (MIS) must be planned once the cusp of the permanent tooth has appeared on the vestibular aspect of the alveolar process, since dental eruption is a rapid process and inevita- bly would destroy the gingival tissue between the deciduous tooth and the corresponding permanent tooth (Agudio et al., 1985). 138 Baccetti et al. The effects of the three different types of surgical procedures (DPF, APF, FGG) all were satisfactory according to their specific pre- operative indications. No statistically significant difference in the amount of saved keratinized tissue was found during the three examined time periods in each surgical group. Mucogingival interceptive surgery proved to be an atraumatic and efficient procedure. The healing process was rapid and uneventful in all treated cases. Only one of the 29 buccally erupting premolars treated with mu- cogingival surgery (APF) and orthodontic fixed appliances exhibited a reduction in the amount of keratinized tissue due to an apical shift of the gingival margin two years subsequent to treatment. The same tooth showed a 1 mm recession after seven years in association with a similar recession (1 mm) on the contralateral premolar (control site). The bilat- eral lesion probably resulted from inadequate tooth brushing habits. Multiple linear regression analysis testing the influence of initial periodontal clinical parameters on the amount of keratinized tissue three months subsequent to mucogingival surgery demonstrated that better results were associated significantly with the width of the gingiva before surgery. The amount of retained keratinized tissue also was associated (with a negative coefficient) with pre-operative bleeding on probing and probing depth. No significant association was found with the baseline plaque index. Agudio and colleagues (1985) reported histological reattachment of the gingival tissue to the tooth in a case where the treated premolar was extracted for orthodontic purposes along with its previously en- trapped gingiva. The histologic findings revealed a shallow sulcus and healthy connective fibers that were inserted in the cementum (Fig. 8). The reattachment that was obtained can explain the strict relationship between the entrapped gingiva and the permanent tooth even during or- thodontic treatment. In conclusion, mucogingival interceptive therapy appears to be a successful procedure to provide buccally erupted premolars with a satis- factory amount of keratinized tissue to withstand unfavorable effects due to inadequate oral hygiene habits during and after orthodontic reposition- ing. Specific surgical techniques will depend on the clinical aspects re- lated to the distance between the buccally erupting cusp of the permanent tooth and the deciduous tooth. Probing depth values remain acceptable and gingival recessions are avoided after seven years. Periodontal health 139 Mucogingival Interceptive Surgery Figure 8. The histologic finding shows an adequate amount of keratinized tissue (previously entrapped gingival) and a healthy connective tissue attachment. - 140 Baccetti et al. and esthetics of those teeth that show an initial anomaly in eruption are obtained through the use of gingival tissue that otherwise would be lost. SURGICALLY TREATED vs. NON-SURGICALLY TREATED CASES The purpose of this longitudinal study was to compare the width of keratinized gingival tissue after orthodontic therapy in buccally erupted permanent teeth pre-treated with mucogingival interceptive sur- gery on one side of the mouth and extraction of the overlying deciduous tooth on the contralateral side. Materials and Methods Study Population. Eight patients, five males and three females between the ages of nine and 12, were examined. The subjects had been referred to private practices due to bilateral buccal eruption of premolars. Informed consent for therapy was obtained from all the patients and their parents. The investigation was conducted in agreement with the Helsinki Declaration on experimentation involving human subjects. In order to participate in the clinical study, subjects were re- quired to meet the following criteria for mucogingival interceptive sur- gery: 1. Presence of a deciduous tooth overlying the buccally erupting premolar; 2. Presence of a healthy band of keratinized tissue be- tween the primary and permanent tooth; and 3. Probing the facial gingival crevice of the primary tooth should not reach the erupting permanent tooth. Surgical Procedures. Bilateral buccally erupted premolars were randomly divided into test sites and control sites using computer soft- ware. The control sites did not undergo any surgical treatment except for the extraction of the deciduous molars. Mucogingival surgery was per- formed on the premolars at the test sites. According to the previously described rationale, mucogingival interceptive surgery consisted of DPFS in two subjects, APFs in four subjects and FGGs in two subjects. The deciduous molars in correspondence with buccally erupting premolars were extracted. 141 Mucogingival Interceptive Surgery Post-surgical Care. An anti-inflammatory drug was prescribed for a few days. Sutures were removed after one week. Two weeks after surgery, patients were instructed to resume mechanical tooth cleaning of the treated areas using a soft toothbrush. Orthodontic Treatment. Three months after initial observation, premolars both in the test and in the control sites were erupted suffi- ciently to start orthodontic treatment for the alignment and expansion of the dental arches using fixed appliances. The duration of orthodontic treatment ranged from 18 to 21 months. Follow-up. The patients were recalled monthly for professional tooth cleaning during orthodontic treatment. Follow-up periodontal evaluation of both test and control sites was carried out three months and two years subsequent to initial observation. Data Collection. 1. Pre-operative (baseline) measurements. The fol- lowing measurements were performed in both the test and the control sites with a manual pressure-sensitive periodontal probe. Measures were rounded to the nearest 0.5 mm. Probing depth (PDO) and the amount of keratinized tissue (KTo) was recorded on the buc- cal aspect of the deciduous molar. KTo was measured as the extension of entrapped gingiva between the gingival margin of the deciduous tooth and the erupt- ing cusp. Plaque index (Plo; Mühlemann and Son, 1971) and bleeding on probing (BOPo; Boyd, 1978) also were recorded before pre-surgical professional tooth cleaning. 2. Post-operative and follow-up measurements. Prob- ing depth (PD1, PD2) and amount of keratinized tissue (KT1, KT2) were recorded three months and two years Subsequent to initial observation (completion of or- thodontic treatment) on the buccal aspects of the pre- molars in both test and control sites. Plaque index (PI2) and bleeding on probing (BOP2) were recorded two years subsequent to initial observation after pro- fessional tooth cleaning of the premolars. The pres- ence of gingival recession two years subsequent to surgery also was evaluated. 142 Baccetti et al. Statistical Analysis. A comparison was performed using the non- parametric Wilcoxon signed ranks test (P<0.05) of the amount of kerati- nized tissue between the test site and the control site in the eight subjects before mucogingival treatment (KTo), and three months (KTI) and two years subsequent to initial observation (completion of orthodontic treat- ment, KT2). RESULTS A comparison of the amount of keratinized tissue between test and control sites (KT), KT1, KT2) is listed in Table 3. There was no sta- tistically significant difference between test and control sites at initial observation (KTo). The amount of KT was significantly greater in the surgically treated sites (test) than in the surgically untreated sites (con- trol) three months and two years subsequent to initial observation (i.e., completion of orthodontic treatment; Fig. 9). At the two-year visit, two control sites showed 1 mm of gingival recession (Fig. 10). At the three- month and two-year Visits, the mean loss of gingival tissue width at con- trol sites was approximately 1.8 mm (62%) and 1.6 mm (53%), respec- tively. Mean PDO was 1.63 mm in the test site and 1.72 mm in the con- trol site, respectively. Mean PD, and PD2 in the control sites were 0.98 mm and 1.14 mm, and 0.85 mm and 1.22 mm in the test sites. In the test sites, mean PIO recorded on the buccal aspect of the deciduous tooth was 50% and 13% on the premolar. In the control sites, mean PIO recorded on the buccal aspect of the deciduous tooth was 38% and 25% on the pre- molar. In the test sites, mean BOP0 and BOP2 were 63% and 13%, re- spectively, whereas in the control sites, mean BOPo and BOP2 were 50% and 13%, respectively. DISCUSSION An adequate amount of gingival tissue is a fundamental require- ment for periodontal health. The findings of the present study show that mucogingival interceptive therapy in patients with buccally erupting teeth is successful in saving the keratinized tissue entrapped between the erupting tooth and the deciduous tooth, maintaining a satisfactory width for the permanent tooth. On the contrary, surgically untreated buccally erupted teeth tend to destroy the entrapped gingiva during eruption. Three months subsequent to initial observation, the statistical comparison of the amount of keratinized tissue in sites treated with mucogingival 143 Mucogingival Interceptive Surgery Table III. Amount of keratinized tissue (mm) before treatment and at two post- operative observations. KTo was measured on the deciduous tooth in both the test and control sites. KT, and KT2 were measured on the permanent tooth in both the test and control sites, ns = not significant. Amount of keratinized tissue No Test site Control site Wilcoxon (KT) * | Mean + SD Mean + SD signed-rank test (mm) KTo (baseline) 8 3.06 0.68 2.94 0.50 InS KT1 (after thre months) 8 2.87 0.44 1.12 0.44 0.008 KT2 (after two years) 8 2.93 0.86 1.37 0.79 0.008 Figure 9. A. Right side of patient. B. Left side of patient. C. The right side was not treated Surgically; note the lack of attached gingiva at the end of the eruption process. D. Left side underwent mucogingival interceptive surgery (APF). The entrapped gingival was retained completely. interceptive surgery and in control sites demonstrated a highly significant loss of gingival tissue in untreated sites. 144 Baccetti et al. Figure 10. Same patient as in Figure 9. A. Magnification of the control side (left) during orthodontic treatment with a rapid maxillary expander. Note the develop- ing gingival recession on the untreated site. B. Magnification of the test site treated with MIS (right) during orthodontic treatment with a rapid maxillary expander. At the completion of orthodontic treatment (two years after ini- tial observation), mean gingival width in control untreated sites (1.37 mm) was less than half of that in surgically treated sites (2.93 mm). The Severe reduction in keratinized tissue of two surgically untreated sites Was associated with 1 mm of gingival recession, which uncovered the cemento-enamel junction. These findings confirm that the lack of kerati- nized tissue can be associated with gingival recession due to the possibil- ity of an accumulation of plaque and/or traumatic tooth brushing during Subsequent orthodontic treatment (Boyd, 1978; Coatoam et al., 1981; Ericsson and Lindhe, 1984; Wennström, 1996). The different surgical interventions (APF, DPF, FGG) were as- signed to individual patients according to specific indications. Although the number of cases is limited to test statistical significance, the three procedures resulted in similar clinical outcomes in terms of amount of keratinized gingival tissue. In the surgically treated sites, the amount of keratinized tissue remained stable throughout orthodontic treatment and no gingival reces- Sion was present two years after surgery. It also should be stressed that no recession had been documented in surgically treated buccally erupted teeth after orthodontic therapy. | 45 Mucogingival Interceptive Surgery Interestingly, at control and test sites, an increase in the amount of keratinized tissue occurred during orthodontic treatment, most proba- bly due to the creeping of the gingival margin coronally. This has been documented previously in orthodontically treated teeth (Cozzani et al., 1997). Two years after surgery, gingival width was increased by 0.5 mm in two of the surgically treated sites and by 0.5 to 1 mm in five of the untreated sites. The reasons for the greater amount of creeping in control sites compared to surgically treated sites are not known and require fur- ther investigation. In conclusion, a certain amount of keratinized tissue is beneficial in patients scheduled for orthodontics. In cases that present buccal erup- tion of permanent teeth, mucogingival interceptive surgery should be performed before orthodontic tooth repositioning. REFERENCES Agudio G, Pini Prato G, De Paoli S, Nevins M. Mucogingival intercep- tive therapy. Int J Periodontics Restorative Dent 1985;5:48-59. Aida E. An experimental study on tooth eruption. 2. Eruptive state of the permanent successors under infected deciduous teeth. Aichi-Gakuin J Dent Sci 1984:22:603-632. Ainamo J, Bay I. Problems and proposals for recording gingivitis and plaque. Int Dent J 1975:25:229-235. Artun J, Osterberg SK, Joondeph DR. Long-term periodontal status of labially erupted canines following orthodontic treatment. J Clin Pe- riodontol 1986; 13:856-861. Atack NE, Sandy JR, Addy M. Periodontal and microbiological changes associated with the placement of orthodontic appliances: A review. J Periodontol 1996:67:78-85. Batenhorst KF, Bowers GM, Williams JE Jr. Tissue changes resulting from facial tipping and extrusion of incisors in monkeys. J Periodon- tol 1974;45:660-668. Boyd RL. Mucogingival considerations and their relationship to ortho- dontics. J Periodontol 1978:49:67–76. Bowers GM. A study of the width of attached gingival. J Periodontol 1963:34:201-209. 146 Baccetti et al. Busschop JL, Van Vlierberghe M, De Boever J, Dermaut L. The width of the attached gingiva during orthodontic treatment: A clinical study in human patients. Am J Orthod 1985;87:224–229. Coatoam GW, Behrents RG, Bissada NF. The width of keratinized gin- giva during orthodontic treatment: Its significance and impact on periodontal status. J Periodontol 1981:52:307-313. Cozzani G, Tonetti MS, Cozzani M. Long-term stability of root coverage following orthodontic treatment and oral hygiene of a labially erupted lower incisor: Case report with 15 years follow-up. Periodontal In- sights 1997;4:4–6. Dorfman HS. Mucogingival changes resulting from mandibular incisor tooth movement. Am J Orthod 1978;74:286-297. Ericsson I, Lindhe J. Recession in sites with inadequate width of the keratinized gingival: An experimental study in the dog. J Clin Perio- dontol 1984; 11:95-103. Hall WB. Present status of soft tissue grafting. J Periodontol 1977; 48:587-597. Hall WB. Orthodontics and gingival grafting. In: Hall WB, ed. Decision Making in Periodontology. Philadelphia; BC Decker 1988:90-91. Lauterstein AM, Pruzansky S, Barber TK. Effect of deciduous mandibu- lar molar pulpotomy on the eruption of succedaneous premolars. J Dent Res 1962:41: 1367–1372. Maynard GJ, Ochbseinben C. Mucogingival problems prevalence and therapy in children. J Periodontol 1975;46:543–552. McCormick J, Filostrat DJ. Injury of the teeth of succession by abscess of the temporary teeth. J Dent Child 1967:34:501-504. McDonald RE, Avery DR. Dentistry for the Child and Adolescent. 4th ed. St Louis: CV Mosby 1983:611-613. Mühlemann HR, Son S. Gingival sulcus bleeding: A leading symptom in initial gingivitis. Helv Odontol Acta 1971; 15:107-113. O'Leary TJ, Drake RB, Naylor JE. The plaque control record. J Perio- dontol 1972:43:38. Parfitt GJ, Mjör I. A clinical evaluation of local gingival recession in children. J Dent Child 1964:31:257-262. Pini Prato G, Baccetti T, Franchi L, Giorgetti R, Marinelli A. Relation- ship between pulpal involvement of primary molars and eruption pat- tern of premolars. Eur J Pediatr Dent 2001;2:73–78. 147 Mucogingival Interceptive Surgery Pini Prato G, Baccetti T, Giorgetti R, Agudio G, Cortellini P. Mucogin- gival interceptive surgery of buccally erupted premolars in patients scheduled for orthodontic treatment. II. Surgically treated versus non- surgically treated cases. J Periodontol 2000b;71:182-187. Pini Prato G, Baccetti T, Magnani C, Agudio G, Cortellini P. Mucogin- gival interceptive surgery of buccally erupted premolars in patients scheduled for orthodontic treatment. I. A 7-year longitudinal study. J Periodontol 2000a:71: 172–81. Pini Prato G, Clauser C, Cortellini P. Periodontal plastic and mucogingi- val surgery. Periodontol 2000 1995;9:90-105. Pini Prato G, Clauser C, Zuccati G. Pure mucogingival concerns of pa- tients scheduled for orthodontics: A European view. In: Hall WB, ed. Decision Making in Periodontology. 2nd ed. St Louis: CV Mosby 1993:96–97. Steiner GG, Pearson JK, Ainamo J. Changes of the marginal periodon- tium as a result of labial tooth movement in monkeys. J Periodontol 1981:52:314-320. Valderhaug J. Periapical inflammation in primary teeth and its effect on the permanent successors. Int J Oral Surg 1974;3:171-182. Wennström JL. Lack of association between width of attached gingival and development of soft tissue recession: A 5-year longitudinal study. J Clin Periodontol 1987;14;181-184. Wennström JL. Mucogingival therapy. Ann Periodontol 1996; 1:671-701. Wennström JL, Lindhe J, Sinclair F, Thilander B. Some periodontal tis- sue reactions to orthodontic tooth movement in monkeys. J Clin Pe- riodontol 1987; 14:121-129. 148 ORTHODONTIC TREATMENT OPTIONS FOR PERIODONTALLY COMPROMISED PATIENTS Roger Wise and David M. Kim ABSTRACT Adults with reduced periodontium represent different challenges for orthodon- tists than children and adolescents. A determination of the level of activity of periodontal disease needs to be made prior to the initiation of tooth movement in order to achieve a predictable outcome when treating complex clinical problems. However, with properly planned and executed treatment, extensive orthodontic tooth movement can be achieved in adults with a reduced but healthy periodon- tium without further periodontal destruction. Combined periodontic and ortho- dontic treatments show repeated clinical success that has provided patients with pleasing esthetics, healthy function and increased longevity of their natural den- titions. Orthodontic treatment once had been regarded as an appropriate and effective treatment modality to manage malocclusion only in chil- dren and adolescents. Over the years, however, there has been a gradual increase in the number of adults seeking orthodontic therapy. Conse- quently, the evolution of scientific and technological advances in recent years has made it more feasible and predictable to treat adult malocclu- sions (McDonald and Cobourne, 2007). COLLABORATION BETWEEN PERIODONTISTS AND ORTHODONTISTS Traditionally, periodontists and orthodontists often have been at odds as a consequence of their lack of comprehensive knowledge of the other’s discipline (Bednar and Wise, 1998). Starting in the early 1970s, however, the intimate relationship between periodontics and orthodontics began to evolve in the clinical literature. Combined education has pro- duced a wealth of knowledge regarding the benefits of treating the results of periodontal disease through a combination of both surgical interven- tion and tooth movement (Bednar and Wise, 1998). During that era, the sub-specialty of orthodontics known as “adult orthodontics” started to gain a foothold, and the impact of orthodontic treatment in adult perio- 149 Orthodontic Treatment Options dontium has been evaluated through a number of investigations (Cor- rente et al., 2003). Early studies demonstrated that in dentitions with a reduced periodontium, orthodontic forces and tooth movement did not induce periodontal tissue damage if good oral hygiene was instituted, but in the presence of plaque-induced inflammation, similar forces might cause rapid periodontal tissue breakdown (Lindhe and Svanberg, 1974; Ericsson et al., 1977). INTIMATE ASSOCIATION BETWEEN PERIODONTICS AND ORTHODONTICS Clinicians over the years have discovered that adult patients were distinctly different or even more difficult to treat than children and adolescents because many adults presented with periodontal considera- tions and limitations that children and adolescents had not acquired. Thus, the challenge of adult orthodontics by the 1980s impacted general orthodontic practices significantly, as many adults now were consulting orthodontists to enhance their esthetics and improve their function (Artun and Urbye, 1988; Melsen et al., 1989). The research of Polson and col- leagues (1984) demonstrated that it was not possible to gain connective tissue attachment with orthodontic movement into infrabony pockets in monkeys. If complete elimination of subgingival infection was per- formed before the orthodontic movement, however, angular bony defects could be eliminated with orthodontic treatment (Polson et al., 1984). Through all the years that adult orthodontics has been performed, it was not until 1986 that Melsen demonstrated the possibility of coronal reattachment with an intrusive movement of a tooth in a compromised periodontium (Melsen, 1986; Melsen et al., 1988, 1989). Melsen (1986) and coworkers (1988, 1989) suggested in both animal and clinical studies that the combination of periodontal treatment and orthodontic intrusion might result in a new attachment formation and clinical attachment gain provided excellent plaque control is maintained. This possibility of ob- taining reattachment of the periodontium after tooth movement was con- firmed by Geraci and colleagues (1990) in another experimental study on monkeys. A later investigation in dogs by Wennström and coworkers (1993) demonstrated that tooth movement may enhance the rate of de- struction of the connective tissue attachment around teeth with inflamed, infrabony pockets. In conclusion, animal studies have confirmed that orthodontic movement was not detrimental for periodontal tissues when good plaque 150 Wise and Kim control was provided, but in the presence of inflammation it could lead to further periodontal breakdown (Corrente et al., 2003). Accordingly, Thi- lander’s clinical study (1996) in humans confirmed the results reported by Polson and Wennström. Her findings emphasized that the plaque- induced lesion must be eliminated prior to orthodontic treatment and proper oral hygiene must be maintained during the entire course of therapy. CONTEMPORARY ADULT ORTHODONTICS What we realized by the 1990s was that the compromised perio- dontium often can be treated through orthodontic therapy that includes uprighting, extrusion, intrusion, rotation and a host of other tooth move- ments (Bednar and Wise, 1998). For example, some of the most common orthodontic movements in adults were molar uprighting and the correc- tion of pathologic migration related to periodontal disease and/or bite collapse (Wise and Kramer, 1983; Nevins and Wise, 1990; Steffensen and Storey, 1993). Understanding that untreated angular defects might exhibit more disease progression than lesions with an even bone level, it became critical for clinicians involved in combined therapy to have a comprehensive knowledge of the treatment of both periodontal disease and orthodontic mechanotherapy (Papapanou and Wennström, 1991; Bednar and Wise, 1998). As we moved to the year 2000 when adults began to occupy a significant portion of the patient pool in orthodontic practices, interdisci- plinary collaboration among different specialists, along with the ad- Vances in both basic and clinical research in periodontics and orthodon- tics, has allowed adult patients with history of moderate to advanced periodontal disease to undergo combination therapies to achieve satisfac- tory clinical outcomes (Mathews and Kokich, 1997; Zachrisson, 2008). A 12-year follow-up study by Re and colleagues (2000) on 276 patients reported a long-term stability of adult periodontal patients following or- thodontic-periodontic combined treatment with the use of light and con- tinuous orthodontic forces when gingival inflammation was controlled. In 2001, the first Interdisciplinary Care Conference was orga- nized by five different specialties: orthodontics, periodontics, prostho- dontics, pediatric dentistry and general dentistry (Dallas, TX). This occa- Sion was a unique meeting as it brought together diverse dental disci- plines and emphasized how important they are to each other in determin- ing complex multidisciplinary treatment plans. Thus, the realization came that orthodontic treatment no longer was automatically contraindi- 151 Orthodontic Treatment Options cated in the therapy of periodontally compromised adult patients who were able to maintain a healthy periodontal status after the active perio- dontal treatment (Ong and Wang, 2002). In addition, in the case of bony defects adjacent to pathologically migrated teeth, it has been shown that orthodontic therapy is an effective therapeutic approach once the perio- dontal infection has been eliminated (Cardaropoli et al., 2001: Re et al., 2002: Corrente et al., 2003: Nevins et al., 2005). Thus, orthodontic treatment for realignment of migrated periodontally involved teeth was to be initiated only after the control of the periodontal inflammation has been achieved. CLINICAL CONSIDERATIONS In order to treat these special groups of periodontally compro- mised adult patients optimally, several considerations need to be kept in mind. First of all, special attention must be given to the current periodon- tal status of the adults with periodontally compromised dentition because they can be susceptible to recurrent periodontal disease. Poorly executed orthodontic treatment in periodontal patients can contribute to further periodontal tissue breakdown (Zachrisson, 2002). In particular, the com- bination of inflammation, orthodontic forces and occlusal trauma may produce a more rapid destruction than would occur with inflammation alone (Kessler, 1976). Figure 1 shows the problem with orthodontic movement of teeth into infrabony defects. As this individual’s mandibu- lar incisor spaces were closed, angular osseous lesions became deeper and narrower radiographically, and no gain of connective tissue attach- ment Was Seen. Secondly, the past history of periodontal disease may make it necessary to consider compromising ideal orthodontic end points of ther- apy in favor of more practical treatment objectives (Bednar and Wise, 1998). Achieving a functional occlusion in a periodontally compromised patient may be a more practical and secure approach than the pursuit of a perfect occlusion at the expense of long-term periodontal stability (Bed- nar and Wise, 1998). Thirdly, it is important to determine the sequence of definitive treatment that will produce the most predictable result for the patient (Bednar and Wise, 1998). Some patients will benefit from the initiation of orthodontic therapy before periodontal treatment and others may real- ize the most benefits through a reversal of these procedures. Prior to the initiation of therapy, it is essential to establish goals for definitive perio- 152 Wise and Kim Figure 1. A: Radiographic examination revealed vertical osseous lesions around mandibular anterior teeth. B: Without proper periodontal treatments, bodily movement of teeth deepened angular osseous lesions. dontal care, final esthetics and a functional occlusion (Bednar and Wise, 1998). For example, pre-orthodontic gingival grafting or other soft tis- Sue enhancement procedures, sometimes in conjunction with osseous regeneration, may prevent a number of problems that can result from hard and soft tissue loss during orthodontic tooth movements (Wehrbein et al., 1996). These procedures also may help improve resistance to in- flammation that might occur during the orthodontic therapy (Lang and Lóe, 1972). Figure 2 represents a case in which the maxillary left canine has a significant infrabony lesion on the mesial. This area underwent Open flap debridement surgery first. The canine later was extruded, the mesial bony lesion was leveled orthodontically and a final bridge was placed. This case was followed for 15 years and the mesial bone en- hancement from the extrusive tooth movement has been maintained Fourthly, there are no definite limits in terms of probing depths or loss of attachment when orthodontic tooth movement no longer can be performed (Zachrisson, 2002). Each individual treatment plan may depend 153 Orthodontic Treatment Options Figure 2. A. Clinical examination revealed a 7 mm probing depth on mesial of maxillary left canine. B. This clinical finding was confirmed by the radiographic evaluation. C. After performing an open flap debridement of the involved area. D: Orthodontic extrusion and distalization eliminated the osseous defect, and created shallower sulcus. E. Fifteen-year post-operative clinical evaluations re- 154 Wise and Kim (Continued) vealed stability of the achieved result. F: Fifteen-year post- operative radiographic evaluations revealed stability of the achieved result. on a variety of factors and can be limited by biomechanical considera- tions, periodontal risk factors or limited patient motivation and coopera- tion (Zachrisson, 2002). Thus, it is important to identify patients who are Susceptible to the more severe manifestations of the disease and to con- trol the existing disease before initiating a comprehensive orthodontic treatment plan. Although short roots certainly are something about which to be concerned before engaging a patient in orthodontic care, Figure 3 presents an example of such a patient who was treated successfully. A permanent intracoronal wire and composite stabilization allowed this patient to retain these teeth for 10 years. Lastly, it is important that the orthodontic therapy results in sta- bility and esthetics with a minimum detriment to the periodontium (Bed- nar and Wise, 1998). Figure 4 shows the comparison of pre- and post- treatment radiographs after intrusion of a maxillary right central incisor. After the orthodontic movement was completed, the spacing became Smaller but the crestal osseous lesion became deeper. Figure 5 demon- strates that uprighted and distalized maxillary molars can be stable for more than 30 years. The sequence of treatment, design of surgical proce- dures, choice of tooth movement and orthodontic mechanotherapy are some of the options that must be considered and integrated (Bednar and Wise, 1998). With the evolution of dental implants, this groundbreaking disci- pline has been incorporated into multidisciplinary treatment, which has come to have great importance today in our thought process relative to the interdisciplinary care (Spear et al., 1997). Orthodontics plays a key role in implant site development from the standpoint of positioning teeth ideally prior to implant placement and bone enhancement with extrusion and/or mesial distal movements. Thus, new treatment horizons never imagined previously have been a part of this growth phenomenon (Mantzikos and Shamus, 1998). 155 Orthodontic Treatment Options 156 Wise and Kim Figure 3 (previous page and this page). A. Patient presented with congenitally Short roots. B: Patient requested orthodontic treatment to improve esthetics and function. C. Ten-year clinical evaluations revealed stability of both periodon- tium and teeth. D. Ten-year radiographic evaluations revealed stability of both periodontium and teeth. 157 Orthodontic Treatment Options A Figure 4. A. Orthodontic intrusion can enhance esthetics. B. Radiographically infrabony lesion may deepen. Figure 5. A and B: Mesially tipped maxillary second molar can be orthodonti- cally treated by distalization and extrusion. C and D: The outcome of this case has been maintained for 30 years. 158 Wise and Kim Case 1: Interproximal Stripping Figure 6 shows a patient who has crowding and 50% horizontal bone loss of the mandibular incisors. Treatment options were to extract one of the incisors to eliminate the crowding or to consider interproximal stripping of teeth to avoid extraction (Tuverson, 1980). Although inter- proximal reduction may result in tight embrasures and narrow inter- proximal septa, it frequently is utilized to resolve limited tooth/arch size discrepancies (Bednar and Wise, 1998). It can be a useful clinical modal- ity in resolving crowding when there is accompanying loss of supporting bone because stripping can provide space for the elimination of crowding without necessitating complex bodily movement (Bednar and Wise, 1998). Both short- and long-term (>10 years) follow-up studies have demonstrated that no harmful side effects were observed subsequent to the procedure after extensive reduction of teeth (Zachrisson and Mjör, 1975; Thordarson et al., 1991). The amount of enamel that is removed from each tooth by the stripping is normally 0.5 to 0.75 mm and the den- tin will not be exposed (Zachrisson, 2002). For the patient in Figure 6, the consideration was whether to move teeth mesially-distally in a compromised periodontium orthodonti- cally with the chance of exacerbating the interproximal periodontal breakdown from the slight movements of the incisors. The decision was made to strip the incisors mesial-distally to avoid excessive mesial-distal movement (Sheridan, 1985; Sheridan and Hastings, 1992). This conser- Vative approach of utilizing interproximal reduction to avoid additional interproximal bone loss is a valuable treatment consideration as an alter- native to extraction (if possible) in periodontally compromised cases. Case 2: Extraction / GRB-GTR/Bodily Movement Human studies have shown that teeth with reduced but healthy periodontium could be moved orthodontically with no enhanced perio- dontal destruction, provided pre-orthodontic periodontal treatment is un- dertaken and forces were maintained within physiological limits (Elias- Son et al., 1982). In addition, orthodontic tooth movement into edentu- lous areas with reduced bone height and into extraction sites could be performed while the level of the connective tissue attachment of the sup- porting apparatus was maintained (Reed et al., 1985; Lindskög-Stokland et al., 1993). Figures 7 through 9 present a case that needed the extraction of the mandibular right central incisor because of ongoing periodontal dis- 1.59 Orthodontic Treatment Options 160 Wise and Kim <- Figure 6. A and B: The patient presented with incisor crowding accompanied by horizontal bone loss. C. This case first was treated with apically repositioned flap surgery. D. Orthodontic treatment accompanied by interproximal enamel stripping followed. E. Post-operative clinical examination revealed stability of the interproximal bone level and open embrasures. F. Radiographic examination revealed stability of the interproximal bone level and open embrasures. ease. Following extraction, guided bone regeneration (GBR) to augment the extraction site in conjunction with guided tissue regeneration (GTR) of the defect over the root of the left central incisor was performed. GBR is considered ideal preparation before orthodontic movement of teeth into alveolar processes with deficient bone volume (Zachrisson, 2002). An animal study by Araújo and coworkers (2001) demonstrated that it was possible to move a tooth orthodontically into an area of an alveolar ridge previously augmented with bovine bone grafts, and that the augmented bone region did not impede orthodontic tooth movement. A clinical study by Cardaropoli and colleagues (2006) also reported suc- cessful movement of teeth into the defect augmented with Bio-Oss colla- gen. A non-resorbable titanium reinforced membrane was placed over the GBR-GTR site and was removed two months later. The area then underwent orthodontic space closure as opposed to implant placement. This area was evaluated radiographically at two years and was reopened Surgically at two years post-treatment. A small angular interproximal Osseous lesion still remained and was recontoured surgically and re- moved. This treatment was followed longitudinally, with the radio- graphic result remarkable in terms of the ability to undergo pre- orthodontic GBR and GTR and remain periodontally healthy over 15 years. 161 Orthodontic Treatment Options Figure 7. A. A 9 mm probing depth was iden- | tified on the distal of the mandibular right central incisor. B: Radiographic examination revealed advanced bone loss of all incisors. C. Extraction of periodontally involved central incisor was performed with anticipation of performing both GTR and GBR procedures. D: FDBA was placed into the defect and covered with a titanium reinforced nonresorb- able membrane. E. The membrane was re- moved at two months. F. The flap was re- placed. 162 Wise and Kim Figure 8. Radiographic sequences of orthodontic treatment rendered. 163 Orthodontic Treatment Options Figure 9. A. Residual osseous defect after Orthodontic treatment was eliminated surgically. B: Re-entry of the site was performed two years later. C and D. Fifteen-year post- operative results. Case 3: Extraction of Lateral Incisor and Implant Placement Treatment options for congenitally missing maxillary lateral in- cisors, which are the second most commonly missing teeth, can range from their replacement by the canine, fabrication of a fixed bridge or their replacement with a dental implant. In this scenario, orthodontic treatment can create an adequate space to accommodate a dental implant, or it can facilitate the implant option by providing either vertical (i.e., selective orthodontic extrusion of one single tooth movement) or horizon- 164 Wise and Kim zontal ridge augmentations (i.e., movement of a premolar into the eden- tulous space and to place the implant in the position previously occupied by the premolar; Salama and Salama, 1993; Spear et al., 1997; Zuccati and Bocchieri, 2003; Zachrisson, 2008). Figures 10 through 13 present an example of orthodontic care whereby an unerupted maxillary canine had dissolved the root of the maxillary left lateral incisor, resulting in the extraction of the incisor. Orthodontics was utilized to extrude the canine into position and then distalize it to create an ideal implant site development for the missing lateral incisor. Through this procedure, an ideal implant site development of approximately 7 mm was achieved (with adequate bone both mesial and distally for the proposed implant). Labiolingually, there was 6 mm thickness of bone as evidenced by the final cone-beam CT (CBCT) scan of this area, in conjunction with interproximal two-dimensional periapi- cal radiographs. º - --~ Figure 10. Patient presented with retained primary canine. 1.65 Orthodontic Treatment Options Figure 11. The patient also presented with a resorbed lateral incisor root that resulted from the ectopic eruption of the adjacent permanent canine. Case 4: Intrusion Orthodontic intrusion can be utilized to treat teeth with horizon- tal bone loss or infrabony pockets, or to increase the clinical crown length of a single tooth (Zachrisson, 2008). The benefit of the intrusion for improvement of the periodontal condition around teeth is controver- sial, however, because this procedure involves initiation of orthodontic intrusion of a tooth with a diseased root while simultaneously trying to increase its attachment (Bednar, 1998; Zachrisson, 2008). Even though some positive clinical and histologic findings have been reported, this approach must be considered with great caution because positive results are not universal (Melsen, 1986; Melsen et al., 1988, 1989; Cadaropoli et al., 2001, 2004: Re et al., 2004; Zachrisson, 2008). Furthermore, GTR or other regenerative procedures appear to be more predictable when at- tempting to create a new attachment (Cortellini and Tonetti, 2004; Nevins et al., 2005). 166 Wise and Kim Figure 12. Both primary canine and lateral incisors were removed and the per- manent canine was orthodontically erupted and distalized to create an adequate implant site. Case 5: Extrusion Orthodontic extrusion (forced eruption) can be utilized to de- crease or eliminate intraosseous defects, or to increase clinical crown length of a single teeth (Ingber, 1974; van Venrooy and Yukna, 1985; Wagenberg et al., 1986; Zachrisson, 2008). With forced eruption, den- toperiosteal fibers at the base of infrabony defects are stretched, stimulat- ing the deposition of bone along their length (Bednar and Wise, 1998). The level of bone that occurs with extrusion in the area of the defect may be significant enough to obviate the need for periodontal surgery (Bednar and Wise, 1998). The clinician must consider the possibility that reverse OSSeous topography might be created on another surface of the tooth (Bednar and Wise, 1998). This problem may be eliminated via a selec- tive crestal fiberotomy, thereby inhibiting any undesirable osseous in- crease on the normal side (Bednar and Wise, 1998). 167 Orthodontic Treatment Options E. Figure 13. A and B. Six-year post-implant placement and restoration. C. Cone- beam CT (CBCT) scan revealed presence of 1.95 mm of buccal plate. CONCLUSION Adults with reduced periodontium represent different challenges for Orthodontists than children and adolescents. A determination of the level of activity of periodontal disease needs to be made prior to the ini- tiation of tooth movement in order to achieve a predictable outcome when treating complex clinical problems. However, with properly planned and executed treatment, extensive orthodontic tooth movement 168 Wise and Kim can be achieved in adults with a reduced but healthy periodontium with- out further periodontal destruction (Zachrisson, 2002). Combined perio- dontic and orthodontic treatments show repeated clinical success that has provided patients with pleasing esthetics, healthy function and increased longevity of their natural dentitions. In the treatments described in this chapter, the result of seeing no significant additional periodontal tissue breakdown in these patients was the result of carefully controlled treatment planning considerations. Good oral hygiene at home and professional maintenance visits are imperative during and following active orthodontic and periodontal treatments. Pre- vious reports have demonstrated that, with adequate plaque control, teeth with reduced periodontal support can undergo successful tooth move- ment without compromising their periodontal situation (Eliasson et al., 1982; Wagenberg, 1988; Boyd et al., 1989). However, when oral hy- giene is inadequate, tipping and intrusion of the teeth may shift supragin- givally located plaque into subgingival position, resulting in periodontal destruction (Ericsson et al., 1977, 1978). Thus, if efforts to maintain ex- cellent to good oral hygiene are unsuccessful, orthodontic treatment should be terminated (Machen, 1990). REFERENCES Araújo MG, Carmagnola D, Berglundh T, Thilander B, Lindhe J. Ortho- dontic movement in bone defects augmented with Bio-Oss: An ex- perimental study in dogs. J Clin Periodontol 2001:28:73-80. Artun J, Urbye KS. The effect of orthodontic treatment on periodontal bone support in patients with advanced loss of marginal periodon- tium. Am J Orthod Dentofacial Orthop 1988;93:143-148. Bednar JR, Wise JR. Interaction of periodontal and orthodontic treat- ment. In: Nevins M, Mellonig JT, eds. Periodontal Therapy: Clinical Approaches and Evidence of Success. Carol Stream: Quintessence Publishing Co. Inc., 1998:149-164. Boyd RL, Leggot PJ, Quinn RS, Eakle WS, Chambers D. Periodontal implications of orthodontic treatment in adults with reduced or nor- mal periodontal tissues versus those of adolescents. Am J Orthod Dentofacial Orthop 1989;96:191-198. Cardaropoli D, Re S, Corrente G, Abundo R. Intrusion of migrated inci- sors with infrabony defects in adult periodontal patients. Am J Orthod Dentofacial Orthop 2001;12:671-675. 169 Orthodontic Treatment Options Cardaropoli D, Re S, Corrente G, Abundo R. Reconstruction of the max- illary midline papilla following a combined orthodontic-periodontic treatment in adult periodontal patients. J Clin Periodontol 2004:31:79- 84. Cardaropoli D, Re S, Manuzzi W, Gaveglio L, Cardaropoli G. Bio-Oss collagen and orthodontic movement for the treatment of infrabony de- fects in the esthetic zone. Int J Periodontics Restorative Dent 2006; 26:553–559. Corrente G, Abundo R, Re S, Cardaropoli D, Cardaropoli G. Orthodontic movement into infrabony defects in patients with advanced periodon- tal disease: A clinical and radiographic study. J Periodontol 2003;74: | 104-1 109. Cortellini P, Tonetti MS. Long-term tooth survival following regenera- tive treatment of intrabony defects. J Periodontol 2004;75:672–678. Eliasson LA, Hugoson A, Kurol J, Siwe H. The effects of orthodontic treatment on periodontal tissues in patients with reduced periodontal support. Eur J Orthod 1982;4:1-9. Ericsson I, Thilander B, Lindhe J. Periodontal condition after orthodontic tooth movements in the dog. Angle Orthod 1978;48:210-218. Ericsson I, Thilander B, Lindhe J, Okamoto H. The effect of orthodontic tilting movements on the periodontal tissues of infected and non- infected dentitions in dogs. J Clin Periodontol 1977;4:278-293. Geraci TF, Nevins M, Crossetti HW, Drizen K, Ruben MP. Reattach- ment of the periodontium after tooth movement into an osseous defect in a monkey. Part I. Int J Periodontics Restorative Dent 1990; 10:184- 197. Ingber JS. Forced eruption. Part I. A method of treating isolated one and two wall infrabony osseous defects: Rationale and case report. J Pe- riodontol 1974;45:199-206. Kessler M. Interrelationships between orthodontics and periodontics. Am J Orthod 1976;70:154-172. Lang NP, Lóe H. The relationship between the width of keratinized gin- giva and gingival health. J Periodontol 1972;43:623-627. Lindhe J, Svanberg G. Influence of trauma from occlusion on progres- sion of experimental periodontitis in the beagle dog. J Clin Periodon- tol 1974; 1:3-14. 170 Wise and Kim Lindskóg-Stokland B, Wennström JL, Nyman S, Thilander B. Orthodon- tic tooth movement into edentulous areas with reduced bone height: An experimental study in the dog. Eur J Orthod 1993; 15:89-96. Machen DE. Legal aspects of orthodontic practice: Risk management concepts. Periodontal evaluation and updates: Don't abdicate your duty to diagnose and supervise. Am J Orthod Dentofacial Orthop 1990:98:84-85. Mantzikos T, Shamus I. Case report: Forced eruption and implant site development. Angle Orthod 1998;68: 179-186. Mathews DP, Kokich, VG. Managing treatment for the orthodontic pa- tient with periodontal problems. Semin Orthod 1997;3:21-38. McDonald F, Cobourne M. Adult orthodontics: Perils and pitfalls. Prog Orthod 2007;8:308-313. Melsen B. Tissue reaction following application of extrusive and intru- sive forces to teeth in adult monkeys. Am J Orthod 1986;89:469-475. Melsen B, Agerbaek N, Eriksen J, Terp S. New attachment through periodontal treatment and orthodontic intrusion. Am J Orthod Dento- facial Orthop 1988;94:104-116. Melsen B, Agerbaek N, Markenstam G. Intrusion of incisors in adult pa- tients with marginal bone loss. Am J Orthod Dentofacial Orthop 1989:96:232-241. Nevins M, Giannobile WV, McGuire MK, Kao RT, Mellonig JT, Hin- richs JE, McAllister BS, Murphy KS, McClain PK, Nevins ML, Paquette DW, Han TJ, Reddy MS, Lavin PT, Genco RJ, Lynch SE. Platelet-derived growth factor stimulates bone fill and rate of attach- ment level gain: Results of a large multicenter randomized controlled trial. J Periodontol 2005;76:2205–2215. Nevins M, Wise RJ. Use of orthodontic therapy to alter infrabony pock- ets. Part II. Int J Periodontics Restorative Dent 1990;10:198-207. Ong MM, Wang HL. Periodontic and orthodontic treatment in adults. Am J Orthod Dentofacial Orthop 2002;122:420-428. Papapanou PN, Wennström JL. The angular bony defects as indicator of further alveolar bone loss. J Clin Periodontol 1991; 18:317-322. Polson A, Caton J, Polson AP, Nyman S, Novak J, Reed B. Periodontal response after tooth movement into intrabony defects. J Periodontol 1984;55:197-202. 171 Orthodontic Treatment Options Re S, Corrente G, Abundo R, Cardaropoli D. Orthodontic movement into bone defects augmented with bovine bone mineral and fibrin sealer: A reentry case report. Int J Periodontics Restorative Dent 2002:22: 138–145. Re S, Corrente G, Abundo R. Cardaropoli D. Orthodontic treatment in periodontally compromised patients: 12-year report. Int J Periodontics Restorative Dent 2000:20:31–39. Re S, Cardaropoli D, Abundo R, Corrente G. Reduction of gingival re- cession following orthodontic intrusion in periodontally compromised patients. Orthod Craniofac Res 2004;7:35-39. Reed BE, Polson AM, Subtelny JD. Long-term periodontal status of teeth moved into extraction sites. Am J Orthod 1985;88:203-208. Salama H, Salama M. The role of orthodontic extrusive remodeling in the enhancement of soft and hard tissue profiles prior to implant placement: A systematic approach to the management of extraction site defects. Int J Periodontics Restorative Dent 1993; 13:312-333. Sheridan J.J. Air-rotor stripping. J Clin Orthod 1985; 19:43–59. Sheridan JJ, Hastings J. Air-rotor stripping and lower incisor extraction treatment. J Clin Orthod 1992:26:18-22. Spear FM, Mathews DM, Kokich VG. Interdisciplinary management of single-tooth implants. Semin Orthod 1997;3:45-72. Steffensen B, Storey AT. Orthodontic intrusive forces in the treatment of periodontally compromised incisors: A case report. Int J Periodontics Restorative Dent 1993; 13:433-442. Thilander B. Infrabony pockets and reduced alveolar bone height in rela- tion to orthodontic therapy. Semin Orthod 1996:2:55-61. Thordarson A, Zachrisson BU, Mjör IA. Remodeling of canines to the shape of lateral incisors by grinding: A long-term clinical and radio- graphic evaluation. Am J Orthod Dentofacial Orthod 1991; 100:123- 132. Tuverson DL. Anterior interocclusal relations. Part I. Am J Orthod 1980; 78:361-370. van Venrooy JR, Yukna RA. Orthodontic extrusion of single-rooted teeth affected with advanced periodontal disease. Am J Orthod 1985;87:67- 74. Wagenberg BD. Periodontal preparation of the adult patient prior to or- thodontics. Dent Clin North Am 1988:32:457-480. 172 Wise and Kim Wagenberg BD, Eskow RN, Langer B. Orthodontics: A solution for the advanced periodontal or restorative problem. Int J Periodontics Re- storative Dent 1986;6:36-45. Wehrbein H, Bauer W, Diedrich P. Mandibular incisors, alveolar bone, and symphysis after orthodontic treatment: A retrospective study. Am J Orthod Dentofac Orthop 1996;l 10:239-246. Wennström J.L, Stokland B, Nyman S, Thilander B. Periodontal tissue response to orthodontic movement of teeth with infrabony pockets. Am J Orthod Dentofacial Orthop 1993; 103:313-319. Wise RJ, Kramer GM. Predetermination of osseous changes associated with uprighting tipped molars by probing. Int J Periodontics Restora- tive Dent 1983; 1:68-81. Zachrisson BU. Orthodontics and periodontics. In: Lindhe J, Karring T, Lang NP, eds. Clinical Periodontology and Implant Dentistry. Co- penhagen: Munksgaard 2002:741–793. Zachrisson BU. Tooth movements in the periodontally compromised pa- tient. In: Lang NP, Lindhe J, eds. Clinical Periodontology and Im- plant Dentistry. Oxford: Blackwell Munksgaard 2008:1241–1279. Zachrisson BU, Mjör IA. Remodeling of teeth by grinding. Am J Orthod 1975;68:545-553. Zuccati G, Bocchieri A. Implant site development by orthodontic extru- sion of teeth with poor prognosis. J Clin Orthod 2003:37:307-311. 173 174 THE ORTHODONTIST’S ROLE IN DENTAL IMPLANT SITE MAINTENANCE AND DEVELOPMENT Chester S. Handelman, Yana Nedvetsky, Nolen Levine ABSTRACT The orthodontist’s role in implant site preservation and development is illus- trated by a series of eight clinical cases. The importance of maintaining the re- storative space following extraction of teeth is emphasized. Implant site devel- opment by increasing the length of the edentulous area is illustrated by cases of lateral incisor agenesis that required uprighting of the roots of the adjacent teeth. Development of the restorative space of the missing first molar via molar up- righting of the second molar is illustrated with emphasis on establishment of optimal periodontal maintenance. Vertical and horizontal tooth movement can be used to increase the volume of bone in the edentulous site. Slow vertical ex- trusion of teeth can be used to eliminate vertical periodontal defects. Extruding a hopeless tooth prior to its extraction can increase the vertical height of the alveo- lus and its overlying soft tissue in a more predictable manner as compared to bone grafting. Two patients are presented that demonstrate when a tooth is hori- zontally moved into a reduced alveolus; it not only carries bone in front of the tooth being moved, but also leaves an enhanced alveolus in the vacated region. Both vertical and horizontal tooth movement can provide bone necessary to support an implant where bone grafting procedures may be problematic. With- out orthodontic care, the eight patients presented could not have been treated using implant supported restorations. The introduction of dental implants has expanded the role of or- thodontics in the rehabilitation of partially edentulous patients due to agenesis or extraction. The orthodontist must interact and meet the re- quirements of the restorative dentist and implant specialist. This paper will address implant site preservation briefly and, in more detail, implant site development by increasing the mesio-distal length of the implant site and the volume of bone in the implant site. 175 Dental Implant Site Maintenance IMPLANT SITE PRESERVATION Dentists are familiar with the need for space maintenance in children who lose deciduous teeth to prevent loss of arch length due to drifting into the extraction site. Following the loss of an anterior tooth, the dentist will replace it with a temporary removable retainer as soon as feasible because of the aesthetic needs of the patient. Following the loss of a posterior tooth, either before or after implant placement but prior to restoration, dentists frequently fail to place a retainer. It is well known (Hirschfeld, 1937) that the loss of a first molar results in mesial drift and tipping of second molars and often distal drift of the premolars. So why are dentists failing to maintain the restorative space in the posterior den- tition? Possibly because of the belief that the adult occlusion will prevent drifting and that the negative changes will be slow. While this is often the case, the following patient presented with rapid and extensive loss of adequate space for the restoration on her implant due to failure to pre- serve the length of the implant site. Case 1 A 32-year-old female lost her maxillary left first molar due to a crown fracture that extended to the floor of the pulp chamber. Her denti- tion and periodontium were healthy otherwise. Following extraction and placement of the implant, the premolars drifted distally and the second molar tipped mesially with a mesial-palatal rotation, probably due to the pull of the transseptal gingival fibers. It appears the healing cap limited further migration into the extraction site (Fig. 1A). A super-elastic coil spring was placed on a 0.016” x 0.022” B-titanium wire (TMA” wire, Ormco Corp., Orange, CA) between the premolars and the second molar. The wire was placed into the 0.045” headgear tube to prevent binding and allow distal tipping and rotation correction of the second molar (Fig. 1B). A bypass wire was placed for retention prior to prosthetic restora- tion of the implant (Fig. 1 C). Treatment time was four months. Ortho- dontists must educate our restorative and surgical colleagues about the need for space maintenance following extraction of teeth to prevent the embarrassing loss of restorative space at the implant site. 176 Handelman et al. Figure 1. A. A 32-year-old female had her maxillary left first molar extracted with failure to preserve the implant site. The adjacent premolars drifted distally and the second molar rotated, drifted and tipped mesially. B. At the start of treatment (left), a super-elastic spring is placed on a 0.016’ x 0.022.” B-titanium Wire that is inserted into the headgear tube on the second molar. After two months of treatment (center) and after four months at the completion of treat- ment (right). C. Bypass wire placed after orthodontic correction (left); final im- plant supported restoration (right). 177 Dental Implant Site Maintenance IMPLANT SITE DEVELOPMENT: INCREASING THE SIZE OF THE IMPLANT SITE This section will address the problems inherent in creating a me- sio-distal site of sufficient size for placement of an implant for treatment of lateral incisor agenesis, as well as rehabilitation of the edentulous first molar site. While the orthodontist may be called upon to create space prior to implant placement for any number of sites in the dental arch, these are the two most common and perplexing situations. Maxillary Lateral Incisor Agenesis. A frequent presentation in the orthodontic office is an adult who had orthodontic treatment as an adolescent for agenesis of one or both maxillary lateral incisors and sub- sequently was restored with a bonded bridge. The bridge frequently debonds over time (Priest, 1996; Wood et al., 1996). The patient may wish the bridge replaced because of poor aesthetics caused by the palatal metal which prevents natural transmission of light. Many patients were treated in this manner prior to the common use of implants. At that time, the orthodontist may not have considered root angulation and only focused on providing adequate prosthetic space for the lateral incisor pontic. Coil springs to open space between the cen- tral incisors and canines not only will provide space for the pontic, but also will converge the roots of these teeth. Bonded bridges are forgiving of improper root angulation – implants are not. According to Misch (2005), the minimum size of a two-piece implant in this region is 3.25 to 3.5 mm. One-piece and two-piece 3 mm implants recently have become available. According to Tarnow and col- leagues (2000), the space between the implant and the root of the adja- cent tooth should be 1.5 mm. Not only is it important to insure that the adjacent teeth are not injured, but the osseous width between the implant and adjacent root also is critical in support of the soft tissue papillae in the anterior esthetic zone (Tarnow and Eskow, 1996). The total size of the implant and the 1.5 mm of interproximal bone adds up to 6.25 to 6.5 mm required for the implant at the alveolar crest, and approximately 1 mm less between the apical ends of the adjacent roots if the implant is tapered (Fig. 2). When the dentition tends to be small (microdontia) or the posterior teeth tend to a Class II occlusion, providing adequate space will be difficult. 178 Handelman et al. Figure 2. Diagram of space requirements for a 3.5 mm two- piece implant. Case 2 The biomechanics of uprighting a cuspid with a mesial root an- gulation is challenging, since a continuous light wire in pre-angulated brackets is more likely to extrude the central incisors and intruded the first premolars than upright the cuspids. One solution is to segment the uprighting system. A 0.016.” x 0.022.” B-titanium wire placed into the Central incisor brackets with a 30° V-bend facing the occlusal direction Will converge their roots by reciprocal moments (Fig. 3). Alternatively the brackets could be angulated (mesial apical-distal occlusal). One of the problems of the straight wire systems is that most of the force to upright a tooth would be delivered to the adjacent teeth through a short length of wire. To circumvent this problem, one of the authors (CH) has developed a canine uprighting spring (Fig. 3) using 0.016° x 0.022.” B-titanium wire that is tied into the anchor unit from first and second premolars through the first molar (additional anchorage can be provided by joining the right and left first molars with a transpalatal Wire). The wire spring then returns at the gingival level via two right an- 179 Dental Implant Site Maintenance º - Figure 3. Photographs of a 26-year-old male with bilateral agenesis of the maxil- lary lateral incisors that were restored as an adolescent with two bonded bridges. Use of a segmented technique is shown with a V-bend directed incisally to upright the central incisors and the rectangular shaped spring to upright the canines, both in 0.016’ x 0.022.” B-titanium wire. Pre-treatment (top), four months in treatment (center), seven months and at completion of uprighting the roots (bottom). gle bends to pass beyond the canine. Again, two right angle bends allow the wire to be tied into the canine. The second bend can have a more oblique angle as required for further uprighting of the canine. The spring has great length allowing a moderate and long-acting uprighting moment to the canine (Fig. 3, center). The bracket on the first molar cannot be a closed tube. Use of a central incisor or a converted first molar bracket will allow tying in the rectangular shaped spring. The effectiveness of this uprighting system is demonstrated in a 26-year-old male with bilateral agenesis of the lateral incisors. Previous orthodontic treatment provided space for lateral incisor pontics restored with bonded bridges. The bonding of the right maxillary canine eventu- ally failed (Fig. 4). After discussion with his dentist and implantologist (author NL), it was decided that replacement should involve implant supported individual crowns. Unfortunately, convergence of the adjacent roots, especially on the right side, compromised the space required for implant placement. The bonded bridges were removed and a removable retainer supporting lateral incisor denture teeth was fabricated. The up- righting of the canines and central incisors was completed in seven months. 180 Handelman et al. Figure 4. Radiographs show that the right canine abutment has debonded. The right canine and central incisor roots converge (top). Uprighting of the canines and central incisors is shown at four months (center) and at the completion of uprighting the roots at Seven months (bottom). 181 Dental Implant Site Maintenance five of those months with uprighting springs (Figs. 3 and 4). Following this, the patient had onlay bone grafting to increase the width of the al- veolus at the implant site. The patient recently had one-piece implants placed and tempo- rary crowns secured with resin-bonded cement to these implants on the same day. These temporary crowns were out of occlusion in centric and excursive movements (Figs. 5 and 6). same day. Case 3 A 32-year-old female patient requested implant-supported re- placement of her bonded bridges because of unfavorable aesthetics of the pontic laterals and adjacent abutments (Fig. 7), which had different col- oration as well as reduced translucency. The problem was the decreased space between the right central and cuspid due to the mesial root angula- tion of the cuspid (Fig. 8). Following uprighting of the canines and cen- 182 Handelman et al. Figure 7. Photographs of a 32-year-old female with unfavorable aesthetics Of her bonded bridges because of poor coloration and lack of life-like translucence. Figure 8. Pre-treatment radiographs show convergence of the roots of the centrals and cuspids on the right side. tral incisors using the previously described method (Case 2), there was sufficient room for implant placement (Fig. 9). The lateral incisor im- plants were restored with individual crowns, the central incisors with Veneers resulting in satisfying aesthetic improvement (Fig. 10). Loss of First Molars. The loss of permanent first molars early in life results in a series of unfortunate events: the second molars will mi- grate and incline mesially and the premolars may drift distally, resulting in spacing (Hirschfeld, 1937). Replacement of the lost molar with an im- plant faces two major problems: the site may be too small to place even a Smaller premolar size implant and the implant may compromise the peri- 183 Dental Implant Site Maintenance Figure 9. Post-treatment radiographs show corrected root an- gulations with placement of implants. Figure 10. Post-treatment photographs showing implant-supported lateral incisor crowns and central incisors restored with veneers. odontal health of the tipped second molar. When the second molar tips mesially, a pseudo-pocket is formed as the junctional epithelium and supporting bone are brought to a more apical position. If the space to the mesial of the tipped molar is open, the mesial periodontium can be main- tainable with home and professional care. If the space to the mesial of the tipped molar is narrow or the mesial inclination extreme, the pocket be- comes inaccessible to cleaning and periodontal health at this site will be difficult to maintain, especially in a periodontally prone individual. Placement of an implant-supported crown at the mesial of a tipped Sec- ond molar will compromise further the periodontal health of the second molar. Lundgren and coworkers (1992) have shown that the tipped mo- lar will stabilize over time rather than continue to incline. They com- pared the periodontium on the mesial of a tipped molar to the contralat- 184 Handelman et al. eral upright molar with its first molar in place. They found similar levels of periodontal health; their subjects, however, were largely free of perio- dontal disease. The issue of periodontal maintenance becomes the critical deci- Sion in whether or not to treat a tipped molar. Tipped molars do not re- quire uprighting if they are periodontally sustainable and have reasonable occlusion (Fig. 11). Often the third molar, which may be in a satisfactory occlusion, would have to be extracted as part of an expensive and time consuming orthodontic, implant and prosthetic rehabilitation. Indications for molar uprighting are as follows: periodontal health would be difficult to maintain without correction; occlusion is de- ficient or unstable; and the presence of a severely tipped third molar can predispose the distal of the second molar to caries or periodontal disease. The implant is part of the restorative solution for the previously stated indications and not an indication per se without the previously stated functional problems. Figure 11. A 30-year-old female with loss of her mandibular left first molar. The second molar has migrated mesially and moderately inclined forward. The patient is healthy periodon- tally and the occlusion of the second and third molars is stable. Treatment for implant placement is not indicated. Case 4 A 47-year-old female patient was referred because her periodon- tist indicated that the periodontal lesions on the mesial of her tipped mo- lars would deteriorate progressively over time, as she was a periodontally 185 Dental Implant Site Maintenance prone individual. On her right side, the second molar inclination was se- Vere and probed 5 mm. The maxillary first molar had erupted beyond the plane of occlusion (Fig. 12). On her left side, the mesial inclination was severe and there was significant loss of attachment and bone due to periodontal disease (Fig. 13). The mesial probed 8 mm. The mandibular third molar was tipped and overerupted because of lack of an occlusal opponent. This tooth was extracted prior to orthodontic treatment. The patient received periodontal maintenance visits every two to three months during orthodontic treatment (Handelman, 2001). Her lower incisors were super-erupted resulting in an anterior deep bite. A continuous 0.016.” x 0.022” stainless steel wire was placed from the left to the right second premolar. A separate 0.016” stainless steel wire was placed into the rectangular tubes on the bonded brackets. Because of the angulation of the molar tubes, this wire projected into the labial sulcus. It then was elevated and tied as an overlay onto the base wire (Fig. 14). This reciprocal force system resulted in both the intrusion of the incisors and uprighting and distalization of the second molars. The osseous and soft tissue anatomy on the mesial of both the right and left mandibular second molars were improved greatly, resulting in predict- able periodontal maintainability (Fig. 15). Limitation in her financial re- sources has delayed placement of the implants. Permanent retaining wires bonded into grooves cut into the crowns of the second premolars and second molars, however, will maintain the correction until the im- plant-supported crowns are placed (Fig. 15). Figure 12. A 47-year-old female prone to periodontal disease lost her mandibu- lar first molars at an early age. The right second molar is severely tipped and the maxillary second molar has super-erupted. 186 Handelman et al. Figure 13. The left mandibular second molar has bone loss with a deep pocket on its mesial associated with severe tip and mesial migration. The mandibular third molar was super-erupted and later was extracted. Figure 14. The second molars were uprighted using a 0.016” stainless steel wire that was overtied onto the premolar-to-premolar segment that was stabilized With a 0.016.” x 0.022” stainless steel wire. Figure 15. Both right and left second molars have been uprighted and the crest of the bone has followed the mesial elevation of the molars. 187 Dental Implant Site Maintenance Case 5 A 46-year-old female was referred by her periodontist (author NL) for molar uprighting prior to implant placement to restore her defi- cient occlusion (Fig. 16). The right side was limited to a premolar occlu- sion; the left was compromised by the loss of the mandibular second premolar and first molar. In addition, she had an anterior open bite. Her periodontium was healthy. Most of the springs used to upright molars exert an extrusive force on the molar that can result in bite opening. This extrusion is a problem especially on this patient’s right side because of the absence of occlusal opponents in the maxillary arch to resist the ex- trusive force on the mandibular second molar. The distal of this tooth already was beyond the occlusal plane. Roberts and coworkers (1982) have discussed this problem and offered solutions by equalizing the 2. and f components of the uprighting system. A new molar uprighting spring is now available (Forestadent", St. Louis, MO) using a 3-titanium arm to the second molar that is joined by a sliding connector to a stainless steel arm. The stainless steel arm is bent at 135° and inserted into a vertical tube that is secured to the anchor unit (Zachrisson and Bantleon, 2005). Using this uprighting spring (Fig. 17), the mandibular right second molar was distalized and uprighted without its extrusion (Fig. 18). Superimpositions of the oblique radio- graphs demonstrate the efficacy of this uprighting spring (Fig. 19). Im- plants were placed in a site that now has sufficient restorative space and a second molar that has improved periodontal anatomy (Fig. 20). - º - - - - Figure 16. Photographs of a 47-year-old female who required implants to restore her deficient posterior occlusion due to several missing teeth, including the man- dibular first molars. 188 Handelman et al. Figure 18. Oblique (45°) cephalometric radiographs of the right side with pre- treatment (left) and post-treatment (right) views. º Figure 19. Superimposed pre-treatment and post-treatment tracings of radiographs seen in Figure 18. The right second molar was uprighted with some intrusion. 189 Dental Implant Site Maintenance Figure 20. Radiographs after implant placement. VERTICAL RIDGE AUGMENTATION Ridge augmentation to bulk out the buccolingual width of the implant site is a highly predictable procedure (Nevins and Mellonig, 1995; Buser et al., 1996). Ridge augmentation in a vertical direction, however, is not predictable as several investigators have shown inconsis- tent results (Hämmerle and Jung, 2008). The most predictable technique for vertical augmentation of the ridge is slow orthodontic extrusion, which activates the bone remodeling process mediated via the periodon- talligament. The periodontal ligament allows the orthodontist to move the teeth to more ideal positions (Oppenheim, 1942). This same ligament allows the orthodontist to manipulate the adjacent bone and soft tissue to correct vertical periodontal defects (Ingber, 1974). Figure 21 provides an example of slow extrusion to correct a vertical periodontal defect. Taking this phenomenon further, slow extrusion and then extraction of a hope- less tooth will cause alveolar bone remodeling resulting in an increase of the vertical height and volume of alveolar bone and developing an ade- quate recipient site for implants (Salama and Salama, 1993; Zachrisson, 2003). 190 Handelman et al. her maxillary right lateral incisor (left). Slow extrusion at three months (center) and seven months of treatment (right) has brought down sufficient bone to cor- rect the defect. There was adequate root structure to maintain this tooth. Case 6 A 43-year-old male presented with an isolated periodontal pocket on the distal of the maxillary left lateral incisor that probed 9 mm (Fig. 22). Periapical radiographs and periodontal probing revealed a wide and deep two-walled pocket. He otherwise was healthy periodontally. In Order to provide sufficient bone for retention of an implant, one of the authors (NL) recommended slow vertical extrusion to bring bone oc- clusally to fill in the defect. A 0.016” stainless steel bypass wire main- tained the arch form and stabilized the teeth adjacent to the maxillary left lateral. A piggyback 0.016” superelastic nickel titanium wire was tied to the lateral incisor bracket, which was progressively positioned apically (Fig. 23). The crown of the lateral was reduced incrementally to accom- modate the extrusion. The lateral incisor was stabilized for three months Once Sufficient vertical bone growth was achieved. The incisor then was extracted and a lateral onlay bone graft was placed to increase the width of the implant site (Fig. 24). The slow extrusion of the hopeless though useful lateral incisor developed vertical height necessary for implant placement (Fig. 24). The maxillary lateral implant was restored with a full ceramo-metal crown (Fig. 25). 191 Dental Implant Site Maintenance Figure 22. A 43-year-old male with an extremely deep and wide perio- dontal lesion on the distal of his maxillary left lateral incisor. The pho- tograph on the left shows probing of 9+ mm. The radiograph on the right shows a deep and wide lesion. This tooth was declared hopeless but useful to mobilize bone for implant site development. Figure 23. Slow extrusion by crown reduction and use of a 0.016.” stainless steel bypass wire with a 0.012” x 0.016.” nickel titanium su- per-elastic overlay wires. HORIZONTAL AUGMENTATION OF THE ATROPHIC ALVEOLAR RIDGE In the field of implant dentistry, augmentation of an atrophic al- veolar ridge commonly is needed to increase bone volume at the implant recipient site; augmentation is accomplished most frequently by bone grafting surgery. However, this approach often yields limited improve- ment due to anatomical constraints. In some patients, the residual bone in the edentulous ridge is too thin and avascular to be utilized as a recipient site for a bone graft. Often the soft tissue in the edentulous area is defi- cient in volume, therefore hindering adequate coverage of the graft. If the 192 Handelman et al. Figure 24. Radiographs show the vertically restored alveolus (left) and the prosthetic crown supported by the implant (right). Figure 25. Photographs of the restoration of the maxillary left lateral incisor Supported by the implant. patient presents with more than one atrophic edentulous area, multiple Surgeries may be required before any implants can be placed. Finally, should several adjacent teeth be missing and the edentulous area exten- sive, extraoral sources of bone may be required, thus greatly increasing the morbidity and cost of the treatment. Orthodontic ridge augmentation by horizontal tooth movement for implant site development can be used in patients with advanced alveolar atrophy avoiding the preceding prob- lems with predictable results. 193 Dental Implant Site Maintenance Following extraction of teeth, the alveolus atrophies because it is the tooth and its periodontal ligament that sustains the alveolus (Pietro- kovski and Massler, 1967). When a tooth is moved into this reduced al- veolus, it not only will carry bone in front of the tooth being moved, but also will leave behind a healthy size alveolus in the vacated region (Lindskog-Stokland et al., 1993; Zachrisson, 2003). In this way, the periodontal ligament of the translated tooth as well as the periosteum of the alveolus responding to bending forces (Melsen, 1999) can mediate bone regeneration for enhancement of a reduced alveolar ridge. Case 7: Enhancement of the Anterior Alveolus A 54-year-old male presented with a complex malocclusion that included absence of three mandibular incisors: the right central, left cen- tral and left lateral. The anterior ridge was atrophied both in width and height and not suitable for bone grafting and an implant-supported pros- thesis (Fig. 26). The mandibular right.lateral has adequate bone height. Treatment for the atrophic anterior ridge was to move the mandibular right lateral incisor across the atrophic ridge to the left canine orthodon- tically. The patient has been in treatment only seven months, including four months of horizontal tooth movement. The principles of horizontal tooth movement to augment a thin atrophic alveolus are demonstrated in Figure 26. Case 8: Enhancement of the Posterior Alveolus A 52-year-old woman had extensive tooth extractions done at an earlier age; however, the remaining teeth had a healthy periodontium. She had maxillary and mandibular fixed prostheses replacing several missing teeth. The mandibular anterior bridge had fractured three times; the last time the mandibular left canine was fractured below the gingival margin (Fig. 27). This tooth was judged non-restorable and was ex- tracted. We only will consider the mandibular arch, which was a pros- thetic nightmare. All the incisors, the right first molar and second premo- lar, the left cuspid and first molar were absent. The anterior space from the right cuspid to the left first premolar was too long a span for a fixed bridge (Fig. 28). A SimPlant” (SimPlant”, Materialise Dental NV, Leu- ven, Belgium) cross-section of the anterior alveolus (Fig. 29) demon- strates advanced alveolar atrophy with no medullary space separating buccal and lingual cortices. The right posterior quadrant from second molar 194 Handelman et al. Figure 26. A 54-year-old male with an atrophic anterior ridge that is not suitable for bone grafting. Horizontal tooth move- ment of the remaining right lateral demonstrates an excellent ridge left behind and the ability to carry bone in advance as it is moved into the atrophic alveolus. Figure 27. A 52-year-old woman with failure of the third reconstruction of her mandibular arch, this time due to fracture of the mandibular left canine below the osseous crest, as seen on PA radiographs. to first premolar was too long a span for a traditional fixed bridge due to guarded prognosis for its retention. The ridge was too atrophic for im- plants (Figs. 28 and 29). The left posterior region also was too atrophic for an implant though a fixed bridge was feasible (Figs. 28 and 29). In consultation with the patient’s restorative dentist/implantolo- gist (author YN), the following treatment plan was developed. On the left side, the mandibular first premolar was to be advanced mesially into the Space vacated by the extracted canine. The second premolar was to be moved distally, opening a premolar size space for an implant. The man- dibular left first premolar now was substituting for the canine, which al- lowed for a fixed bridge from the right canine to the left first premolar With four incisors as pontics. Surgical implant site development in this area was not considered feasible due to limitations posed by hard and soft 195 Dental Implant Site Maintenance Figure 28. Models of the mandibular arch with the old reconstruction removed. Left: Arrows point to the atrophic ridges. The X indicates the hopeless left cus- pid that later was extracted. Right: Arrows indicate the proposed horizontal movement of the premolars to develop implant sites, two on the right and one on the left. The left first premolar was advanced to replace the extracted canine. Figure 29. SimPlant" view of the mandible demonstrates the atrophic alveolar ridges. Cross-section through the anterior alveolus is seen on the right. The atrophic ridge (arrow) was considered too thin and avas- cular to be a successful recipient site for a bone graft. tissue deficiencies which compromised graft fixation, adequate vascu- larization and soft tissue coverage (Fig. 29). On the right side, the plan was to distalize the mandibular first premolar to develop an implant site between the canine and first premo- lar. A second implant site was planned between the first premolar and second molar, provided the orthodontic distalization of the first premolar 196 Handelman et al. also enhanced this region. Figure 30 illustrates the proposed tooth movement and reconstruction. The preceding was accomplished using a series of two temporary splints, allowing distalization of the right first premolar and left second premolar and advancement of the mandibular left first premolar into the canine space. Figures 31 and 32 illustrate the tooth movements on stone casts from pre- to post-treatment. The tooth movements are documented on superimposed oblique radiographs (Fig. 33). Post-treatment periapical radiographs demonstrate the three implants in place (Fig. 34). The final reconstruction achieved the proposed treatment that included three free- Standing implants, two on the right and one on the left (Fig. 35). In addi- tion, orthodontic repositioning of teeth improved the quality of the two fixed bridges by decreasing the length of the inter-abutment distances. This complex dental reconstruction would not have been possible with- out horizontal implant site development. When moved in a vertical or horizontal direction, the periodontal ligament of the tooth proves to be the most reliable method of bone enhancement for implant site develop- ment. Figure 30. Schematic drawing of the planned orthodontic and restorative treatment. The top drawing is pre-treatment; the arrows indicate the direction of the premolar horizontal movement. The bottom drawing shows the proposed restora- t|On. 197 Dental Implant Site Maintenance - - Figure 31. Pre-treatment model (left) and post-treatment model (right). The horizontal tooth movement of the mandibular right first premolar developed implant sites both mesial and distal of this tooth. Figure 32. Pre-treatment (left) and post-treatment (right) models. The mandibu- lar left first premolar was advanced to substitute for the canine. The horizontal movement separating the first and second premolars developed an implant site between these teeth. 198 Handelman et al. ſº I'ſ wº Figure 33. Drawing of superimposition tracings of pre- and post-treatment oblique radiographs, demonstrating the orthodontic translation of the premolars to develop implant sites. Figure 34. Radiographs of the implants: two placed on the right and one on the left in formally atrophic ridges whose sites were developed by horizontal tooth In OVement. Figure 35. Photos of final reconstruction. Arrows indicate freestanding restored implants. CONCLUSION The orthodontist’s role in the eight cases presented in this paper Was indispensable in providing osseous volume and restorative space for the placement of endosseous implants. None of these patients could have been treated as successfully without the orthodontist’s participation as a member of the interdisciplinary restorative team for optimal patient care. 199 Dental Implant Site Maintenance REFERENCES Buser D, Dula K, Hirt HP, Schenk RK. Lateral ridge augmentation using autographs and barrier membranes: A clinical study in 40 partially edentulous patients. J Oral Maxillofac Surg 1996:54:420-432. Hämmerle CHF, Jung RE. Ridge augmentation procedures. In: Lindhe J, Lang WP, Karrig NP, Karring T, eds. Clinical Periodontology and Implant Dentistry. Vol. 2. Blackwell: Oxford 2008: 1083–1098. Handelman CS. Orthodontic care of the periodontically compromised patient followed long-term: Part I. Maximizing favorable outcomes. 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The effect of inter-implant distance on the height of inter-implant bone crest. J Periodontol 2000;71:546- 549. Tarnow DP, Eskow RN. Preservation of implant esthetics: Soft tissue and restorative considerations. J Esthet Dent 1996;8:12-19. Wood M, Kern M, Thomson VP, Romberg E. Ten-year clinical and mi- croscopic evaluation of resin-bonded restorations. Quintessence Int 1996:27:803-807. Zachrisson BU. Implant site development by horizontal tooth movement. World J Orthod 2003;4:266-272. Zachrisson BU, Bantleon HP. Optimal mechanics for mandibular molar uprighting. World J Orthod 2005;6:80-87. 201 202 THE AIRWAY: ASSESSMENT OF THE PATIENT WITH OBSTRUCTIVE SLEEP APNEA Stephen A. Schendel ABSTRACT A thorough understanding of airway anatomy and its association with the skele- ton and sleep-disordered breathing (SDB) can be obtained from the patient work-up, including the history, clinical exam and relevant studies such as radio- graphs, polysomnogram and nasopharyngoscopy. Specialists treating individuals with obstructive sleep apnea (OSA) or craniofacial malformations must have a thorough understanding of the anatomical airway and its relationship to SDB. Three defined anatomic levels in the upper-airway need to be addressed: nose, palate and base of tongue. Each may be partially or totally blocked in patients with obstructive sleep apnea syndrome (OSAS). The end goals are two: to en- large the airway by repositioning or removing the obstruction at each respective level without creating a complication; and to obtain a normal occlusion and den- tofacial form. Cone-beam computerized tomography (CBCT) scans, especially with newer software programs, easily clarify the relevant anatomy and are in- valuable in treatment planning. The orthodontic specialty is positioned ideally to recognize these conditions at an early age as many of these individuals seek treatment for skeletal malocclusions. A thorough understanding of airway anatomy and its association with sleep-disordered breathing (SDB) is crucial to the treatment of indi- viduals with dentofacial deformities and malocclusion. Additionally, in order to develop a treatment plan effectively, a clear understanding of both medical and surgical management used in obstructive sleep apnea (OSA) is necessary. The treatment of obstructive sleep apnea syndrome (OSAS) or the relatively newer term sleep-disordered breathing (SDB), which includes snoring, upper airway resistance syndrome (UARS) and OSAS, presently is accomplished by medical and/or surgical manage- ment. Neither of these two modalities is successful always, but each has its place in OSAS management. Medical management primarily is ac- complished by way of continuous positive airway pressure (CPAP), which is the most conservative and logical first treatment of choice since it is reversible and non-invasive. The partial or total obstructed upper 203 Obstructive Sleep Apnea airway in OSAS/UARS, however, is an anatomic problem primarily and, therefore, truly a surgical problem. The relationship between dentofacial form and breathing has been recognized intuitively by practitioners for some time. Only recently, though, with the advent of sleep medicine has the full extent of this asso- ciation been appreciated. A thorough understanding of this relationship is imperative especially in children and adolescents, as the consequences of OSA or SDB at this time are not fully apparent until much later in life. Pediatric sleep apnea is a frequent condition that can result in complica- tions if not diagnosed and treated in a timely manner. In fact, it has been found in 11% of children in a general pediatric clinic and 21% of children with noninfectious respiratory indications (Archbold et al., 2002). In cleft palate, the incidence is 30% (MacLean et al., 2009), which can have adverse effects on somatic growth, induce cardiovascular alterations and neurobehavioral defects that may not be irreversible (O’Brien and Gozal, 2005; Sheldon et al., 2005; Tran et al., 2005). Many of these children have tonsillar hypertrophy or obesity as the cause of SDB, however jaw deformities also can be present frequently. Adenotonsillar hypertrophy has been shown in the literature to be responsible for 60% of pediatric airway obstructions. Tonsillectomy and adenoidectomy, however, do not resolve the problem in 27% of this group. In fact, many children with daytime symptoms and snoring dem- onstrate a steep mandibular plane angle and crossbite with airway space reduction by as early as five years of age (Zucconi et al., 1999). Com- mon among the jaw deformities are crossbite, increased lower anterior facial height and a reduction in rhinopharynx space with base of tongue malposition (González Rivera et al., 2004; Niikuni et al., 2004). SDB is caused by a number of factors such as adenotonsillar hy- pertrophy, paranasal sinus disease, soft palate abnormalities, macroglos- sia and tracheal malformations (Nishimura and Suzuki, 2003). When identified in children or adults, OSA must be managed either medically by modalities such as CPAP and positioning devices, or by surgery that may be soft tissue, skeletal or both. Bell and Turvey (2001) have shown good results with skeletal advancement for the treatment of OSA in chil- dren. Specialists treating either OSA patients or patients with craniofacial malformations must have a thorough understanding of the anatomical airway and its relationship to SDB. The orthodontic specialty is positioned ideally to recognize these conditions at an early age since many of these individuals seek orthodontic treatment for skeletal malocclusions. 204 Schendel Since the early 1970s, dentofacial morphology manifested pri- marily by excessive anterior vertical facial height and facial retrusion has been recognized under various names such as adenoid faces, extreme clockwise rotation, high angle and skeletal open bite. These multiple clinical terms were assembled together by Schendel and coworkers (1976) under the title long face syndrome (Bell, 1971; Nahoum, 1971; Blanks et al., 1988: Peltomaki, 2007). The common denominator in this group is excessive vertical growth of the maxilla and posterior rotation of the maxillomandibular complex that results in the typical facial form (Fig. 1). Difficulty with nasal respiration and enlarged tonsils and ade- noids commonly are associated with this dentofacial morphology. The causative mechanism is thought be secondary to several factors such as oral respiratory pattern and abnormal secretion of growth hormone and its mediators (Zettergren-Wijk, 2006; Peltomaki, 2007). Lee and col- leagues (2009) have shown that OSA can be predicted accurately based on a craniofacial photographic analysis that clarifies maxillomandibular retrusion. They could predict correctly individuals with OSA 76% of the time. These individuals tended to have smaller mandibles and anterior neck space with wider faces. Early surgery, which is most frequently adeno-tonsillectomy, can normalize the dentofacial growth pattern in this group. In children, though, CPAP and jaw surgery also may be the indi- cated treatments (Marcus, 2005; Zettergren-Wijk, 2006; American Acad- emy of Sleep Medicine, 2008; Lee et al., 2009). Although CPAP is not without side effects such as nasal symptoms, skin ulceration, eye irrita- tion and inability to tolerate the device, it remains the main medical treatment for OSA. Mandibular micrognathia associated with such congenital mal- formations such as Pierre Robin, Treacher Collins, Nager’s and Hemifa- cial Microsomia is another well-recognized cause of OSA in infants and young children (Miller et al., 2007; Peltomaki, 2007). In these children, the most frequent cause of OSA is obstruction of the airway by the tongue secondary to glossoptosis resulting from micrognthia. Choanal atresia, tracheal malformations and macroglossia also can cause OSA in this group. Mandibular distraction has been shown to be a safe and effective means in relieving the airway obstruction in micrognathic infants (Carl- Sand Sailer, 1998; Burstein and Williams, 2005; Denny and Amm, 2005; Lin et al., 2006; Miller and Schendel, 2006; Miller et al., 2007). Internal 205 Obstructive Sleep Apnea Sº Figure 1. Long face syndrome, profile drawing. Note the typi- cal long lower facial height and retruded maxillomandibular profile. devices generally are preferred because of their efficacy and patient ac- ceptance. In addition, the use of an internal curvilinear device provides distraction vectors that lengthen both the ramus and body, duplicating normal mandibular growth. The curved distractor mimics the normal logarithmic growth curve of the mandible that has been shown by MOSS and colleagues (1974) and Ricketts (1982) and avoids the anterior open bite seen with linear internal distractors (Schendel and Linck, 2001, 2004). Another issue of emerging importance in micrognathic infants with airway problems is feeding. Swallowing disorders in patients with Pierre Robin sequence have been documented with electromyography and have been shown to occur in approximately 85% of patients (Monasterio et al., 2004). These 206 Schendel disorders often are severe enough to necessitate nasogastric feeding and occasionally, a gastrostomy for feeding. They reported performing dis- traction on 19 infants with micrognathia and isolated Pierre Robin se- quence and airway issues. Following distraction, the feeding problems generally resolved. We also found that nonsyndromic children with mi- crognathia have relatively quick improvement in feeding as evidenced by ability to wean from nasogastric nutritional supplementation. Midface retrusion also can be a cause of OSA in infants with such congenital de- formities as Apert, Crouzon and related conditions. OSA in adults is associated not only with airway disorders and abnormal dentofacial morphology, but also with an increased body mass index (BMI ~ 35) in many cases (Schendel and Powell, 2007). The two can be related in a circular manner, with each augmenting the other as OSA is known to cause a increase in the hunger drive and incidence of diabetes. Many of these adults also present with bimaxillary retrusion and a structural airway problem that is a continuation of the facial pattern seen in these individuals as children and in children with OSA. In these patients, skeletal advancement of both the maxilla and mandible is the indicated treatment when CPAP cannot be tolerated. In other patients, removal of the redundant soft tissues by procedures such as the uvulo- palatoplasty and/or genioglossus advancement may be indicated alone or in conjunction with bimaxillary advancement (Schendel and Powell, 2007). Enlargement and decreased collapsibility of the velo- orophayngeal airway are the goals by anterior displacement of the soft tissues, musculature, dentition and musculature. Treatment of adult pa- tients generally involves a maxillomandibular (MMA) of 10 mm to treat the lax soft tissues even if the cephalometric analysis does not indicate a skeletal deformity of this magnitude. Correction of transverse maxillary and mandibular problems with expansion as part of the overall treatment also has been shown recently to be successful (Conley and Legan, 2006). Treatment using MMA usually is 75% to 100% successful in correcting the OSA. Cephalometric studies have shown good skeletal stability after MMA advancement, while long-term studies also have demonstrated that the result is stable (Schendel and Powell, 2007). EXAM A thorough understanding of airway anatomy and its association with the skeleton and SDB can be obtained by the patient workup includ- 207 Obstructive Sleep Apnea ing the history, clinical exam and relevant studies such as radiographs, polysomnogram (PSG) and nasopharyngoscopy. There are three defined anatomic levels (nose, palate, base of tongue) in the upper airway. Each may be blocked partially or totally in patients with OSAS. The goal is to enlarge the airway by repositioning or removing the obstruction at each respective level without creating a complication. It is more difficult to treat the more distal portions of these airway levels from the nose to the larynx. This difficulty is due in part to the increasing amount of soft tissue encoun- tered as one moves distally (nose vs. tongue). Furthermore, it is common that the adult sleep patient is far more difficult to treat than usually is expected. Because multifactoral etiologies exist, it is easy to overestimate the chance for control of all variables. There are two major principles that should be understood for surgical management of OSAS: they are different, yet are of near equal importance. The first principle is the “behavioral derangement” in OSAS, which is secondary to excessive daytime somnolence (EDS). EDS is the result of nocturnal arousals during sleep due to airway collapse and usu- ally manifests as sleepiness and/or fatigue to such a degree the subject lacks vigilance and does not function normally during the day. Symptoms may include: Snoring, apneas, morning headache, fatigue, sleepiness after lunch, memory loss, irritability, poor work performance, altered family relationships and in some cases, alterations in libido. These symptoms may be minimal to the point where the patient denies sleepiness and/or severe to the point that the subject will fall asleep while driving. Regardless of the number of symptoms, they are not correlated necessarily with severity as measured by using only the apnea hypopnea index (AHI). The second principle is the “pathophysiologic derangement” that can be associated with OSAS and is, in part, cardio-respiratory in nature. It is well known that at some level of OSAS severity, there is an in- creased risk for myocardial infarction, stroke and sudden death. Three important well-known physiologic processes are involved in OSAS that predispose to these risks: hypoxemia, negative intrathoracic pressure and disequilibrium of the autonomic nervous system (ANS). Surgical Indications in OSAS • Excessive daytime sleepiness (EDS) • Respiratory disturbance index (RDI) of > 20 episodes per hour of sleep (or in cases where the RDI is ~ 20 associated with marked objective EDS) 208 Schendel • Oxygen desaturation of ~ 90% * Hypertension and/or arrhythmia * Negative esophageal pressures more negative than negative 10 cm H2O • Anatomical abnormalities of the upper airway • Failure of medical management (one of the most common rationales but not an acceptable metric by it- self) These indications are similar to those of medical management with CPAP. The patient’s history and complaints generally are associated with snoring and/or EDS; rarely do these patients visit to discuss respira- tory or cardiac derangements as their chief complaint. It is imperative, therefore, that a basic understanding of this metric exists when evaluat- ing such patients. This observation is especially true in light of the fact there are multiple other causes for the behavioral derangements of EDS other than OSAS including volitional sleep deprivation, alcoholism, in- Somnia and narcolepsy. Furthermore, not all snorers develop OSAS. As intermittent Snoring turns to habitual snoring, however, the airway collapses progres- sively and as a rule of thumb. If the bed partner frequently leaves the bedroom, there is about an 80% chance the patient will have some degree of OSAS. A thorough medical and sleep history should be taken regard- less of age, and it is recommended in adults that a subjective question- naire such as the Epworth Sleepiness Scale (ESS) be utilized (Johns, 1991). The ESS assesses the propensity of sleep in eight situations. It is not perfect and does not always correlate with OSAS severity, but does give some information of the patients waking sleepiness. A clinical examination of the head and neck, along with a 3D cone-beam computerized tomography (CBCT) radiographic exam fol- lowed with a fiberoptic nasopharyngoscopy is recommended. Careful evaluation of the following is suggested: nasal airway obstruction, the palatal region to include the lateral pharyngeal walls along with the size and character of the tonsils (if present), oral soft tissues, malocclusions or other skeletal abnormities, and tongue and tongue base. This portion of the clinical examination then can be correlated with the radiographic exam and fiberoptic nasopharyngoscopy, along with data from an objective overnight PSG and the subjective symptoms of the patient. In many instances, the patient will not have had a PSG prior to their visit. The polysomnographic study is an essential part of the 209 Obstructive Sleep Apnea Surgical workup and must be conducted pre- and post-surgery; otherwise the patient’s PSG parameters and the clinician’s success rates will not be appreciated. Some of the parameters to insist on from an attended PSG in- clude: name, age, BMI, total sleep time (TST) of at least 240 minutes for a valid study, sleep stages NREM, REM and percentage of sleep in each, apnea index (AI), mean and maximum duration in seconds, hypopnea index (HI), mean and maximum duration in seconds, awake SaC2, lowest SaO2, stratifications of the percent of time below 90%, 80%, 70%, etc., heart rate fluctuations (brady/tachy arrhythmias) and periodic leg move- ments (PLM). The severity as an index is summarized as the respiratory disturbance index (RDI) or more frequently now the apnea-hypopnea index (AHI). An AHI of s 5 is considered normal for an adult. The infant and child should not have any events. Be aware that the PSG should be cur- rent (6 to 12 months) and, if possible, not a split-night study (one half diagnostic and one half therapeutic). Split-night studies apply CPAP for the second half of the night and may underestimate the severity of OSAS. This finding is common because the TST does not meet diagnos- tic criteria. Due to medical and ethical reasons, a split-night study is mandated in certain cases, especially for patients who are hypoxemic, have arrhythmias or exhibit hypertension during the study. Again, it is suggested that all sleep studies for a surgical patient be an attended over- night PSG. Home monitoring is acceptable in some cases but not sug- gested for surgical evaluation in that the majority of these types of stud- ies lack detailed information on actual sleep parameters. One should avoid trying to make a diagnosis or treatment plan by the use of an isolated cephalometric headfilm, as it is only a small part of the workup. This film is used routinely in orthodontics and should be evaluated for the usual anthropomorphic measurements. Measurements that have been used commonly for evaluating soft tissue and bony anat- omy in OSAS include: SNA, SNB, PNS-P, PAS and MP-H. These have been described previously as have other techniques such a MRI, ultra- sound and CT scanning. The use of nasopharyngolaryngoscopy can fur- ther help to identify regions (nose, retropalatal and tongue base) in the airway that may be a part of nocturnal obstruction. In addition, it is useful to rule out other causes of upper airway obstruction such as tumors, cysts and laryngeal pathology. 210 Schendel Pediatric Considerations. The pediatric population consists of two basic groups that are considerably different. The first are those con- genital craniofacial malformations such as hemifacial microsomia, Treacher Collins, Nager’s Syndrome and micrognathia. The condition generally is recognized right away or in the first several years of life. In this group, severe OSA is seen and tracheostomies frequently have been the initial treatment. Associated conditions such as failure to thrive, gas- troesophageal reflux and tracheomalacia are common. The pediatric evaluation is multi-specialty based on a through history and physical ex- amination. Objective studies such as CT scans, MRI, chest x-rays and cardiac studies frequently are indicated. Additionally, testing for gas- troesophageal reflux and upper airway studies are needed. Children may have daytime somnolence or hyperactivity, and in some children these hyperactive symptoms have been misdiagnosed as attention deficit hy- peractivity disorder (ADHD). A thorough history will reveal a child who has snoring and/or apneic episodes. In syndromic children or those with severe malforma- tions this is obvious, but in others the symptoms may be overlooked eas- ily. The overnight PSG in children is the gold standard and simple oxy- gen saturation studies are not sufficient. In contrast to adults, the pediat- ric PSG should not demonstrate any apneic events or desaturations. In children age three to five years, the average obstructive apneas are 0.03 per hour of total sleep time. In children older than six years of age, it is 0.05 while central apneas are 0.82 and 0.45 per hour. Infants may have central apneas that usually disappear with brain maturation; these should be separated from the obstructive apneas or hypopneas. Increased intracranial pressure and brain stem compression seen in craniosynostosis also can cause central apnea. Many older children have tonsillar hypertrophy or obesity as the underlying cause, and the rate varies from 3.2% to 12.1% of all children (Bower and Gungor, 2000; Montgomery-Downs et al., 2006). Major craniofacial anomalies and skeletal abnormalities are well-known causes, however, and may play a role especially in recurrent OSA after tonsil and adenoidectomies (Con- tencin et al., 2003). Indirect or direct laryngoscopy also must be per- formed to evaluate the airway and specifically rule out tracheomalacia. In children with micrognathia, skeletal correction is indicated. Such sur- gical intervention may consist of mandibular or midface advancement usually by distraction osteogenesis (Bell and Turvey, 2001; Cohen et al., 2002; Lin et al., 2006; Mathijssen et al., 2006). 211 Obstructive Sleep Apnea The second pediatric group consists of those young adults with developmental maxillomandibular retrusion and or adenotonsillar hyper- trophy. Young women with condylar resorption of an idiopathic or rheumatoid origin can comprise another group with sleep symptoms that is smaller in number and that has mandibular retrusion as the causative mechanism. This older young adult population in our experience is re- lated most commonly to developmental mandibular retrusion. The max- illa, if involved, is mildly retrusive but frequently vertically long as stated earlier. In pediatric and adolescent populations, the OSA is related more closely to the skeletal deformity and not to lax or excessive oropharyn- geal soft tissues, as is seen in the adult population. The soft palate and tongue usually are normal. Cephalometric measurements consistently demonstrate a reduced SNB angle of ~ 82°. Mandibular advaňcement may be performed concomitantly with maxillary surgery depending on the severity of the OSA. dº Loss of posterior facial height significantly affects the airway, thus contributing to OSA in some of the more severe cases. In this group, distraction of the mandible is advantageous because of the shortened ra- mus height and large advancements needed (> 1 cm) to correct the de- formity. When combined with maxillary surgery, this becomes distrac- tion orthognathics (Schendel et al., 2008). Clinical Exam. The airway extending from the tip of the nose to the epiglottis can be visualized on a conventional CBCT scan (Fig. 2). Since the scan also includes the jaws, teeth, cranial base, spine and soft tissues, there is an opportunity to evaluate the functional and devel- opmental relationships among these structures. Skeletal support for the airway is provided by the cranial base (superiorly), spine (posteriorly), nasal septum (anterosuperiorly) and jaws and hyoid bone (anteriorly). The airway valves include the nose, soft palate, tongue and epiglottis. If airway obstructions or encroachments are present, visualiza- tion and calculation of the airway dimensions may identify and localize the source of the obstruction. The airway can be divided into three ana- tomical sections for evaluation and treatment of SDB: nose, retropalatal and retroglossal (Fig. 3). Airway obstruction may occur in one or more of these areas simultaneously; thus a thorough knowledge of the anatomy in each area and its influence on the airway is necessary. The airway de- scription in this chapter will deal with the internal anatomy and support- ing structures. The reader is referred to the article by Schendel and Car- 212 Schendel Airway Volume = 74862.8 mº - Figure 2. CBCT scan image of the upper airway and sinuses. lotti (1991) for a description of the external and esthetics aspects of the nasal anatomy in orthognathic treatment planning. The nose prepares the air for the lower respiratory tract by Warming and humidifying it. Any deformity of the internal nose will af. fect airflow, and the surgeon and orthodontist should be concerned with nasal aerodynamics. The nares act as a funnel guiding the airstream to- Ward the two valve areas that generally is the narrowest area of the nose. Deformities or collapse of the alar cartilages will cause airflow reduction at the external nasal valve. The angle between the caudal end of the up- per lateral cartilages and the septum is called the internal nasal valve. This angle is normally between 10° to 15° (Meyer, 1998). The total nasal area at this point has been estimated between 55 mm and 64 mm and normally is the smallest part of the airway. Any stricture or stenosis in this region can cause restricted airflow or cause turbulence (Fig. 4). Airflow symptoms at this level can be evaluated by the 213 Obstructive Sleep Apnea Figure 3. Schematic of the upper airway, divided into three sections for evaluation: 1) Nasal cavity; 2) Retropalatal area; and 3) Retroglossal area. the Cottle test: while the patient breathes quietly, the cheek is retracted laterally, thus opening the nasal valves. If the Cottle test improves the breathing, it is considered a positive Cottle test and indicates a valve problem. Septal deviations also obstruct the nose in addition to causing airflow turbulence and secondary problems such as dryness and bleeding. The turbinates, of which the inferior is the most important in regard to airflow dynamics, are in a constant cycle. One side is congested while the other is decongested, however, the total nasal resistance remains relatively constant (Fig. 5). The turbinates rapidly heat the air from 0° to 36° Centigrade 214 Schendel Figure 4. External nares. Internal nasal valve. The junction of the upper lateral cartilages and the nasal septum. Generally this is the narrowest part of the nose. and humidify it. Enlarged inferior turbinates can obstruct the nose and greatly reduce airflow; thus, surgical reduction may be indicated. The overall width of the face, especially the maxilla, also influ- ences the nasal cavity, as the floor of the nose is the hard palate. Maxil- lary constriction seen with crossbite type malocclusions and low tongue positions will decrease the nasal width negatively affecting the airflow. Area 2 in Figure 2 is the retropalatal area consisting of the Space behind the soft palate and anterior to the posterior wall of the pharynx. Airflow dynamics here are influenced by the position of the maxilla, soft palate and adenotonsillar structures. A retruded maxilla will decrease the available space behind the hard palate and the airway. This condition is Seen most clearly in cases of midfacial retrusion such as Apert’s Syn- drome, Crouzon’s Syndrome and clefting, but also can be found in ordi- nary maxillary retrusion. The length and thickness of the soft palate also is important; ei- ther a very thick or long palate will cause obstruction. Airway problems “an be seen after cleft palate surgery, especially following pharyngeal 215 Obstructive Sleep Apnea Figure 5. The nasal turbinates of which the inferior is most important for airflow dynamics. flaps or sphincter type procedures. In the adult with chronic SDB and Snoring, the palate thickens, elongates and descends, further compound- ing the airway problem. In adolescents, though, the most common condi- tion is lymphoid hyperplasia with enlargement of the adenoids and ton- sils. This reduces the retropalatal airway causing OSA and is stated to be the cause of airway problems 60% of the time in this group. Area 3 is the retroglossal region that is most influenced by the position of the mandible and the tongue. Retrusion of the mandible car- ries the base of the tongue posteriorly and with relaxation during sleep, the tongue may drop further back, obstructing the airway leading to ap- neic or hypopneic spells. Posterior tongue position also can influence palatal position, causing secondary obstruction at the palatal level as well. Some idea of the tongue position can be gained from a lateral cephalometric radiograph; however, more complete visualization of the tongue and the airway can be gained from 3D imaging as seen in CBCT exams and nasopharyngoscopy. The size of the tonsils also contribute greatly to airway size at this level, mainly in the transverse width. 216 Schendel RADIOGRAPHIC EXAM The radiation dose from CBCT scans is significantly less than other computed tomographic imaging methods such as medical CT and is within the range of traditional dental imaging methods. The superior anatomic information available from 3D imaging is establishing CBCT as the preferred imaging modality in for airway evaluation in the adoles- cent and adult populations. Medical CT imaging is best for infants and young children with SDB. Airway anatomy and evaluation is accurate and informative when 3D imaging is utilized (Schendel and Hatcher, 2009). Secondary to this imaging is an increased awareness among prac- titioners regarding the relationship between craniofacial structures, air- way anatomy and obstructed SDB. Other applications using 3D imaging include evaluation of the changes in the airway resulting from surgery on the oral soft tissues and the jaws. The accuracy of predicting airway space changes from lateral cephalometric radiographs is +/- 1.5 mm. In a study by Muto and col- leagues (2008), a setback of the mandible of 1 cm showed a 0.4 mm de- crease of the airway in the anteroposterior dimension only. The useful- ness of these cephalometric studies also is limited since data is obtained in only two dimensions. Computed tomography imaging is superior, both in accuracy and the ability to measure in three dimensions. Airway space measurement has been shown to be reasonably accurate using CBCT scans (Yamashina et al., 2008). Multivariate analysis shows both ret- roglossal space (p = 0.027) and retropalatal space (p = 0.0036) to be pre- dictive of RDI. Li and coworkers (2003) also have demonstrated a relationship between the airway area and the likelihood of OSA. There is a high probability of severe OSA with an airway area less the 52 mmº, an in- termediate probability if the airway is between 52 to 110 mm and a low probability if the airway is greater than 110 mm. Lowe and colleagues (1986) demonstrated that the majority of the constrictions occur in the oropharynx with a mean airway volume of 13.89 +/- 5.33 cm'. Barkdull and coworkers (2008) demonstrated a correlation between the retrolin- gual cross-sectional airway and OSA when this area was less than 4% of the cross-sectional area of the cervicomandibular ring. 217 Obstructive Sleep Apnea Schendel and Hatcher (2009) have shown that measurement of the 3D airway using a semi-assisted software program from CBCT data is accurate, reliable and fast. The difference in measured Volume was F/- 0.15 cc. The program easily identified the smallest airway area and the largest area while analyzing the airway in successive slices. Imaging of the upper airway using CBCT data, therefore, is valuable to identify the exact location and nature of the obstruction in OSA together with the other parameters. Incorporation of this into daily practice will allow practitioners to evaluate readily and screen their patients for anatomic related SDB (Figs. 6-8). This ability is especially important in the ado- lescent population where many already seek orthodontic treatment for dentofacial deformities associated with OSDB and where radiographs already are obtained routinely. AIRWAY CHANGES AND SURGERY Common nasal surgical procedures include septoplasty and infe- rior turbinate reduction by resection or radiofrequency. Airway collapse and a decreased internal nasal angle are treated by spreader grafts or other rhinoplasty techniques to expand and stabilize the cartilaginous structures of the nose. These changes can be seen easily on a nasal exam with speculum or nasendoscope, but are difficult to quantify without us- ing rhinometry. Subjective changes are noticed readily by the patient. The main soft palate procedure is the uvulopalatopharyngoplasty (UPPP), which shortens the soft palate and removes redundant tissue. This procedure may be accompanied by tonsillectomy if the tonsils are still present. Frequently a geniohyoid-genioglossus procedure is per- formed concomitantly with the palatal procedure, as research has shown a higher cure rate when the two procedures are combined (Riley et al., 2000). Studies of these procedures have looked mainly at the change in the PSG with occasional lateral cephalometric support. Sophisticated 3D airway studies are absent except for that of Fairburn and coworkers (2007). Maxillomandibular surgery is performed when there is clinical and radiographic evidence of jaw retrusion in adolescents or adults. In addition, maxillomandibular advancement surgery is performed in those individuals who may have a normal dentofacial skeleton but who have not responded completely to the other surgical treatments and cannot tolerate CPAP. The rule of thumb here has been an advancement of 1 cm. Studies generally show good results as previously stated. These out- comes, however, have relied primarily on findings from the PSG and have 218 Schendel Figure 6. Vultus airway analysis. Lateral view with airway analysis segments calculated after midline airway points are marked. used different criteria for cure; 3D airway studies generally are few (Conradt et al., 1997; Prinsell, 1999: Waite et al., 1999; Hendler et al., 2001; Li et al., 2001, 2002; Goh and Lim, 2003; Smatt and Ferri, 2005; Fairburn et al., 2007; Lye et al., 2008). Two-dimensional (2D) anatomic airway changes in lateral cephalometric films in individuals undergoing bimaxillary advancement show pharyngeal depth increases in the magnitude of 48% of the maxil- lary advancement (Li et al., 2003). In addition, these studies demonstrate anatomical differences between individuals with OSA and normal sub- jects, but they are limited because of their 2D basis (Djupesland et al. 1987: Blanks et al., 1988: Tsuchiya et al., 1992; Hochban and Branden- burg, 1994; Pracharktam et al. 1994; Avrahmi and Englender, 1995; Tangugsorn et al. 1995a,b; Ogawa et al., 2007; Muto et al., 2008). - Three-dimensional (3D) studies of airway changes following bimaxillary surgery are limited but demonstrate that the surgically in- duced change is not only in the anteroposterior dimension but also in the 219 Obstructive Sleep Apnea ". - " " " ": | - | Figure 7. Coronal, axial and lateral radiographic views with automatic segmen- tation lines (top two views) and highlighted lateral airway view (bottom right). Lower left shows segmented airway area in one slice. lateral dimension. Fairburn and coworkers (2007) examined 20 patients with OSA who underwent bimaxillary advancement and had pre- and post-Surgery PSGs and CT scans. They found that bimaxillary advance- ment enlarged the entire velopharynx by elevating the tissues attached to the jaws and hyoid. Airways with a decreased ratio of lateral airway di- mension to anteroposterior dimension were more prone to collapse. Our group recently evaluated airway changes using CBCT Scans and PSGs in three patients undergoing bimaxillary advancement (Schendel and Powell, 2007). The airway was evaluated by a semi- automated analysis program from 3DMD. The mean maxillomandibular ad- 220 Schendel 0.0 - CSA: 311.48 mm: -- 3.0 - CSA: 310.34 mm: - - - º - - 12.0 - . - - -- - . 73 mm: 2.0 - CSA: 235.02 mm: E * CSA; 340.73 m. Figure 8. Vultus airway analysis. Automated airway analysis at each segment with smallest airway segment automatically highlighted as red and calculated. Vancement was 9 mm. The pre-operative AHI was 26 and the smallest air- Way area was 34 mm. Post-operatively, the average AHI was 6 mm and 221 Obstructive Sleep Apnea the smallest airway was 200 mm. Airway changes were both in the an- teroposterior and lateral directions. These data are consistent with stated Figure 9. Coronal, axial and lateral pre-operative radiographic views with automatic segmentation lines and highlighted lateral airway view. 222 Schendel airway sizes and corresponding severity of the OSA as measured by PSGs (Figs. 9-11). 0.0 - CSA: 311.43 mm: ſ 3.0 - CSA; 310.34 mmº- 50 CSA. 233.49 mm: Figure 10. Post-operative segmented airway sections showing the change. 223 Obstructive Sleep Apnea - - - - - º Figure 11. Bimax study. Pre-operative analysis of airway with the Smallest airway segment area marked. CONCLUSION Airway evaluation should be part of the routine history and den- tal exam for orthodontists and oral and maxillofacial surgeons. These professionals must have a thorough understanding of the structural air- Way and its relationship to OSA and SDB. In order to plan care compre- hensively for these individuals, objective tests such as PSG, nasopharyn- goscopy and CBCT radiography need to be incorporated into the clinical practice. Newer software programs developed to create a patient specific 224 Schendel anatomical reproduction (PSAR) are beneficial in clarifying the individ- ual patient anatomy by combining images from radiography and other sources. 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J Oral Maxillofac Surg 1989;47: 1256-1261. 229 Obstructive Sleep Apnea Yamashina A, Tanimoto K, Sutthiprapaporn P, Hayakawa Y. The reliability of computed tomography (CT) values and dimensional measurements of the oropharyngeal region using cone beam CT: Comparison with multidetector CT. Dentomaxollofac Radiol 2008:37:245-251. Zettergren-Wijk L, Forsberg CM, Linder-Aronson S. Changes in dentofacial morphology after adeno-ſtonsillectomy in young children with obstruc- tive sleep apnea: A 5-year follow-up study. Eur J Orthod 2006:28:319- 326. Zucconi M, Caprioglio A, Calori G, Ferini-Strambi L, Oldani A, Castronovo C, Smirne S. Craniofacial modifications in children with habitual snoring and obstructive sleep apnoea: A case-control study. Eur Respir J 1999; 13:411–417. 230 THE FACE OF OBSTRUCTIVE SLEEP APNEA R. Scott Conley ABSTRACT Introduction: Obstructive sleep apnea (OSA) is a growing health concern. It affects middle-age men predominantly, but increasingly is affecting women and adolescents. With this increase in prevalence, larger numbers of affected indi- viduals are likely to present to the orthodontic office either as patients or as par- ents of patients. It is important to recognize signs and symptoms of the disease so that undiagnosed patients can receive the required life-saving treatment. Fa- cial analysis, if accurate, is one easy and beneficial way to recognize individuals most likely to be affected by OSA. Several forms of treatment exist for patients diagnosed with OSA including continuous positive air pressure (CPAP), weight loss, oral appliances and orthognathic surgery. One of the most successful treatments requires significant (10 mm or more) maxillomandibular advance- ment (MMA). Multiple reports demonstrate over 90% success rates in patients who undergo MMA. With such large advancements, there is substantial concern regarding the potential effect two-jaw advancement may have on facial esthetics. Methods: A previous study by Conley and Boyd (2007) analyzed pre- and post- treatment radiographs of 31 consecutive patients diagnosed with OSA who un- derwent surgical MMA. In the original study, the radiographs were used to de- termine the magnitude of maxillary and mandibular skeletal advancement and to understand the effect of these movements on the soft tissue envelope. From this analysis, ratios of soft to hard tissue movements were developed. The current follow-up study uses Conley and Boyd’s 2007 data to determine the accuracy of their newly developed soft tissue to hard tissue ratios for individual patient pre- dictions. The current study compared the predicted soft tissue changes with pre- dictions using accepted historical ratios of changes in soft tissue to hard tissue and comparing both to individual post-surgical outcomes. Results: Utilizing a leading imaging program, the soft tissue to hard tissue ratio of 0.9:1.0 derived from our previous study was found to be more accurate in depicting the ex- pected outcome of the patient than the accepted historical ratios. Conclusions: Thus, individualized patient soft tissue predictions can be performed with en- hanced levels of accuracy for patients who are about to undergo MMA surgery. Though these patients are undergoing the MMA treatment as a life-saving measure, it is important to demonstrate their facial presentation will not be af- fected adversely. 231 The Face of Obstructive Sleep Apnea Depending on the disease progression, chronic obstructive sleep apnea (OSA) can be a severe and debilitating disorder. Individuals of all ages can be affected, but middle-age adult males who are moderately to severely overweight have the highest prevalence of the disease (Young et al., 1993). Women also are affected by OSA but to a lesser degree (Strollo and Rogers, 1996). More recently, OSA is being seen in greater numbers in the pediatric and adolescent age ranges (Marcus, 2001). The appearance of OSA at an earlier age is of significant concern because the effects of the disease process are progressive if not corrected. The onset of OSA at younger ages may produce complications from the disease earlier and may result in decreased life expectancy for affected individuals. Many patients are unaware of their condition and may not see their primary care physician routinely (Smith et al., 2002). During their visit to the orthodontic office, adults may demonstrate signs and symp- toms of OSA, enabling referral for definitive diagnosis. Once diagnosed, several treatment modalities exist to improve a patient’s sleep pattern (Scrima et al., 1982; Sanders et al., 1983; Smith et al., 1985; Coleman, 1998). Because of the orthodontist’s expertise in facial growth as well as in craniofacial and dentofacial anomalies, the orthodontist is one of the best equipped of healthcare professionals to collaborate and provide successful treatment for OSA. Many forms of treatment can be performed in the orthodontic of fice or in collaboration with an oral and maxillofacial surgeon (Schmidt- Nowara et al., 1995; Lowe, 1999; Prinsell, 2002). Successful treatment will improve both a patient’s subjective and objective assessment of day- time alertness (Milleron et al., 2004; Campos-Rodriguez et al., 2005; Lavie et al., 2005). The same treatment modalities that the orthodontic professional commonly performs to achieve alignment and improvement in function also now can provide a significant health benefit and service beyond improving a patient’s smile and self-esteem. DIAGNOSIS AND CLASSIFICATION OF ADULT OBSTRUCTIVE SLEEP APNEA (OSA) Adult orthodontics has become more prevalent in recent years. As a result, an increased potential exists for the undiagnosed OSA patient to seek care at the orthodontic office. The classic presenting symptom is excessive daytime sleepiness. A valuable yet inexpensive screening tool is the Epworth Sleepiness Exam. This exam, which is reported in several 232. Conley papers and is available on the Internet, asks a series of questions enabling the health practitioner to assess the patient’s relative sleep health. Unfor- tunately, while this test will help determine that a patient has sleep- disordered breathing, it is unable to differentiate OSA from the many other types of sleep-disordered breathing (e.g., restless leg syndrome). Reducing OSA severity can have a significant effect on the qual- ity of life and lifespan of patients. Patients with severe manifestations of OSA have a 37% greater five-year morbidity and mortality than unaf- fected individuals and successfully treated OSA patients (Marti et al., 2002). Therefore, a simple, accurate, non-invasive and powerful tool to differentiate a simple snorer easily from a mild OSA patient and a mild from a more severe OSA patient is essential. To assist in identifying which patients to refer for complete evaluation, cephalometric investigations have attempted to determine whether OSA and snoring patients are distinctly different from non- snoring patients. Currently, the studies on this topic provide conflicting evidence. Two papers (Maltais et al., 1991; Zucconi et al., 1993) report a cephalometric continuum involving differences in specific cephalometric Values between these groups of subjects. Thus, individuals who snore demonstrate larger mandibular plane to hyoid distances than non-snoring individuals; OSA patients have larger mandibular plane to hyoid dis- tances than patients who snore. In addition, soft palate length in snoring individuals was larger than the soft palate length in non-snoring indi- viduals. While this information is promising, two other studies were unable to demonstrate any differences in cephalometric findings between these groups of individuals (Anderson and Brattstrom, 1991; Cistulli, 1996). Among the patients affected by OSA, multiple investigators have reported several cephalometric indicators that can be used to assist in a preliminary diagnosis. While these cephalometric measures are insuffi- cient to diagnose OSA, they provide enough information for screening purposes and to indicate whether additional testing is required. One of these measures is the linear distance from the mandibular plane to the hyoid bone. A distance greater than 15.4 mm indicates that a person is at risk for OSA (Riley et al., 1983; Fleischer and Krieger, 2007). These elevated values indicate a collection of soft tissue, frequently adipose tissue, present in the submental area (submental lipomatosis). Generally the adipose tissue is not confined to the submental area, but also is pre- sent around the airway. This collection of tissue creates pressure that can make airway collapse easier. 233 The Face of Obstructive Sleep Apnea Another cephalometric measure reported to be indicative of a greater risk of OSA is an increased mandibular plane angle. This meas- ure is associated frequently with a steep occlusal plane, over-erupted posterior dentition, a large gonial angle and anterior open bite. This col- lection of features historically was referred to as “adenoid facies” (Lowe et al., 1986) and more recently as vertical maxillary excess. In addition to the skeletal markers that potentially indicate a greater risk of OSA, some soft tissue measures, especially those associated with soft palate dimensions, are reported. A longer soft palate (PNS – P; Riley et al., 1983; Fleischer and Krieger, 2007) and a wider soft palate can combine to reduce the posterior airway space (PAS; Tsuchiya et al., 1992; Tan- gugsorn et al., 1995b, Cistulli, 1996). The combination of these factors is represented in a figure in an article by Cistulli (1996) that demonstrates differences between a subject with a normal airway and a patient with a reduced airway (Fig. 1). As OSA has become more recognized, attempts have been made to develop a simplified series of facial characteristics one examines to develop a quick, easy and inexpensive screening method. Multiple pa- pers report that maxillary deficiency alone, mandibular deficiency alone, or combined maxillomandibular deficiency can predispose a patient to OSA (Tangugsorn et al., 1995a). Despite these observations, no clear, accurate and comprehensive examination has been developed. In addi- tion, it is critical to analyze Class I, II and III patients separately in that the cephalometric averages that result from combining groups can lead to erroneous conclusions. At this time, no studies have been performed that are large enough to distinguish airway differences between Class I, II and III patients. While both maxillary and mandibular deficiency can contribute to the disease process, more investigators have focused on mandibular deficiency as a contributing factor in the development of OSA. A series of cephalometric evaluations of OSA patients concluded that mandibular deficiency was present in 16 to 60% of their study group populations (Halperin et al., 1979; Riley et al., 1983; deBerry-Borowiecki et al., 1988; Lyberg et al., 1989; Tangugsorn et al., 1995a). Unfortunately, this observation means that 40 to 84% of the study population consisted of patients without mandibular deficiency. Combining the studies demon- strates that one cannot rely solely on the facial profile to diagnose OSA. Another risk factor for OSA is obesity (Ferguson et al., 1995). In several cephalometric studies, obese OSA patients have been shown to exhibit only minimal skeletal differences from non-OSA patients (Tsuchiya 234 Conley Normal A Figure 1. A. Lateral cephalometric comparison of a patient unaffected by OSA with (B) a patient affected with OSA. Note the longer lower face height, the steeper mandibular plane orientation and the narrower airway in the OSA patient. (Reprinted with permission from Cistulli, Respirology 1996.) et al., 1992; Sakakibara et al., 1999; Yu et al., 2003). As a result, the predisposing factor in the development of OSA is considered to be the increased parapharyngeal adipose tissue stemming from obesity rather than an underlying skeletal discrepancy. The most severely affected pa- tients, however, tend to demonstrate both obesity and an underlying skeletal discrepancy. In these severely affected individuals, it appears as if the obesity and the resulting adipose tissue around the airway work synergistically with the mandibular or maxillary deficiency to create a more severe restriction of the airway and presentation of the disease. These trends of mandibular deficiency and obesity appear to be maintained across different cultures as well. Reports from China, Japan and other countries also demonstrate distinct presentation of OSA pa- tients (Sakakibara et al., 1999; Yu et al., 2003). In general, the obese group of patients appears to present with abnormal upper airway soft tis- Sue abnormalities, while the non-obese OSA group appears to present with altered skeletal structures. Finally the third group, which typically is the most severely affected group, appears to have both abnormal upper airway soft tissue structures as well as craniofacial skeletal discrepancies. 235 The Face of Obstructive Sleep Apnea From this spectrum of cephalometric presentations, one is forced to con- clude that patient’s facial presentations may indicate a possible predispo- sition to OSA; the facial presentation, however, still is insufficient for definitive diagnosis. Accurate and appropriate diagnosis of OSA requires an over- night polysomnography (PSG) exam (Chesson et al., 1997). Both full- service hospitals and free-standing sleep clinics have the appropriate equipment to perform this test. The PSG combines multiple tests includ- ing electroencephalography, electrocardiography, electrooculography, electromyography, respiration rate, tidal Volume, inspiration and expira- tion volume, number of apneas and a number of hypopneas. An apnea is defined as any cessation in breathing for ten seconds or more with an arterial oxygen desaturation of 2 to 4% (AASM Task Force, 1999). A hypopnea is defined as a 50% decrease in airflow for ten seconds with a concomitant drop in arterial oxygen saturation (AASM Task Force, 1999). The exact magnitude of desaturation for a hypopnea varies in the literature. It also is important to differentiate between cen- tral apnea and obstructive apnea (Abad and Guilleminault, 2004). With obstructive apnea, respiratory effort is present but the patient is unable to ventilate adequately, i.e., the pathway is blocked. In central apnea, there is an absence of respiratory effort from the brainstem. The distinction between central apnea and obstructive apnea is one factor that aids in determining the most appropriate type of treatment for the individual patient, because certain forms of treatment will be effective only for ob- structive apnea but not for central apnea. The result of the PSG typically gives the patient an ap- nea/hypopnea index (AHI) score reflecting the number of times breath- ing ceased and the number of times breathing decreased. This also may be reported as a respiratory disturbance index (RDI). The two are differ- ent slightly but essentially interchangeable. In the adult patient, normal sleep has an AHI of 5 or less; mild sleep apnea has an AHI of 5 to 15; moderate sleep apnea typically is in the range of 15 to 30 events per hour while severe apnea results when 30 or more events per hour are observed (AASM Task Force, 1999). While anything over 30 is considered severe, the more apneas and hypopnéas a patient undergoes, the more oxygen deprivation they experience. To illustrate the clinical significance of this scale, a patient with an AHI of 60 stops breathing or has a significant oxygen desatura- tion for at least 10 seconds each minute. The individuals affected most 236 Conley severely may have an AHI approaching 120 or more. Because of the cu- mulative reduction in oxygen perfusion to the brain, these severely af- fected individuals are more likely to experience adverse and life- threatening complications including stroke, myocardial infarction and death from OSA. The guideline for successful treatment of OSA varies widely. The primary goal of treatment is to decrease the morbidity and mortality associated with the sleep-disordered breathing. To attain these reductions, most treatment strategies try to achieve at least a 50% reduction in the AHI or an AHI of less than 20. More stringent criteria for success aim to achieve an AHI of 10 or less. Beale and colleagues (2000) stated that successfully treated patients have no increased morbidity or mortality compared with subjects who have a normal pattern of sleep. For un- treated individuals with OSA, there is a 37% higher five-year morbidity and mortality than normal (Marti et al., 2002). These morbidity and mortality statistics result from direct com- plications of OSA such heart attack, stroke, arrhythmia and hypertension, or indirect causes such as motor vehicle accidents and workplace injuries. Such injuries result from the sleep-deprived OSA patients being more tired and less alert than treated OSA individuals or healthy normals. One study concluded that the incidence of motor vehicle accident with OSA can be compared with driving while intoxicated, which presents a major public health risk (Horne and Reyner, 1995). A second study (George, 2001) demonstrated a significant reduction in motor vehicle accidents in OSA subjects when the condition was treated successfully. TREATMENT OPTIONS Several non-surgical treatment options exist for the treatment of OSA. The gold standard and first line of treatment is continuous positive air pressure (CPAP). One of the advantages of CPAP is its universal abil- ity to treat both central and OSA successfully. By blowing pressurized air into the patient, the airway is maintained constantly and consistently. Though successful, it does have some significant limitations including a higher incidence of upper respiratory infection, feeling of dryness and low patient compliance. Other non-surgical treatments include various forms of behavior management including diet modification and alcohol cessation (Scrima et al., 1982), weight loss (Smith et al., 1985) and altering sleep position 237 The Face of Obstructive Sleep Apnea (Phillips et al., 1986). Though weight loss has tremendous health bene- fits beyond reducing OSA, only approximately 10% of people who at- tempt to lose weight will achieve their goal successfully. Of the 10% who are successful, only about 10% of those are able maintain their re- duced weight, meaning that only about 1% of individuals successfully maintain their weight loss. Another form of treatment includes oral appliances to aid in keeping the mandible forward during sleep. Several types of mandibular advancement appliances have been designed (Ferguson et al., 1996; Cohen, 1998). These appliances may be either custom-made or “stock,” but their goal is similar: hold the mandible in a forward and inferior posi- tion to induce stretching of the genioglossus and geniohyoid musculature. This tension provides support for the airway, thereby diminishing its ability to collapse. Historical Surgical Options: Genioplasty and Mandibular Advancement Historically, a minimally invasive and simple surgical therapy for OSA is an advancement genioplasty. The best candidates have a nearly ideal occlusion, appropriate Sagittal jaw positions, but a deficient bony chin (retrogenia) or a severely deficient chin (microgenia). Both microgenia and retrogenia must be distinguished from retrognathia, which is a distinctly different entity. With retrognathia, the entire mandi- ble is small or positioned posteriorly. When performing the genioplasty, it is essential to include the genial tubercles (the site of attachment for the genioglossus and geniohyoid muscles) in the segment that will be advanced (Fig. 2). By bringing these muscle attachments forward, ten- sion is placed on the muscles, making airway collapse more difficult. Failure to include the genial tubercles in the surgical advancement results in an esthetic improvement but no functional improvement. An alternate osteotomy design includes advancing a full thickness block (labial cortex to lingual cortex) of the mandibular symphysis that contains the genial tubercles (Fig. 3). Once the lingual cortex of the core of bone is buccal to the buccal cortex of the body of the mandible, the core is rotated 90° to maintain the advanced position. Other variations in osteotomy design exist based on anatomical restrictions and surgical preference. Even with the best genioplasty pro- cedures, often only partial resolution of the OSA symptoms is obtained. Due to these limitations, Baer and Priest (1980) proposed using man- dibular advancement as a superior surgical procedure for OSA correction. 238 Figure 2. A. The typical inferior border osteotomy performed for an advance- ment genioplasty is shown on a plastic model. It is important when performing the procedure for the OSA patient that the genial tubercles be present in the infe- rior segment. B: When the inferior segment is advanced, the genioglossus and geniohyoid muscles are stretched, reducing the tendency for the tongue to fall posteriorly and obstruct the airway. This procedure appeared to work adequately, but it was inadequate to correct the more severe OSA patients. Because of the failures resulting from both of the preceding techniques, the development of a second phase of surgical procedures that involve advancing both the maxilla and mandible was initiated. These maxillomandibular advancements (MMA) have been effective in resolving OSA. Because of their high success rate, MMA has supplanted isolated genioplasty and mandibular advance ments to become the first line of orthognathic surgery treatment for OSA (Prinsell, 2002). Maxillomandibular Advancement (MMA) Multiple reports are available in the literature discussing the sig- nificant benefits of MMA to increase airway patency (Guilleminault et al., 1989; Hochban et al., 1994; Prinsell, 2002). Because of this instant increase in patencey, some OSA patients will elect to pursue MMA to obtain quick resolution of their symptoms. Unfortunately, this approach does not allow the necessary pre-surgical orthodontic treatment to be performed. As a result, one of the published risks associated with MMA includes post-operative malocclusion. To avoid this complication, the preferred approach should ad- dress the pre-treatment malocclusion first. A basic knowledge of surgical Orthodontics generally is adequate for the orthodontist to provide appro- priate pre-surgical orthodontic therapy to prepare the dental arches effec- tively. CPAP or alternative forms of OSA treatment can be used to address 239 The Face of Obstructive Sleep Apnea ºMHº:º --º - -- " & º- Figure 3. An alternate genioplasty design developed by Riley and Powell. In this diagram, a full thickness section of the mandible that includes the genial tubercles is cut free. The Segment is brought anteriorly so that the lingual cortex of the bony segment is positioned on the buccal aspect of the mandi- ble. For additional tension, suspension wires can be placed from the inferior border of the mandible to the hyoid bone. (Reprinted with permission from Riley and Powell, Otolaryn- gol Head Neck Surg 1993.) excessive daytime somnolence and the negative effects of OSA during this pre-surgical orthodontic phase. Once the dental arches complement one another, both an improved airway and an improved occlusion can be 240 Conley obtained concurrently. Following MMA and resolution of the OSA, CPAP therapy can be discontinued. Interestingly, orthognathic surgery often will cause patients to lose ten or more pounds that, if maintained, can be an additional mechanism for health improvement and symptom resolution. Since orthognathic surgery has become one of the most success- ful treatment strategies for OSA, various treatment protocols have been tested, refined and adopted. In a retrospective analysis, patients with modest MMAs improved, but did not have complete resolution of their OSA. This finding subsequently has led to a nearly standardized 1 cm sagittal advancement of the maxilla and mandible. While it would be beneficial to titrate the amount of advancement performed precisely to the amount of advancement needed, this determination currently is not possible. If a patient has a pre-existing maxillomandibular skeletal discrepancy (i.e., Class II or Class III jaw relationship), the relative amount of maxillary to mandibular advancement must be altered. Thus, Class II patients will undergo similar 1 cm maxillary advancement with larger mandibular advancement (approximately 1.7 cm if full cusp Class II pre-treatment). In contrast, patients with Class III malocclusion may have smaller amounts of mandibular advancement relative to the maxil- lary advancement. One question that largely has remained unaddressed is what ef- fect MMA will have on the profile of the patient. In that these surgical advancements are larger than the surgical movements made for non-OSA patients, it is plausible that the soft tissue to hard tissue changes that oc- cur are different from what typically is observed in non-OSA orthog- nathic Surgery cases. Historical Soft Tissue to Hard Tissue Response to Orthognathic Surgery To understand the changes that may occur from MMA surgery, one first must review the literature investigating the soft tissue response to the isolated maxillary and mandibular advancement surgeries. Over the years, maxillary surgery has been shown to result in several different Soft to hard tissue results. Early reports showed that the soft tissue re- sponse was approximately 50% of the skeletal change (Dann et al., 1976). These results were of limited value, however, due to the small sample size (8 patients), which also included two cleft lip and palate patients. The scarring present in the cleft patients could have caused an underes- timation of the soft tissue response. 241 The Face of Obstructive Sleep Apnea Stella and coworkers (1989) attempted to resolve the limitations of the previous study by including a larger sample that excluded patients with clefting. They report similar results: soft tissue change approximates 46% of hard tissue change. A study by Mansour and colleagues (1983), considered by some to be a landmark study, demonstrated approximately 60% change in the soft tissue at the upper lip relative to hard tissue movements. While this investigation had a reasonable sample size, it was hindered by the fact that the study cohort included those with multiple surgical procedures (advancement-only patients were combined with ad- vancement and impaction), which may have affected the findings on the Soft tissue changes. The largest soft tissue changes to date have been ob- served in distraction osteogenesis (Wen-Ching et al., 2000). In their sample, approximately 80% change in the soft tissue was observed at the upper lip and nearly 100% change at the superior sulcus. For mandibular surgery, the results have been remarkably similar over time. Initial investigations demonstrated approximately 1:1 soft tis- sue to skeletal response (Quast et al., 1983). Of the several follow-up studies, Ewing and Ross (1992) also reported a 1:1 ratio. In fact, unlike maxillary surgery, mandibular distraction osteogenesis demonstrates the same 1:1 soft tissue to skeletal response as observed in standard bilateral sagittal split ramus osteotomies (Melugin et al., 2006). To date, limited studies have examined the soft tissue response following MMA. Louis and coworkers (2001) described the changes in a small number of cephalometric landmarks (nasolabial angle, subnasale and upper lip change) using a limited sample size of 15 OSA patients. Their results demonstrated approximately 80% soft to hard tissue re- sponse at the upper lip. Conley and Boyd (2007) attempted to address the limitation of Louis’ study. Conley and Boyd utilized a larger, consecu- tively treated sample that examined the entire soft tissue envelope. Their results indicate a nearly uniform 1:1 soft tissue to skeletal response over the entire maxillomandibular region in MMA subjects. The difference in the findings of the previously mentioned two studies likely results from the type of wound closure performed. Louis and colleagues (2001) performed simple wound closure while Conley and Boyd (2007) describe the use of a V-Y or double V-Y closure tech- nique. In Cárlotti’s original description of the V-Y closure technique in isolated maxillary advancement surgery, a larger soft to hard tissue re- sponse (80 to 90% vs. 60% for simple wound closure) is reported (Carlotti et al., 1986). Because Louis and coworkers observed nearly 242 Conley 80% change without V-Y closure, it seems reasonable that Conley and Boyd would report significantly higher soft tissue changes when the V-Y closure was employed. PREDICTING PATIENT-SPECIFIC OUTCOMES The use of average values for soft to hard tissue response of maxillary and mandibular osteotomies does not does not necessarily pre- dict how individual patients will respond following surgery. When the data are scrutinized more closely, tremendous individual variation in soft to hard tissue response is observed. Some patients will exceed the re- ported averages while others will have less soft to hard tissue change. As a result, it usually is difficult to determine how the individual patient will look following surgery. It is possible that such large maxillomandibular movements may not be tolerated well by all patients. Prior to observing the outcomes of a typical OSA patient, some clinicians were concerned that patients would appear bimaxillary protrusive following a 1 cm ad- Vancement of the maxilla and mandible (Fig. 4). As a result, an attempt was made to determine the predictive value of Conley and Boyd’s re- ported results. To assess the predictability of soft tissue outcomes of MMA, two prediction methods were performed for comparison. Two patients were Selected, neither of whom was part of the original Conley and Boyd (2007) sample. To simulate the surgery that was performed accurately, the computer predictions were performed using the operative note and measurement of the 24-hour post-operative lateral cephalometric radio- graph. The first prediction for each patient utilized the commonly accepted “historical” soft tissue changes associated with maxillary and mandibular osteotomies (i.e., 0.6:1.0 soft to hard tissue ratio). The second prediction utilized the newly developed soft tissue to hard tissue ratios obtained with MMA in OSA subjects involving a 0.9:1.0 soft tissue to hard tissue change (Boyd and Conley, 2007). The two predic- tions were compared visually to one another and to the patient’s actual results to determine which method predicted the final profile more accu- rately. The exact ratios used can be seen in Table 1. In both predictions, the order of operations was maintained and performed just as it was in the operating room. The maxilla was moved and fixated first, followed by the mandible. Once the MMA movements were mimicked, the gen- ioplasty was addressed. 243 The Face of Obstructive Sleep Apnea Figure 4. Concern was present initially regarding the esthetics of significant max- illary and mandibular advancements. A. Pre-treatment representation of a non- OSA patient. B-D: Simulation of a 5 mm, 10 mm and 20 mm maxillary and man- dibular advancement. With the first two MMA predictions, reasonable balance is preserved. With the final simulation, one can observe that there are esthetic limi- tations on the amount of jaw advancement that must be taken into account. For Patient One (Fig. 5), the “historic" soft to hard tissue predic- tion values were used to simulate a maxillary advancement of 9.6 mm along with a slight lengthening of 2.4 mm. Once completed, the mandi- ble then was advanced 11.2 mm. Due to the maxillary inferior position- ing, the mandible also was moved inferiorly a similar amount (2.2 mm). 244 Conley tip Molar MB cusp tip Pog # Pog. - Genioplasty 0.0 00 +2.3 +5. Figure 5. A. The pre-treatment profile of a patient with a cephalometric tracing demonstrates a well-balanced face. B. Simulation of a 9.6 mm maxillary ad- Vancement. The maxilla is moved first just as it would be in surgery. C. Simula- tion of the mandibular advancement. D. Simulation of the advancement gen- ioplasty. Each simulation adjusts the position of the skeletal bases and the over- lying soft tissues using historical orthognathic surgery norms. (Pre-treatment photo courtesy of S.B. Boyd.) Finally, the genial segment was advanced 2.3 mm with a 6 mm Vertical reduction. The final surgical prediction using the historical Soft tissue ratios can be observed in Figure 5D. For the “OSA” predic- tion (Fig. 6), the exact same jaw movements were performed; however the new soft tissue values were added to the computer prediction package. The same process was followed for Patient Two with similar results. When comparing the OSA soft tissue ratios with the standard ra- tios, the most significant difference can be observed at the area of subna- Sale and the upper lip (Fig. 7). In the OSA prediction rules, subnasale and the soft tissue of the upper lip were advanced substantially more than in the patient treated with the “historic" prediction package rules. However, 245 The Face of Obstructive Sleep Apnea Mdſ tip --- Mdſ tºp Molar MB cusp tip --- - º MB cusptºp B point - º' Figure 6. A. The same pre-treatment profile of the patient in the previous figure. B-D. The surgical moves are simulated in the same order as in Figure 5. This simulation uses the soft tissue to hard tissue ratios published by Conley and Boyd that are larger than historic values. (Pre-treatment photo courtesy of S.B. Boyd.) the changes in the mandible were similar in both predictions for both patients. When comparing the “historic" soft tissue ratios with the OSA ratios to determine the accuracy with the final results of treatment, it is observed that the OSA ratios reflect the changes more accurately. While the changes associated with the OSA prediction rules do not match the final outcome exactly, they are much closer to predicting the result than the predictions that utilize the standard soft tissue prediction ratios. For patients about to undergo life-changing and life-enhancing Surgery, it is important to share the results of what the potential facial changes may be. For some, the changes will be positive while for others it could result in some limitations in esthetic outcomes. For all, it should be explained clearly that though the results demonstrated are close to what can be expected, individual variations can and will occur. These pre- 246 Conley Figure 7. A. Side-by-side comparison of the historical soft tissue prediction. B: Newly developed soft tissue values. One readily can see that the majority of the differences between the two simu- lations are primarily in the region of subnasale and the upper lip. The newer ratios result in an increased fullness and greater balance in this region than the simulation produced by the older historic predictive values. C. The actual post-treatment result. It appears that the newer soft tissue prediction is closer to the actual results than the his- torical prediction ratios. (Pre- and post-treatment photos courtesy of S.B. Boyd.) Surgical predictions, therefore, are best guesses and not a guarantee of the post-surgical results. As orthognathic surgery to address OSA continues to evolve, other treatment modalities are being implemented. Current surgical op- tions include varying techniques to obtain even larger advancement of the maxilla and mandible. For some, this approach includes the use of dis- traction osteogenesis to obtain as much as 20 to 25 mm of MMA. Other indications for treatment include transverse distraction osteogenesis. Skeletal expansion in adolescents is proving to be a useful and success- ful treatment technique. When applied to the mature craniofacial skele- ton, this must involve transverse distraction osteogenesis of the maxilla and the mandible. Conley and Legan (2006) demonstrate the successful use of this treatment modality but it does not describe the amount of cor- rection that results from the transverse expansion vs. the amount of cor- rection resulting from the second stage of MMA. Future investigations *Tº recommended highly to attempt to determine the role transverse ex- 247 The Face of Obstructive Sleep Apnea pansion and greater skeletal advancements on OSA treatment esthetic and functional outcomes. REFERENCES Abad VC, Guilleminault C. 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Yu X, Fujimoto K, Urushibata K, Matsuzawa Y, Kubo K. Cephalometric analysis in obese and nonobese patients with obstructive sleep apnea syndrome. Chest 2003; 124:212-218. Zucconi M, Ferini-Strambi L, Palazzi S, Curci C, Cucchi E. Smirne S. Craniofacial cephalometric evaluation in habitual snorers with and without obstructive sleep apnea. Otolaryngol Head Neck Surg 1993; 109:1007-1013. 252 EVALUATION OF FINISHING AND SURGICAL ENHANCEMENT PROCEDURES IN ORTHODONTIC PATIENTS RELATIVE TO CHANGES DUE TO AGING: A REVIEW Veronica Giuntini, Tiziano Baccetti, Lauren M. Sigler, Lorenzo Franchi To become old is still the only possible way to live a long life... Saint-Beuve ABSTRACT The aim of this chapter is to review current knowledge concerning the physio- logical modifications that occur in the various components of the dentofacial complex from late adolescence through the sixth and seventh decades of life. The physiologic craniofacial changes due to aging can be divided into three categories: skeletal, occlusal and soft tissue. With regard to skeletal changes, female subjects present with an elongation of the skeletal anterior component of the face (2 to 3 mm) in association with an increase in the skeletal retrusion of the midface (1.5 mm). In male subjects, this same modification in the midface is associated with advancement at Pogonion (2 mm). Both genders experience a reduction in arch depth of both dental arches (1.5 mm) associated with a reduc- tion in arch perimeter of both arches (2 to 3 mm) from late adolescence through late adulthood. In the associated soft tissue, both genders show a retrusion (1.5 to 3 mm) and elongation of the upper lip (3 to 4 mm) along with a reduction in the thickness of both upper and lower lips. A significant “droop” of the tip of the nose (3 to 4 mm) also can be observed. During aging, male subjects present with advancement of soft tissue Pogonion (3 mm). Along with the changes in the fa- cial profile, the gingival tissue of the upper incisors shows a recession tendency. Based on information now available about the physiologic changes in the hard and soft dentofacial tissues from late adolescence through late adulthood, we can derive valuable recommendations in order to treat patients orthodontically, or- thopedically and surgically, keeping in mind the perspective of the natural modi- fications due to aging. 253 Aging Craniofacial Complex With the exception of orthodontic treatment performed in adult patients (which still is only 15% to 20% of all patients treated orthodon- tically), the main target of orthodontic/orthopedic therapy is the growing population (Buttke and Proffit, 1999; Keim et al., 2008). Classically, or- thodontic treatment is completed in the permanent dentition after the pu- bertal growth spurt in late adolescence. Too often the orthodontist’s at- tention is focused on the patient’s occlusal, skeletal and soft tissue rela- tionships at the time of completion of therapy. Less frequently, the ortho- dontist implements a long-term perspective approach to treatment with the goal in mind of finishing the case with the expected physiologic modifications produced by aging. The occlusion, skeletal balance, smile and face of the patient should meet the patient’s expectations not only at the end of active or- thodontic treatment, but also throughout his/her lifetime. The occlusal and esthetic outcome obtained at the conclusion of orthodontic therapy is just the starting point for the dental and facial esthetic condition of the adult, who eventually will go through various stages of the aging proc- ess. These concepts were elucidated long ago by Peck and Peck (1971) who warned that, “Apparently, orthodontists abandon the soft tissue pro- file at maturity. Few if any have investigated post-adolescent soft tissue changes, those due to natural aging.” The importance of this observation has become even more obvi- ous in contemporary times because the profession has developed many esthetic and Surgical adjuncts to orthodontics (e.g., elongating clinical crowns and reducing gummy Smiles). The use of these procedures must be weighed against the natural changes that occur to the teeth and the as- sociated periodontal tissue as a natural consequence of aging. In some instances, ignorance or negligence of this information may lead to unde- sired long-term effects or over-treatment. On the other hand, the smile and occlusion created by the orthodontist should serve the patient for at least 50 years, with crucial events occurring in social and professional life that are assisted by long-lasting function of the occlusion and esthet- ics of the smile and face. While the orthodontist tends to “abandon” the patient at matur- ity, the patient usually takes better care of him/herself with more aware- ness of dentofacial esthetics. In 2008, the market for cosmetic products in Italy (a relatively small country with about 1/6 of the U.S. population) was more than $11 billion (U.S.), which is an increase of 2.5% from pre- vious years. The number of facial esthetic surgery or cosmetic interven- tions in 2007 in the United States was approximately 12,000,000; men 254 Giuntini et al. accounted for almost 20% of these interventions. The cost and possible complications for such interventions in aging adults is considerable. The aims of this chapter are: 1. To review our current knowledge on the physiologi- cal modifications that occur in the various compo- nents of the dentofacial complex from late adoles- cence through old age (sixth and seventh decades of life); and 2. To attempt a critical evaluation of the orthodontist’s role in keeping the patient’s smile and face relatively younger for a longer time. A better understanding of these concepts will provide orthodontists not only a goal of obtaining perfect dentofacial outcomes at the completion of treatment, but also keeping the effects of aging in mind. PHYSIOLOGIC MODIFICATIONS IN THE DENTOFACIAL HARD AND SOFT TISSUES OVER TIME Recent studies that analyzed physiologic changes in the hard and soft tissue of the dental arches and faces of subjects between the ages of 20 and 70 years were reviewed. Some studies focused on different partial intervals (i.e., from late adolescence to mid-adulthood or from mid- adulthood to late-adulthood); the various pieces of information were pooled and combined in order to derive trends of change throughout the entire adult life. The physiologic craniofacial changes due to aging can be di- vided into three categories: skeletal, occlusal and soft tissue. For some of the dentofacial districts, the modifications will be described separately for female and male subjects, as significant sexual dimorphism may exist regarding changes due to the aging process. Skeletal Changes Due to Aging Female Subjects. Female subjects present with an average in- crease in both total and lower anterior facial heights ranging from 2 to 3 mm (Figs. 1 and 2), according to the various longitudinal studies, most of which were performed in U.S. or European growth studies (Behrents, 1985; Lewis and Roche, 1988; Bishara et al., 1994; West and McNa- mara, 1999; Pecora et al., 2008). West and McNamara (1999) and Pecora and coworkers (2008) provide information derived from “recall” studies 255 Aging Craniofacial Complex – T1 17y 2m – T348y 4m _-T O ( \ i / Figure 1. Increase in facial height measures in female subjects with aging (interval from 17 to 48 years of age). — T231y 0m — T343y 10m O( \ _- 7. Figure 2. Increase in facial height measures in female subjects occurs also during the interval from 31 to 44 years of age. 256 Giuntini et al. performed on the subjects originally enrolled in the University of Michi- gan Growth Study. Male Subjects. Male subjects present with an average increase in the sagittal advancement of Pogonion of about 2 mm (Figs. 3 and 4; Be- hrents, 1985; Lewis and Roche, 1988; Bishara et al., 1994; West and McNamara, 1999; Pecora et al., 2008). Female and Male Subjects. In both females and males, the max- illa becomes more retruded by about 1.5 mm between ages 18 and 70 years (Behrents, 1985; Lewis and Roche, 1988; Bishara et al., 1994; West and McNamara, 1999; Pecora et al., 2008). The analysis of changes due to aging in the craniofacial skeleton indicates that female subjects present with an elongation of the skeletal anterior component of the face, in association with an increase in the skeletal retrusion of the midface. In male subjects, this same modifica- tion in the midface is associated with advancement at Pogonion, thus leading to a trend to develop “Class III-like” sagittal skeletal characteris- tics along with aging. Occlusal Changes Due to Aging Female and Male Subjects. Both genders experience a reduction in arch depth of both dental arches of about 1.5 mm from late adoles- cence through late adulthood (Fig. 5). During the same 50-year interval, the perimeter of both upper and lower arches presents with an average reduction of 2 to 3 mm in both genders (Fig. 4). This information is de- rived primarily from the University of Michigan Growth Study (Carter and McNamara, 1997) and the investigations of Harris (1997). The modi- fications of the dental arches due to aging show a consistent, progressive tendency toward a loss of space in both arches mesial to the molars in both genders. Another dental change that has been correlated with the aging process is a significant increase in the interincisal angle as measured on a lateral cephalogram, due to incisor uprighting in both arches from late adolescence to adulthood (Humerfelt and Slagsvold, 1972). These modi- fications may contribute to an increased crowding tendency and a re- duced support for the lips with maturation. Facial and Gingival Soft Tissue Changes Due to Aging The most relevant modifications due to aging occur in the soft tissues, especially in those affecting the facial profile and, therefore, fa- 257 Aging Craniofacial Complex – T1 17y 6m – T347y 4m _-T / Figure 3. Advancement at hard- and soft-tissue Pogonion in male subjects with aging (interval from 17 to 48 years of age). T231y 5m _ T344y 4m Figure 4. Advancement at hard- and soft-tissue Pogonion in male subjects occurs also during the interval from 34 to 44 years of age. 258 Giuntini et al. Figure 5. Decrease in arch depth and arch perimeter in both female and male subjects with aging. cial esthetics. These changes are related to the physiologic reduction in the elasticity and tone of the skin, as well as to the soft tissue layers be- low the skin, both of which are characteristic of aging. Female and Male Subjects. The upper lip becomes more retruded along with a reduction in its thickness (Fig. 6). The progressive retrusion of the upper lip averages 1.5 mm in females and almost 3 mm in males (Peck and Peck, 1971; Behrents, 1985; West and McNamara, 1999; Pecora et al., 2008). The upper lip also becomes more elongated With increasing age; the progressive elongation of the upper lip averages 3 mm in females and 4 mm in males (Fig. 7; Peck and Peck, 1971; Be- hrents, 1985; West and McNamara, 1999; Sarver et al., 2000; Pecora et al., 2008). Due to the loss of elasticity and significant vertical elongation in adult life, the upper lip tends to cover the upper incisors during smil- ing, which is a common unesthetic consequence of aging. According to Sarver and colleagues (2000), subjects younger than 30 years of age show on average 3 to 3.5 mm of upper incisor display and less than 0.5 mm of lower incisor display; the situation is completed reversed after age 60 years. The lower lip becomes thinner as well, leading to a progressive retrusion of the lower lip of approximately 1.5 mm in both genders (Peck and Peck, 1971; Behrents, 1985; West and McNamara, 1999; Pecora et al., 2008). 259 Aging Craniofacial Complex Figure 6. Tendency to retrusion of both lips with aging. Figure 7. Droop of the tip of the nose and ver- tical elongation of the upper lip with aging. 260 Giuntini et al. In the meantime, the aging process determines a significant “droop” of the tip of the nose (Fig. 7) that is consistent with the elonga- tion of the upper lip. In facts, the nasal “droop” averages 3 mm in fe- males and 4 mm in males (Peck and Peck, 1971; Behrents, 1985; Sarver et al., 2000; West and McNamara, 1999; Pecora et al., 2008). A comprehensive evaluation of the facial soft tissue changes af- fecting the profile from late adolescence to late adulthood highlights a progressive retrusion of both the upper and lower lips, while the tip of the nose and the upper lip become more elongated, thus “hiding” pro- gressively the upper dentition in the smile. In male subjects, the bi- retrusive tendency of the lips is accentuated by the significant advance- ment of the chin. Along with changes in the facial profile, recent observations have described modifications in the gingival tissues due to aging. A re- cession tendency of the gingival tissue of the upper permanent incisors has been reported from young adulthood until late adulthood, the conse- quence of which is a progressively increasing height of the clinical crown of these teeth. Similar changes also are observed at a 10-year ob- servation following the end of orthodontic treatment (Theytaz and Kil- iaridis, 2008). Male Subjects. During aging, male subjects present with an ad- Vancement of soft tissue Pogonion that reflects the advancement of the skeletal portion of the chin. The amount of forward displacement of the chin soft tissue averages 3 mm (Fig. 8; Peck and Peck, 1971; Behrents, 1985; West and McNamara, 1999; Pecora et al., 2008). Effects of Aging on Tooth Display with Relaxed Lips and While Speaking The physiologic changes in the lips described above, with a de- crease in muscular tone and elasticity of the upper lip and its consequent Vertical elongation, deserve to be emphasized not only from a static point of view, but also more meaningfully from a dynamic one. In a contempo- rary treatment plan incorporating an esthetic evaluation, probably the most important diagnostic record is to perform an appraisal of the posi- tion of maxillary central incisors relative to the upper lip. This assess- ment is made with the patient’s upper lip at rest and while speaking (Zachrisson, 2007). An acceptable amount of incisal edge display at rest depends on the patient’s age, in that the amount of incisal display de- creases proportionally with advancing age. In a 30-year-old person, 3 mm of incisor display at rest is appropriate, whereas in a 60-year-old per- 261 Aging Craniofacial Complex Figure 8. Advancement at soft tissue Pogonion in male subjects with aging. son, an incisor display of 1 mm or less is expected (Vig and Brundo, 1978; Dong et al., 1999), once again as a consequence of the changes in the upper lip due to aging. TREATMENT PLANNING WITH THE FUTURE IN MIND On the basis of the information now available about the physiol- ogic changes in the hard and soft dentofacial tissues from late adoles- cence through late adulthood, we can derive valuable recommendations in order to treat patients orthodontically with the perspective of the natu- ral modifications due to aging in mind. This attitude will avoid over- treatment and will provide the patient with more long-lasting esthetic outcomes of orthodontic therapy, which will show and persist adequately during the central decades of the patient’s life. These recommendations include: 1. Finish orthodontic treatment with the teeth in a slightly protruded position. Besides any obvious de- terminations based upon the racial group of the pa- tient and his/her dentoskeletal relationships, it is pref- erable to finish the case with the teeth in a slightly protrusive position on the profile. This will assist in 262 Giuntini et al. holding the lips in a more protruded position because lips tend to become thinner and more retruded with age. In a recent investigation on Smile characteristics, the fullness and Sagittal position of the lips resulted as one of the major determinants of the attractiveness of the smile (McNamara et al., 2008). . Perform extractions of teeth only when they are indi- cated. Due to the above-mentioned reasons, the re- duction of dental support to the lips should be limited and should follow strict indications related to severe tooth-size/arch discrepancy. A judicious interproxi- mal enamel reduction of teeth with abnormal shape is preferred many times over premolar extractions to solve mild-to-moderate crowding problems because this procedure has the advantage of producing es- thetically pleasant teeth with intact gingival papillae. There also is less chance of dark triangles occurring between the teeth (Zachrisson, 2004). . Provide an adequate retention of dental arch size and shape for adult life. When finishing a case, the ortho- dontist should be aware of the significant tendency of both dental arches to become shorter and more crowded during adult life. Procedures intended to promote the stability of occlusion after the end of treatment (improvement of interdental contact points – with or without stripping, establishment of connec- tor areas or reliable fixed retention protocols) are rec- ommended and have been recognized in clinical or- thodontics for many years (Zachrisson, 1986). . Do not increase the vertical dimension of the face in female patients (if not indicated). The anterior total and lower anterior facial heights of female subjects elongate naturally during adult life (2 to 3 mm). With the exception of those patients in whom an improve- ment of the vertical dimension is needed because of a strongly reduced facial and/or intermaxillary diver- gence, the orthodontist should limit treatment-induced elongation of the face in female subjects. . Overcorrect Class III malocclusion in male subjects. Class III malocclusion always benefits from overcor- 263 Aging Craniofacial Complex rection of the sagittal dentoskeletal relationships (Westwood et al., 2003). This statement is important particularly in male subjects, as it has been demon- strated that males present with a progressive retrusion of the midface in association with 2 to 3 mm of ad- vancement of the chin during adult life. These natural changes do not assist the outcomes of Class III treat- ment in the long term and may affect the profile nega- tively. 6. A slight amount of excessive gingival display is al- lowed (and in some instances, desirable) at the com- pletion of orthodontic treatment. Taking into consid- eration the progressive elongation of the upper lip in both genders during adult life, with an increased cov- erage of the upper dentition in the smile, the presence of a slight amount of gingival smile (2 to 3 mm) at the end of orthodontic treatment can be seen as a preven- tion measure to warrant an adequate smile line during late adulthood. It also can be mentioned that ortho- dontists appear to be overly concerned with “gummy smiles” when compared with lay people (Kokich et al., 1999). As a corollary, the intrusion of upper inci- sors in deep bite patients should be limited as often as possible in order not to worsen the natural tendency of aging (Sarver et al., 2000). The intrusion of the upper incisors is detrimental particularly when it de- termines a significant reduction of incisor display at rest and while speaking (Zachrisson, 2007). There- fore, anytime dental intrusion is required, the intru- sion of lower teeth should be preferred to the intru- sion of upper teeth. 7. Do not provoke excessive vertical elongation of clini- cal crowns of the upper incisors. In some instances in which the patient presents with rather short clinical crowns and excessive gingival display, the use of gingivectomy or gingivoplasty to reduce the gingival tissue may be indicated. However, a warning of pru- dence comes from recent observations that describe a physiologic tendency of gingival recession and clini- cal crown elongation of the upper frontal teeth with 264 Giuntini et al. aging (Theytaz and Kiliaridis, 2008). Caution should be used, therefore, when planning gingivectomy in young patients. ACKNOWLEDGEMENTS The authors wish to thank Drs. 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Long-term effects of Class III treatment with rapid maxillary expan- sion and facemask therapy followed by fixed appliances. Am J Or- thod Dentofacial Orthop 2003;123:306–320. - Zachrisson BU. Facial esthetics: Guide to tooth positioning and maxil- lary incisor display. World J Orthod 2007;8:308-314. Zachrisson BU. Interdental papilla reconstruction in adult orthodontics. World J Orthod 2004;5:67–73. Zachrisson BU. JCO interviews Dr. Bjorn Zachrisson on excellence in finishing. Part 1.J Clin Orthod 1986:20:460-482. 266 THE IMPORTANCE OF ANALYZING SPECIFIC GENETIC FACTORS IN FACIAL GROWTH FOR DIAGNOSIS AND TREATMENT PLANNING James K. Hartsfield, Jr., Jing Zhou, Song Chen ABSTRACT As useful as facial growth predictions based upon expected growth curves may be, more valid prediction must incorporate and account for the variation associ- ated with individual genetic factors, particularly those that are highly pertinent to the pubertal growth spurt. These include CYP19A1, which encodes aromatase that catalyzes estrogen biosynthesis by converting androgens. Our null hypothe- sis was that the single nucleotide polymorphism rs2470.144 linked to CYP19A1 is not associated with Sagittal jaw growth during adolescence. rs2470.144 geno- types of 82 subjects (47 females, average age 12.03 years; 35 males average, age 12.67 years) who started their orthodontic treatment at cervical Stage 3 were determined by TaqMan” PCR genotyping. Pre- and post-treatment lateral cepha- lometric radiographs were measured with Dolphin software. Pre-orthodontic measurements and annualized average changes of maxillary and mandibular sagittal lengths were compared among rs2470.144 genotypes by ANOVA (p s 0.05) and Holm-Sidak pair-wise multiple comparisons test. There was no differ- ence for pre-orthodontic facial measurements among different rs2470.144 geno- types in either gender. The average annual increases of the maxillary and man- dibular sagittal lengths were different significantly among males according to rs24701.44 genotype. This may be due to linkage disequilibrium of rs2470.144 and the CYP19A1 exon/promoter I.1. The findings in this study suggested the potential of genetic analysis as part of orthodontic diagnosis and prognosis pre- dictors in treatment, including orthognathic surgery. These findings suggest that contemporary growth studies should include the analysis of genetic factors and their association with growth. Edward H. Angle stated in 1907: “In studying a case of maloc- clusion, give no thought to the methods of treatment or appliances until the case shall have been classified and all peculiarities and variations from the normal type, occlusion and facial lines have been thoroughly comprehended. Then the requirements and proper plan of treatment be- comes apparent.” Skeletal classification of craniofacial structure has 267 Genetic Factors in Facial Growth been an essential part in orthodontic diagnosis and treatment planning from that time until the present (Kanas et al., 2008). The determination of facial skeletal classification is essential prior to the utilization of dif- ferent therapeutic modalities including orthodontics, orthopedic growth modification and surgery. Research and discussion about facial growth and treatment in the literature have focused either on the timing of the greatest amount of fa- cial growth, particularly for the mandible (Gu and McNamara, 2007; Hunter et al., 2007; Verma et al., 2009) or the estimated extent of facial growth to be attained (Chvatal et al., 2005; Turchetta et al., 2007). In order to best diagnose and treat the child or adolescent patient, the ortho- dontist needs to know as much as possible about the patient’s growth potential. As useful as predictions based upon expected growth models starting from early in the patient’s life may be, prediction must incorpo- rate and account for the variation associated with individual genetic fac- tors, especially those that are highly, pertinent to the pubertal growth spurt. Toward this end, we present preliminary data on the first example of a specific genetic polymorphism being associated with variation in facial growth during puberty. Estrogens are a group of hormones involved in growth and de- velopment (Honjo et al., 1992). Estrogen stimulates chondrogenesis, promotes the progressive closure of the epiphyseal growth plate (Grumbach, 2000), has an anabolic effect on the osteoblast and an apop- totic effect on the osteoclast, and increases bone mineral acquisition in axial and appendicular bone during adolescence and into the third decade (Grumbach, 2000). Aromatase (also known as estrogen synthetase) is a key cytochrome P450 enzyme involved in estrogen biosynthesis (Bulun et al., 2003). This steroidogenic enzyme catalyzes the final step of estro- gen biosynthesis by converting testosterone and androstenedione to es- tradiol and estrone, respectively (Guo et al., 2006). CYP19A1 is the gene that encodes aromatase. It is located at chromosome 15q21.2 and spans over 123 kb (Guo et al., 2006). Several groups recently have identified polymorphisms in CYP19A1 (Ma et al., 2005; Guo et al., 2006; Yang et al., 2006). Some of these are associated with an increased risk of estrogen-dependent diseases (Bulun et al., 2003) including breast cancer (Huang et al., 1999; Healey et al., 2000; Kristensen et al., 2000; Arvanitis et al., 2003; Haiman et al., 2003; Hu et al., 2007) and osteoporosis (Xiong et al., 2006). A single nucleotide polymorphism (SNP) rs2470144 (C/T) is located near the exon/promoter I.1 of the -93 kb 5’-UTR regulatory region that contains multiple pro- 268 Hartsfield et al. moters (Guo et al., 2006). It was suggested that this SNP may be linked with functional alleles influencing the gene expression of CYP19A1 by regulating its transcription rate (Guo et al., 2006). Regulation of this gene’s transcription is critical for the testosterone/estrogen (T/E) ratio in the body since aromatase plays an important role in the conversion of androgens to estrogens. Some studies have shown that the T/E ratio is critical in the development of sex-indexed facial characteristics (Schaefer et al., 2005, 2006) such as the growth of cheekbones, the mandible and chin, the prominence of eyebrow ridges and the lengthening of the lower face. To predict and take advantage of the growth acceleration of pu- berty, it is helpful for the orthodontist to understand jaw growth and the development of sex-indexed facial characteristics during adolescence. To date, there is limited specific information about how the products of genes, such as CYP19A1, can affect jaw growth during adolescence. The objective of this study is to test the null hypothesis that the CYP19A1 linked SNP rs2470.144 is not associated with sagittal jaw growth during adolescence. MATERIAL AND METHODS Skeletal Age Analysis Existing pre- and post-treatment lateral cephalometric radio- graphs of adolescents that had been taken as a routine part of orthodontic treatment at a private orthodontic practice were used in this study. This study had Institutional Review Board (IRB) approval as part of a study on external apical root resorption. The pre-treatment radiographs were taken no more than one month before the start of orthodontic treatment and the post-treatment radiographs were taken on the day of debanding. The serial treatment films of 800 Caucasian subjects were analyzed for inclusion in this study. The skeletal ages of subjects were classified visually with the cervical vertebral maturation (CVM) staging method on the cephalomet- ric radiographs (Baccetti et al., 2005). Briefly, cervical vertebral matura- tion stages (CVM-CS) were identified according to the CVM method by presence of a concavity at the lower border and the shape of the body of C2, C3 and C4. CVM-CS Stage 3 (CS3), the stage in which pubertal growth is expected to commence (Baccetti et al., 2005), is defined as when concavities are present at the lower borders of both C2 and C3. At this stage, the bodies of C3 and C4 may be either trapezoid or rectangular 269 Genetic Factors in Facial Growth horizontal in shape. The subjects who had their orthodontic treatment started at this stage were recruited as our study samples for rs2470.144 genotyping. According to the CVM staging methods, out of the 800 sub- jects analyzed for inclusion in the study, 82 subjects were at CS3 on their pre-orthodontic treatment lateral cephalometric radiographs. The chronological ages of these subjects were calculated according to their birth dates and the dates when the pre- and post-treatment radiographs were taken. Of the 47 female subjects, one was still in CS3 on the post- treatment radiograph, 19 were in CS4, 23 were in CS5 and four could not be identified. Of the 35 male subjects, none were in CS3, 19 were in CS4, 14 were in CS5 and two could not be ascertained. These post- treatment stages of development support the presumption that these pa- tients generally progressed through the cervical skeletal maturation asso- ciated with the pubertal growth spurt. DNA Sample Collection and CYP19A1 Genotyping DNA samples of the subjects were collected following informed consent by buccal swabs. Briefly, the inside of the cheek was scraped 10 times with two sterile nylon bristle brushes. Genomic DNA were isolated with the Puregene method (Gentra Systems, Minneapolis, MN) and stored at -80°C until utilized for genotyping. rs2470.144 genotypes were determined by polymerase chain re- action (PCR) using an ASI Prism 7000 Sequence Detection System (Ap- plied Biosystems, Forster City, CA). The reaction mix was prepared ac- cording to the TaqMan" Drug Metabolism Genotyping Assay protocol (Applied Biosystems, Forster City, CA). Each vial of the 96 well plate contained 12.5pil 20X TaqMan" Universal PCR Master Mix, 10.75pl DNase free water, 1.25pl TaqMan" Drug Metabolism Genotyping Assay (including the reaction primer and probes), and 0.5pul (1–2ng) genomic DNA sample. The context sequence for the PCR is AGGCCAG- CAAGGCCAGGGCCA-TGA[C/T]GGAGGGAAATTTTACAAGGTA- AACA. VIC and FAM were the fluorescence reporters. Two non- template controls (double-distilled water) were utilized in each reaction plate. The reaction mix was then centrifuged at 3000 rpm for four min- utes and then loaded into the detection system. Thermal cycling condi- tions of the PCR were: 95°C for 10 minutes followed by 50 cycles of 92°C for 15 seconds and 58°C for 90 seconds. Allelic discrimination re- sults were recorded based on SNP probe fluorescence differentiation and labeled as CC, TT and CT for rs24701.44 SNP homozygous and het- erozygous. 270 Hartsfield et al. Comparison of Jaw Growth in Different Genotypes Craniofacial structure of the subjects was assessed by Dolphin software (Version 10.0; Dolphin Software Inc., Lake Oswego, OR) on the scanned 300 dpi digital images of their lateral cephalometric radio- graphs. Measurements from the Michigan Surgery Cephalometric Analy- sis were used (Fig. 1) for the 82 subjects who were in CVM-CS3 at the beginning of their orthodontic treatment. Pre- and post-treatment maxil- lary and mandibular lengths (condylion to anterior nasal spine, Co-ANS, and condylion to hard tissue pogonion, Co-Pog) were measured and an- nualized over the treatment time for each subject. Figure 1. Measurements from the Michigan Surgery Cephalometric Analysis. Statistical Tests All cephalometric measurements were performed by one exam- iner (JZ). CVM staging was performed twice in a blind manner by the same examiner over a three months interval. An analysis of variance (ANOVA) was performed to compare the ages, as well as the average 271 Genetic Factors in Facial Growth annual increase of maxillary and mandibular lengths of the subjects ac- cording to their rs2470.144 genotypes by using SigmaStat software (Ver- sion 3.5; Systat Software Inc., San Jose, CA). The Holm-Sidak method (SigmaStat Version 3.0) was used for pair-wise multiple comparisons between groups after a significant (p → 0.05) ANOVA test. RESULTS Genotype Distributions and Average Ages at CS3 The rs2470.144 genotype distributions for the 82 subjects were 34.04% for CC (n = 16), 46.81% for CT (n = 22) and 19.15% for TT (n = 9) in females; and 20% for CC (n = 7), 60% for CT (n = 21) and 20% for TT (n = 7) in males. The average age at the time of the initial pre- orthodontic treatment lateral cephalometric radiograph in CS3 was 12.03 years for females and 12.67 years for males. There is no significant dif- ference in the average ages among different CYP19A1 genotypes in each sex (Table 1). Table 1. Average ages of individuals at CS3 according to different rs2470.144 genotypes. SD = standard deviation. Females Males - Mean SD Il Mean SD Il CC 12.16 1.28 19 12.86 1.37 12 All CT 12.10 1.21 26 13.26 1.13 31 patients at CS3 TT 12.24 1.67 14 13.55 1.41 15 p 0.946 0.361 º CC 11.97 1.19 16 12.33 1.50 7 Patients | CT | 1206 | 1.19 22 1297 | 1.02 || 21 started at CS3 TT 11.77 1.51 9 12.79 0.81 7 p 0.818 0.400 sº CC 13.25 1.44 3 13.60 0.77 5 Patients | CT | 12.38 | 1.51 || 4 || 13.93 | 1.14 | 10 finished at CS3 TT 13.28 1.70 5 14.31 1.48 8 p || 0.669 0.586 272 Hartsfield et al. Pre-orthodontic Cephalometric Measurements in Different Genotypes Mean cephalometric measurements of the pre-treatment radio- graphs are listed in Tables 2 and 3 according to different CYP19A1 geno- types. All pre-orthodontic measurements are not significantly different among different CYP19A1 genotypes in each sex. Table 2. Pre-treatment cephalometric measurements of females at CS3 accord- ing to different CYP19A1 rs2470144 genotypes. SD = standard deviation. Female CC Female CT Female TT (n = 16) (n = 23) (n = 10) Mean SD Mean SD Mean SD P value SNA (*) 81.38 2.58 81.17 3.01 79.65 2.44 0.321 SNB (9) 78.3 2.98 77.89 2.77 76.92 2.91 0.490 ANB (°) 3.09 1.90 3.27 2.41 2.73 1.63 O.800 Mx Unit Length (Co-ANS) 83.8 4.86 83.88 4.88 82.73 4.45 0.805 Md Unit Length (Co-Pog) 106.02 || 7.17 102.84 7.11 103.76 6.37 0.381 MP - SN (°). 34.62 5.96 33.72 3.97 35.65 2.74 (),524 U6 - PP (UPDH) (mm) 19.9 2.70 19.38 2.40 19.71 2.12 0.801 L6 – MP (LPDH) (mm) 26.98 || 2.61 26.25 2.50 27.03 2.35 0.585 N-Me (mm) 1 11.19 || 7.67 106.70 7.83 1 1 0 5.12 0.156 LFH (ANS-Me || FH) (%) 55.39 2.65 54.38 2.75 55.2 1.58 0.431 Face Ht Ratio (N-A/A-Gn) (%) 108.56 || 10.20 108.08 8.53 107.49 7.56 0.957 Table 3. Pre-treatment cephalometric measurements of males at CS3 according to different CYP19A1 rs2470144 genotypes. SD = standard deviation. Male CC Male CT Male TT (n = 7) (n = 23) (n = 8) Mean SD Mean SD Mean SD P value SNA (*) 81.46 2.93 81.90 3.43 83.18 4.33 0.598 SNB (9) 77,73 2.47 79.40 3.30 79.36 2.63 0.436 ANB (°) 3.74 0.70 2.48 2.61 3.81 2.77 0.286 Mx Unit Length (Co-ANS) 85.44 || 5.70 87.88 7.53 91.51 7.87 0.276 Md Unit Length (Co-Pog) 108.11 || 10.26 110.98 7.16 112. 8.13 0.617 MP - SN (9) 35.71 4.79 34.85 4.43 30.6 6.31 0.084 U6 - PP (UPDH) (mm) 20.71 2.29 22.10 2.75 22.06 3.15 0.496 L6 – MP (LPDH) (mm) 28.41 2.49 28.56 2.43 29.66 2.95 0.537 N-Me (mm) 113.97 || 13.02 114.67 6.82 115.11 7.86 0.966 LFH (ANS-Me || FH) (%) 55.2 1.85 56.44 2.12 56.05 3.20 0.475 Face Ht Ratio (N-A/A-Gn) (%) 106.53 || 5.90 100.75 6.59 102.89 9.10 0.174 273 Genetic Factors in Facial Growth Growth Rate of Maxilla and Mandible in Different Genotypes The average yearly increases of maxillary and mandibular lengths in each sex are listed in Table 4 for females and Table 5 for males according to different rs2470.144 genotypes. The average time be- tween pre- and post-treatment radiographs for CYP19A1 CC, CT and TT genotypes were 21.72, 22.73 and 21.96 months respectively in females, and 20.88, 23.59 and 24.12 months respectively in males. Females with CC genotype showed greater yearly increases of maxillary and mandibular lengths than the TT genotype, although the differences are not significant statistically (Table 4 and Fig. 2). Males with CC genotype, however, showed smaller yearly increases of maxil- lary and mandibular lengths than males with TT genotype (Table 5 and Fig. 3). There was a larger yearly increase of the average mandibular length than the average maxillary length during pubertal growth period in both sexes. The differences of the maxillary and mandibular growth rates among males with different genotypes were significant statistically. Males with TT genotype had significantly larger yearly increases of max- illary length than the CT genotype (p = 0.015) and larger yearly increases of mandibular length than the CC genotype (p = 0.017). Table 4. Average yearly increases (mm/year) of maxillary and mandibular length during treatment according to different CYP19A1 rs24701.44 genotypes in female subjects. SD = standard deviation. Female CC Female CT Female TT (n = 16) (n = 23) (n = 10) Mean | SD | Mean | SD | Mean | SD | P value Mx length increase | 2.52 || 2.87 || 2.58 2.10 | 1.89 | 1.95 || 0.727 Mn length increase || 4.90 || 4.71 || 4.14 || 2.76 || 4.04 || 2.65 || 0.759 Table 5. Average yearly increases (mm/year) of maxillary and mandibular length during treatment according to different CYP19A1 rs2470.144 genotypes in male subjects. SD = standard deviation. Male CC Male CT Male TT (n = 7) (n = 23) (n = 8) Mean | SD | Mean | SD | Mean | SD | P value Mx length increase | 2.26 | 1.80 || 2.12 | 1.41 || 3.81 | 2.08 || 0.045 Mn length increase 3.00 2.48 || 3.99 || 1.91 || 5.59 1.83 0.048 274 Hartsfield et al. 6.00 Mandible 5.00 4.00 Maxilla 3.00 2.00 1.00 0.00 C cº CC cº * zºº” .** * “.…" Figure 2. Average yearly increases (mm/year) of maxillary and mandibular length during treatment according to different CYP19A1 rs2470.144 genotypes in female subjects. DISCUSSION To the best of our knowledge, this is the first study to examine the association between CYP19A1-linked polymorphism with sagittal jaw growth during adolescence. Sagittal jaw growth rates were studied by measuring maxillary and mandibular lengths before and after treat- ment during adolescence over an approximate two-year treatment time. Our null hypothesis was rejected. The average yearly increases of the maxillary and mandibular sagittal lengths were significantly different among males of different rs2470.144 genotypes. This might be explained by SNP rs2470.144 being located near the exon/promoter I. 1 of CYP19A1 (Guo et al., 2006). This SNP may be associated with functional alleles influencing the expression of CYP19A1 by regulating its transcription rate. This regulation at transcriptional level may influence the CYP19 enzyme activity and androgen and estrogen levels in the body. It has been reported that CYP19A1 SNP rs2470.144 is related closely to the levels of circulating estrogen in pregnant women (Means et al., 1989, 1991). Estrogen is produced in males as well as fe- males. Although the role of estrogen in male development is not clear yet, estrogens are involved in bone modeling during puberty in both males and females (Ho and Weissberger, 1992). Our study suggests that by regulating the conversion of androgen to estrogen, the CYP19A1 product aromatase may play a role in jaw growth of male adolescents. 275 Genetic Factors in Facial Growth It is interesting that this SNP seems to have a different impact on jaw growth in female and male. Females with CC genotype had larger yearly increases of their maxillary and mandibular lengths than the TT genotype (Fig. 2), although the difference is not significant. In contrast, males with CC genotype had smaller yearly increases of their maxillary and mandibular length than the TT genotype (Fig. 3). This influence pattern of the two genotypes is consistent in both maxillary and mandibular growth. 6.00 - - - 5.00 Mandible 4. 0. 0. Maxilla 3.00 * - 1.00 0.00 ~ º cc ** ** cº ** ** CC *A* cº ** Figure 3. Average yearly increases (mm/year) of maxillary and mandibular length during treatment according to different CYP19A1 rs2470.144 genotypes in male subjects. Regarding the question of the CYP19A1 genotypes affecting maxillary and mandibular growth in a linear manner in each subject: lin- ear regression for each genotype in the females shows a slightly greater slope for those with the TT than the other two genotype, although there is not a great difference in the slopes of the three genotypes with R2 values of 0.7 and 0.9 (Fig. 4). This indicates, as before, that different genotypes of this SNP do not have a marked effect on sagittal jaw growth. In con- trast, although there is a marked difference in slope, especially for the TT genotype (vs. 0.5 vs. 0.9) in males than in females, the R2 values in males are lower (0.4 to 0.6) than for the females (Fig. 5). This indicates that there is more individual variation in how maxillary and mandibular jaw growth is coordinated in males than females, and may represent the variable interaction of other factors in addition to the CYP19A1 geno- type. Differences among CYP19A1 genotypes account for some of all the variation in male Sagittal jaw growth at puberty. 276 Hartsfield et al. 9. - 8. y=0.8.077x-0-8073 - - R*=0.6669 (CC) 7 6. y=0.5555x-01308 - - Cº. R*=0.7384 (CT) - CT - s - TT > 4 - Linear(CC) - Linear (CT) 3. - LineartſT) 2 | - 1 - 32 0 - - 0. 2. 4. º 8. 10. 12. Mn Figure 4. Average increases (mm/year) of Mx and Mn length during treatment according to different rs2470.144 genotypes in females. 3. y=0.8796x-1-1041 7 R*=0.5953 (TT) - 6 y=0.4728×40.8376 - R*=0.4244 (CC) - Cº. 5 - CT º: - TT > 4 - - Linear(CC) 3. Linear (CT) LineartſT) 2. 1. y=0.532.9X-0.0453 R*=0.5389 (CT) 0. - - 0. 2. 4. º 3. 10 Mn Figure 5. Average increases (mm/year) of Mx and Mn length during treatment according to different rs2470.144 genotypes in males. This difference of skeletal developmental rate among CYP19A1 genotypes might indicate a differential impact between the sexes of this gene and its product on sagittal jaw growth. Since P450 aromatase plays an important role in conversion of androgen to estrogen, regulation of 277 Genetic Factors in Facial Growth this gene transcription is critical for the T/E ratio in the body. It indeed has been reported before that the T/E ratio is critical in the development of sex-indexed facial characteristics (Schaefer et al., 2005, 2006) such as the growth of cheekbones, mandible and chin, the prominence of eye- brow ridges, as well as the lengthening of the lower facial bones. It is hypothesized that the CYP19A1 CC genotype encodes the enzyme with greater specific activity while the lower specific activity enzyme is encoded by the TT genotype. This difference in enzyme activ- ity then leads to a higher E/T ratio in females with CC genotype and a higher T/E ratio in males with TT genotype. Females with higher E/T ratio and males with higher T/E ratio may have a higher growth rate of the jawbones compared to the alternate genotypes. Further investigations are indicated to elucidate whether CYP191A through its aromatase prod- uct is critical in determining the testosterone and estrogen levels in dif- ferent sexes, and the molecular mechanisms of sex-indexed sagittal jaw growth during adolescence. It is important to understand how genetic variation affects growth and development during adolescence. Further analyses of this type are needed for evaluation not only of the effect of treatment and growth during puberty, but also the factors that may influence growth and treatment during that growth interval. The findings in this study sug- gested the potentially important role of genetic analysis as part of ortho- dontic diagnosis and treatment planning. CONCLUSION rs2470.144 alleles are associated with variation in sagittal jaw growth in or after CS3 in males during adolescence over the approxi- mately two-year treatment time, but account for only part of the varia- tion. 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J Bone Miner Res 2006:21:1678–1695. Yang TL, Xiong DH, Guo Y, Recker RR, Deng HW. Association analy- ses of CYP19 gene polymorphisms with height variation in a large sample of Caucasian nuclear families. Hum Genet 2006; 120: 119-125. 281 282 EFFECTS OF SURGICAL TONGUE VOLUME REDUCTION: OUTCOME MEASURES ON FUNCTION AND GROWTH Zi-Jun Liu ABSTRACT To understand the outcomes in function and growth by surgical tongue Volume reduction, this comprehensive study characterizes the masticatory function, load production and growth effect in 11 young sibling pairs of Yucatan minipigs. Each pair received surgery on the same day, one for reduction and the other for sham surgery (incision only without tissue removal). Masticatory function was evaluated through the observation of feeding behavior and longitudinal records of tongue deformation (distance changes in various dimensions) during mastica- tion using implanted ultrasonic crystals and microsonometric system. The load productions (bone strains and pressures) on the facial bones directly contacted by the tongue were measured immediately after the surgery using strain gauges and miniature pressure transducers. The growth effect was tracked longitudi- nally using periodic cephalometrics and direct osteometric measures post-mortem. The results indicate that using the mandible instead of the anterior tongue to ingest food and “inertial” chewing/swallowing pattern were the major changes in feeding behaviors, and decreased and compensatory deformational capacities were seen in the anterior and posterior tongue, respectively, after Sur- gery. However, these functional distortions were transient and gradual restora- tion was seen over time. A volume-reduced tongue resulted in an overall de- crease in masticatory loads at all recorded sites without altering the strain domi- nance and polarity, and the osseous components of anterior oral cavity mostly were affected. The surgery did not suspend overall growth of craniofacial bones and formation of dental arch, but slowed down bone and dental arch expansions in certain areas in which nasomaxillary bones composing the anterior oral cavity and mandible were mostly affected. These results suggest that when surgical tongue volume reduction is undertaken in young subjects, special cautions should be placed on its short-term effects on masticatory function and long-term negative effects on the growth of the Osseous components in the anterior oral cavity and in all three dimensions of the mandible. 283 Surgical Tongue Volume Reduction Surgical tongue Volume reduction is a relatively common part of treatment for Class III skeletal malocclusion, severe open bite and bimaxil- lary dentoalveolar protrusion to enhance treatment outcomes and lessen the chance of relapse (Ruff, 1985; Deguchi, 1993). Because of the unique “hy- drostat” feature that makes the tongue Volume constant during function (Kier and Smith, 1985; McClung and Goldberg, 2000; Gilbert et al., 2007), the functional performance and load production of the tongue should be volume dependent. On the other hand, mechanical environment is a key factor in de- termining and modulating bone growth (Rafferty and Herring, 1999; Mao and Nah, 2004); thus, changes of load production by a volume-altered tongue should have a profound influence on the craniofacial growth and dental arch formation. Therefore, it can be postulated that surgical tongue Volume reduction would result in a series of consequences in tongue func- tion, loading and craniofacial growth. Unfortunately, most of these conse- quences of tongue Volume reduction are understood poorly and the time course of functional modification and growth effect largely is unknown. Combining both longitudinal and short-term approaches, this comprehensive study was designed to characterize these consequences in a well-established pig model. It is hypothesized that a volume-reduced tongue would disturb feeding behavior, distort tongue deformation, alter the loading regimen on the osseous tissues around the tongue and affect growth of facial bones and development of dental arch in a young growing animal model negatively. MATERIALS AND METHODS Animals and Tongue Surgery Eleven sibling pairs (five females and six males) of 12-week-old Yucatan miniature pigs from Sinclair Bio-Resources (Columbia, MO) were included in this study. After acclimation to the experimental envi- ronment by daily training for three to five days, each animal received tongue and dental impressions, baseline EMG recordings, and jaw and tongue movement tracking by regular and high-speed Video cameras as reported elsewhere (Liu et al., 2009). Each sibling pair received the tongue surgery on the same day; one had an actual surgery to reduce the volume by removing tongue tissue and the other had a sham surgery to make the same incisions only without tissue removal. Of 11 pairs, six pairs were euthanized on the surgery day (short-term study) and five pairs were raised for four weeks after the surgery (longitudinal study). 284 Liu The surgery was modified from the uniform type for human tongue volume reduction (Davalbhakta and Lamberty, 2000). Briefly, under nostril-mask anesthesia using isoflurane and nitrous oxide and fol- lowing a local infiltration of lidocaine HCI 0.5% and epinephrine 1:200,000 Solution (3 to 5 ml), the incisions were made using an electrosurgical cautery unit (SSE 2L; Valleylab, Boulder, CO) such that the apex of the incisions was in the middle of the two circumvallate papillae. The bilateral incisions diverged to meet the lateral margin anteriorly. Cutting diathermy was used to undermine and create lateral muco-muscular flaps and excise a conical Wedge (above the tongue neurovascular bundles) from the central tongue (Fig. 1A). This method removed tongue tissue, reduced tongue volume uni- formly in all three dimensions and preserved the neurovascular bundle of the tongue (Fig. 1B). After hemostasis, the incisions were closed in layers with absorb- able sutures (Vicryl 4.0). The excised tongue tissue was preserved in a 50% alcoholic solution and its volume was measured by an overflow method. Its Weight and linear dimensions also were measured. The entire surgical area Was circumscribed by six ultrasonic crystals that were implanted into the tongue body right before (short-term study) or one week prior to (longitudi- nal study) the surgery (see below). The post-operative care and longitudinal tracking included the administration of antibiotics and pain relief medica- tion, body weight measurements and tongue impressions. All procedures Were approved by the IACUC of University of Washington. 3 3. A B Figure 1. Incisions line and tissue removal area (black) by the surgical tongue vol- ume reduction. A: Dorsal view. B: Coronal view. Two dots indicate the locations of the neurovascular bundle of the tongue. Ultrasonic Crystal Implantation (Fig. 2) The detailed technique of ultrasonic crystal implantation has been described elsewhere (Liu et al., 2007; Shcherbatyy and Liu, 2007; Liu et al., 2008b; Shcherbatyy et al., 2008). These implanted crystals function as tiny ultrasonic transducers that report the real-time distance changes (in mm) 285 Surgical Tongue Volume Reduction between pairs of crystals with a claimed resolution of 0.02 mm (Sono- metric Co., London, Canada). The six crystals formed a wedge-shaped configuration and provided the following seven-dimensional measure- ments dynamically (Fig. 2A): Anterior width (C1-C2); Posterior dorsal width (C3-C4); Ventral width (C5-C6); Left length (C2-C4); Right length (C1-C3); Left thickness (C4-C6); and 7. Right thickness (C3-C5). The silastic-coated leads of these crystals were sutured on their adjacent soft tissues and connected to a microsonometric system for the short-term study. For animals assigned to the longitudinal study, a skin button set was used to guide these crystal leads passing a subcutaneous tunnel to the back where an interface was secured on the skin for periodic recordings (Fig. 2B). These tracking records of tongue functional deformation were performed right before the surgery (P0) and repeated one (P1), two (P2) and four weeks (P3) after the surgery. Placements of Strain Gauges and Pressure Transducers (Fig. 3) Stacked rosette and single-element strain gauges (Vishay Micro- measurement Group, Raleigh, NC) and miniature pressure transducers (Konigsberg Co., Pasadena, CA) were placed on the bone surfaces directly contacted by the tongue. These sites included: the right palatal surface of the premaxilla (PM, rosette gauge); the lingual surfaces of mandibular alveolar bones between the second and third incisors (MI, rosette gauge), and below the third molar and 5 to 6 mm distant to their alveolar ridges (MM, rosette gauge); the right premaxillary-maxillary suture on the palatal surface (PMS, single-element gauge); across the lingual surface of the mandibular symphy- sis, 6 to 8 mm below the alveolar ridge of the central incisors (MSP, single- element gauge); palatal surface underneath the palatal raphé 10 mm distant to the alveolar ridge (PAL, pressure transducer); and the mandibular alveolar process between the canine and the first molar 8 to 10 mm distant to their alveolar ridges (MAN, pressure transducer). These gauges and transducers were placed immediately after the surgery for the short-term study only; the details are described elsewhere (Liu et al., 2008a). 286 Liu posterior " Middle _ A (base) Figure 2. Illustrations of implanted ultrasonic crystal array and the skin button device for longitudinal tracking of the tongue deformation. A. Configuration of six crystals (solid dots) inside the tongue body. C1-C2; anterior width (AW); C3-C4 and C5-C6: posterior dorsal and ventral widths (PDW and PVW); C1-C3 and C2-C4: right and left lengths (RL and LL); C3-C5 and C4-C6: right and left thickness (RT and LT). CP = circumval- late papillae (empty dots). Insert: B-barb crystals. B. A cephalometric radiograph show- ing implanted crystal wirings (W) and the skin button connector (S). The dashed white line outlines the tongue shape and the solid black lines depict the wedge-shaped configu- ration of six implanted crystals (white dots). Insert: Skin button connector (female part). Cephalometric, Osteometric and DEXA Measures These measures were carried out for longitudinal growth tracking. In order to corroborate accuracy of superimposition of longitudinal tracings of cephalographic images, five metallic markers (0.8 mm stainless steel miniscrews) were implanted into the following osseous sites during crystal implantations as the superimposing landmarks for both lateral and axial Cephalometric images: alveolar ridges of upper and lower central incisors, 287 Surgical Tongue Volume Reduction Figure 3. Osseous sites for the placements of bone strain gauges and pressure trans- ducers. Top: Palatal view of osseous components of the oral cavity. Bottom: Lingual view of mandible. R and red squares = rosette gauges (inserta); S and black rectan- gles = single-element strain gauges (insert b); P and blue circles = miniature pressure transducers (insert c). Other letters indicate tooth names: II, I2, and 13 = incisors: C = canines; M1, M2 and M3 = molars. Dotted line in the top panel indicates the premaxillary-maxillary suture. - 288 Liu Figure 4. Cephalometric radiographs. Top. Lateral projection. Bottom: Axial projection. Arrows indicate implanted Stainless steel miniscrews for longitudinally superimposing tracings. left upper and lower second molar, and right upper second molar (Fig. 4). The cephalometric radiographs were taken before the surgery and repeated two and four weeks post-surgery. The references points were composed of 16 linear and 14 angular variables on the lateral, and 13 linear variables on the axial cephalometric images, as illustrated in Figure 5 and listed in Table 1. 289 Surgical Tongue Volume Reduction Figure 5. Reference points (black dots) of lateral (A) and axial (B) cephalometric tracings. In = the most posterior point of external occipital protuberance; Ba = the most anteroinferior point of occipital condyle; E = intersection between the frontal bone and the most supero-anterior point of posterior limit of ethmoid bone; Sp = intersection between the body and posterior border of pterygoid process of sphe- noid; N = front-nasal suture point; Na = the most anterior point of the nasal bone; Pr= the most infero-anterior point of the labial alveolar process of the maxillary incisor; Ui = the incisal edge of the maxillary incisor; Mx = the most convex point of the maxillary anterior limit; Prm = the most concave point of the anterior border of premaxilla; Ma = intersection between maxillary alveolar process and the me- sial surface of the maxillary first molar; Mp = intersection between maxillary al- veolar process and distal surface of maxillary third molar; Sm = intersection be- tween the pterygoid process of sphenoid and the anterior border of mandibular ramus; Gp = the most posterior point of the angular process of the mandible; Gi = the most inferior point of the angular process of mandible; Mn = the deepest point of the antegonial notch; Me = the most inferior point of the mandibular symphysis; Id = the most supero-anterior point of the labial alveolar process of mandibular incisor; Li = the incisal edge of the mandibular incisor; Ma’ = intersection be- tween the mandibular alveolar process and the mesial surface of the mandibular first molar; Mp’ = intersection between the mandibular alveolar process and the distal surface of mandibular third molar; Prmx = the most anterior point of the mandible; Mxp = intersection of pre-maxilla and maxilla; Ms = the most promi- nent point of mandibular symphysis; Mpa = intersection point of maxilla and pala- tine; Pc = intersection point of pterygoid and occipital bones; Zy/Zy' = intersec- tion between the line through Pc and bilateral zygomatic arches; Gp = intersection between the mid-sagittal line and the line connecting Gp and Gp’; Mdc/Mdc’ = the most posterior point of the mandibular canine cusp; Mxc/Mxc’ = the most poste- rior point of the maxillary canine cusp; Md.1/Md.1’ = the most prominent point of 290 Liu (Figure 5 Continued) the mandibular first molar; Mx 1/Mx1 = the most prominent point of the maxillary first molar; Md2/Md2 = contact point of mandibular sec- ond and third molars; Md:}/Md3’ = the most posterior point of the mandibular third molar; Mx3/Mx3’ = central fossa of maxillary third molar. Note that the dot- ted and dashed lines indicate the significant decrease of linear distances and angu- lation (o) at two and/or four weeks after the surgery respectively in the reduction as compared to the sham animals. Table 1. Linear and angular variables of craniofacial skeletons and dental arches from cephalograms. LATERAL-LINEAR LATERAL-ANGULAR Na-In: superior cranial length Ba-In-E: neurocranial height to cranial vault Pr-Ba: inferior cranial length In-Ba-Sp: neurocranial height to posterior cranial base Sp-E: anterior cranial base length In-E-Sp: cranial vault angle Sp-Ba: posterior cranial base length Na-N/Sp-E: nasal bone angle E-In: neurocranial length Pr-E-In: premaxilla to cranial vault Ba-In: neurocranial height Pr-E-Sp: premaxillary angle Pr-E: exterior viscerocranial length Ui-E-In: maxillary incisor to cranial vault Ma-E: anterior viscerocranial height Ui-E-Sp: maxillary incisor angle Mp-E: posterior viscerocranial height Ui-Pr-Ma: maxillary incisor inclination Na-N: nasal bone length Ma-Mp/E-Sp: palatal angle Mx-Prm: mid-premaxillary length Li-Id-Ma’; mandibular incisor inclination Pr-Ma: maxillary incisor-molar distance Gi-Mn-Me: antegonial notch angle Id-Ma': mandibular incisor-molar distance Me-Gi/E-Sp: mandibular plane angle Sm-Id: mandibular dorsal length Gp-Sm/Me-Gi: gonial angle Gp-Id: mandibular ventral length Gp-Sm: height of mandibular angle Axial LINEAR Mdc-Mdc’: inter-mandibular canine width Mxc-Mxc’: inter-maxillary canine width Md 1-Md.1”: inter-mandibular 1st molar width Mx1-Mx1’: inter-maxillary 1st molar width Md2-Md.2’: inter-mandibular 2nd molar width Md3-Md.3’: inter-mandibular 3rd molar width Mx3-Mx3’: inter-maxillary 3rd molar width Zy-Zy’: bi-zygomatic width Gp-Gp’: bi-gonial width Pmx-Mxp: premaxillary palatal length Mxp-Mpa: maxillary palatal length Pmx-Ms: mandibular symphysis length Pmx-Gpi; mandibular total length Animals in the longitudinal study were euthanized four weeks after Surgery and the heads were harvested. All soft tissues and tongues were dis- sected and removed from these heads to expose all craniofacial sutures. By using the defined 21 osteologic and six dental landmarks (Fig. 6), osteometric 291 Surgical Tongue Volume Reduction Perietal Figure 6. Osteometric landmarks in craniofacial bones in lateral, parietal, palatal and lingual views. Blue and black dots indicate landmarks on bones and teeth, respectively. 1-2; mandibular ramus height: 1-4: mandibular total length: 2-3: mandibular border length; 3-5: mandibular body height: 4-5: mandibular ante- rior length; 4–21; mandibular symphysis length; 6-7: maxillary buccal length; 7- 10: maxillary height; 8–9: mid-premaxillary length; 11-12: zygomatico-lacrimal suture length: 13-14: nasal bone length: 14-15; frontal bone length: 15-16: bregma-lambda length; 17-18; premaxillary palatal length; 18–19; maxillary palatal length; 19-20: palatine bone length: 1-1 and 2–2°: mandibular widths at condyle and angle, respectively; 3-3’ and 5-5’: ventral and dorsal widths of ante- rior mandible, respectively; 6-6’: premaxillary width: 7–7°: maxillary posterior width; 8–8 and 9-9': anterior and posterior nasal widths respectively; 10-10'. front width of brain case; 11-11’ and 12-12°: posterior and anterior midfacial widths: 22–22°, 23–23° and 24–24°: maxillary dental arch widths at canine, the first and third deciduous molars, respectively; 25-25°, 26–26 and 27-27’; man- dibular dental arch widths at canine, the first and third molars, respectively. Note that purple and green double-arrowed dash lines represent significantly smaller value in bones and dental arches, respectively, in the tongue reduction as compared to the sham animals. 292 Liu Figure 7. En-bloc bone pieces (left column) and DEXA images (right column). Upper Left and right pre-maxilla/maxilla pieces. Middle. Mandibular symphy- sis piece. Lower: Left and right mandibular corpus pieces. measurements were performed to calculate 33 linear distances on the skull using a digital caliper and a needle compass. After osteometry of the skulls, five en-bloc bone pieces were cut at the following sites: bilateral premaxillary/maxillary pieces, bilateral man- dibular corpus pieces and mandibular symphysis piece (Fig. 7, left column). 293 Surgical Tongue Volume Reduction These osseous pieces were scanned by a dual photon/energy x-ray absorpti- ometry (DEXA) for the measurement of bone mineral density and content (Fig. 7, right column). RESULTS Morphological Changes of the Tongue after the Reduction Surgery As demonstrated in Figure 8, surgical incisions healed completely four weeks after the surgery and the Volume-reduced tongue was signifi- cantly shorter and narrower in its body as compared to the sham tongue, which resulted in the entire lower dental arch being visible. The tongue cast and post-mortem measurements further indicate that despite ongoing growth (compare before and after for sham animals in Table 2), the reduction sur- gery significantly reduced the length and width of tongue body and resulted in about 15% loss of both volume and weight of the tongue over the four- week period post-operatively (Table 2). Functional Changes after the Reduction Surgery While no noticeable change was found in sham animals, significant modifications in feeding behaviors were observed in the reduction animals during both short-term and longitudinal experiments. Typically, a reduction pig utilized the mandible, instead of the anterior tongue, to shovel food into the mouth for ingestion, and moved and shook the head intentionally for chewing and swallowing as a way to take advantage of gravity (inertial pat- tern). The feeding session lasted significantly longer in tongue reduction than in sham pigs. The food leaking from the mouth corners during mastica- tion was seen often at the initial week after the surgery in reduction pigs. However, the amount of daily food consumption of reduction pigs was simi- lar to that of sham pigs; both groups showed significant body weight gain over time with no significant differences being noted between the two groups at any time (Fig. 9). 294 Liu Figure 8. Comparison of tongue morphology and its relation to mandibular dentition four weeks after surgery. Top: Tongue received sham surgery (sham). Bottom: Tongue received reduction surgery (reduction). Note that the remarkable decreases in tongue body length and width (double-arrowed red lines) in the reduction as com- pared to the sham tongues. 295 Surgical Tongue Volume Reduction Table 2. Comparison of tongue dimension and mass between sham and reduc- tion tongues. Dimension measures on tongue casts (body only, anterior 2/3) and mass measures on post-mortem tongue specimens. Percentage of loss calculated by specimen volume (weight)/removed part volume (weight) x 100%. * = p < 0.05 before and four weeks after surgery in each group. # = p < 0.05 between the two groups four weeks after surgery. DIMENSIONS (mm) Length Width Thickness Sham Before 103.5 + 4.9 60.2 + 2.2 7.9 + 0.3 4W After | 13.1 + 5.2 67.8 + 0.6* 9.2 + 0.6* Reduction Before 104.5 + 3.7 57.9 + 2.3 8.0 + 0.3 4W After 83.00 + 4.7% 50.7 ± 2.4% 10.5 + 0.3% MASS Volume (ml) Loss (%) Weight (g) Loss (% Sham Before n/a n/a n/a n/a 4W After 71.5 + 2.2 n/a 71.4 + 1.5 n/a Reduction | Before n/a n/a n/a n/a 4W After 60.6 + 0.9} 15.2 + 0.8 59.4 + 1.3H 15.2 + 0.2 Kg 16" --O-- Sham Fisham) = 6.18” —e— Reduction FRedu) = 5.98° * 147 - 121 T. r. 1 |_ _ _ _ _ 10." 8TWT W 0 W 1 W. 2 W 3 W4. Figure 9. Comparison of body weight gain over the six-week experimental per riod. W-1: one week before the surgery; W0: day of surgery; W1, W2, W3 and W4: one, two, three and four weeks after the surgery, respectively. Asterisks indicate statistically significant gain of body weight over time in each group by ANOVA (superscripted at F values) and Bonferroni post-hoc (above the dots) tests. * = p < 0.05; ** = p < 0.01. 296 Liu Tongue deformations during natural mastication were recorded by a microsonometric system through six implanted ultrasonic crystals and the skin button set. These periodic tracking records revealed the following char- acteristics of the masticatory tongue deformation after the reduction surgery: 1. There was no noticeable impairment on tongue func- tional deformation during mastication (see Fig. 10, P0), and tongue functional deformations were un- changed over time by sham surgery as compared to the normal non-surgery animals previously reported (Shcherbatyy and Liu, 2007); 2. Significant distortions were seen over time in animals receiving reduction surgery (see Fig. 10, P1, P2 and P3). At Pl, more frequent and longer ingestion episodes were interposed in the masticatory sequence in the tongue reduction as compared to the sham group. Relative to the baseline tongue activity (P0), masticatory tongue deformations decreased significantly in the anterior width (AW) and body length (LENG), but increased significantly in the posterior thickness (THICK), and dorsal and ventral widths (PDW and PVW). Furthermore, the difference of tongue deformational pattern seen at base- line between chewing and ingestion episodes became less distinct, par- ticularly in the tongue body length changes. At P2, the reduced deforma- tional capacity in the anterior tongue (AW and LENG) slightly restored with the better regularity of stereotypical chewing cycles than those seen at P1. However, the increased deformation in the posterior tongue (THICK, PVW and PDW) diminished as compared to those seen at P1. At P3, the restoration of anterior tongue deformation continued, but the deformational range in the posterior tongue further decreased and almost returned to those seen at baseline (P0). These time-course changes in tongue functional deformation clearly indicate that although there was a short-term loss of deforma- tional capacity in the anterior tongue and a compensatory enhanced de- formational capacity in the posterior tongue, these distorted features were diminishing over time, as seen by the restoration of reduced deformation in the anterior tongue and the disappearance of enhanced deformation in the posterior tongue gradually over time. However, the complete restora- tion of the deformational capacity in the anterior tongue was not seen at the four-week point (Fig. 11). This type of functional modification in tongue 297 Surgical Tongue Volume Reduction P2 * | w/º: Wºº WWW LENG |W * Wºw WWW row º WW.W. Awºſº. Wºº- ºw WWWW WWWW WWWW WWW ~ W ºf WWW w Figure 10. Raw tracings of masticatory tongue deformation from a reduction animal at the baseline (P0, pre-surgical) and one, two, and four weeks (P1, P2, and P3) after the surgery. AW = anterior width; LENG = body length; PDW = posterior dorsal width; PVW = posterior ventral width: THICK = posterior thickness. deformation most likely stems from muscular plasticity and adaptation and also can be attributed to the motor learning process after the surgery. Therefore, surgical tongue volume reduction may produce significant im- pact on feeding behaviors and tongue functional deformations. Changes of Load Production after the Reduction Surgery Compared to the sham animals, the basic pattern in term of the prin- cipal strain dominance (tension or compression dominant for rosette gauges) and strain polarity (tensile or compressive strain for single-element gauges) remained unchanged after the reduction surgery, i.e., compression-dominant at the PM, tension-dominant at the MI and the MM, tensile strain at the PMS and compressive strain at the MSP. However, an overall decrease (18 to 48%) in strain magnitudes at all three rosette gauge sites (PM, MI and MM) were found. Comparisons of principal strain magnitudes and orientation be- tween the sham and the reduction animals clearly revealed that the two ante- rior sites, the PM and the MI, underwent not only a decrease in magnitudes of principal tensile and compressive strains, but also the alterations of orien- tation from lateroanterior to lateroposterior direction of the principal tensile strains. However, the magnitude and orientation alterations at the posterior site (MM) were relatively small (Fig. 12). 298 Liu % AW -o-- Sham —e— Reduction 30.1% THICK 40 " Fs = 0.40 Fr = 9.31* FS = 0.80 Fr = 68.70" 25 30 - 20 ºm my mº, sº tº Eº E = :--------É------ 20 - 15–F P 1 P2 P 3 25 T *% PDW Fs = 0.80 Fr = 7.12” P0 P 1 P2 P 3 20 20 - ". LENG Fs = 1,40 Fr = 16.90° 15 - 10 - s p0 T' p 1 p2 P3 T Figure 11. Comparisons of masticatory tongue deformational ranges of each dimen- sion over time between the reduction and sham animals. Fs and Fr represent F values of ANOVA tests in the sham and reduction animals, respectively, and asterisks Superscripted at F values indicate statistical significance across four time points in the reduction animals. Asterisks above the data points indicate significantly larger or Smaller deformational ranges at each time point between the reduction and sham animals. All values were converted to percentages of altered distance/initial distance of each dimension. Refer to Figure 10 for other captions. B. " p0 P 1 p2 P3 Interestingly, although both the PMS and the MSP are located at the anterior oral cavity, significant decrease of strain magnitude was found only in the PMS, and the reduction surgery had little effect on the MSP (Fig. 12). However, the pressure measures indicated that both palatal (PAL) and man- dibular (MAN) sites received significantly less masticatory pressure after the reduction surgery, and the decrease of masticatory pressure was much larger at the MAN than PAL, surpassing 50% compared to the sham animals (Fig. 13). Growth Effects after the Reduction Surgery Of the 16 and 13 linear variables measured from lateral and axial cephalometric radiographs, respectively (Table 1), an overall increase was identified in both sham and reduction animals over the period of five weeks 299 Surgical Tongue Volume Reduction --- Figure 12. Average masticatory principal strains from three rosette (red arrow- headed lines from red squares) and two single-element (blue arrow-headed lines from blue retangles) gauge sites, only working side illustrated. A. Palatal view. B: Lingual view. Arrows heading toward and away from the gauge site indicate compressive and tensile strains, respectively. In the reduction animals (dash lines), decreases in the strain magnitudes and/or changes in the principal tensile strain orientations were seen at the PM, MI and PMS, and little change was seen at the MSP and MM as compared to the same animals (solid lines). Note that different scales of strain magnitude for rosette (R) and single-element (S) gaugeS. (W0-W4), with significant increases being noted in the mandibular dorsal (Sm-Id) and ventral (Gp-Id) lengths, the inter-maxillary canine (Mxc-Mxc'). and the bizygomatic (Zy-Zy’) and bigonial (Gm-Gm’) widths. However, increases in the premaxillary palatal (Pnx-Mxp) and mandibular symphysis (Pms-MS) lengths were significantly less in the tongue reduction as com- pared to the sham animals. Of 13 angular variables from lateral cephalomet- ric radiographs (Table 1), significant increases were identified in both sham and reduction animals at the angles of premaxilla to cranial vault (Pr-E-In). maxillary incisor to cranial vault (Ui-E-In) and mandibular antegonial notch (Gi-Mn-Me). However, the sham and tongue reduction groups demonstrated opposite growth direction in the gonial angle (Sm-Gp/Me-Gi), which de- creased in the sham and increased in the reduction animals over the five- week period. More importantly, relative to the sham animals, the reduction group showed significantly smaller values in the premaxillary angle (Pr-E- Sp) and the intermaxillary canine width (Mxc-Mxc’) at the two-week time points, the intermandibular first molar width (Md.1-Mdl’) at the four-week time points, and the premaxillary palatal length (Prmx-Mxp) and the man- dibular symphysis length (Prmx-Ms) at both two- and four-week time points (Fig. 5). 300 Liu PAL MAN kPa i 10 8- - Figure 13. Comparisons of of bone pressures at the palatal Surface of right palatal process (PAL) and lingual surface of right mandibular alveolar bone between the right canine and 1st molar (MAN). W = Working side; B = Balancing side. ** = p < 0.01; *** = p < 0.001. Osteometric measures revealed that the reduction animals presented significantly smaller values in the following variables: mandibular ramus height (1-2); anterior mandibular length (4-5); maxillary palatal length (18- 19); posterior midfacial width (11-11’); mandibular symphysis length (4-21); dorsal width of anterior mandible (5–5); and bilateral mandibular canine Width (25-25°). It should be noted that the majority of these reduced values (five of seven) involved the mandible. In addition to these negative effects on craniofacial skeletons and dental arch, the reduction surgery also affected bone quality. The DEXA examination indicated that both bone mineral density and content were less in the reduction than sham animals and the samples from the mandible were affected more than those of premaxilla/maxilla. The bone mineral content in the piece of mandibular symphysis was significantly lower in the reduction than the sham animals (Fig. 14). 301 Surgical Tongue Volume Reduction 0.60 - - Reduction g 8.00 0.50 - 7.00 0.40 - 6.00 5.00 0.30 - 4.00 0.20 - 3.00 2.00 - 0.10 - 1.00 0.00 - 0.00 --- - - - Premax|Max Man.Corp. Man. Symp. PremaxiMax Man.Corp. Man. Symp. A B Figure 14. Comparisons of bone mineral density (A) and bone mineral content (B) between the sham and reduction animals. Premax/Max = premaxil- lary/maxillary pieces; Man.Corp = mandibular corpus pieces; Man.Symp = mandibular symphysis pieces. Measurements from left and right premaxil- lary/maxillary and mandibular corpus pieces were combined in each group. * = statistical significance between the two groups. DISCUSSION Through various positional and shape changes, the tongue performs motor function and places mechanical effects on its surrounding tissues. AS an incompressible “hydrostat” muscular organ filling the majority of the space in oral cavity (Kier and Smith, 1985; Gilbert et al., 2007), the tongue volume plays a predominant role in its functional performance and ensuing mechanical environment. On one hand, the volume alterations in soft tissues induces corresponding Osseous reactions (apposition or resorption) at the growth sites of bones (Fränkel and Fränkel, 1989). On the other hand, tongue volume forms its local mechanical environment (Kier and Smith, 1985) and mechanical factors play a profound role in bone formation, growth and remodeling (Rafferty et al., 2000; Ruff, 2003). Surgical tongue volume reduction, therefore, may cause a chain reaction in the craniofacial region, involving the modification of functional performance, alterations of local mechanical environment and consequently to alterations in craniofacial skeletal growth and dental arch formation. This comprehensive study char- acterized the changes in each of these aspects of this reaction chain. The longitudinal tracking of feeding behaviors and masticatory tongue deformations demonstrates the effects of functional compensation, adaptation and motor learning process on a volume-reduced tongue. At the 302 Liu initial stage, food leaking from the mouth corner and extended ingestion and chewing episodes often were observed in the reduction animals. This type of functional deficiency diminished gradually over time. However, the “inertial pattern” of chewing and swallowing, along with shoveling food into mouth using the anterior mandible, persisted over time. This persistent functional deficiency suggests that the ability of food ingestion and transportation dur- ing mastication could be damaged permanently due to the loss of anterior tongue mass by the reduction surgery. The ultrasonic tracking records further indicate that both rhythm and amplitude of tongue dimensional changes (masticatory deformation) modified over time. First, the regularity of rhythm was distorted profoundly by the surgical volume reduction, particularly in anterior width (AW), length (LENG) and posterior dorsal width (PDW; Fig. 10, comparison of P0 and Pl). This type of distorted rhythm of tongue deformation improved over time and restored to almost the normal level four weeks after the surgery (Fig. 10, P2 and P3). Second, the contribution of various dimensional changes to masticatory tongue deformation was affected greatly by the sur- gery. The typical alterations were the significant decrease in the anterior width (AW) and the body length (LENG), and large compensatory en- hancement in the posterior width (both dorsal and ventral) and thickness (Figs. 10 and 11). Interestingly, the compensatory enhanced dimensional changes in the posterior tongue lessened along with gradual restoration of lost dimen- sional amplitudes in the anterior tongue. While the restoration of the defor- mation in the anterior tongue did not reach to the pre-surgical level (P0) four weeks after the surgery, the enhancement of the deformation in the posterior tongue diminished and returned to the level close to that before surgery. These outcomes strongly suggest that the decreased and enhanced deforma- tional capacity in the anterior and posterior tongue respectively occurring immediately after the reduction surgery may be a transient effect, rather than a permanent consequence of a volume-reduced tongue (Shcherbatyy et al., 2008). These results also suggest that although the volume loss of the tongue by the reduction surgery might be permanent, the distorted capacity of tongue deformation can be restored through progressive functional adapta- tion and motor leaning. However, the restoration of this capacity in the ante- rior tongue may be limited because of substantial mass loss in the tongue body by the reduction surgery (Table 2). Given that the major modifications in functional performance after Surgery are the alteration in feeding behaviors (ingestion mode, chew- ing/Swallowing pattern) and the loss of deformational capacity in the ante- 303 Surgical Tongue Volume Reduction rior tongue, it is necessary to explore the ensuing changes in the local me- chanical environment in order to bridge these functional outcomes with the consequences in craniofacial skeletal growth and dental arch formation. Un- fortunately, the data on loading outcomes at the endpoint of four-week lon- gitudinal tracking were not available at the time this chapter was prepared. Nevertheless, the short-term recordings on masticatory bone strains and pressures disclose that while the dominance and polarity of bone surface and suture strains were not affected, the reduction surgery did alter both magni- tudes and orientations of the strains and pressures. Corresponding to the short-term changes of masticatory tongue deformation previously found (Shcherbatyy et al., 2008), these modifications in bone strains and pressures were found mainly in the bones around the anterior rather than posterior oral cavity, presented by the decreased magnitudes of loading (strains and pres- sures) and posteriorly-shifted orientation of principal tensile strain. The other typical feature in the local mechanical environment after the reduction surgery is that the weak compressive strain at the lingual man- dibular symphysis was barely affected by the reduction surgery (Fig. 12B), even though this site is the most anterior of all recorded sites in the oral cav- ity. Given that this strain magnitude was ten times smaller in the lingual than that in the labial mandibular symphysis (Herring et al., 2008), it is a reason- able inference that the local mechanical environment on the lingual surface of this fused and concave-shaped symphysis is derived mainly from strong eversion of the bilateral mandibular borders by the puling forces of jaw muscles and jaw joint reaction force, instead of direct contacts of the tongue body during mastication. - A large number of clinical studies have claimed that tongue Volume is associated with dental arch form (Vig and Cohen, 1974b; Cohen and Vig, 1976; Lowe et al., 1985; Turner et al., 1997), jaw size and posture (Vig and Cohen, 1974a; Enlow, 1982; Tamari et al., 1991; Yoo et al., 1996) and fa- cial height (Doual-Bisser et al., 1989), although a few other studies rejected a role for tongue volume in mandibular prognathism and cranial size (Ruff, 1985; Yoo et al., 1996). A series of cross-sectional studies in a pig model also have demonstrated that tongue volume influences midfacial and man- dibular growth (Becker et al., 1988; Hubner et al., 1988; Pommerenke et al., 1988; Schumacher et al., 1988; Schumacher, 1997). The present longitudinal study demonstrates for the first time the characteristics of tongue internal kinematics and functional loading as the consequences of a volume-reduced tongue, and directly links these out- comes with craniofacial skeletal growth and dental arch formation. The find- 304 Liu ings set forth three features of negative effects on growth by a Volume- reduced tongue: 1. All three dimensions of craniofacial bones were affected (length, width and height). These include reduced lengthening in the premaxilla, mandibular symphysis and palatal process of maxilla; flattened gonial angle and decrease in the premaxillary angle; narrowed widths in the midface, zygomatic arch and anterior dental arch; and decrease in the height of mandibular ramus. 2. The skeletal components of anterior oral cavity are af- fected most. These components include the lengths of anterior mandible and premaxilla, and the widths of an- terior mandible and bilateral canine. 3. The growth of mandible is influenced more prominently than those of nasomaxillary skeletons; these influences are not only in all its height (ramus height), length (ante- rior mandible) and width (anterior mandible and bilat- eral canine), but also in its mineralization (symphysis and corpus; Fig. 14). Therefore, when taking tongue Volume reduction as an adjunct pro- cedure to lessen the chance of relapse after dentofacial orthopedic treatment, to correct functional disorders caused by an acquired macroglossia or to treat a true macroglossia, the potential functional consequences and growth ef- fects should be taken carefully into account. This study suggests that while the functional disturbance in terms of tongue deformation may be transient and can be restored partially over time, the influence on craniofacial growth and in particular that of the osseous components of anterior oral cavity and mandible could be a permanent consequence of tongue reduction. Because the majority of this adjunctive intervention is performed in young subjects who might be in a rapid growth period, special caution on this issue is par- ticularly important. A careful tracking of the growth should be undertaken in these subjects and certain approaches to improve or guide bone growth may need to be considered. ACKNOWLEDGEMENTS The author would like to thank Dr. Jonathan Perkins for help with tongue surgery and Dr. Volodymyr Shcherbatyy for help with experiments and data collections. The efforts for this comprehensive study were sup- ported by the grant R01 DE15659 from the National Institute of Dental 305 Surgical Tongue Volume Reduction and Craniofacial Research (NIDCR), the National Institutes of Health (NIH). REFERENCES Becker R, Hubner A, Pommerenke F, Schumacher GH. The tongue as a fac- tor in craniofacial growth. Part 2. The influence of the width dimension of the lower jaw. [In German.] Anat Anz 1988; 167:81–86. Cohen AM, Vig PS. A serial growth study of the tongue and intermaxillary space. Angle Orthod 1976:46:332–337. Davalbhakta A, Lamberty BG. Technique for uniform reduction of mac- roglossia. Br J Plast Surg 2000:53:294-297. Deguchi T. Case report: Three typical cases of glossectomy. Angle Orthod 1993;63:199-207. Doual-Bisser A, Doual JM, Crocquet M. Hypoglossal balance and vertical morphogenesis of the face. Orthod.Fr 1989;60:527–532. Enlow DH. Handbook of Facial Growth. 2nd ed. Philadelphia: WB Saun- ders Co., 1982. Fränkel F, Fränkel C. Orofacial Orthopedics with the Function Regulator. Basel: Karger 1989. Gilbert RJ, Napadow VJ, Gaige TA, Wedeen VJ. Anatomical basis of lin- gual hydrostatic deformation. J Exp Biol 2007:210:4069–4082. Herring SW, Rafferty KL, Liu ZJ, Sun Z. 2007. A nonprimate model for the fused symphysis: In vivo studies in the pig. In: Vinyard CJ, Ra- vosa MJ, Wall CE, eds. Primate Craniofacial Function and Biology; Developments in Primatology Series. New York: Springer 2007. Hubner A, Pommerenke F, Schumacher GH, Becker R. [The tongue as a factor in craniofacial growth. Part 3. The influence of the height and an- gle of the lower jaw.] Anat Anz 1988;167:191-197. Kier WM, Smith KK. Tongues, tentacles and trunks: The biomechanics of movement in muscular-hydrostats. Zool J Linn Soc 1985;83:307-324. Liu ZJ, Kayalioglu M, Shcherbatyy V, Seifi A. Tongue deformation, jaw movement and muscle activity during mastication in pigs. Arch Oral Biol 2007:52:309-312. Liu ZJ, Shcherbatyy V, Kayalioglu M, Seifi A. Internal kinematics of the tongue in relation to muscle activity and jaw movement during feeding. J Oral Rehabil 2009:32:660-674. 306 Liu Liu ZJ, Shcherbatyy V, Perkins JA. Functional loads of the tongue and con- sequences of volume reduction. J Oral Maxillofac Surg 2008a;66:1351- 1361. Liu ZJ, Yamamura B, Shcherbatyy V, Green JR. Regional volumetric change of the tongue during mastication in pigs. J Oral Rehabil 2008b; 35:604-6 12. Lowe AA, Takada K, Yamagata Y, Sakuda M. Dentoskeletal and tongue Soft-tissue correlates: A cephalometric analysis of rest position. Am J Or- thod 1985;88:333-341. Mao JJ, Nah HD. Growth and development: Hereditary and mechanical modulations. Am J Orthod Dentofacial Orthop 2004; 125:676-689. McClung JR, Goldberg SJ. Functional anatomy of the hypoglossal inner- vated muscles of the rat tongue: A model for elongation and protrusion of the mammalian tongue. Anat Rec 2000:260:378-386. Pommerenke F, Schumacher GH, Becker R, Hubner A. The tongue as a fac- tor in craniofacial growth. Part 4. Results of animal experiments. [In German.] Anat Anz 1988;167:281-287. Rafferty KL, Herring SW. Craniofacial sutures: Morphology, growth, and in vivo masticatory strains. J Morphol 1999:242:167-179. Rafferty KL, Herring SW, Artese F. Three-dimensional loading and growth of the zygomatic arch. J Exp Biol 2000:203:2093-2104. Ruff C. Growth in bone strength, body size, and muscle size in a juvenile longitudinal sample. Bone 2003:33:317-329. Ruff RM. Orthodontic treatment and tongue surgery in a class III open-bite malocclusion: A case report. Angle Orthod 1985;55:155-166. Schumacher GH. Principles of Skeletal Growth. In: Dixon AD, Hoyte DAN, Ronning O, eds. Fundamentals of Craniofacial Growth. Boca Raton: CRC Press 1997:1-21. Schumacher GH, Becker R, Hubner A, Pommerenke F. The tongue as a fac- tor in craniofacial growth. Part 1. Modification of the linear dimensions of the lower jaw. [In German.] Anat Anz 1988;166:309-315. Shcherbatyy V, Liu ZJ. Internal kinematics of the tongue during feeding in pigs. Anat Rec (Hoboken) 2007:290:1288–1299. Shcherbatyy V, Perkins JA, Liu ZJ. Internal kinematics of the tongue fol- lowing volume reduction. Anat Rec (Hoboken) 2008;291:886-893. 307 Surgical Tongue Volume Reduction Tamari K, Shimizu K, Ichinose M, Nakata S, Takahama Y. Relationship between tongue volume and lower dental arch sizes. Am J Orthod Dento- facial Orthop 1991; 100:453-458. Turner S, Nattrass C, Sandy JR. The role of soft tissues in the aetiology of malocclusion. Dent Update 1997:24:209-214. Vig PS, Cohen AM. The size of the human tongue shadow in different man- dibular postures. Br J Orthod 1974a; 1:41-43. Vig PS, Cohen AM. The size of the tongue and the intermaxillary space. Angle Orthod 1974b;44:25-28. Yoo E, Murakami S, Takada K, Fuchihata H, Sakuda M. Tongue volume in human female adults with mandibular prognathism. J Dent Res 1996; 75:1957–1962. 308 RECENT INSIGHTS INTO TOOTH ERUPTION AND FUTURE PROSPECTS FOR TREATING UNERUPTED TEETH David A. Covell, Jr. ABSTRACT In recent years, many advances have been made in our understanding of biological processes involved in tooth eruption. In this review, results of recent investigations are presented that provide details on eruption mechanisms related to the role of the dental follicle. Molecular factors and interactions involved in regulating osteoclastic and osteogenic activity have become increasingly well defined, but ambiguity remains as to the nature of the force that brings about movement of the tooth within the follicle. Evidence strongly suggests that osteoblastic activity, and bone deposition in particular, is as critical for tooth eruption as is bone resorption occlusal to the tooth’s crown. Current research also has focused on improving the ability to diagnose variations on eruption failure such as “primary failure of eruption,” a condition where teeth cannot be erupted even when using orthodontic traction. Future applications of improved knowledge on the molecular interactions involved in tooth eruption may lead to use of molecular agents to assist with the process; however, there are many obstacles to such clinical applications. While the traditional approach of surgical exposure and orthodontic traction currently provides the most viable means of assisting eruption, it is possible in the future that improved diagnostic procedures and possibly bioactive therapy aimed at modifying molecular mechanisms of tooth eruption may become applicable for identifying and rectifying specific deficits in the eruption process. Investigations into the biological processes involved in normal tooth eruption have been ongoing for over 50 years and although much progress has been made, many important questions remain. Greater knowledge of eruption mechanisms is important when considering how best to manage failures of eruption and for developing new therapeutic approaches aimed at restoring eruption when the natural process is deficient. The purpose of this review is to provide an update on recent findings on the biological processes involved in tooth eruption, particularly those arising from applications of new technology aimed at defining events at the molecular level. Based on these advances, an 309 Insights into Tooth Eruption evaluation is made of future prospects and challenges for applying biological agents aimed at assisting with tooth eruption. Tooth eruption has been categorized into several stages based on the position of the tooth and the amount of eruption taking place (Proffit et al., 2007). Prior to erupting into the oral cavity, tooth eruption has been termed pre-emergent eruption, encompassing the intra-Osseous and mucosal penetration phases. Following entrance of the tip of the crown into the oral cavity, the tooth enters the post-emergent phase of eruption, consisting of an accelerated, pre-functional eruption until the tooth contacts an opposing tooth or intervening soft tissue (e.g., with tongue or digit habits), followed by an occlusal equilibrium stage where teeth continue erupting slowly throughout life in accordance with facial growth patterns. Although much remains to be learned about post- emergent eruption, this review will focus on the pre-emergent stage of eruption. PRE-EMERGENT TOOTH ERUPTION AND BONE RESORPTION During development of the crown, the forming tooth is housed within the dental follicle and the follicle remains relatively stationary within alveolar bone until a time coincident with the completion of the crown and initiation of root formation (see review by Cahill et al., 1988). At this point, the tooth enters pre-emergent or the intra-osseous stage of eruption where the dental follicle elongates toward the oral cavity by resorbing alveolar bone or roots of primary teeth, clearing an eruption tunnel. Using surgical interventions in dogs where a partially developed premolar was removed from its follicle or replaced by an inanimate object, Marks and Cahill (1984) demonstrated that an eruption tunnel will form whether the developing tooth remained in the follicle or not. In addition, when the developing tooth was replaced by a metal replica of the crown, the replica was found to erupt similar to the eruption pattern of control teeth (Marks and Cahill, 1984; Marks and Schroeder, 1996). Thus, once the pre-emergent eruption stage has begun, it is the follicle that is responsible primarily for forming the eruption pathway, a process involving osteoclastic activity along the coronal region of the follicle (Cahill and Marks, 1980; Marks and Cahill, 1984; Marks and Schroeder, 1996). Consistent with the observation that the cellular activity within the dental follicle forms an eruption channel, subsequent studies have demonstrated that the follicle serves as an attractant for monocytes, 310 Covell which are precursors of osteoclasts (Wise and Fan, 1989; Wise and Yao, 2006). Various investigations using a rat model of molar eruption have shown that recruitment of monocytes is mediated by the dental follicle through the release colony stimulating factor-1 (CSF-1) and monocyte chemotactic protein-1 (MCP-1; Wise et al., 1995; Que and Wise, 1997) as well as endothelial monocyte activating polypeptide (Liu and Wise, 2008). As found in other examples of bone modeling and remodeling activity, recruitment of monocytes and regulation of osteoclastic activity is controlled in large part by receptor activator of nuclear factor kappa B ligand (RANKL) and its competitive inhibitor, osteoprotegrin (OPG; Wise et al., 2000, 2005). At the start of eruption, levels of OPG have been found to decrease, corresponding to a burst in osteoclast formation. Several days later, a second wave of osteoclast formation is observed coincident with an up-regulation of RANKL. These findings demonstrate the importance of the RANKL/OPG ratio in controlling bone resorption in the dental follicle during tooth eruption (Wise and King, 2008; Wise, 2009). Failures of tooth eruption observed in osteopetrotic rats deficient in CSF-1 (Van Wesenbeeck et al., 2002) and in RANKL knockout mice (Kong et al., 1999) have added to evidence supporting the importance of Osteoclastogenesis in tooth eruption. These and other findings on Osteoclastogenesis in the coronal portion of the dental follicle clearly show that multiple, and in many cases redundant, molecular factors and pathways are involved in controlling the creation of an eruption tunnel (Wise, 2009). PRE-EMERGENT ERUPTION AND BONE FORMATION Another important process during pre-emergent tooth eruption is formation of bone at the apical end of the dental follicle. The presence of osteoblastic activity concomitant with tooth eruption clearly has been demonstrated by various experimental techniques (Marks and Cahill, 1987) and correlates closely with the amount of movement of the tooth within the dental follicle as it migrates toward the crest of the alveolus (Cahill, 1970). As with the osteoclastic activity along the coronal surface of the dental follicle, intervention studies have shown that osteoblastic activity will occur along the apical surface of the follicle in the absence of a tooth or when the tooth is replaced with an inanimate object (Marks and Cahill, 1984). Increased expression of bone morphogenetic protein-2 (BMP-2) has been associated with the basal half of the dental follicle 3.11 Insights into Tooth Eruption (Wise and Yao, 2006), with increases in BMP-2 gene expression correlating with more rapid rates of bone formation and tooth eruption (Wise et al., 2004). This association has led to the suggestion that BMP- 2 gene expression is at least in part responsible for the osteogenic events leading to tooth eruption (Wise et al., 2007). With osteoclastic activity occurring at one end of the follicle and osteoblastic activity taking place at the opposite end, a developing tooth or an experimentally-introduced object within the dental follicle such as a metal replica of a tooth crown (Marks and Cahill, 1984) is translocated within the follicle as the follicle drifts toward the oral cavity. Currently, it is unknown if a force is required to move the tooth within the follicle, and if so, the exact nature of the force. The experimental evidence cited above shows a strong correlation between bone formation and tooth movement as the dental follicle translates toward the oral cavity. Additional evidence is needed to resolve whether bone formation exerts an eruption “force” on the tooth or if bone formation occurs secondarily to fill a void as the tooth erupts due to some other force. Histological examination has shown that connective tissue separates the developing tooth from the forming alveolar bone (Wise et al., 2007) and that the periodontal ligament does not form until the tooth penetrates the oral mucosa and enters the oral environment (Cahill and Marks, 1982; Wise et al., 2007). Anecdotal clinical observations by oral surgeons (personal communications) and investigations reported in animal models (Wise et al., 2007) indicate that non-erupted teeth within the dental follicle have little to no discernable mechanical attachment to the bony wall of the follicle. Thus, movement of the developing tooth within the follicle may require minimal force and could reflect drifting of the tooth according to changes in the space available within the capsule formed by the dental follicle. This suggestion would provide an explanation for the observations of Marks and Cahill (1984) where metal replicas of the developing teeth placed within dental follicles showed relatively normal eruptive movements. It generally is recognized that osteoblast-lined periosteal surfaces of bone are relatively pressure intolerant. For example, with growth at sutures, bone deposition is thought to occur secondary to displacements or separation of adjacent bones; because of the physiological limitations of surfaces lined by osteoblasts, bone formation cannot be a primary cause of bone displacement (Enlow and Hans, 1996). Thus, if bone formation is the mechanism or force that translates the tooth within the follicle (Wise et al., 2007), the amount of 312 Covell force required would have to be light, a process that is tenable if the developing tooth is considered to be relatively free-floating within the follicle. DISTURBANCES IN PRE-EMERGENT TOOTH ERUPTION Failures in the process of tooth eruption during the pre-emergent phase are manifested largely by a cessation or significant reduction in the rate of eruption, or misdirection of the eruption pathway leading to ectopic eruption or impactions. Significantly delayed or halted pre- emergent eruption is associated with a number of syndromes, such as cleidocranial dysplasia (Jensen and Kreiborg, 1990) and oculocere- brorenal syndrome of Lowe (Wise et al., 2002; Brooks and Ahmad, 2009). Mechanical obstructions such as supernumerary teeth or bony cysts often will block the eruption pathway, as will lack of space due to crowding of previously erupted teeth (Proffit and Frazier-Bowers, 2009). Surgical removal of the obstruction often allows for natural eruption to resume (Serra e Silva et al., 2007), or in other cases orthodontic assistance can be applied to assure success (Becker et al., 2009). Dramatic demonstrations of the process of pre-emergent eruption are found in case reports of ectopic eruption where a dental follicle with the erupting tooth have migrated great distances, e.g., a mandibular premolar or molar migrating from its normal developmental position into the coronoid (Wong et al., 2007) or condylar processes (Silva et al., 2007). Because bone resorption is necessary in forming the eruption passageway, factors that inhibit resorption also should impede tooth eruption. During the past decade, bisphosphonates have become used widely to combat bone resorption, particularly in the axial skeleton. Animal studies have shown dramatic effects of bisphosphonates on tooth eruption, substantiating the role of osteoclastic activity in normal tooth eruption (Grier and Wise, 1998; Bradaschia-Correa et al., 2007). Although much of the clinical use of bisphosphonates relates to post- menopausal osteoporosis, there are recent reports of use of bisphosphonates in pediatric populations, including those with juvenile chronic arthritis or osteonecrosis (Ward et al., 2005). Thus, a thorough medical history should not be overlooked when evaluating causes for eruption failures, particularly when multiple teeth are affected. Failures in pre-emergent eruption often are idiopathic. One form of impaction that affects primarily posterior teeth has been termed 3.13 Insights into Tooth Eruption “primary failure of eruption” (PFE) and relates to cessation of eruption at pre- or post-emergent stages that does not involve ankylosis (Proffit and Vig, 1981; Ahmad et al., 2006; Sivakumar et al., 2007; Frazier-Bowers et al., 2007, 2009). With PFE, the eruption pathway is cleared by the follicle, but the teeth fail to erupt. When attempts are made to assist eruption using orthodontic forces, the teeth fail to move and become ankylosed. Case studies of PFE show that non-syndromic PFE can be familial or non-familial and teeth can be affected in one or multiple quadrants, unilaterally or bilaterally (Proffit and Frazier-Bowers, 2009). Genetic studies currently are underway to improve the diagnosis and potentially the treatment options for this condition (Wise et al., 2002; Frazier-Bowers et al., 2007, 2009). A recent report implicates a genetic mutation in the formation of G protein-coupled receptor for parathyroid hormone-like hormone (PTHR1) in 15 individuals with PFE. This finding suggests deficient communication between osteoclasts and presumptive mesenchymal progenitors of osteoblasts, resulting in a deficiency in osteoblastic activity (Decker et al., 2008). Other suggestions of the importance of osteoblasts, and by extension bone deposition, in the process of pre-emergent tooth eruption can be seen with cleidocranial dysplasia (CCD) syndromes. Over the past dozen years, a transcription factor, core binding factor al (Cbfal, also called Runx2), has been identified as an important regulator of osteoblast differentiation (Ducy et al., 1997). Mice that have deficiencies in Cbfal expression (e.g., when missing one of the two alleles for Cbfa1) show delayed ossification and other skeletal defects. These defects are similar to those seen in humans with CCD that include individuals with defects related to at least one allele of Cbfal (Wise et al., 2002). Expression of Cbfal has been shown to localize to osteoblasts but not to osteoclasts (Ducy et al., 1997; D’Souza et al., 1999), suggesting a direct role for osteoblasts and bone deposition for tooth eruption, and/or the role of osteoblasts in coordinating both bone deposition and resorption through communication with osteoclasts (Wise et al., 2002). One last line of research will be reviewed where eruption was disrupted through a mechanism that again points to the potential, direct role of osteoblasts and bone formation in the eruption of teeth. In a study, Bartlett and colleagues (2003) investigated the effects of deficiencies in membrane type-1 matrix metalloproteinase (MT1-MMP) on mouse tooth development. In general, matrix metalloproteinases (MMPs) play an im- 3.14 Covell portant role in the development and remodeling of many tissue components of the extracellular matrices. Because MT1-MMP is highly expressed in cells of calcifying and cartilaginous tissues, the investigators anticipated finding anomalous tooth development in mice deficient for this MMP. Instead, they found that in the absence of MT1- MMP, tooth formation was relatively normal, despite greatly reduced bone formation in the maxilla and mandible. They also found that tooth eruption was delayed markedly despite evidence of marked bone resorption occlusal to the teeth. The investigators likened their findings to the eruption of metal replicas of teeth as discussed above (see review by Marks and Schroeder, 1996), concluding that because bone resorption is increased in MT1-MMP deficient mice, the delay in eruption was indicative of the importance of alveolar bone formation in the eruption process (Bartlett et al., 2003). FUTURE PROSPECTS FOR ENHANCING TOOTH ERUPTION Anomalies of nature have provided graphic examples of the inherent potential for teeth to undergo pre-emergent eruption over great distances (Silva et al., 2007; Wong et al., 2007) due to coordinated osteoclastic activity at the coronal end of the dental follicle and Osteoblastic activity at apical end. As demonstrated by the studies of Marks and colleagues (1984, 1987, 1996), the tooth is translocated Within the migrating follicle and plays a relatively passive role during the intra-osseous stage of eruption. Evidence reviewed shows that failures or marked delays in pre-emergent tooth eruption can come about due to any one or a combination of altered biological factors. Failures in eruption have been created by interfering with biological processes related to Osteoclastic activity such as recruitment of progenitor cells, as seen with CSF-1 and MCP-1 expression deficiencies (Wise et al., 1995; Que and Wise, 1997), or formation and activation of osteoclasts as shown with the effects of bisphosphonates (Grier and Wise, 1998; Bradaschia-Correa et al., 2007). Seemingly of equal importance is the need for bone formation to occur in order for teeth to move into the channel created by the osteoclastic activity, as suggested by Cbfal (Ducy et al., 1997) and MT1-MMP (Bartlett et al., 2003) deficiencies. However, the extent to which tooth eruption is related to the direct effects of bone formation vs. communication from osteoblasts to other cells such as the osteoclasts, or involving some other cellular mechanism(s) remains to be determined. 315 Insights into Tooth Eruption In considering potential therapies based on our increasing knowledge of the molecular biology of tooth eruption, the existence of multiple factors and processes involved in tooth eruption points to the need for a refined diagnosis of the deficiency causing failure of eruption specific to each individual. Clearly application of therapeutics to augment bone resorption would be contraindicated if the deficiency was related to deficient bone formation; similarly, approaches aimed at augmenting bone formation would be ineffective if the basis of an eruption failure was related to deficiencies in bone resorption. Thus, until we understand the mechanisms of tooth eruption more fully, particularly the role of osteoblasts and bone formation, and can diagnose precisely the deficiency in individual patients with failed eruption, it would be inappropriate to attempt to modify cellular pathways involved in eruption clinically with the hope of encouraging tooth eruption. Efforts aimed at defining the genetic etiology of failures in tooth eruption will provide important diagnostic information. For example, a genetic diagnosis would improve treatment efficiency and outcomes if individuals affected by PFE could be diagnosed in advance of attempting surgical and orthodontic assistance of tooth eruption (Wise et al., 2002). Development and exploration of treatment options using animal models of genetic defects, such as those that can now be done with CCD, offers a promising means to explore the application of molecular biological approaches for treatment (Wise et al., 2002; Decker et al., 2008; Frazier- Bowers et al., 2009). Similar to considerations that have been given to potential uses of bioactive agents to accelerate orthodontic tooth movement (Wise and King, 2008; King, 2009), application of pharmacological approaches to address eruption failure faces many challenges including: • Targeting the enhancements to only the areas needed; • Designing appropriate methods for delivery of the agents; • Having the ability to assess the risk/benefit of a given approach; and * Managing the regulatory issues related to admin- istration of drugs. With teeth that are not erupting or that are erupting in an inappropriate direction, Surgical exposure to facilitate applying orthodontic traction has proven to be a successful approach (Becker, 2007; Becker et al., 2009), with the exception noted for teeth that are or 316 Covell become ankylosed, such as found with PFE (Proffit and Frazier-Bowers, 2009). The amount of bone removal occlusal to and surrounding the crown that is necessary to assure successful eruption is subject to controversy. Becker and colleagues’ review (2009) suggests minimal bone removal does not affect the subsequent eruption potential adversely When using orthodontic assistance, whereas excessive bone removal may predispose a tooth to future periodontal compromise. These observations suggest that in many cases of eruption failures, deficiencies in biological mechanisms of bone resorption may not be significant. The studies further suggest that these deficiencies may relate more to biological factors involved in pathway selection by the dental follicle or the force mechanism that normally would be attendant to the eruption process within the dental follicle. CONCLUSIONS It is intriguing to think that in the future when a tooth is not erupting as expected for reasons other than mechanical obstruction, there likely will be clinically accessible and affordable means available to diagnose the etiology of an eruption failure. In addition, with continued progress, it may be that bioactive agents aimed at rectifying various eruption deficiencies will become available. These agents could be applied in a controlled manner to a targeted area such that the overall intervention is less invasive and more convenient than the surgical- orthodontic options available today. Although in recent years great strides have been made in our understanding of tooth eruption and the etiology of failures of tooth eruption, translation of these findings to the clinic seemingly is many years away. For the immediate future, traditional surgical and mechanical approaches that have been employed successfully for decades most likely will remain the primary if not exclusive means for assisting with tooth eruption. ACKNOWLEDGEMENTS The author wishes to express his appreciation for the added insight on the topic of tooth eruption provided by several speakers at the 2008, 4th Biennial Conference of the Conferences on Orthodontic Advances in Science and Technology (COAST) titled Biomedicine in Orthodontics: From Tooth Movement to Facial Growth. These speakers include Adrian Becker, Sylvia Frazier-Bowers, Greg King, William Proffit and Gary Wise. 317 Insights into Tooth Eruption REFERENCES Ahmad S, Bister D, Cobourne MT. 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Proffit WR, Fields HW Jr, Sarver DM, eds. Contemporary Orthodontics. 4th ed. St Louis: Mosby 2007:86-93. 3.19 Insights into Tooth Eruption Proffit WR, Frazier-Bowers S. Mechanism and control of tooth eruption: Overview and clinical implications. Orthod Craniofacial Res 2009; 12:359-366. Proffit WR, Vig KW. Primary failure of eruption: A possible cause of posterior open-bite. Am J Orthod 1981:80:173-190. Que BG, Wise GE. Colony-stimulating factor-1 and monocyte chemo- tactic protein-1 chemotaxis for monocytes in the rat dental follicle. Arch Oral Biol 1997:42:855-860. Serra e Silva FM, Sawazaki R, de Moraes M. Eruption of teeth asso- ciated with a dentigerous cyst by only marsupialization treatment: A case report. J Dent Child 2007;74:228-230. Silva GC, Silva EC, Gomez RS. Migration of an unerupted second molar to the condyle: Report of a case with sequential radiographs. J Oral Maxillofac Surg 2007;65:570-572. Sivakumar A, Valiathan A, Gandhi S, Mohandas AA. Idiopathic failure of multiple permanent teeth: Report of 2 adults with a highlight on molecular biology. Am J Orthod Dentofacial Orthop 2007; 132:687- 692. Van Wesenbeeck L, Odgren PR, MacKay CA, D-Angelo M, Safiadi FF, Popoff SN, Van Hul W, Marks SC, Jr. The osteopetrotic mutation toothless (tl) is a loss-of-function frameshift mutation in the rat CSF-1 gene: Evidence of a crucial role for CSF-1 in osteoclastogenesis and endochondral ossification. Proc Natl Acad Sci USA 2002:99: 14303- 14308. Ward K, Cowell CT, Little DG. Quantification of metaphyseal modeling in children treated with bisphosphonates. Bone 2005:36:999-1002. Wise GE. Cellular and molecular basis of tooth eruption. Orthod Craniofac Res 2009;12:67–73. Wise GE, Ding D, Yao S. Regulation of secretion of osteoprotegrin in the rat dental follicle cells. Eur J Oral Sci 2004; 112:439-444. Wise GE, Fan W. Changes in the tartrate-resistant acid phosphatase cell population in dental follicles and bony crypts of rat molars during tooth eruption. J Dent Res 1989;68:150-156. Wise GE, Fan F, Zhao L. Transcription and translation of CSF-1 in the dental follicle. J Dent Res 1995;74: 1551-1557. Wise GE, Frazier-Bowers S, D’Souza RN. Cellular, molecular, and genetic determinants of tooth eruption. Crit Rev Oral Biol Med 2002; 13:323-334. 320 Covell Wise GE, King GJ. Mechanisms of tooth eruption and orthodontic tooth movement. J Dent Res 2008;87:414-434. Wise GE, Lumpkin SJ, Huang H, Zhang Q. Osteoprotegrin and osteoclast differentiation factor in tooth eruption. J Dent Res 2000;79: 1937–1942. Wise GE, Yao S. Regional differences of expression of bone morphogenetic protein-2 and RANKL in the rat dental follicle. Eur J Oral Sci 2006; 1 14:51.2-516. Wise GE, Yao S, Henk W.G. Bone formation as a potential motive force of tooth eruption in the rat molar. Clin Anat 2007:20:632-639. Wise GE, Yao S, Odgren PR, Pan F. CSF-1 regulation of osteoclastogenesis for tooth eruption. J Dent Res 2005;84:837-841. Wong YK, Liew JCH, Tsui SHC, Cheng JCF. Ectopic molar near the cornoid process: Case report. Quintessence Int 2007:38:597–600. 321 322 SURGICALLY ENHANCING THE SPEED OF TOOTH MOVEMENT: CAN WE ALTER THE BIOLOGY 2 Flavio Uribe, Carlos Villegas, Ravindra Nanda ABSTRACT Surgical treatment indeed can enhance the outcomes of orthodontic treatment. Another potential benefit of surgical intervention is the possibility of expediting orthodontic treatment. This chapter provides an overview of corticotomy- assisted orthodontics and its application to molar protraction using temporary anchorage devices. The regional acceleratory phenomenon is considered to be a potential biological mechanism for achieving increased tooth movement velocity during corticotomy-assisted orthodontics. This phenomenon also might enhance the speed of the post-surgical Orthodontic phase in patients undergoing orthog- nathic surgery. The possibility of eliminating the pre-surgical phase in combina- tion with increased tooth movement in the post-Surgical phase may result in shorter treatment times for these patients. Two case reports will illustrate the concepts of corticotomy-assisted molar protraction with miniscrews and the “Surgery first” concept using miniplates. The variety of materials, concepts and techniques of modern or- thodontics has evolved incrementally since the time of Edward Angle. Some may argue that the fundamentals of tooth movement remain the same. However, although the principles of physics may be immutable, definite progress has occurred in the area of material sciences. Indeed, development of new wires, brackets and springs has populated the ortho- dontic literature for the last 40 years. Even now, new brackets are being designed with the ambition of improving efficiency and esthetics. Clearly, treatment efficiency is one of the goals of every practi- tioner. Improved efficiency is accomplished by managing those aspects of orthodontics that are amenable to modification such as biology and mechanics. For example, many current appliances claim to reduce fric- tion or “eliminate it” all together. These “frictionless” appliances purport no loss of the applied force and, therefore, greater predictability of the biomechanics. How this reduction in friction is accomplished, however, 323 Surgically Enhancing Tooth Movement has not been well substantiated. Moreover, based on the evidence, im- proved efficiency using these new appliances is controversial at the very least. Juxtaposed against the uncertainty of these new appliances’ benefits is a comprehensive understanding of bone biology in response to orthodontic tooth movement. Substantial research has been published in the area of biology of orthodontic tooth movement in animal models. It has become clear that bone biology can be modified in order to increase treatment efficiency. In the studies that have been performed primarily in animal models, the physiologic and biologic players have been well de- lineated. These models revealed that the presence of cytokines, such as RANKL, enhances the speed of orthodontic tooth movement. For many reasons, the clinical application of these biological substances in humans is unlikely to be adopted in the near future. Although injecting cytokines into humans may not be feasible, a more gross manipulation of the biological bone cascade – by means of segmental alveolar decortications – currently is becoming an attractive technique used to increase the efficiency of orthodontic tooth movement. The underlying theory with this method is that corticotomy surgery alters the bone biology through mechanical perturbation of the dentoalveolar complex. Further, this biologic agitation appears to enhance tooth movement resulting from the subsequent application of mechanical stimulus of an orthodontic force. HISTORY Surgical segmentation of alveolar bone of the teeth has been re- ported since the end of the 19th century (Guilford, 1898). Köle (1959) thoroughly described the clinical application of orthodontically moving teeth after interproximal bone segmentation as a means to expedite tooth movement. He suggested that teeth can be segmented and moved as “small boxes” through bone remodeling without involving the periodon- tal ligament. His technique was described as an adjunct in the correction of numerous types of malocclusions, including tooth protrusion and deep bites combined with different treatment protocols such as nonextraction and space closure approaches. Using this method, he claimed orthodontic treatment could be accomplished in six to twelve weeks. Köle’s surgical technique for the correction of crowding con- sisted of elimination of the interproximal cortical bone on both labial and lingual aspects of the teeth up to and including the entire alveolar height 324 Uribe et al. while leaving the spongy bone intact (Köle, 1959). Additionally, a sub- apical osteotomy was performed below the segmented teeth. The ortho- dontic appliance he described was a removable plate with a labial bow and a screw that was activated for sagittal movement of 0.25 mm per Week. Alternatively, he suggested an Angle appliance could be used for tooth movement. Adjustments were made with unspecified force values. However, based on a weekly 0.25 mm activation of the expansion screw, it can be inferred that these forces were relatively high. No side effects such as loss of vitality, root resorption or deleterious periodontal effects were reported. Gantes and coworkers (1990) reported on the periodontal status of five adult patients with different malocclusions (majority Class II) who received orthodontic treatment assisted by corticotomies. This sam- ple was compared to a group of orthodontically treated patients of the Same age and with the same type of malocclusion. The corticotomies consisted of an interproximal vertical groove through the labial and lin- gual cortical plate of the six anterior teeth. Patients in the corticotomy group who had extractions had the buccal and lingual cortical plate re- moved at the extraction sites. The reported mean treatment time was 14.8 months for the corticotomy group vs. 28.3 months for the experimental group. Due to the segmental technique used for tooth movement in the corticotomy group, however, the frequency of appointments and total chair time was similar for both groups. Although treatment times were reported, the primary focus of this article was on the periodontal clinical effects. Both groups had similar probing pocket depths and slight at- tachment level changes. Unlike previous findings, apical root resorption was observed in the corticotomy group as well as the control group. Wilcko and colleagues (2001) reported on two adult patients with a Class I malocclusion and moderate to severe crowding who re- ceived corticotomies to accelerate tooth movement. The surgical proce- dure consisted of interproximal vertical grooves on the labial and lingual cortices of all teeth. A subapical horizontal scalloped corticotomy con- nected the vertical grooves. In addition, numerous circular perforations were drilled on the cortical bone surfaces and a resorbable allograft was packed over the corticotomies and exposed cortical bone. They called this procedure Periodontally Accelerated Osteogenic Orthodontics (PAOO). Orthodontic adjustments were performed on average every two weeks. Treatment duration for both patients was approximately six months, including twelve orthodontic adjustments. No periodontal se- quelae or apical root resorption was observed. A second exploratory sur- 325 Surgically Enhancing Tooth Movement gery for one of the patients fifteen months after the corticotomies re- Vealed increased bone thickness and adequate amount of bone covering the roots of the teeth, even after obtaining significant expansion of the dental arches with the orthodontic treatment. REGIONAL ACCELERATORY PHENOMENON The reported increase in the rate of tooth movement with corti- cotomy-assisted orthodontics has been attributed to a biological process denominated regional acceleratory phenomenon (RAP). This process was described initially by Frost (1989a,b) based on observations of bone frac- ture healing. In summary, he described a series of orchestrated events consisting of increased cellular activity during healing around the frac- ture site. These events were characterized by reduction in bone density due to the accelerated bone turnover. The cortical bone porosity appeared to be related to osteoclastic activity that may have contributed to tooth mobility. It has been suggested that the peak of such phenomenon is one or two months after the insult, with effects lasting six to 24 months (Yaffe et al., 1994). Mueller and coworkers (1991) not only reported on a regional acceleratory phenomenon, but also observed a systemic acceleratory phenomenon, where increased osteoblastic activity is apparent at a dis- tant site to the fracture healing area. Wilcko and colleagues (2008) rebut with the claim that the transient osteopenia and increased tissue turnover is related directly to the proximity and intensity of the surgical insult. ANIMAL EXPERIMENTS Recent studies have been published using different animal mod- els in order to understand the remodeling process after corticotomy- assisted orthodontics. Iino and colleagues (2007) evaluated tooth move- ment velocity in twelve Beagle dogs. The methodology was a split mouth design with corticotomies on the buccal and lingual alveolar bone of the mandibular third premolar, and a coil spring delivering a 0.5N mesial orthodontic force. The contralateral third premolar received the same orthodontic force but without the corticotomy. An increase in the speed of tooth movement was reported in the first two weeks in the corticotomy quadrant. The rate of tooth movement thereafter was similar on the ex- perimental and sham sides. Histologically, it was shown that hyaliniza- tion was present in the periodontal ligament every week on the control side, while the experimental side had hyalinization only during the first 326 Uribe et al. week. An increase in tartrate resistant acid phosphatase (TRAP) positive cells on the experimental side also was noted, suggesting increased os- teoclastic activity. The findings demonstrate that corticotomies combined with orthodontic force application increases the rate of tooth movement and is associated with histological changes reflecting increased bone turnOVer. In a study in rats, Lee and coworkers (2008) set out to compare the rate of tooth movement between a group of rats subjected to ortho- dontic force application alone and two additional groups of rats subjected to the same orthodontic force in combination to a corticotomy or an os- teotomy. In addition, they evaluated bone density at three time points for up to two months in all the groups with surgically-assisted orthodontic tooth movement and groups with corticotomy and osteotomy alone. No significant difference was found in the rate of tooth movement at 21 days between the control orthodontic force only group and those in which or- thodontic forces were applied in conjunction with corticotomy or osteot- omy, although a tendency for more movement was seen with osteotomy- assisted orthodontics. Bone density among all groups was highly vari- able. The changes in corticotomy-assisted orthodontics were consistent with RAP after 21 days. After two months, there were no differences in bone density levels surrounding the bone of the experimental and contra- lateral teeth. CORTICOTOMIES TO EXPEDITE MOLAR PROTRACTION INTO EDENTULOUS SPACES Corticotomies have been advocated by some clinicians for adult patients with severe crowding who request short orthodontic treatment duration. This technique also has been used recently as an adjunct to other orthodontic tooth movements. Oliveira and colleagues (2008), as well as Hwang and Lee (2001) described a case report of corticotomies as an aid for molar intrusion. Spena and coworkers (2007), using a case report, described corticotomy-assisted maxillary molar distalization. Both of these publications reported a reduction in treatment time. Fischer (2007) reported on six consecutive patients with bilateral palatally impacted canines that were subjected to corticotomies in con- junction with the exposure procedure. The results indicated an approxi- mate 30% reduction in treatment time between the canine with corti- cotomy-assisted orthodontic eruption in comparison to the contralateral Orthodontics-alone eruption. Chung and colleagues (2001) and Lee and 327 Surgically Enhancing Tooth Movement coworkers (2007) also reported a reduction in treatment time for patients with bimaxillary protrusion with space closure after corticotomies and extraction of four premolars. More recently, with the advent of skeletal anchorage, clinicians have been exploring the option of closing edentulous spaces in the poste- rior region through protraction of teeth adjacent to the edentulous space. Traditional orthodontics-only mechanics in these patients is time con- suming, with a rate of tooth movement of approximately 0.5 mm per month (Roberts et al., 1990). Considering that molar edentulous sites often are large, molar protraction could take up to 20 months for a 10 mm space. Nagaraj and colleagues (2008) recently published a case re- port of molar protraction using miniscrews involving 8 mm of space clo- sure in 15 months, with a total treatment duration of 28 months. It is im- portant to note that space closure using miniscrews in these types of pa- tients primarily consists of movement of one unit (protraction of the pos- terior segment); thus, space closure occurs from only one front. As op- posed to the more demanding and time-consuming space closure involv- ing only one front, patients with minimum anchorage requirements where the space is closed symmetrically will undergo faster space clo- SUITC. Corticotomies potentially could reduce the treatment time dra- matically in patients who require significant amount of molar protraction. Figure 1 shows a patient who previously had three years of orthodontic treatment. She was concerned with the prognosis of the retained primary second molars. The panoramic radiograph revealed moderate to severe root resorption of the second primary molars, most notably the right mo- lar. Additionally, a significant amount of recession was detected on the mesial root of both molars, which extended almost to the apex. Both primary molars had increased mobility. Occlusally the patient had an anterior openbite accentuated by a significant bilateral openbite at the premolars. The primary molars had no occlusal contact. The maxillary arch was constricted moderately with mild crowding. The mandibular arch was crowded moderately. The patient also had a crossbite tendency in the buccal segments with the left second molars in crossbite. The patient had been referred to the orthodontic clinic by the Di- vision of Prosthodontics with the concern that an implant required to re- place exfoliating primary molars would not receive any occlusal func- tion, and an unesthetic outcome would result if an occlusal contact was to be obtained in the final restoration. Following consultation with the 328 Uribe et al. Figure 1. Pre-treatment images depicting the poor prognosis of the mandibular primary second molars and the absence of the second premolars. The patient also presented with a dolicofacial pattern with anterior and lateral openbite with no occlusal contacts other than the first and second molars. Orthodontic Division, it was proposed to the patient to extract the pri- mary molars and close the spaces with orthodontic treatment, thereby addressing the openbite and eliminating the need to restore the missing Second premolars. Because the patient wanted to expedite the treatment time with fixed appliances, a protocol involving corticotomies on the 329 Surgically Enhancing Tooth Movement mandibular first and second molars was followed. The upper arch was to be treated with clear aligners with the specific objective of arch align- ment and slight expansion in the molar region. A lingual arch with loops connecting the bands of the permanent first molars was cemented with 3 mm clearance off the lingual surface of the mandibular incisors. The second molars were bonded and a passive stainless steel wire segment (0.016" x 0.022") connecting the first and second molars was cinched back behind the second molars. The patient then was referred to the periodontist for extraction of the primary second molars. Two weeks later, mucoperiostal flaps were elevated and inter- proximal vertical corticotomies made on the labial aspect of the man- dibular molars with a piezosurgical microsaw (Fig. 2; Vercellotti and Podesta, 2007). The vertical groove corticotomies were performed mesial to the first and second molars bilaterally and extended just below the cre- stal bone to the apex. Dried-freeze demineralized bone allograft (DFDBA) was packed on the buccal surface covering the grooves and exposed labial cortical bone surface, including a dehiscence on the first molar. The grafted bone increased the width of the edentulous ridge, cre- ating an adequate bone trough for the translation of the mandibular mo- lars. The flaps were approximated with closure by first intention, and a miniscrew was placed distal to the right and left first premolars. The pa- tient was allowed to heal for two weeks; thereafter, power arms were placed extending from the auxiliary tube of the first molar. A NiTi coil connected the power arms to the miniscrews delivering a mesial transla- tory force. The patient was evaluated every four weeks for adjustment of the lingual arch as the molars protracted. After approximately 5 mm of molar protraction, obtained during a six-month period, it was decided to bond the teeth anterior to the edentulous space in order to add control to the appliance as the first molars had tipped moderately in a mesial direction. Figures 3 through 6 show the progress and current treatment status. Two millimeters of space closure remains on the right edentulous site with full closure on the left side. However, the lower arch needs to be leveled with some intrusion of the mandibular second molars. This level- ing will be accomplished though indirect anchorage from the miniscrew. The arch will be leveled from first molar to first molar and thereafter the whole arch will be connected to the screw and an intrusive force delivered to the second molar. To complete the orthodontic treatment, alignment and slight expansion in the maxilla will be obtained using clear aligners. 330 Uribe et al. Figure 2. A and B: Corticotomy procedure using a piezosurgical microsaw. C. Dried-freeze demineralized bone allograft (DFBDA) was packed on the cortical bone to cover the bone dehiscences and build the volume of the edentulous site. D. A miniscrew was placed distal to the first premolar. Overall, the majority of the edentulous space has been closed, al- though at the expense of moderate tipping of the first and second molars. Although the mechanics delivered were intended to translate the poste- rior segments, tipping could not be obviated as these teeth were supra- erupted and needed to be displaced not only anteriorly but also inferiorly. Space closure occurred at a rate that appears to be 40% faster than tradi- tional orthodontic mechanics for this type of tooth movement. This ex- ample is only one case, however, and any conclusion on Speed of tooth movement is difficult to make as space closure rate depends on type of tooth movement (translation vs. tipping). Moreover, it is well known that significant intra-individual and inter-individual variation is common in tooth movement rates (Ren et al., 2003). Finally, although these types of patients could benefit from en- hanced speed of tooth movement, it still is not clear if this surgical bone perturbation enables faster orthodontic treatment. Moreover, the biolog- cal mechanism involved is obscure; therefore, the type and extent of the corticotomies needed to trigger an accelerated tooth movement response remain unknown. The techniques described herein involved interdental 331 Surgically Enhancing Tooth Movement Figure 3. Occlusal view of treatment progress. A. Two weeks after corticoto- mies. B. After two months. C. After four months. D: After six months. E. After eight months. F. After ten months. vertical grooves on the labial side. In contrast, others have described in- terdental vertical grooves on both the labial and lingual sides. Still others have combined labial and lingual interproximal vertical grooves and cor- tical round groove indentations. Wilcko and colleagues (2003) found no difference in rates of tooth movement in a split mouth design between vertical grooves and cortical round groove perforation. However, these findings are based on a report of one patient in whom only vertical groove corticotomies were performed on the buccal side. It also appears that grafting may be an important prerequisite, especially as the teeth move at a faster rate into a deficient edentulous ridge. 332 Uribe et al. Figure 4. Right lateral view of treatment progress. A. Two weeks after cortico- tomies. B. After two months. C. After four months. D. After six months. E: After eight months. F. After ten months. REGIONAL ACCELERATORY PHENOMENON IN PATIENTS UNDERGOING ORTHOGNATHIC SURGERY WITH ORTHODONTICS Patients with dentofacial deformities generally require complex treatments involving combined orthodontics and orthognathic surgery. The prevalent treatment paradigm for these patients involves a three- phase approach. In the first phase, decompensations of the teeth are accom- plished, usually at the expense of a transitory esthetic outcome. Depend- ing on the severity of the crowding and if extractions are involved, this phase usually lasts a period of nine to twelve months. The second phase 333 Surgically Enhancing Tooth Movement Figure 5. Left lateral view of treatment progress. A. Two weeks after corticoto- mies. B. After two months. C. After four months. D. After six months. E. After eight months. F. After ten months. is the surgical procedure to correct the basal bone relationships and achieve a good occlusion. Finally, the third stage consists of the finishing stage that may last another nine to twelve months of treatment. Typically, the pre-surgical orthodontic phase in these patients is needed in order to establish the direction and magnitude of the surgical movements predictably. In addition, this decompensation phase elimi- nates potential occlusal interferences, enabling a good occlusal outcome right after surgery (Proffit and White, 2003). This outcome is achieved through proper tooth alignment until the insertion of rigid archwires al- lows the mobilization of the whole arch during surgery. 334 Uribe et al. - º Figure 6. Frontal view of treatment progress. A. Two weeks after corticotomies. B. After two months. C. After four months. D. After six months. E. After eight months. F. After ten months. An alternative strategy for these patients may involve the elimi- nation of the first phase of treatment. By eliminating the pre-surgical phase and implementing a “surgery first approach, the patient does not have to endure an additional period of time with the dentofacial deform- ity, which is aggravated during the first phase of treatment. In addition, the elimination of one of the phases has the potential benefit of signifi- cantly reducing treatment time. This reduction in treatment time is ob- tained simply through the elimination of initial decompensation phase that reduces treatment time by nine to twelve months. The “surgery first" approach also may trigger the regional acceleratory phenomenon. Al- though this topic needs further investigation, it may be hypothesized that the osteotomies have a regional effect on the dental osseous environ- ment, possibly resulting in physiologic conditions that are conducive to an accelerated alignment phase following the Surgery. 335 Surgically Enhancing Tooth Movement SURGICAL TECHNIQUE Because the proper tooth inclinations and alignments are achieved after Surgery, this approach involves formulating a careful surgical plan. The surgery is planned based on the predicted orthodontic movements and the most ideal facial esthetic outcome desired. In order to ensure a good occlusal outcome, surgical skeletal anchorage plates are placed. Skeletal anchorage has redefined the practice of orthodontics. The envelope of discrepancy for orthodontic correction, described by Proffit and Ackerman (1994) has been broadened and now has a new layer. With skeletal anchorage, teeth can be moved over larger spans. This new envelope, therefore, blurs the line between the range of move- ment yielded with surgery and movement achieved by means of conven- tional orthodontic appliance therapy alone. Taking advantage of this po- tential, the placement of skeletal anchorage plates during “surgery first” cases serves as insurance in achieving the desired occlusal outcome when pre-surgical orthodontic phase is to be circumvented. For example, if the patient relapses or minor errors occur in the surgical outcome, the plates allow for controllable, predictable dental movements and ultimately more efficient attainment of optimal occlusion. CASE REPORT A patient who underwent a “surgery first” approach is presented in Figure 7. This 16-year-old female patient presented with a severe den- tofacial deformity including a severe facial concavity due to maxillary retrognathism and moderate mandibular prognathism. A mild vertical and transverse asymmetry was evident in frontal view. More specifically, the occlusal plane was slightly lower on the right side and the mandible deviated approximately 3 mm toward the right side. A slight crossbite tendency was noticed in the buccal segments due to the anteroposterior discrepancy in the dental arches. Maxillary and mandibular incisor inclinations were nearly ideal. The incisor display was deficient both at rest and upon smiling. The occlusal canine relationship was Class III with a significant reverse overjet. The maxillary first premolars were missing due to extraction performed by her dentist at an earlier age to alleviate crowding. 336 Uribe et al. Figure 7. Pre-treatment records of a 16-year-old female with a concave profile and Class III malocclusion. 337 Surgically Enhancing Tooth Movement Figure 8. A and B: Digital pre- Surgical treatment plan. C-E: Mounting in articulator depicting the surgical movements. 338 Uribe et al. The treatment plan for the patient was 3 mm of maxillary ad- vancement with 2 mm of downward displacement in the anterior region. The mandible was to be set back 4 mm on the left and 3 mm on the right to address the mandibular asymmetry and dental midline deviation (Fig. 8). Occlusally, the patient was to finish in a Class II molar and a Class I canine occlusion. Fixed appliances were bonded one week prior to the orthog- nathic surgery procedure. Brackets distal to the lateral incisors had hooks in order to be able to fix the surgical splints during the surgical proce- dure. No orthodontic wires were placed for the surgical intervention. The maxilla was mobilized anteriorly and rotated clockwise to improve smile display. Vertically it was impacted posteriorly 1 mm on the left side to resolve the occlusal cant. The mandible was set back through a BSSO 4 mm on the left and 3 mm on the right. Third molars were extracted at the time of surgery. Two plates were placed in the maxilla in order to fix it in its new position. In addition, two skeletal anchorage plates were fixed in the infrazygomatic crest. The plates emerged intraorally through the mu- cogingival junction at the first molar area. The mandible was fixed with three bicortical screws. After flap closure, a 0.016" x 0.016" NiTi wire and a 0.014" NiTi wire were placed on the maxilla and mandible, respec- tively. Intermaxillary elastics were prescribed between the maxillary and mandibular buccal segments and from the skeletal anchorage plates to the mandibular premolars (Fig. 9). After two weeks, the patient presented with mild swelling and relative good intermaxillary relationships. Alignment of the arches was continued and intermaxillary elastics were used to obtain a better occlu- sal relationship in the buccal segments. After three months, the occlusal relationship was almost ideal and the finishing phase was started (Fig. 10). Eight months after the surgical procedure, the patient was debonded. A maxillary vacuform retainer was delivered and a mandibu- lar canine to canine fixed lingual retainer bonded. Final records reveal a significant esthetic improvement and a good occlusal result achieved af- ter a short treatment time (Fig. 11). 339 Surgically Enhancing Tooth Movement Figure 9. A. Surgical maxillary LeFort 1 advancement with plate fixation and an additional miniplate emerging intraorally from the infrazygomatic crest through the mucogingival junction. B and C. Immediate intraoral post-surgical result with NiTi archwires inserted during this visit. D and E. Post-surgical x-rays. 340 Uribe et al. Figure 11. Final treatment records after eight months in treatment. - Figure 10. Three-month progress after surgery. 341 Surgically Enhancing Tooth Movement CONCLUSIONS • Understanding the biology of bone remodeling and tooth movement may help elucidate pathways that enable the enhancement in the speed of orthodontic treatment. • Clinical trials may help elucidate whether or not cor- ticotomies increase the rate of tooth movement. • The exact extent of the surgical corticotomy proce- dure that maximizes the efficiency in tooth move- ment, if at all, remains to be determined. • “Surgery first” approach eliminates the pre-surgical phase with a potentially significant reduction in treatment time. • The RAP may enhance tooth movement after orthog- nathic Surgery. ACKNOWLEDGEMENTS The authors are indebted to Dr. Brett Holliday for her contribu- tion to the preparation of this manuscript. REFERENCES Chung KR, Oh MY, Ko SJ. Corticotomy-assisted orthodontics. J Clin Orthod 2001:35:331-339. Fischer T.J. Orthodontic treatment acceleration with corticotomy-assisted exposure of palatally impacted canines. Angle Orthod 2007;77:417- 420. Frost HM. The biology of fracture healing: An overview for clinicians. Part I. Clin Orthop Relat Res 1989a;248:283-293. Frost HM. The biology of fracture healing: An overview for clinicians. Part II. Clin Orthop Relat Res 1989b;248:294-309. Gantes B, Rathbun E, Anholm M. Effects on the periodontium following corticotomy-facilitated orthodontics: Case reports. J Periodontol 1990;61:234-238. 342 Uribe et al. Guilford SH. Orthodontia or Malposition of the Human Teeth: Its Prevention and Remedy. Philadelphia: TC Davis & Sons 1898. Hwang HS, Lee KH. Intrusion of overerupted molars by corticotomy and magnets. Am J Orthod Dentofacial Orthop 2001; 120:209-216. Iino S, Sakoda S, Ito G, Nishimori T, Ikeda T, Miyawaki S. Acceleration of orthodontic tooth movement by alveolar corticotomy in the dog. Am J Orthod Dentofacial Orthop 2007; 131;448:e 1-8. Köle H. Surgical operations on the alveolar ridge to correct occlusal abnormalities. Oral Surg Oral Med Oral Pathol 1959; 12:515-529. Lee JK, Chung KR, Baek SH. Treatment outcomes of orthodontic treatment, corticotomy-assisted orthodontic treatment, and anterior segmental osteotomy for bimaxillary dentoalveolar protrusion. Plast Reconstr Surg 2007;120:1027-1036. Lee W, Karapetyan G, Moats R, Yamashita DD, Moon HB, Ferguson DJ, Yen S. Corticotomy-/osteotomy-assisted tooth movement microCTs differ. J Dent Res 2008;87:861-867. Mueller M, Schilling T, Minne HW, Ziegler R. A systemic acceleratory phenomenon (SAP) accompanies the regional acceleratory phenom- enon (RAP) during healing of a bone defect in the rat. J Bone Miner Res 1991;6:401–410. Nagaraj K, Upadhyay M, Yadav S. Titanium screw anchorage for protraction of mandibular second molars into first molar extraction sites. Am J Orthod Dentofacial Orthop 2008;134:583–591. Oliveira DD, de Oliveira BF, de Araujo Brito HH, de Souza MM, Medeiros P.J. Selective alveolar corticotomy to intrude overerupted molars. Am J Orthod Dentofacial Orthop 2008;133:902-908. Proffit WR, Ackerman JL. Diagnosis and treatment planning in orthodontics. In: Graber TM, ed. Orthodontics Current Principles and Techniques. St Louis: Mosby 1994:3-95. Proffit WR, White RP. Combining surgery and orthodontics: Who does what, when? In: Proffit WR, ed. Contemporary Treatment of Dento- facial Deformity. St Louis: Mosby 2003:245-267. Ren Y, Maltha JC, Kuijpers-Jagtman AM. Optimum force magnitude for orthodontic tooth movement: A systematic literature review. Angle Orthod 2003;73:86–92. 343 Surgically Enhancing Tooth Movement Roberts WE, Marshall KJ, Mozsary PG. Rigid endosseous implant utilized as anchorage to protract molars and close an atrophic extraction site. Angle Orthod 1990;60:135-152. Spena R., Caiazzo A, Gracco A, Siciliani G. The use of segmental corticotomy to enhance molar distalization. J Clin Orthod 2007; 41:693-699. Vercellotti T, Podesta A. Orthodontic microsurgery: A new surgically guided technique for dental movement. Int J Periodontics Restorative Dent 2007:27:325-331. Wilcko WM, Ferguson DJ, Bouquot JE, Wilcko MT. Rapid orthodontic decrowding with alveolar augmentation: Case report. World J Orthod 2003:4: 197-205. Wilcko WM, Wilcko T, Bouquot JE, Ferguson DJ. Rapid orthodontics with alveolar reshaping: Two case reports of decrowding. Int J Periodontics Restorative Dent 2001:21:9-19. Wilcko MT, Wilcko WM, Bissada NF. An evidence-based analysis of periodontally accelerated orthodontic and osteogenic techniques: A synthesis of scientific perspectives. Semin Orthod 2008; 14:305-316. Yaffe A, Fine N, Binderman I. Regional accelerated phenomenon in the mandible following mucoperiosteal flap surgery. J Periodontol 1994; 65:79–83. 344 CLINICAL APPLICATIONS OF THERAPEUTIC ULTRASOUND IN CRANIOFACIAL REPAIR AND REPLACEMENT Tarek El-Bialy ABSTRACT Low Intensity Pulsed Ultrasound (LIPUS) has been used to enhance bone frac- ture healing in orthopedics for a long time. Based on published in vitro and in vivo results, it has been hypothesized that LIPUS can enhance bone formation during mandibular distraction osteogenesis. Preliminary results of an animal study indicated that LIPUS can enhance bone formation and maturation during mandibular osteodistraction. This animal study was followed by many clinical case reports on using LIPUS to enhance bone formation after mandibular dis- traction osteogenesis in humans. In addition, preliminary animal and clinical data showed that LIPUS also can enhance mandibular condylar growth in grow- ing animals and possibly in children. Since the first discovery that LIPUS- stimulated dental tissue formation in rabbits, a clinical pilot study demonstrated that LIPUS can prevent orthodontically induced root resorption in human pa- tients. The mechanisms of the stimulatory effect of LIPUS on bone healing, mandibular condylar growth and dental tissue formation are not understood clearly. Preliminary data from different research groups showed that LIPUS has a stimulatory effect on different gene expressions. These data suggest future in- depth studies on the mechanisms and pathways by which LIPUS enhances for- mation and repair of different tissues should be conducted. LOW INTENSITY PULSED ULTRASOUND (LIPUS) Ultrasound, an acoustic pressure wave at frequencies above the limit of human hearing, is transmitted into and through biological tissues and is being used widely in medicine as a therapeutic, operative and di- agnostic tool (Dyson, 1985; Ziskin, 1987). Therapeutic ultrasound and some operative ultrasound use intensities as high as 1 to 3 W/cm and can cause considerable heating in living tissues. Therapeutic ultrasound is used widely, especially in sports medicine and myofunctional therapy, to decrease joint stiffness, to reduce pain and muscle spasms and to im- prove muscle mobility (Graber, 1997a). Ultrasound also has been used 345 Therapeutic Ultrasound extensively in temporomandibular disorder (TMD) therapy (Graber, 1997b). Therapeutic ultrasound has the potential of becoming a powerful nonviral method for the delivery of genes into cells and tissues (Du- vshani-Eshet et al., 2006a,b). LIPUS has been used for the past few decades to enhance heal- ing of fractured bones (Heckman et al., 1994). Extensive studies about the mechanisms by which LIPUS enhances bone fracture healing have been published. Among these studies, it has been reported that LIPUS is effective in liberating preformed fibroblast growth factors from a macro- phage-like cell line (U937). It stimulates angiogenesis during wound healing (Young and Dyson, 1990), enhances bone growth into titanium porous-coated implants (Tanzer et al., 1996) and enhances bone forma- tion after mandibular osteodistraction (Shimazaki et al., 2000; El-Bialy et al., 2002; Chan et al., 2006; Taylor et al., 2007; El-Bialy et al., 2008a) in rabbit animal models. In human clinical trials, there are contradictory reports in the literature between studies that showed LIPUS is highly ef. fective in achieving maturation of bone, reducing time of distraction os- teogenesis and enhancing the healing of osteoradionecrosis (Esenwein et al., 2004; El-Mowafi and Mohsen, 2005) versus others showing no effect of LIPUS on distraction osteogenesis (Schortinghuis et al., 2008). It is to be noted that clinical results are dependent on patient compliance and responses also are sensitive to application technique. The mechanism by which LIPUS enhances bone fracture healing and bone formation during distraction osteogenesis could be attributed to the stimulatory effect of ultrasound on the expression of bone proteins (osteonectin, osteopontin, bone sialoprotein); this stimulatory effect is dose dependent (Harle et al., 2001). GROWTH MODIFICATION BY LIPUS The first report about the potential growth modification by LIPUS was reported in the early 1970s on long bones in rats (Abramovich, 1970). A contradictory result was published by Spadaro and Albanese (1998) that showed that LIPUS has no effect on growth end plates in rats. Since then, no studies on the effect of therapeutic ul- trasound on bone growth modification have been found in the literature. There has been recent interest among researchers in using therapeutic ultrasound as a non-invasive technique in bone healing, repair and poten- tial growth modification in higher animals and in humans. 346 El-Bialy The first study on the potential use of therapeutic ultrasound to modify the growth of mandibular condyles in growing rabbits was re- ported by our group (El-Bialy et al., 2003a). Interestingly, no similar research can be found in the literature that follows up on our first publi- cation on rabbits. In 2006, we reported again that LIPUS can enhance mandibular condylar growth in growing monkeys; this stimulatory effect was increased when functional appliances were used. Interestingly, the stimulatory response of LIPUS in rabbits was observed in just four weeks; in monkeys, however, the stimulatory effect of LIPUS was ob- served after four months of daily application of LIPUS for twenty min- utes per day. In a recent pilot clinical trial, it has been reported that LIPUS can enhance mandibular growth in growing children with hemifacial mi- crosomia (El-Bialy et al., 2005; Fig. 1). The effect of LIPUS in stimulat- ing mandibular growth, however, took longer than in monkeys. In less severe hemifacial microsomia, the stimulatory response of LIPUS was obtained after a year of daily LIPUS application of twenty minutes per day to the area of the affected TMJ. An important point of caution with regard to these observations: in the absence of a control group of subjects who utilized the hybrid functional appliance alone without LIPUS, it cannot be stated conclusively that the desired response occurred primar- ily from or even at all from LIPUS. Another recent study in tissue culture indicated that LIPUS en- hances cortical bone mineralization and the newly deposited mineral was found perpendicular to the ultrasound path, strongly suggesting that LIPUS accelerates periosteal bone formation. However, contrary to our in vivo studies, zones of epiphyseal, hypertrophic and calcified cartilages did not exhibit any differences between control cartilages and those ex- posed to LIPUS. LIPUS also did not influence the amounts and components of proteoglycan secreted into the culture medium (Lienau et al., 2008; Na- ruse et al., 2009). The lack of effects of LIPUS on cartilage growth in this study is in contrast to previous investigations showing that it has a positive effect on cartilage growth in vitro (Nolte et al., 2001; Takeuchi et al., 2008). Interestingly, it also has been shown recently that LIPUS enhances bone-tendon junction ossification (Qin et al., 2006), which may explain how LIPUS enhances growth in the mandibular condyle and potentially the glenoid fossa where TMJ tendons are attached. 347 Therapeutic Ultrasound Figure 1. Hemifacial microsomia pa- tients treated by LIPUS and a hybrid functional appliance. The treatment regimen included daily 20 minutes of LIPUS device application on the TMJ area and full-time wear of the hybrid functional appliance. The top photo- graphs show before and after treatment, while the bottom photograph shows how the LIPUS was applied to TMJ area. Based on the literature, it seems that although LIPUS may be used in the future to complement functional appliance therapy, the long duration needed to achieve clinically valuable results may limit its clini- cal application. 348 El-Bialy DENTAL TISSUE FORMATION BY LIPUS AND ITS POTENTIAL USE TO TREAT AND PREVENT ROOT RESORPTION An unexpected observation led us to realize that LIPUS can en- hance the growth of the lower incisor apices and accelerates the rate of eruption of teeth in rabbits by stimulating new dental tissue formation (El-Bialy et al., 2003b). This serendipitous finding originally was ob- served when LIPUS was used to enhance bone formation during man- dibular distraction osteogenesis (El-Bialy et al., 2002). Because the biol- ogy of rabbit teeth is different from that of teeth in higher mammals, in- cluding humans, they may not serve as optimal models for deriving clini- cally relevant information. On the other hand, orthodontic patients who require premolar ex- tractions for orthodontic treatment can provide an excellent experimental model to study the effect of LIPUS on orthodontically induced root re- sorption in humans. In a pilot study, we investigated the effect of LIPUS on the healing of root resorption induced by light orthodontic force (50 gram force) in 12 patients (El-Bialy et al., 2004). We found that LIPUS minimized root resorption and accelerated healing of the resorption by reparative cementum and sclerotic dentin over four weeks of simultane- ous tooth movement and LIPUS application. We currently are evaluating the effect of LIPUS on root repair during application of excessive orthodontic force systems (650 gram/mm buccal root torques on human premolars; Fig. 2). These findings indicate that LIPUS prevents excessive buccal root resorption in the LIPUS- treated premolar compared to the palatal root or the control premolar that did not receive LIPUS treatment. Despite the above-mentioned reports, few investigations have been conducted to explore the molecular mechanisms by which LIPUS enhances dentin and cementum formation. Dalla-Bona and colleagues (2006) demonstrated that LIPUS stimulates some genes and their protein transcripts to regulate cementoblast function in vitro. Specifically, they demonstrated that an intensity of 150 mW/cmº was most effective in upregulating calcium content and transcription of alkaline phosphatase (ALP), which plays an important role in the mineralization process by cementoblasts. In contrast, LIPUS had no effect on cell proliferation. In a more recent study, Dalla-Bona and coworkers (2008) found that high-intensity ultrasound induced cementoblastic osteoprotegrin 349 Therapeutic Ultrasound (OPG) synthesis, while receptor activator of nuclear factor kappa B (NF- KB) ligand (RANKL) protein levels were unaffected. RANKL synthesis was low both in sham control and ultrasound stimulated cells. Taken to- gether, this increase in the OPG/RANKL ratio can be expected to result in a net inhibitory effect on the formation and activity of cementoclasts and a subsequent decrease in root resorption. Moreover, it was noted that both low- and high-intensity ultrasound applications enhance cemen- toblast transcripts for ALP and type I collagen (COL-I) in vitro. However, OPG, collagen synthesis and ALP activity were enhanced significantly only by high-intensity ultrasound. The stimulation of collagen synthesis by LIPUS suggests its direct role in cementum formation and the upregu- lation of OPG synthesis suggests an inhibitory effect on cementoblast- mediated osteoclastogenesis. Additional findings showed that LIPUS at 150 mW/cm may be harmful to the dental pulp cells; however, further in vivo studies were recommended to validate this effect of LIPUS (Dalla- Bona et al., 2008). In summary, in that RANKL promotes osteoclastogenesis (Kho- sla, 2001; Kostenuik and Shalhoub, 2001; Karsenty and Wagner, 2002) and further because osteoclastogenesis is dependent on the balance be- tween RANKL and OPG expression in osteoblasts (Vaananen, 2005; Ishii et al., 2006), LIPUS’ increase in OPG/RANKL ratio is likely to have a protective effect against root resorption. In addition, it has been reported that LIPUS regenerates cementum and mandibular bone after flap surgery (Ikai et al., 2008). The above-mentioned studies on the ef- fect of LIPUS on cementogenesis in tissue culture and after periodontal flap suggests that LIPUS can be an effective technique in preventing and repairing orthodontically induced tooth root resorption. An additional effect of LIPUS may include dentine repair. Fol- lowing the first report that LIPUS also enhances sclerotic dentin forma- tion in humans in four weeks (El-Bialy et al., 2004), additional investiga- tions were performed by Scheven and coworkers (2007, 2009). They re- ported that LIPUS increased the expression of collagen type I, osteopon- tin (OPN), transforming growth factor-31 (TGF 31) and the heat shock protein (hsp) 70 by odontoblast-like cells in vitro. Because of the poten- tial for LIPUS to regenerate dentin, these reports also suggest that LIPUS may be used to help repair tooth root fractures or even internal resorption. The report that LIPUS was found to have an anti-inflammatory action (Iashchenko et al., 1994) further suggests its potential use as an effect- 350 El-Bialy US treated premolar Figure 2. LIPUS prevents buccal root resorption after application of 650 gram/mm force buccal root torque. Note severe root resorption in the palatal root of the LIPUS treated premolar compared to the buccal root and the severe root resorption of the buccal and palatal roots of the control (no LIPUS) treated premolars. ive technique in preventing and repairing orthodontically induced root resorption. More recently, it has been shown that LIPUS enhances periodon- tal ligament cell proliferation and differentiation into cementoblasts (Inubushi et al., 2008), which supports our previous animal and human Studies on dental tissue formation and minimization of orthodontically induced root resorption. CRANIOFACIAL TISSUE ENGINEERING To engineer a tissue, three basic elements are needed: 1. Specialized cells or undifferentiated cells to be sub- jected to differentiation into the tissue specific cells; 2. A scaffold to house these cells; and 3. A conditioning medium to differentiate undifferenti- ated cells into the tissue specific cells or to maintain the specialized cells in their differentiated status. 351 Therapeutic Ultrasound Within the craniofacial region, teeth and the TMJ are tissues that most frequently require replacement; hence, there is substantial desire to bio- engineer these tissues. Tooth loss usually occurs due to trauma, deep car- ies and pulp involvement with poor prognosis as well as due to severe periodontal disease that can lead to loss of the supporting structures. De- spite the vast advances in dental materials and technology, tooth re- placement with fixed bridges, removable partial dentures or implants have their own known limitations. Before making a bio-tooth (or tissue-engineered tooth) from cells becomes realistic, several key issues must be resolved. First, cells that can generate teeth must be isolated easily from older patients, the major population suffering from tooth loss. Second, these cells must be ex- panded easily in vitro to yield enough cell populations necessary for the tooth reconstruction. Then, an odontogenic micro-environment must be found that can facilitate these cells to form a three-dimensional bio-tooth in vitro Or in vivo. In addition, the newly formed bio-tooth made from these cells must have the capacity to continue its development, generate functional root-periodontal complex and perform directional eruption at the right place in the environment of adult jaws. Finally, the size and shape of these bio-teeth must be controllable in order to match the patient’s own teeth and erupt into normal occlusion. Taken together, the making of a bio-tooth must comply with the basic principles of tooth growth and de- velopment (Yu et al., 2008). Given the above-mentioned facts that LIPUS enhances dental tissue formation both at the macroscopic and molecular levels, it can be hypothesized that LIPUS may play an impor- tant part in tissue-engineered teeth or creating a bio-tooth in the labora- tory. The second most important tissue that scientists have attempted to engineer is the articular mandibular condyle. In osteochondral defects, bone regeneration can occur readily in the presence of an adequate blood supply up to a certain bony defect size, while articular cartilage has poor capacity for self-regeneration. Once it is damaged, articular cartilage un- dergoes degenerative events such as loss and/or destruction of key struc- tural components, including type II collagen and proteoglycans. The poor capacity of cartilage for self-regeneration is attributed to the paucity of tissue-forming cells, namely chondrocytes (Poole et al., 2001). Because articular cartilage is avascular, it cannot rely on blood flow for the supply of cartilage tissue-forming cells. Thus, the self- 352 El-Bialy regenerating capacity of the articular cartilage depends on the sparsely available chondroprogenitor cells or perhaps mesenchymal stem cells that are habitual residents of the tissue. Furthermore, the articular cartilage is devoid of a nerve supply. Consequently, articular cartilage injuries often are not accompanied by joint pain until the subchondral bone, which is richly innervated, is in- Volved. Therefore, articular cartilage defects, seen in arthritis and injuries, often are osteochondral in nature. The temporomandibular joint (TMJ), like other synovial joints, is susceptible to osteoarthritis, rheumatoid ar- thritis, fractures, ankylosis and dysfunctional syndromes, collectively affecting over 10 million individuals in North America (LeResche, 1997; Ribeiro et al., 1997; Ferrari and Leonard, 1998; Israel et al., 1998; Sano et al., 1999; Goddard and Karibe, 2002). In many of these disorders, structural destruction of the TMJ ne- cessitates surgical replacement. The current TMJ replacement techniques utilize bone/cartilage grafts and artificial materials (Henning et al., 1992; MacIntosh, 2000; Bell et al., 2002). Despite certain levels of reported clinical success, autografts are associated with donor site morbidity, un- predictable clinical outcomes and a relatively high incidence of re- operation (Ware and Brown, 1981; Dodson et al., 1997; Wolford and Karras, 1997). Alloplastic and xenoplastic grafts are associated with po- tential transmission of pathogens, immunorejection and unpredictable clinical outcomes (Mercuri, 2000; Meyer, 2002; van Minnen et al., 2002). Efforts to tissue engineer mandibular/articular condyles for use in reconstruction are increasing exponentially. These efforts include us- ing osteoblasts and chondroblasts/chondrogenic cells from different tis- sue/cell sources (Poshusta and Anseth, 2001; Springer et al., 2001; Chu et al., 2002; Alhadlaq and Mao, 2005; Barnewitz et al., 2006; Shao et al., 2006; Pilliar et al., 2007). However, the engineering of these tissues also faces several challenges including limited number of the stem cells to be differentiated into two types of chondrogenic/osteogenic cells, different bone ingrowth patterns (Chu et al., 2002), different rates between the gel degradation and matrix production, and inferior mechanical properties for clinical use (Alhadlaq and Mao, 2005). Also, a relatively long time is needed for integration of tissue engineered constructs for osteochondral repair, namely three to six months in rabbit femur heads (Barnewitz et al., 2006), six to twelve months in horses (Pilliar et al., 2007) and up to nine months in sheep (Pilliar et al., 2007). 353 Therapeutic Ultrasound A recent in vivo evaluation of osteochondral defect repair used a novel tissue-engineering approach to repair an osteochondral defect in a sheep model. They reported that a long time is needed for in vitro prepa- ration (eight weeks) of the tissue-engineered osteochondral construct before implantation into a sheep knee (Pilliar et al., 2007). The authors recommended future use of mechanical stimulation for better functional integration. In addition, the long time needed for the in vitro construct preparation may be faced with other tissue-culture problems like infec- tion, and lack of consistency resulting from known laboratory and human errors. Thus, tissue-engineering mandibular condyle (TEMC) research is in need of a new technique or method to overcome these limitations. The lack of mechanical strength is considered one of the major roadblocks to cartilage tissue engineering (Mow and Wang, 1999; Si- kavitsas et al., 2001). A previous report demonstrated that the material properties of tissue-engineered cartilage constructs are in the range of kilopascals (LeBaron and Athanasiou, 2000) that are substantially lower than typical articular cartilage, which are in the range of megapascals (Cohen et al., 1992; Narmoneva et al., 1999; Hu et al., 2001; Clark et al., 2002; Goldstein, 2002; Patel and Mao, 2003). Attempts using pulsed electromagnetic fields (PEMF) showed that this stimulation increases chondrocyte and osteoblast-like cell proliferation (Hartig et al., 2000; De Mattei et al., 2001). Recent attempts using bioreactors have been made to enhance the material properties of tissue-engineered cartilage constructs (Pei et al., 2002; El Haj et al., 2005; Service, 2005; Stevens et al., 2005; Vance et al., 2005; Vunjak-Novakovic et al., 2005; Gemmiti and Guldberg, 2006; Janssen et al., 2006; Haasper et al., 2008). Cyclic compressive loading has been demonstrated to induce phenotypic changes between cartilagi- nous and osseous tissues (Elder et al., 2001; Davisson et al., 2002; Mi- zuno et al., 2002; Huang et al., 2004). It also has been shown that me- chanical stimulation enhances vascular endothelial growth factor (VEGF) that is important for angiogenesis and bone formation in the mandibular condyles (Rabie et al., 2002). Since optimum parameters have not been established yet, the findings of these studies cannot be util- ized clinically. Moreover, such approaches involving bioreactors and mechanical stimulation would be difficult to apply clinically. Findings using LIPUS suggest its potential use in tissue engi- neering. For example, it has been shown that LIPUS enhances periosteal cell expansion (Leung et al., 2004). Other studies also have demonstrated 354 El-Bialy that LIPUS stimulates expansion of bone marrow stromal cells (BMSC) and their differentiation into chondrocytes (Ebisawa et al., 2004; Cui et al., 2006). Moreover, another report showed that LIPUS increases matrix production and proliferation of the intervertebral disc cell culture (Iwa- shina et al., 2006). In addition, LIPUS has been reported to be a pre- ferred method of mechanical stimulation or as a “preferred bioreactor” (Cui et al., 2006). The optimized application of LIPUS for in vitro and in vivo application for bone healing and stimulation has been investigated before, and a conclusion has been made that daily application of LIPUS for 20 minutes provides significant stimulation of bone healing within three to four weeks (Tsai et al., 1992). One of the most important considerations in tissue engineering is enhancing integration between the engineered tissue and native surround- ing tissue. This integration could be achieved best by enhancing angio- genesis (new blood vessel formation) around and into the engineered tissue. Findings that LIPUS enhances angiogenesis (Young and Dyson, 1990; El-Bialy et al., 2003a, 2006) suggests its potential attributes in modulating angiogenesis. We have demonstrated that LIPUS can en- hance stem cell expansion and differentiation in monolayers (Aldosary et al., 2008; Ang et al., 2008) and in collagen scaffold in vitro as well as enhance tissue-engineered mandibular condyles in a pilot study in vivo (El-Bialy et al., 2008b). However, the optimum parameters for using LIPUS to enhance TEMC have not been characterized. Moreover, previous research has shown LIPUS to be safe and no deleterious effects have been reported (Mende et al., 1996; Hata et al., 1997; Blass and Eik-Nes, 1998; Turnbull and Foster, 2002). Finally, it has been shown recently that LIPUS minimizes apoptosis and enhances viability of human stem cells in vitro (Lee et al., 2007). From the litera- ture summarized above, it seems feasible that LIPUS can become an in- tegral part of craniofacial tissue engineering in the future. MOLECULAR MECHANISM OF ACTION OF LIPUS Despite multiple studies concerning the biological effects of therapeutic ultrasound, the physical process through which low level ul- trasound interacts with living tissue remains unknown. The difficulty in resolving this issue lies in the complex response of living tissue to these high frequency acoustic stimuli. On passing through the tissue, the ultra- Sonic energy is absorbed at a rate proportional to the density of the tissue. This differential absorption may play a critical role in targeting the ultra- 355 Therapeutic Ultrasound sound to the cells present inside and around the hard tissue (e.g., bone and teeth). Wide-ranging in vitro and in vivo studies have been conducted to probe the biologic mechanism(s) responsible for the observed ultrasound augmentation of osteogenesis and fracture healing. One of the first such in vitro studies reported that ultrasound induced changes in rates of in- flux and efflux of potassium ions in rat thymocytes (Chapman et al., 1980). It also has been reported that low intensity ultrasound increases calcium incorporation in differentiating cartilage and bone cell cultures (Ryaby et al., 1989a, 1992). Calcium uptake in fibroblasts with reversi- ble efflux of the calcium after exposure also has been demonstrated (Mortimer and Dyson, 1988). Another study has concluded that ultrasound-stimulated synthe- sis of cell matrix proteoglycan associated with accelerated fracture heal- ing is mediated by intracellular calcium signaling (Parvizi et al., 2002). In vitro, ultrasound at a spatially averaged temporally averaged intensity (ISATA) of 20 to 30 mW/cmº has been shown to modulate adenylate cyclase activity (Ryaby et al., 1989b, 1990, 1992), transforming growth factor beta (TGF-3) synthesis (Ryaby et al., 1991; McCauley and No- hutcu, 2002) and effects bone morphogenic protein. Tsai and colleagues (2006) studied the optimum ultrasound dura- tion and intensity for bone fracture repair and reported that the optimum stimulation results were obtained by applying ultrasound with 0.5 W/cmº, 1.5 MHz for 15 minutes per day. Most of the recent commercially avail- able LIPUS devices were designed based on these results. Tsai and co- workers (1992) and Tanzer and colleagues (1996) reported that LIPUS effect is optimum during the first two to three weeks of treatment. CONCLUSION Many potential applications of LIPUS are available to enhance dental and skeletal repair, modulate growth of craniofacial structures and for tissue engineering. Future studies are needed to validate several of these findings and to establish clinical protocols for each of the potential applications of LIPUS. 356 El-Bialy REFERENCES Abramovich A. Effect of ultrasound on the tibia of the young rat. J Dent Res 1970:49:1182. Aldosary TA, Uludag H, Doschak M, Chen J, Tsui Y, El-Bialy TH. Ef- fect of ultrasound on human umbilical cord perivascular-stem cell ex- pansion. J Dent Res 2008;87(Spec Iss B):874. Alhadlaq A, Mao J.J. Tissue-engineered osteochondral constructs in the shape of an articular condyle. J Bone Joint Surg Am 2005;87:936-944. Ang WT, Yu C, Chen J, El-Bialy TH, Doschak M, Uludag H, Tsui Y. 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Peters, Woosung Sohn, Carlos González-Cabezas ABSTRACT The most common negative effect of orthodontic treatment with fixed appli- ances is the development of incipient carious lesions around brackets. The ob- jectives of this chapter are to present some of the results of two studies aiming: 1) to evaluate patients treated with comprehensive orthodontics to determine the incidence of new carious lesions during treatment; and 2) to investigate the po- tential of ACP-containing resin cement and other treatments (fluoride varnish, resin sealer, MI Paste) to prevent incipient carious lesions on bracketed teeth. In the first study, 350 orthodontic patients were selected randomly. The pre- and post-treatment photographs of the patients were examined to determine lesion development. The labial surface of each tooth was scored with a standardized system based on the International Caries Determination and Assessment System II. The independent variables were collected by chart abstraction. In the second study, 100 extracted human premolars were allocated randomly to five groups (N = 20). Brackets were bonded with ACP-cement (Aegis-Ortho), Transbond XT (Control), Transbond XT followed by application of fluoride varnish (Van- ish), resin sealer (Pro-seal) and CPP-ACP paste (MI Paste). All teeth were pH cycled for 15 days in demineralization solution and artificial saliva. The extent of demineralization in each group was assessed using Quantified Light-induced Fluorescence (QLF) and Confocal Laser Scanning Microscopy (CLSM). The incidence of patients who developed at least one new white-spot lesion during treatment was 73%. Treatment length was associated significantly with new white-spot lesion development. The independent variables of gender, age and extraction/non-extraction were not associated with lesion development. Fluores- cence loss and lesion depth measurements demonstrated that the Pro-seal and Vanish groups had the least amount of demineralization. The control group showed the most demineralization. Although the MI Paste and Aegis-Ortho groups experienced less demineralization than controls, neither was significant statistically. Only the Pro-seal and Vanish groups had significantly smaller le- sions than the control group for both QLF and CLSM. Thus, the development of new lesions appeared to be related to treatment duration and, to a lesser degree, to initial oral hygiene score. Light-cured filled sealer (Pro-seal) and the fluoride Varnish (Vanish) have the potential to prevent enamel demineralization adjacent to orthodontic brackets exposed to cariogenic conditions. 367 White-Spot Lesions One of the most common negative side effects of orthodontic treatment with fixed appliances is the development of incipient carious lesions around brackets and bands, particularly in patients with poor oral hygiene (Fig. 1). Incipient carious lesions (i.e., white spots) are charac- terized by their opacity and mineral loss when compared to healthy enamel (Mizrahi, 1982; Arends and Christoffersen, 1986). Studies have shown that white-spot lesions (WSL) can take only one month to develop (O’Reilly and Featherstone, 1987; Øgaard et al., 1988; Gorton and Featherstone, 2003). The incidence rate and prevalence of WSL in or- thodontic studies has been reported to be significantly high (Gorelick et al., 1982; Mizrahi, 1982; Lovrov et al., 2007). Orthodontists have turned to various products and preventive measures to reduce this problem. Although fluoride varnish does not prevent WSL formation to- tally, it reduces its incidence significantly (Stecksén-Blicks et al., 2007). In a prospective clinical study, there were 44% fewer caries lesions noted for teeth that had been treated with fluoride varnish during orthodontic treatment (Vivaldi-Rodrigues et al., 2006). Just as sealants prevent caries in molars with deep fissures, resin sealers have been applied on facial surfaces of bracketed teeth to prevent enamel demineralization. A recently developed highly filled resin prod- uct Pro-seal (Reliance Orthodontic Products, Itasca, IL) has been mar- keted as a sealer that is more resistant to toothbrush abrasion than earlier generations (Buren et al., 2008). The manufacturer also claims it releases fluoride. Recently, there has been increased interest in calcium phosphate- based remineralization technology. One of the newest modalities in pre- ventive dentistry is the introduction of amorphous calcium phosphate (ACP) into methacrylate composites, gum, pastes and other dental prod- ucts. Aegis-Ortho (Bosworth, Skokie, IL) is a resin bonding cement with the potential added benefit of caries prevention. The manufacturer claims that the acidic challenge to the surrounding bracket area will trigger the release of calcium and phosphate from the cement, inhibiting deminerali- zation and promoting remineralization. Aegis-Ortho has the advantage in that it does not need any additional chair time in the orthodontic office. A similar chemical process is expected from MI Paste (GC America, Alsip, IL). The casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) containing paste is applied topically to affected areas. The manufacturer indicates that this product will prevent lesion form- 368 Arruda et al. Figure 1. Incipient caries lesions (white spots) develop around brackets and bands due to poor oral hygiene. ation and can reverse lesions after three months of use post-debonding. A recent systematic literature review found insufficient clinical trial evi- dence to make a recommendation regarding the long-term effectiveness of casein derivatives, specifically CPP-ACP, in preventing caries in vivo (Azarpazhooh and Limeback, 2008). With all the treatment modalities flooding the marketplace, the orthodontist might find it difficult to sort out what works best and why when oral hygiene deteriorates. The objectives of this chapter are to highlight the results of two recent studies that investigated: 1. The incidence of new WSLS before and after Ortho- dontic treatment using photographic records; and 2. The potential of ACP-containing resin cement and other treatments (fluoride varnish, resin sealer, MI Paste) to prevent incipient caries lesions next to bracketed teeth. METHODS AND MATERIALS: PART I Selection of Subjects From a population of 2,296 patients treated in the graduate or- thodontic clinic at the University of Michigan School of Dentistry (UMSD) between 1997 and 2004, 350 patient records were selected ran- domly using a random number sequence. Inclusion criteria for record Selection consisted of patients who: 369 White-Spot Lesions 1. Underwent comprehensive orthodontic treatment util- izing full fixed appliances on labial tooth surfaces; 2. Had complete initial and final series of intraoral pho- tographs; and 3. Had complete treatment log information within their chart. Chart Abstraction Data collection from de-identified patient charts included gender and age at initiation of orthodontic treatment, and treatment variables such as extraction therapy and comprehensive treatment time. Compre- hensive treatment time was defined as the period between initiation of full fixed appliance therapy and removal of all active fixed appliances. Initial oral hygiene score, frequency of oral hygiene discussion, oral hy- giene instruction and fluoride application and/or rinse were recorded from progress notes in the chart. Photography Intraoral pre-treatment (initial) and post-treatment (final) photo- graphs of each patient were taken as part of standard orthodontic record- keeping procedures. All photographs, stored as 35 mm slides, were taken in the Clinical Photography Department at the UMSD by two profes- sional photographers utilizing a standardized intraoral photography pro- cedure. Individual slides were scanned into digital format using a Nikon Slide Feeder SF-200 (S) and Super Coolscan 4000 ED scanner. Scanned images were enlarged 325% and imported into an individual Microsoft PowerPoint presentation for each patient. Dental Caries Determination Images were evaluated by trained investigators using a scoring system specifically adapted for use with photographed images (Interna- tional Caries Detection and Assessment System II; Ismail, 2005). Visible labial surfaces examined included maxillary and mandibular central and lateral incisors, canines, first and second premolars, and first molars. The evaluators scored each visible labial tooth surface before and after ortho- dontic treatment. The scores were combined to determine the labial caries incidence for each patient. Teeth were examined and scored from first molar to first molar, maxilla and mandible (Fig. 2). 370 Arruda et al. Figure 2. Tooth labial surfaces were examined and scored from left first molar to right first molar, maxilla and mandible, before and after orthodontic treatment. RESULTS: PART I The overall incidence of patients who developed at least one WSL during orthodontic treatment was 72.9% (N = 255; Table 1 and Fig. 3), while for newly developed cavitated lesions that were unrestored on the final record was 2.3%. Of the eight patients that developed cavitated lesions during orthodontic treatment, four (1.1%) developed one new cavitated lesion, three (0.9%) developed two new cavitated lesions and one (0.3%) developed four new cavitated lesions. Of the maximum 24 surfaces investigated per patient, on average 4.2 surfaces in each patient showed new WSL. The average of surfaces with new cavitations was 3.71 White-Spot Lesions only 0.04 and 0.05 with restorations. Even though infrequently, some early WSL regressed to sound (0.07 per patient). Demographic variables of gender and age at initiation of treat- ment were not related significantly to development of new decalcified or cavitated lesions. There was a significant relationship between increased treatment length and number of newly developed lesions (P = 0.03; Ta- ble 2). The mean number of labial surfaces per patient that developed new WSL was 3.01 for patients with a treatment length of less than 22 months. This increased to 5.28 teeth for patients with therapy longer than 33 months. The number of new cavitations, however, showed only a non- significant trend (P = 0.08) with increased treatment time. In addition, the number of newly developed lesions (both WSL and cavitations) showed no significant association with extraction or non-extraction treatment protocols (Table 3). Although no relationship was demonstrated between pre- treatment oral hygiene scores, and lesion development, the recorded number of oral hygiene discussions between provider and patient were associated significantly with development of both white-spot (P - 0.0001) and cavitated (P = 0.0006) lesions. The mean number of new lesions for patients with whom oral hygiene discussions had never been noted in the chart was 3.08, while the mean number of decalcified lesions for patients who were given oral hygiene instruction on three or more oc- casions increased to 7.78. A similar increase was exhibited for the mean number of cavitated lesions for patients given three or more oral hy- giene discussions (mean = 0.20) vs. those with whom oral hygiene was not discussed after initial instruction (mean = 0.01). Age group (P=0.03), treatment length (P=0.01) and number of oral hygiene discussions (P<0.0001) were associated with development of WSL. There was a decrease in WSLs associated with increasing age group (regression coefficient = -0.59). An increase in WSLS was associ- ated with both increased treatment time (regression coefficient = 0.07) and increased number of oral hygiene discussions (regression coefficient = 1.88). METHODS AND MATERIALS: PART II Sample Preparation One hundred human premolar teeth were collected from various oral surgery practices located in southeast Michigan. Only premolars presenting a healthy facial enamel surface were included. All teeth were 372 Arruda et al. assigned randomly to five equal groups of 20 teeth. One of the groups had brackets bonded with Aegis-Ortho resin cement while the remaining groups were bonded with Transbond XT. Of the four Transbond XT groups, one served as a control, another received Vanish (3M, Espe, MN) fluoride varnish, another received MI Paste and the final received a coat of Pro-seal as adjunctive treatments. Demineralization Protocol Teeth were exposed to a pH cycling system to develop caries- like lesions. Each day teeth were incubated in demineralization solution (lactic acid and Carbopol [pH = 5.0], 50% saturated with hydroxyapatite) Table 1. Incidence of white-spot lesions (WSLs). Number of teeth With newly Frequency Percent e g developed of patients of total Cumulative | Cumulative WSL (N) patients frequency percent () 95 27.1 95 27.1 | 57 16.3 152 43.4 2 48 13.7 200 57.1 3 18 5.1 218 62.2 4 21 6.0 239 68.3 5 18 5.1 257 73.4 6 21 2.3 265 75.7 7 11 3.1 276 78.9 8 10 2.8 286 81.7 9 9 2.6 295 84.3 10 6 1.7 301 86.0 11 5 1.4 306 87.4 12 8 2.3 3.14 89.7 13 6 1.7 320 91.4 14 5 1.4 325 92.9 15 7 2.0 332 - 94.9 16 5 1.4 337 96.3 17 4 1.1 341 97.4 18 4 1.1 345 98.6 19 1 0.3 346 98.9 20 2 0.6 348 99.4 21 1 0.3 349 99.7 22 1 0.3 350 100.0 373 White-Spot Lesions Table 2. Multivariable regression model. * = P-value significant at P º 0.05. Parameter Standard Variable estimate error t–value P-value Sex –0.73 0.55 - 1.33 0.19 Age group -0.59 0.28 –2.12 0.03% Treatment 0.07 0.02 2.76 0.01% length Initial oral –0.08 0.56 –0.14 0.89 hygiene SCOre Number of 1.88 0.39 4.86 <0.00% oral hygiene discussions Table 3. Inferential statistics. Adjusted R-square = 0.11. This model accounts for 11% of the variation in WSL development. Age Trend, fewer new lesions as age increases Treatment length Trend, 0.08 new lesions per month of treatment Oral hygiene Counter-intuitive trend, number increases as number of discussions increased 100 - 90 + 80 - 70 - of e *... 50 - . 50 - 40 - 30 - 20 - 10 - - * > . 0. WSL Cavitations Restorations Figure 3. Distribution of patients with at least one new lesion. for eight hours, rinsed with de-ionized water and placed in artificial Sa- liva for 30 minutes, followed by two seconds of brushing with a power- brush (Sonicare, Philips) and fluoridated dentifrice (NaF, 1,100 ppm F). rinsed again and placed back in artificial saliva until next demineraliza- 374 Arruda et al. tion period (next day). Solutions were refreshed daily during the experi- mental period of 15 days. On day 15, all teeth were removed from the saliva solution, rinsed under tap water and stored in 100% humidity. To assess demineralization, Quantitative Light-induced Fluorescence (QLF) and Confocal Laser Scanning Microscopy (CLSM) were used. Both pro- cedures were carried out at the Oral Health Research Institute (IU) in Indianapolis, IN. RESULTS: PART II Demineralization assessed by QLF is shown in Table 4. The Pro- seal group had the least amount of fluorescence loss followed by the Vanish group. Aegis-Ortho group, MI Paste group and the control group (Transbond) had the most fluorescence loss and were not different sig- nificantly. Demineralization assessed by CLSM is shown in Table 5. No de- tectable lesion depth was seen in any of the specimens of Pro-seal and Vanish groups. The greatest lesion depth was found in the control group (Transbond), but it was not different significantly from Aegis-Ortho and MI Paste. Table 4. Loss of fluorescence per group (N = 20). *Groups not different significantly (P º 0.05). AF = fluoresce loss. Treatment Group Mean AF SD Tbx T + Pro-Seal –7.0 4.4 Tbx T + Vanish - 19.7 3.5 * Aegis-Ortho –22.9 3.7 * Tbxt + MI Paste –25.0 6.2 * Transbond XT (TbxT) – Control –29.6 8.2 Table 5. Lesion depth for each group (N = 20). *Groups not different significantly (P º 0.05). AF = lesion depth. Treatment Group Mean AF SD Tbx'T + Pro-Seal 0.0 0.0 TbxT + Vanish 0.0 0.0 * Aegis-Ortho 15.9 7.4 * Tbxt + MI Paste 16.4 15.8 * Transbond XT (TbXT) – Control 32.9 19.3 375 White-Spot Lesions DISCUSSION The use of intraoral photographs for caries determination in or- thodontic patients is a well-accepted method. Standardized photographs taken before and after appliance placement are available readily as a standard procedure in orthodontic care. Color photography as a means of recording prevalence of enamel opacity is a powerful method (Ellwood, 1993). Studies have shown that assessment of enamel demineralization from color images appears to be more reproducible than direct clinical observation utilizing only the naked eye (Benson et al., 1998). Moreover, photographic records provide an efficient means to capture the appear- ance of enamel and provide a permanent record at a given time point. It allows an examiner, therefore, to assess the caries experience of a patient blindly and randomly. Based on pre- and post-orthodontic treatment photographic pa- tient records, this study showed a high, incidence of new WSLs (72.9%) in patients treated with comprehensive orthodontics, while the incidence of new cavitated lesions in this population was 2.3%. Gender, age and oral hygiene at start of treatment were not associated with lesion devel- opment, while a significant association was evidenced with treatment duration. Patients in treatment for less than 22 months developed on av- erage three WSLs, while patients in treatment for 33 months or longer developed on average more than five lesions. Linear regression analysis suggested that as the duration of fixed appliances increased one month, 0.08 new WSLs were developed. - The in vitro study sought to test four different treatments, which comprise much of the currently available therapies to prevent WSLs. The four experimental groups differed in their application, chemistry and physical properties. The Aegis-Ortho cement serves as a replacement for a typical bracket bonding cement. This ACP-containing material suppos- edly reduces the incidence of enamel demineralization with the release of calcium and phosphate ions – not only to reduce demineralization, but also to promote the remineralization of enamel. The fluoride varnish group received the same bonding cement as the control plus an applica- tion of Vanish, a popular fluoride varnish used for caries prevention. Un- like fluoride rinses that require patient compliance, the delivery of Van- ish takes place in the dental chair and could be applied at the monthly orthodontic appointment. The CPP-ACP group teeth received an adjunctive daily applica- tion of MI Paste, whose chemical mechanism of action resembles that of 376 Arruda et al. the ACP cement. Instead of having ACP just residing in the bracket ce- ment, the preventive protocol for MI Paste demands a daily application and, thus, a certain degree of patient compliance. MI Paste is claimed to have the ability to prevent WSLs during orthodontic treatment. Teeth in the final group received a light-cured filled sealant as adjunctive treat- ment. Though it claims to offer some fluoride release, Pro-seal at its core functions as a protective physical barrier against the acid attacks. Compared with the control group, the Pro-seal group had a sta- tistically significant difference in regard to both outcome measures (i.e., lesion depth and fluorescence loss). The CLSM results indicated that there was no demineralization on any of the specimens in this group. Similarly, the QLF test demonstrated that teeth treated with Pro-seal had the least amount of fluorescence loss by far. The findings of this study confirmed that the Pro-seal functions as a protective barrier that is im- permeable to the daily acid challenge. This impressive display of demin- eralization prevention under in vitro cariogenic conditions also has been observed in other studies (Hu and Featherstone, 2005; Buren et al., 2008). When interpreting the results of the current study, it is important to examine the experimental methods used. Obviously, the oral cavity of the typical teenager presents a much more dynamic and abrasive envi- ronment than those used in this in vitro study. However, it has been shown that Pro-seal sealant also displays physical properties when sub- jected to abrasion (Hu and Featherstone, 2005). Pro-seal prevented enamel demineralization convincingly and, thus, seems to be a reason- able treatment option that requires zero patient compliance. The results from this study also indicated that teeth treated with the fluoride varnish had less enamel demineralization than the control and the ACP groups. Although it had a statistically significant difference in both lesion depth and fluorescence loss when compared to the control group, the difference was not nearly as dramatic in the QLF test. Cur- rently, there are no other in vitro studies in the literature that examine fluoride varnish around orthodontic brackets with both CLSM and QLF. In that there was zero demineralization measured with the CLSM but some degree of fluorescence loss found with the QLF raises questions. In spite having the specimens brushed daily, for the most part the fluoride Varnish remained unexpectedly on the tooth surface throughout the ex- periment and had to be removed with a plastic scaler at the end of the experiment. Therefore, its mechanism of action must be considered. In addition to the anti-cariogenic properties of fluoride as rationale for use, 377 White-Spot Lesions the fluoride may not have been the only mechanism of action in this in vitro experiment in that the varnish formed a physical barrier to the acid challenge. In this study, the Aegis-Ortho group and the MI Paste group showed less demineralization numerically than the control group for both the CLSM and QLF test, though neither had statistical significance. Thus, both Aegis-Ortho and MI Paste were not different from the control group. The similar numerical levels of effectiveness for Aegis-Ortho and MI Paste are not surprising, given their similar mode of action. In analyz- ing these two treatments, the obvious disadvantage for the MI Paste group is that it requires daily application, whereas the ACP in Aegis- Ortho simply resides in the bracket bonding cement. While the results of this study help us better understand the pre- vention potential of these products, in vitro experimental conditions can- not encapsulate all the complexities of a living oral cariogenic environ- ment. The ultimate answer on efficacy of these products has to come from well-designed controlled clinical trials. An in vivo randomized con- trolled trial study that employs proven methods for clinical evaluation of incipient lesions around brackets and also includes the patient compli- ance factor would provide the highest level of evidence with respect to the preventive treatment modalities discussed. CONCLUSIONS The incidence of WSLs in patients treated with comprehensive orthodontics was very high, suggesting that any preventive therapy pro- vided appeared to be ineffective. This widespread problem poses an alarming concern and warrants significant attention from both patients and providers that should result in greatly increased emphasis on effec- tive caries prevention. Results from this study suggest that both the light- cured filled sealer (Pro-seal) and the fluoride varnish (Vanish) have the potential to prevent enamel demineralization next to orthodontic brackets exposed to cariogenic conditions. REFERENCES Azarpazhooh A, Limeback H. Clinical efficacy of casein derivatives: A systematic review of the literature. J Am Dent Assoc 2008;139:915- 924. 378 Arruda et al. Buren JL, Staley RN, Wefel J, Qian F. Inhibition of enamel deminerali- zation by an enamel sealant, Pro-seal: An in vitro study. Am J Orthod Dentofacial Orthop 2008; 133:S88-S94. Gorelick L, Geiger AM, Gwinnett A.J. Incidence of white spot formation after bonding and banding. Am J Orthod Dentofacial Orthop 1982; 8 || 93–98. Gorton J. Featherstone JDB. In vivo inhibition of demineralization around orthodontic brackets. Am J Orthod Dentofacial Orthop 2003; | 23: 10–14. Hu W. Featherstone JDB. Prevention of enamel demineralization: An in vitro study using light-cured filled sealant. Am J Orthod Dentofacial Orthop 2005; 128:592-600. Ismail A. Rationale and evidence for the International Caries Detection and Assessment System (ICDAS II). In: Stookey G, ed. Clinical Models Workshop: Remin-demin, Precavitation, Caries: Proceed- ings of the 7th Indiana Conference. Indianapolis: Indiana University School of Dentistry 2005:161-222. Øgaard B, Rolla G, Arends J. Orthodontic appliances and enamel demin- eralization. Part 1. Lesion development. Am J Orthod Dentofacial Or- thop 1988;94:68-73. O’Reilly MM, Featherstone JDB. Demineralization and remineralization around orthodontic appliances: An in vivo study. Am J Orthod Dentofacial Orthop 1987;92:33-40. Stecksén-Blicks C, Renfors G, Oscarson ND, Bergstrand F, Twetman S. Caries-preventive effectiveness of a fluoride varnish: A randomized controlled trial in adolescents with fixed orthodontic appliances. Car- ies Res 2007:41:455-459. Vivaldi-Rodrigues G, Demito CF, Bowman SJ, Ramos AL. The effec- tiveness of a fluoride varnish in preventing the development of white spot lesions. 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