CBCT and Cephalometric Analysis of the TMJ Complex After Treatment Using a MARA Appliance Melissa Danette Shotell

Loma Linda University TheScholarsRepository@LLU: Digital Archive of Research, Scholarship & Creative Works

Loma Linda University Electronic Theses, Dissertations & Projects

9-2014 CBCT and Cephalometric Analysis of the TMJ Complex after Treatment Using a MARA Appliance Melissa Danette Shotell

Follow this and additional works at: http://scholarsrepository.llu.edu/etd Part of the Orthodontics and Orthodontology Commons

Recommended Citation Shotell, Melissa Danette, "CBCT and Cephalometric Analysis of the TMJ Complex after Treatment Using a MARA Appliance" (2014). Loma Linda University Electronic Theses, Dissertations & Projects. 220. http://scholarsrepository.llu.edu/etd/220

This Thesis is brought to you for free and open access by TheScholarsRepository@LLU: Digital Archive of Research, Scholarship & Creative Works. It has been accepted for inclusion in Loma Linda University Electronic Theses, Dissertations & Projects by an authorized administrator of TheScholarsRepository@LLU: Digital Archive of Research, Scholarship & Creative Works. For more information, please contact [email protected].

LOMA LINDA UNIVERSITY School of Dentistry in conjunction with the Faculty of Graduate Studies

______

CBCT and Cephalometric Analysis of the TMJ Complex after Treatment Using a MARA Appliance

Melissa Danette Shotell

______

A thesis submitted in partial satisfaction of the requirements for the degree of Master of Science in Orthodontics and Dentofacial Orthopedics

______

September 2014

Melissa Danette Shotell All Rights Reserved Each person whose signature appears below certifies that this thesis in his opinion is adequate, in scope and quality, as a thesis for the degree Master of Science in Orthodontics and Dentofacial Orthopedics.

, Chairperson Joseph Caruso, Professor of Orthodontics

Kitichai Rungcharassaeng, Professor of Orthodontics

R. David Rynearson, Associate Professor of Orthodontics

iii ACKNOWLEDGEMENTS

I would like to express my deepest gratitude to my committee members for their guidance and support throughout this study. Dr. Caruso, Dr. Rungcharassaeng, and Dr.

Rynearson, thank you for lending your time and expertise to this project, and for encouraging me throughout the process. I would like to thank Dr. William Johnston and

Dr. Khaled Bahjri for their work on the statistical analysis of this study. Thank you to

Chris Kabot and IBUR Biosystems for their help with the image analysis.

iv DEDICATION

I dedicate this thesis to my husband Michael Scherer for his support in everything I do.

v CONTENTS

Approval Page ...... iii

Acknowledgements ...... iv

Dedication ...... v

Table of Contents ...... vi

List of Tables ...... vii

List of Figures ...... viii

List of Abbreviations...... ix

Abstract ...... xii

Chapter

1. Review of literature...... 1

2. CBCT and cephalometric analysis of the TMJ complex after treatment using a MARA appliance ...... 7

Abstract ...... 7 Introduction ...... 10 Hypothesis...... 10 Materials and Methods ...... 11

Data Collection ...... 11 Lateral Cephalometric Images ...... 12 3D CBCT Images ...... 15

Metric Analysis of Images ...... 16 Mandibular Length ...... 17 Mandibular Condyle Volume ...... 17

Sample Size ...... 19 Experimental Control ...... 19 Statistical Analysis ...... 19

Results ...... 20

Lateral Cephalometric Images ...... 21

vi 3D CBCT Images ...... 25

Metric Analysis of Images ...... 25 Mandibular Length ...... 27 Mandibular Condyle Volume ...... 28

Discussion ...... 28

Lateral Cephalometric Images ...... 29 3D CBCT Images ...... 30

Metric Analysis of Images ...... 31 Mandibular Length ...... 32 Mandibular Condyle Volume ...... 33

Conclusion ...... 34

3. Extended Discussion ...... 36

Study Improvements and Future Directions ...... 36

References ...... 38

vii TABLES

Tables Page

1. Summary of cephalometric measurements ...... 23

2. Summary of cephalometric statistics ...... 24

3. Analysis of the treatment and time effects on MCW in axial plane using Two-way ANOVA ...... 25

4. Analysis of the treatment and time effects on MCW in frontal plane using Two-way ANOVA ...... 25

5. Analysis of the treatment and time effects on MCD in axial plane using Two-way ANOVA ...... 26

6. Analysis of the treatment and time effects on MCD in sagittal plane using Two-way ANOVA ...... 26

7. Analysis of the treatment and time effects on MCH in frontal plane using Two-way ANOVA ...... 27

8. Analysis of the treatment and time effects on MCH in sagittal plane using Two-way ANOVA ...... 27

9. Analysis of the treatment and time effects on Mandibular Length (mm) using Two-way ANOVA ...... 27

10. Analysis of the treatment and time effects on Mandibular Condylar Volume measured in surface area triangles using Two-way ANOVA ...... 28

viii FIGURES

Figures Page

1. MARA appliance illustration ...... 3

2. MARA appliance illustration ...... 3

3. Measurements on the lateral cephalogram...... 14

4. Detailed measurements of the TMJ complex...... 15

5. Condylar measurements in the axial, frontal and sagittal views...... 16

6. Mandibular Length measurement ...... 17

7. Mandibular Condyle Volume measurement ...... 18

ix ABBREVIATIONS

Ba Basion

CBCT Cone Beam Computerized Tomography

Cont Control Group

FH Frankfort horizontal

LCLM Lower Confidence Level Mean

MARA Mandibular Anterior Repositioning Appliance

MCD Mandibular Condyle Depth

MCH Mandibular Condyle Height

MCW Mandibular Condyle Width

MCV Mandibular Condyle Volume

MD Mandible

ML Mandibular Length

MRI Magnetic Resonance Imaging

MX Maxilla

N Number in Sample

Na Nasion

PtV Pterygoid Vertical

SAT Surface Area Triangles

SD Standard Deviation

UCLM Upper Confidence Level Mean

TMJ Temporomandibular Joint

T1 Pre-Orthodontic Treatment

T2 Post-Orthodontic Treatment

TX Treatment Group

3D Three Dimensional

xi ABSTRACT OF THE THESIS

CBCT and Cephalometric Analysis of the TMJ Complex after Treatment Using a MARA Appliance

Melissa Danette Shotell

Master of Science in Orthodontics and Dentofacial Orthopedics Loma Linda University, September 2014 Dr. Joseph Caruso, DDS, MS, MPH, Associate Dean, Strategic Initiatives and Faculty Practices, Professor and Chair Orthodontics and Dentofacial Orthopedics

Introduction: The mandibular anterior repositioning appliance (MARATM) is a fixed appliance intended for the correction of class II malocclusion. Many advocate the use of the MARA appliance to minimize patient non-compliance with treatment; however, little information is known as to the skeletal changes in the temporomandibular complex. The purpose of this study is to investigate the changes in the temporomandibular complex using both cephalometric and cone beam computerized tomography.

Materials and Methods: The initial and final treatment cone beam computerized tomography (CBCT) scans of 5 patients treated with the MARA appliance were collected from the Loma Linda University Orthodontics Clinic. Lateral cephalograms were constructed from the CBCT scans and a cephalometric tracing was created for each patient prior to treatment (T1) and after treatment (T2) with the MARA appliance. The

T2 cephalometric tracings were evaluated for linear changes in the temporomandibular complex when related to stable cephalometric structures. Cephalometric landmarks were quantified and variations were measured for the mean and standard deviation of each landmark. Three dimensional condylar changes in width, length, depth, height, and volume were evaluated using direct measurements from the initial and final CBCT scans.

xii The cone beam computerized tomography of the same 5 patients was superimposed and color mapped to show changes in the morphology of the temporomandibular joint (TMJ) complex. Measurements were compared using paired t-tests, repeated measures analysis of variation (ANOVA) and pairwise comparison of paired T-test, and a 2-way ANOVA with interaction comparison.

Results: The T2 lateral cephalograms showed changes in the TMJ complex with both the glenoid fossa and mandibular condyle moving posterior in relationship to pterygoid vertical. The center of the condyle had a more inferior position in relation to the

Frankfort horizontal in patients treated with the MARA appliance. Cephalometric study showed a pattern of changes that was consistent with normal growth and development of the TMJ complex. The CBCT images showed changes in the width and depth of the condyle that were not statistically significant for the changes seen in the age matched control. The CBCT evaluation of mandibular length showed an increase in mandibular length, but it was not different from the increase seen in the control. The volume of the mandibular condyle was statistically significantly larger than the volume of the controls both prior to and after treatment.

Conclusions: This study demonstrated that there are changes occurring in the TMJ complex during treatment with a MARA appliance. These changes were determined to be consistent to the changes expected in normal growth and development of the TMJ complex.

xiii

CHAPTER ONE

REVIEW OF THE LITERATURE

Skeletal Class II malocclusion is considered the most common skeletal problem encountered in clinical orthodontics.1-4 The Third National Health and Nutrition

Examination Survey (NHANES III) reports estimates of prevalence of class II skeletal malocclusion in the US population reach as high as 11% of the population.4 While traditionally classified according to Angles distoclusion class II molar relationship, these patients often exhibit 4mm or greater horizontal overjet at the incisors.1 Left untreated, skeletal class II patients may have a higher risk of obstructive sleep apnea and other airway problems, temporomandibular dysfunction, and psycho-social problems associated with severe retrognathia.5-8

During orthodontic correction of class II malocclusion, orthodontists have several treatment modalities available including: elastics, extraction therapy, headgear appliances and pendulum appliances for molar distalization, use of temporary anchorage devices, orthognathic surgery, and fixed or removable functional appliances. By definition, functional appliances are an appliance that “changes the posture of the mandible by holding it open or open and forward. Pressures created by the stretch of muscles and tissue are transmitted to the skeletal and dental structures, moving teeth and modifying growth”.1 Fixed and removable functional appliances are both designed to alter various muscle groups influencing the function and position of the mandible.9 These functional

and positional modifications will ultimately bring about a change in the sagittal and vertical position of the mandible through orthodontic and orthopedic alterations.9

Several different types of fixed appliances are available including: Herbst,

ForsusTM, Jasper JumperTM, and more recently, the Mandibular Anterior Repositioning

Appliance (MARATM). The MARA appliance was first introduced in 1998 by Eckhart and Toll.10 This fixed appliance uses stainless steel crowns or bands on the maxillary and mandibular first molars allowing for inserts to be placed to cause a desired corrective action.11 The maxillary molar band or crown portion of the appliance consists of removable heavy wire elbows (cams) attached at an angle of 90 degrees to the occlusal plane (Figures 1 and 2). The mandibular portion of the appliance consist of abutments extension arms that are fixed to the lower first molars on the buccal surface to engage the elbow extension of the maxillary crowns and cause the corrective action. The mandibular crowns or bands are connected via a lingual arch to minimize mesial lingual rotation of the molars, and maxillary molars are connected with a transpalatal bar to prevent distal lingual rotation. The lower first molar abutment arm extensions function to restrain posterior movement of the lower jaw, without permanent interdigitation of the teeth. The

MARA advances the lower jaw principally by muscular force and the interaction of the maxillary elbow with the mandibular arm extension, this new position readapts via neuromuscular reprogramming.11-13 The maxillary elbow can be activated by adding shims there by allowing for control of mandibular advancement. A principal benefit of the MARA appliance is that it is fixed without a continuous upper to lower connection; this is unique to the MARA when compared to the Forsus or Jasper Jumper.14 Most

importantly, due to being a fixed appliance, patient cooperation is taken out of the treatment equation leading to more predictable results.15

Figures 1 and 2. MARA appliance with stainless steel crowns, maxillary elbow attached to the maxillary crown on the buccal surface, and arm extension attached to the mandibular crown. Figure 1 adjustment shim in place, the shim represents the amount of corrected dental class II.

Several studies have investigated the clinical effectiveness of the MARA appliance pre and post treatment. Authors have found that Class II malocclusion can be successfully treated with MARA appliances via restriction of maxillary growth, slight maxillary molar distalization and mesial migration of the lower molar.14,16 In studies by

Pangrazion and Goner they determined there was not significant mandibular growth or vertical changes with MARA treatment, and class II correction was predominantly due to restriction of maxillary growth and dentoalveolar changes.11,16 Gonner described differences between adults and adolescence treated with the MARA appliance, concluding that the MARA appliance was effective in Class II correction in all age groups.11 Additionally the study showed that neuromuscular reprogramming via a biofeedback mechanism of the masticatory system was the underlying cause for class II

correction, unfortunately, the authors did not evaluate the changes specifically within the temporomandibular joint. In contrast, Guner used single photon emission computerized tomography (SPECT) to evaluate treatment results with the MARA appliance. The evaluation of the metabolic activity of the TMJ before and after treatment using SPECT images indicated increased bone formation of the TMJ complex.17 Siara-Olds also supported the findings that the mandible increased in length during MARA treatment, showing that a 1mm/year increase in the mandibular length occurred in patients treated with MARA when compared to controls, and a steeper occlusal plane resulted.18

Interestingly, this study also supported the findings that MARA can hold the maxilla against normal downward and forward growth. The study by Ghislanzoni supported both the dentoalveolar changes identified by Pangrazio, and the skeletal changes including increase in mandibular length of Siara-Olds study.14

Additional studies have evaluated TMJ and skeletal changes associated with functional appliances. Voudouris addressed the question of analyzing changes in the glenoid fossa during functional appliance therapy and the interaction of the masticatory muscles with non-human primates and the Herbst appliance.19,20 Subjects were evaluated with cephalometrics, EMG muscle evaluation, and histologic dissection of the TMJ complex. This study established the natural growth direction of the glenoid fossa in the downward and backward direction with opposite direction of growth downward and forward in subjects treated with the Herbst appliance. This study also found increased condylar growth in the treatment group and a marked decrease in the muscular function of the masticatory system. Arici study on Forsus appliances found no significant change in the volume of the condyle or glenoid fossa.21 It was suggested that remodeling of the

fossa accounted for this consistency in volume, as seen by the changes in the anterior and posterior joint spaces yet no overall increase or decrease in size of the fossa. In a study by

Rabie the remodeling of the glenoid fossa was investigated using mandibular advancing appliance on rats.22 Histologic dissection determined that the rats treated with the mandibular advancing appliance had more bone formation on the posterior and superior aspect of the glenoid fossa than the anterior portion.22 In all areas of the glenoid fossa there was significantly more bone formation in the treatment group than the controls.22

The study by Hagg investigated the remodeling in the mandibular condyle after use of functional appliances and headgear.23 This study determined that there was significant apposition of bone on the superior aspect of the mandibular condyle in treatment patients, the authors determined that this related to an increase in mandibular prognathism in the patients treated with both headgear and functional appliances.23

Significant controversy exists in the literature as to the actual method of class II correction with functional appliances. Many studies support the findings of growth and remodeling of the TMJ complex through functional appliances,17,18 while many studies refute this finding and support strictly a dentoalveolar change for class II correction.11,14,16

To date the majority of studies addressing the subject of functional appliances and possible changes in the TMJ complex have centered around the use of Herbst or Forsus appliances.19-21,24-26

Cone bean computerized tomography (CBCT) imaging has recently found a more wide spread use in dentistry due to the accuracy of 3D imaging.27 CBCT imaging has been found to accurately measure the volume of the mandibular condyle based on the

Cavalieri principle.28 In a study by Gribel and Lascala CBCT measurements were found

to be as accurate as direct craniometric measurements taken on dry skull specimens.29,30

CBCT constructed images have also been determined to be as accurate as conventional images for representations of the lateral cephalogram.31-35

While the scientific literature contains numerous studies evaluating skeletal changes associated with the use of Herbst, Forsus, and Jasper Jumper appliances, limited information is available evaluating similar changes with MARA appliances.18,25,26,36-39

Knowledge of skeletal changes associated with orthodontic intervention is an essential part of diagnosis and treatment planning for orthodontic therapy as it allows clinicians to reasonably predict treatment outcomes. The use of two-dimensional radiographs and cone-beam computerized tomography in investigating condylar and glenoid fossa remodeling after the use of the Mandibular Anterior Repositioning Appliance is warranted. The ability to measure the osseous changes in the mandibular condyle and the glenoid fossa will give clinicians a better understanding of how dental or orthopedic changes occur with class II correction treatment, and can help clinicians identify patients that can benefit from this functional appliance.

CHAPTER TWO

CBCT AND CEPHALOMETRIC ANALYSIS OF THE TMJ COMPLEX AFTER

TREATMENT USING A MARA APPLIANCE

Melissa Danette Shotell

Abstract

The cone beam computerized tomography of the same 5 patients was superimposed and color mapped to show changes in the morphology of the temporomandibular joint (TMJ) complex. Measurements were compared using paired t-tests, repeated measures analysis of variation (ANOVA) and pairwise comparison of paired T-test, and a 2-way ANOVA with interaction comparison.

Introduction

Skeletal Class II malocclusion is one of the most common conditions encountered in clinical orthodontic. While there are many treatment modalities available to the orthodontist for treatment of class II skeletal maloccusion, most rely on patient compliance. One of the more recent developments in orthodontic technology have been fixed functional appliances designed to correct the class II malocclusion and eliminate the need for patient compliance. Among these fixed appliances is the Mandibular Anterior

Repositioning Appliance (MARATM). The MARA appliance has the benefit of being a fixed appliance; however it lacks the intermaxillary connection of many fixed appliances.

Due to the lack of intermaxillary connection the mandible is allowed a larger range of motion and movement in comparison to other functional appliances for patient comfort.

Until recently there has been little research on the biological changes that result in the class II correction with the MARA appliance. Class II correction can be achieved through a skeletal component, dental-alveolar changes, or a combination of both dental and skeletal changes. The majority of literature that exists on the MARA appliance focuses on the overall skeletal and dental changes. The purpose of this study was to evaluate the potential skeletal changes and remodeling of the temporomandibular joint complex after treatment with the MARA appliance.

Hypothesis

The null hypothesis is that there is no difference in the size, shape, and growth direction of the glenoid fossa and mandibular condyle after the use of the mandibular anterior repositioning appliance. The working hypothesis is that remodeling occurs in the

glenoid fossa and mandibular condyle in size, shape, and growth direction after use of the mandibular anterior repositioning appliance.

Materials and Methods

This study is a retrospective, post-treatment review of the pre- and post-MARA treatment CBCT (NewTom 3G, NewTom 5G, QR, srl, Verona, Italy) images and constructed lateral cephalograms of orthodontic patients who have been treated at the

Loma Linda University, Graduate Orthodontic Clinic and who were treated for class II correction with a functional appliance. IRB approval was granted by Loma Linda

University. It is standard protocol of the Graduate Orthodontic Clinic that all full treatment patients receive: 1) A pre-treatment lateral cephalometric and CBCT image

(T1) at the time of patient records prior to treatment, 2) post-treatment lateral cephalometric and CBCT image (T2).

Data Collection

The charts of patients who were treated with the MARA appliance were reviewed and the following data was collected:

1. Chart Number

2. Gender (male or female)

3. Age at start of treatment (in year-month)

4. Duration of treatment

The information was anonymized by assigning each patient a random number starting with 101, and the corresponding control 101C.

Lateral Cephalometric Images

Lateral cephalometric radiographs were constructed in the orthogonal view using

Dolphin 3D imaging (Dolphin Imaging & Management Solutions), these lateral cephalograms were then imported into digital cephalometric analysis tracing software

(Quick Ceph, Quick Ceph Systems, San Diego, CA). Lateral cephalograms were constructed for the pre-treatment (T1) and post-treatment (T2) time points.

Linear measurements on the lateral cephalograms were modeled after Ricketts,

Ikeda’s, and Chang’s studies.40-42 The anterior cranial base is represented by sella-nasion and measurements were computed based upon the following lines projecting from pterygoid vertical (PtV) and Frankfort Horizontal (FH). Pterygoid vertical was defined as the line perpendicular to Frankfort horizontal through PT point (junction of the pterygo- palatine fossa and foramen rotundum). All measurements were made from the landmark along a line perpendicular to PtV or FH.

1. Maxillary base position (mm): PtV to A-point

2. Mandibular base position (mm): PtV to B-point

3. Porion location (mm): PtV to porion along FH

4. Mandibular condyle horizontal position (mm): PtV to hinge axis

5. Mandibular condyle vertical position (mm): Hinge axis to FH

6. Anterior glenoid fossa horizontal position (mm): PtV to the most

prominent/convex point on the anterior wall of the glenoid fossa

7. Anterior glenoid fossa vertical position (mm): The most prominent/convex

point on the anterior wall of the glenoid fossa to FH

8. Superior glenoid fossa horizontal position (mm): PtV to the most

prominent/concave point on the superior wall of the glenoid fossa

9. Superior glenoid fossa vertical position (mm): The most prominent/concave

point on the superior wall of the glenoid fossa to FH

10. Posterior glenoid fossa horizontal position (mm): PtV to the most

prominent/convex point on the posterior wall of the glenoid fossa

11. Posterior glenoid fossa vertical position (mm): The most prominent/convex

point on the posterior wall of the glenoid fossa to FH

12. Anterior condyle horizontal position (mm): PtV to the most prominent

anterior point on the condyle

13. Anterior condyle vertical position (mm): The most prominent anterior point

on the condyle to FH

14. Superior condyle horizontal position (mm): PtV to the most prominent

superior point on the condyle

15. Superior condyle vertical position (mm): The most prominent superior point

on the condyle to FH

16. Posterior condyle horizontal position (mm):PtV to the most prominent

posterior point on the condyle

17. Posterior condyle vertical position (mm):The most prominent posterior point

on the condyle to FH

Figure 3. Measurements on the lateral cephalogram. Anterior, superior, and posterior points on the glenoid fossa and measurements Anterior, superior, and posterior points on the mandibular condyle and measurements Hinge axis and associated measurements, Porion location, MX and MD Base position Na = Nasion, Ba = Basion, PtV = Pterygoid Vertical, FH = Frankfort Horizontal

Figure 4. Detailed measurements of the TMJ complex. Anterior, superior, and posterior points on the glenoid fossa and measurements Anterior, superior, and posterior points on the mandibular condyle and measurements Hinge axis and associated measurements, Porion location, MX and MD Base position Na = Nasion, Ba = Basion, PtV = Pterygoid Vertical, FH = Frankfort Horizontal

3D CBCT Images

CBCT images were reconstructed and converted to DICOM (Digital Imaging and

Communications in Medicine) images and imported into Mimics software (Mimics

Innovation Suite, Materialise, Leuven, Belgium). In the Mimics software a relative

Hounsfield unit threshold 400-800 HU was established for each scan then a smoothing algorithm was applied to the images to create more defined borders for segmentation.

The images were then segmented using Mimics and direct linear and volumetric measurements were made on the scans.

From the CBCT images, the following linear measurements were made and recorded:

Metric Analysis of Images

Analysis in axial, frontal, and sagittal planes, in each case, measurements were

taken from the slice exhibiting the largest condyle diameter (the central slice)

according to methods outlined by Kinzinger.13

a. Mandibular Condyle Width (MCW): Linear measurements were measured

in the axial and frontal planes at T1 and T2.

b. Mandibular Condyle Depth (MCD): Linear measurements were made in

the axial and sagittal planes at T1 and T2.

c. Mandibular Condyle Height (MCH): Linear measurements were taken in

the frontal and sagittal planes at T1 and T2. Condylar height was measured

with techniques outlined by Kinzinger and Hoppenreljs.13,43

Figure 5. Axial, frontal and sagittal condylar measurements as determined by selecting the largest slice of the condyle when moving through the CBCT volume, and measuring a distance corresponding to height, width, and depth.

Mandibular Length (ML)

Using the Mimics software, the center of the condyle was located in the axial view

by sectioning through the volume and locating the most superior central part of the

condyle (constructed condylion). A line representing ML was then measured from

constructed condylion to gnathion. Left and right sides were averaged together and

used to analyze the length of the mandible between T1 and T2. Measurements were

modified from the methods of Ludlow for accuracy of identification and reproducibility

of landmarks.33

Figure 6. Mandibular length was measured from the superior central point on the condylar head to the midline most inferior point of the mandibular symphysis.

Mandibular Condyle Volume (MCV)

Using the Mimics software, the mandible was isolated from the skull. The

mandibular condyles were sectioned from the body of the mandible following a line

tangent to the distal slope of the coronoid process.28 The change in the volume of the

mandibular condyle was measured in the surface area triangles (SAT) of the two

images. The change in the MCV was measured as the difference between pre-MARA

mandibular condyle volume (MCV 1) and post-MARA mandibular condyle volumes

(MCV 2). A positive ΔMCV indicated a decrease in the volume of the mandibular

condyle.

Fig 7. Mandibular condylar volume measurements made with slicing tool. Area in red indicates area for mandibular volume measurement determined by the line tangent to the posterior slope of the coronoid process.

All cephalometric measurements were performed by 1 examiner (MDS). The 3D

CBCT images were segmented, measured, and superimposed by examiner (CK) at IBUR

BioSystems. Linear measurements were made to the nearest 0.01 mm and volumetric recordings made to the nearest surface area triangle. Standard error for repeated measures was assessed by re-measuring 5 sets of patient images and assessing difference between measures.

Sample Size

A total of 5 T1 and T2 lateral cephalograms were measured and evaluated as well as 5 CBCT data sets were measured and evaluated. A total of 10 mandibular condyles were evaluated for both treatment and control in the CBCT evaluation.

Experimental Control

After the T1 CBCT constructed cephalogram was obtained, a composite tracing was generated and a growth projection of the treatment time was created and used as the control to measure against.40 Composite growth forecast as a control indicates the natural trend for each patient if they had remained untreated.42,44 The growth projections for the treatment controls were calculated to age fifteen for females and age eighteen years for males.

CBCT volumes were compared to CBCT volume controls matched for age and gender. Age of the control patient was matched as close to the patient in treatment with

MARA as possible. The matched controls were found to be within nine months of age of the patients evaluated. Treatment length of control patients were at least 20 months duration. Age-matched control patients for use in comparison had the following requirements: class I malocclusion treated with conventional orthodontics, less than 4 months of class II elastics utilized, and no functional appliances used during treatment.

Statistical Analysis

All statistical analysis was performed using SAS version 9.2 computer software

(SAS Institute Inc., Cary, North Carolina). Statistical analysis includes means and

standard deviations calculated for each variable.

The cephalometric study was statistically evaluated using repeated measures analysis of variation (ANOVA) and pairwise comparison of paired T-test. The lateral cephalograms were measured twice and the mean values for each measurement were compared between initial and final measurements to determine any significant changes between T1 and T2. The T2 measurements were compared against the growth projected controls to evaluate for changes that would be seen during treatment unrelated to normal growth and developments. An intraclass correlation coefficient for reliability was evaluated to assess similarity in the repeated measures. Statistical significance was determined when p < 0.05

Statistical analysis of the CBCT measurements consists of a 2-way ANOVA with interaction comparison. Right and left sides were averaged in the analysis. Interaction comparison was performed to determine interaction of the three subject groups T1, T2, and control; and to determine interaction of time for pre and post treatment. Statistical significance was determined when p < 0.05.

Results

Five patients (3 males, 2 females) with a mean age of 16.25 (range = 11.6-25.0) years were included in this study. Total treatment time for the patients ranged from 22 to

33 months in treatment, with an average treatment time of 27 months. The treatment time with the MARA appliance ranged from 9 to 14 months, with the average MARA treatment time of 11 months. The T1 average ANB angle was 5.8o, and the T2 average

ANB angle was 5.2o.

Lateral Cephalometric Images

The repeated measures ANOVA and pairwise comparison of paired T-test resulted in several measurements with statistically significant changes. A summary of lateral cephalometric data is given in Tables 1 and 2. All five of the lateral cephalometric cases were re-measured and an intraclass correlation coefficient of reliability was evaluated for each area of measurement. The Shrout-Fleiss reliability score for each of the seventeen measurements was 0.99 or greater, for an overall similarity of measurements if 96% or greater.

The Mandibular Base Horizontal position (PtV to B-point) at T2 was significantly greater than at T1 (p = 0.014; Table 2). When examining the directionality of the data B- point was moving in the anterior direction from PtV, but was not statistically significant when compared to the control.

The Mandibular Condyle Horizontal position (Hinge axis to PtV) at T2 was significantly greater than at T1 (p = 0.018; Table 2). The directionality of the changes seen between T2 and T1 shows an increase in distance, with the hinge axis moving posterior to PtV.

The Mandibular Condyle Vertical position (Hinge axis to FH) at T2 was significantly greater than at T1 (p = 0.06; Table 2). At T2 vs Control the T2 was significantly greater than control (p = 0.003; Table 2). This is the only measurement that demonstrated statistical significance (p < 0.05; Table 2) for the comparison of T2 vs. T1 and the comparison of T2 vs. Control. The directionality of the data indicated that the condyle is moving inferior in relationship to FH.

The Superior Glenoid Fossa Horizontal position (superior glenoid fossa to PtV) at

T2 was significantly greater that at T1 (p = 0.021; Table 2). The directionality of the data indicated the superior glenoid fossa was located more posterior in relation to PtV, but was not significantly different than the position of the control.

The Superior Condyle Horizontal position (superior point on mandibular condyle to PtV) at T2 was significantly greater that at T1 (p = 0.015; Table 2), and the data indicated the distance between the superior point on the condyle and PtV was increasing with the superior point on the condyle moving more posterior. See Tables 1 and 2 for statistical analysis.

Table 1. Summary of cephalometric measurements

Measurement Time LCLM Mean UCLM SD N (mm) (mm) (mm) (mm) Maxillary Base Position Control 5 47.1 52.8 58.4 4.6 T2 5 46.5 51.8 57.2 4.3 T1 5 46.4 51.8 57.2 4.4 Mandibular Base Position Control 5 36.6 43.6 50.6 5.6 T2 5 38.0 44.0 50.0 4.8 T1 5 35.4 42.6 49.8 5.8 Porion Location Control 5 34.6 41.1 47.7 5.3 T2 5 34.7 41.2 47.6 5.2 T1 5 33.8 40.7 47.5 5.5 Mandibular Condyle Horizontal Position Control 5 22.4 28.4 34.5 4.8 T2 5 22.7 29.1 35.5 5.2 T1 5 21.9 28.2 34.4 5.0 Mandibular Condyle Vertical Position Control 5 3.8 6.4 9.0 2.1 T2 5 4.6 7.1 9.7 2.0 T1 5 3.7 6.3 8.9 2.1 Anterior Glenoid Fossa Horizontal Position Control 5 15.6 21.9 28.2 5.1 T2 5 15.9 21.8 27.6 4.7 T1 5 15.3 21.7 28.1 5.1 Anterior Glenoid Fossa Vertical Position Control 5 1.7 4.2 6.7 2.0 T2 5 1.8 4.6 7.5 2.3 T1 5 1.7 4.2 6.6 2.0 Superior Glenoid Fossa Horizontal Position Control 5 24.1 29.9 35.8 4.7 T2 5 24.9 30.7 36.4 4.6 T1 5 23.6 29.6 35.6 4.8 Superior Glenoid Fossa Vertical Position Control 5 -2.6 0.1 2.9 2.2 T2 5 -3.5 0.1 3.8 2.9 T1 5 -2.6 0.1 2.8 2.2 Posterior Glenoid Fossa Horizontal Position Control 5 31.9 36.7 41.6 3.9 T2 5 31.6 37.2 42.8 4.5 T1 5 31.3 36.4 41.4 4.1 Posterior Glenoid Fossa Vertical Position Control 5 5.9 8.7 11.4 2.2 T2 5 4.9 8.7 12.6 3.1 T1 5 5.9 8.6 11.2 2.2 Anterior Condyle Horizontal Position Control 5 18.1 23.8 29.4 4.5 T2 5 17.9 23.6 29.2 4.5 T1 5 17.8 23.5 29.2 4.6 Anterior Condyle Vertical Position Control 5 2.7 4.7 6.7 1.6 T2 5 3.0 5.0 7.0 1.6 T1 5 2.7 4.7 6.6 1.6 Superior Condyle Horizontal Position Control 5 23.7 29.4 35.0 4.5 T2 5 23.8 30.0 36.1 5.0 T1 5 23.3 29.1 34.8 4.7 Superior Condyle Vertical Position Control 5 0.1 2.5 5.0 2.0 T2 5 -0.4 2.7 5.8 2.5 T1 5 0.1 2.5 4.9 1.9 Posterior Condyle Horizontal Position Control 5 27.3 33.5 39.8 5.0 T2 5 26.9 33.5 40.1 5.3 T1 5 26.7 33.2 39.7 5.2 Posterior Condyle Vertical Position Control 5 5.8 8.6 11.4 2.3 T2 5 4.8 8.2 11.7 2.8 T1 5 5.7 8.5 11.3 2.3

N = Number in Sample, LCLM = Lower Confidence Level Mean, UCLM = Upper Confidence Level Mean, SD = Standard Deviation

Table 2. Summary of cephalometric statistics.

Measurement Time Time P-value Maxillary Base Position Control T2 0.083 Maxillary Base Position T2 T1 0.967 Mandibular Base Position Control T2 0.447 Mandibular Base Position T2 T1 0.014* Porion Location Control T2 0.946 Porion Location T2 T1 0.132 Mandibular Condyle Horizontal Position Control T2 0.081 Mandibular Condyle Horizontal Position T2 T1 0.018* Mandibular Condyle Vertical Position Control T2 0.006* Mandibular Condyle Vertical Position T2 T1 0.003* Anterior Glenoid Fossa Horizontal Position Control T2 0.772 Anterior Glenoid Fossa Horizontal Position T2 T1 0.868 Anterior Glenoid Fossa Vertical Position Control T2 0.130 Anterior Glenoid Fossa Vertical Position T2 T1 0.095 Superior Glenoid Fossa Horizontal Position Control T2 0.084 Superior Glenoid Fossa Horizontal Position T2 T1 0.021* Superior Glenoid Fossa Vertical Position Control T2 0.958 Superior Glenoid Fossa Vertical Position T2 T1 0.958 Posterior Glenoid Fossa Horizontal Position Control T2 0.301 Posterior Glenoid Fossa Horizontal Position T2 T1 0.075 Posterior Glenoid Fossa Vertical Position Control T2 0.849 Posterior Glenoid Fossa Vertical Position T2 T1 0.645 Anterior Condyle Horizontal Position Control T2 0.559 Anterior Condyle Horizontal Position T2 T1 0.877 Anterior Condyle Vertical Position Control T2 0.159 Anterior Condyle Vertical Position T2 T1 0.118 Superior Condyle Horizontal Position Control T2 0.080 Superior Condyle Horizontal Position T2 T1 0.015* Superior Condyle Vertical Position Control T2 0.519 Superior Condyle Vertical Position T2 T1 0.446 Posterior Condyle Horizontal Position Control T2 0.902 Posterior Condyle Horizontal Position T2 T1 0.223 Posterior Condyle Vertical Position Control T2 0.140 Posterior Condyle Vertical Position T2 T1 0.297

3D CBCT Images

Metric Analysis of Images

The CBCT measurements were evaluated using a 2-way ANOVA with interaction comparison. The statistical analysis was designed to show interaction of both time (T1 and T2) and group (treatment and control). The results of multiple comparisons showed statistically significant changes in the shape of the mandibular condyle.

The Mandibular Condyle Width measured in both the axial and frontal planes demonstrated a statistical significant p-value in relation to time but not to group, and no interaction of time and group. Both the treatment and the control group demonstrated a statistically significant increase in the width of the condyle in both the frontal and axial planes from T1 to T2 (p < 0.05; Tables 3 and 4).

Table 3. Analysis of the treatment and time effects on MCW in axial plane using Two- way ANOVA at α = 0.05

Mean ± SD T1 T2 P-value Tx 16.71 ± 2.26 17.50 ± 2.27 0.0311a,* Control 17.66 ± 2.47 18.52 ±1.66 0.43b 0.93c a = Time effect, b = Tx effect, c = Interaction

Table 4. Analysis of the treatment and time effects on MCW in frontal plane using Two- way ANOVA at α = 0.05

Mean ± SD T1 T2 P-value Tx 14.42 ± 1.93 15.91 ± 3.38 0.040a,* Control 15.01 ± 1.01 115.80 ±1.82 0.84b 0.49c a = Time effect, b = Tx effect, c = Interaction

The Mandibular Condyle Depth measured in both the axial and sagittal planes demonstrated a statistically significant increase in condylar depth in relation to time but not to group, and there was no interaction of group and time. Both the treatment and control group showed a significant increase in the condylar depth from T1 to T2 (p <

0.05; Tables 5 and 6).

Table 5. Analysis of the treatment and time effects on MCD in axial plane using Two- way ANOVA at α = 0.05.

Mean ± SD T1 T2 P-value Tx 7.71 ± 0.96 8.04 ± 1.10 0.01a, * Control 7.93 ± 1.10 8.14 ± 0.98 0.79b 0.51c a = Time effect, b = Tx effect, c = Interaction

Table 6. Analysis of the treatment and time effects on MCD in sagittal plane using Two- way ANOVA at α = 0.05

Mean ± SD T1 T2 P-value Tx 9.77 ± 1.35 10.12 ± 1.68 0.002a, * Control 9.49 ± 1.02 9.97 ± 1.31 0.78b 0.52c a = Time effect, b = Tx effect, c = Interaction

Mandibular Condyle Height measured in both the frontal and sagittal planes did not show statistical significant change for either time or group (p > 0.05; Tables 7 and 8).

Table 7. Analysis of the treatment and time effects on MCH in frontal plane using Two- way ANOVA at α = 0.05

Mean ± SD T1 T2 P-value Tx 5.13 ± 1.43 5.06 ± 0.73 0.87a Control 4.95 ± 0.77 5.11 ± 0.51 0.80b 0.69c a= Time effect, b=Tx effect, c= Interaction

Table 8. Analysis of the treatment and time effects on MCH in sagittal plane using Two- way ANOVA at α = 0.05

Mean ± SD T1 T2 P-value Tx 4.03 ± 0.40 4.36 ± 0.36 0.45a Control 4.07 ± 1.40 3.99 ± 1.18 0.76b 0.21c a = Time effect, b =Tx effect, c = Interaction

Mandibular Length

The Mandibular Length showed a statistically significant increase in respect to time, but not group, and no interaction of time and group. The measurements of right and left side were averaged together for treatment and control prior to statistical analysis.

Both the treatment and control patients showed a statistically significant increase in the mandibular length over time (p = 0.004; Table 9).

Table 9. Analysis of the treatment and time effects on Mandibular Length (mm) using Two-way ANOVA at α = 0.05

Mean ± SD T1 T2 P-value Tx 119.44 ± 8.22 122.91 ± 6.50 0.004a, * Control 121.28 ± 5.10 123.74 ± 5.28 0.71b 0.53c a = Time effect, b = Tx effect, c = Interaction

Mandibular Condyle Volume

The MCV demonstrated a statistically significant difference between groups but not time (p = 0.0003; Table 10). This indicated the patients treated with the MARA appliance had a statistically larger condylar volume both at T1 and T2 when compared to controls.

Table 10. Analysis of the treatment and time effects on Mandibular Condylar Volume measured in surface area triangles using Two-way ANOVA at α = 0.05

Mean ± SD T1 T2 P-value Tx 55646.10 ± 29047.37 43526.20 ± 23197.84 0.48a Control 5466.90 ± 2062.62 7578.20 ± 1628.35 0.0003b, * 0.32c a = Time effect, b = Tx effect, c = Interaction

Discussion

The primary focus of previous studies on the MARA appliance addressed the difference between the skeletal and dental correction created by the appliance. The goal of this study was to address if there are changes occurring in the TMJ complex in relation to the use of the MARA appliance. While this study did not seek to evaluate the overall skeletal verses dental changes seen with the MARA appliance all patients included in this study were end-on or full step class II dentally and the patients had an average T1 ANB angle of 5.8o, and T2 ANB angle of 5.2o.

Lateral Cephalometric Images

Statistical significance of the p-values for the cephalometric measurements indicates that there are changes occurring in the TMJ complex during treatment. By looking at the directionality of all of the measurements that had significant p-values, the position of the changes that occurred and these changes are consistent with what would be expected for the age and growth of the patients or with the functional mechanics of the appliance. For example, the Mandibular Base Position measured from PtV to B-point increased with age from T1 to T2. In comparison with previous studies evaluating growth predictions and that B-point would typically project forward, the results of this study in agreement with these findings.18,40

The areas of change seen between T1 and T2 for the Mandibular Condyle

Horizontal position, Superior Glenoid Fossa Horizontal position, and Superior Condyle

Horizontal position were consistent with the pattern of normal growth and development.

All of these measurements followed the direction that would have been consistent with growth potential in the absence of treatment for the T1 to T2 time period. In this study all significant areas of change showed the glenoid fossa and condyle moving posterior in relation to fixed landmarks. The changes in the condylar position were consistent with the changes expected under normal growth as determined by previous studies that demonstrated under normal growth conditions the glenoid fossa will grow posterior and inferior, while the condyle grows posterior and superior.19,20,24

The observed changes in Mandibular Condylar Vertical position observed between T2 vs T1, and T2 vs Control demonstrated an increase in the position of the mandibular condyle inferior to the FH plane. This finding could be consistent with the

function of the appliance distracting the condyle from the glenoid fossa. While there was no observed change in the relationship of the superior point on the mandibular condyle to

FH it can be implied that if the Mandibular Condyle Vertical position increased then for the superior point on the mandibular condyle to remain consistent there must be apposition of bone on the superior surface of the condyle to maintain this positional relationship. Hägg’s research supports the apposition of bone on the superior surface of the mandibular condyle during functional appliance therapy.23 Multiple studies in the literature support bone apposition on the mandibular condyle contributing to the posterior superior direction of growth and remodeling of the mandibular condyle.17,19,20,24

Overall, for the cephalometric data the T2 vs T1 measurements demonstrated more areas of statistically significant changes than the T2 vs Controls. This indicates the functional appliance did not cause an interaction, alter, hinder, or increase growth. This is consistent with the findings of De Oliveria that with functional appliance treatment the overall craniofacial pattern of growth was similar to that of the controls.38 Only the change in the Mandibular Condyle Vertical position demonstrated a possible influence of the functional mechanical effect on the TMJ complex to alter the natural position of the condyle in the glenoid fossa.

3D CBCT Images

When evaluating the 3D images, some of the initial images were taken on the

NewTom 3G unit and final images taken on the NewTom 5G. NewTom 3G images were

12-bit signal grey scale, producing 4096 shades of grey. While the NewTom 5G images were 16-bit signal grey scale, producing 65,536 shades of grey.45-47 Scans were

segmented and enlarged using the Mimics software and smoothing algorithms were applied to produce a consistent area for segmentation rounding the edges of the scans to within 1 pixel for defined borders. Since the average human eye can only can only distinguish up to 64 shades of grey, it was concluded that differences between the

NewTom 3G and NewTom 5G would not have made an appreciable difference when evaluating patient scans.46

Statistical analysis of CBCT images also accommodated for the potential difference in NewTom 3G and 5G scans by utilizing the 2-Way ANOVA with interaction comparison. This analysis by looking at differences between group, time, and the group and time interaction would eliminate influence of the scan machine by addressing differences within the individual groups.

Metric Analysis of Images

The increase in the mandibular condylar width in both the frontal and axial planes occurred over time in both the treatment and control groups. This would appear to be consistent with normal growth since there was not group interaction in the statistical findings. In a previous study based on the Herbst appliance, it has been proposed that the condyle can increase in size due to activity of the lateral pterygoid muscles.19,20 The increase in condylar growth was similar to that of the age matched controls within this study.

The increase in mandibular condylar depth both in the axial and sagittal planes over time in both treatment and control group indicates the interaction of growth in the remodeling of the condyle. Previous studies on non-human primates with Herbst

appliance had demonstrated histologically that an increase of bone on the posterior aspect of the condyle is likely, believed to be a response to pressure from the retrodiscal tissue.19,20 While a previous study detected bone formation on the posterior border of the condyle,48 the results of this study indicated that there was increase in the depth of the condyle, but growth did not exceed that of age matched controls.

In a previous MRI study by Kinzinger it was observed that there were visual changes in the condyle with a similar functional appliance, but not statistically significant metric changes in the dimensions.12 Kinzinger’s study was able to demonstrate an increase in size of the condyle in both the frontal and sagittal planes, with a slight decrease in the axial plane.12 Unfortunately, a comparable MRI or CBCT study demonstrating non-treated patients as a comparison does not exist for comparison.

Due to the lack of statistical group interaction the current study appears to demonstrate growth and remodeling for the mandibular condyle that would appear to be consistent with normal growth and remodeling.

Mandibular Length

The increase in mandibular length seen in both the treatment and control group over time appears to be consistent with normal growth and development. Since there was no statistical group interaction, the MARA appliance did not show an increase growth beyond the normal growth potential; however the treatment patients did have the growth potential consistent with the age matched control. Previous studies have had varying results in regard to mandibular length after treatment with the MARA. In the study by

Pangrazio the results determined there was no overall increase in mandibular length.16

However, in several other studies with functional appliances mandibular growth has been demonstrated to increase during use.14,18,38 In this study the growth did not exceed that of controls. This study supported that the MARA appliance would allow normal growth and development of the mandible, and showed that the mandible did increase in length during treatment to that extent that would be expected for an age matched control.

Mandibular Condyle Volume

The Mandibular Condyle Volume was statistically significantly larger for the class

II treatment patients than the age matched controls, without interaction of time. With remodeling of the TMJ complex due to growth that has been see in other dimensions of the condyle, it would be assumed that the volumes would increase over time if the dimensions of the condyle increased. This study did not demonstrate the alteration in volume, beyond normal growth, than would be expected with remodeling of the TMJ complex for both treatment and control.

The findings of this study are in contrast to the study by Saccucci that determined class II patients have a smaller condylar volume than class I patients.49 In this study the control patients were class I and the treatment patients were class II, so we would not have expected to see that the treatment patients had larger condylar volume regardless of time.49 The control patients were selected as class II to compare treatment to the normal growth and development of the TMJ complex that is not under the influence of class II mechanics.

One of the difficulties in measuring condylar volume with CBCT is establishing the thresholding values (Hounsfield units) for the scans. In a recent study by Mah it was

determined that the relative grey scale values reported with CBCT can be calculated as relative Hounsfield units using a linear regression equation.50 Park’s study identified ranges of bone density in Hounsfield units for various locations within the mouth and associated them with bone quality, establishing a range of relative Hounsfield units for different bone densities.51 Herford’s study supported the use of relative Hounsfield units to describe bone density with microCT.52 For each patient the T1 and T2 scans were approximated as closely as possible for the relative Hounsfield units reported as densities between 400-800. Slight variation in the T1 and T2 scans may contribute to some variability in volume measurements.

Due to the differences between the NewTom 3G and 5G CBCT units there appears to be a scale difference in the measured volumes of the mandibular condyles.

This was statistically accounted for using the 2-way ANOVA with interaction comparison by comparing the ratio differences between the treatment and control groups from T1 to

T2.

Conclusion

The purpose of this study was to evaluate the condylar and glenoid fossa remodeling in size and shape, and alteration in growth direction in patients after using a

MARA appliance. The following are the major findings of the study:

1. Cephalometric analysis indicated that there were changes occurring in the TMJ

complex during the treatment time for both treatment and control patients.

2. Cephalometric analysis showed a pattern of changes consistent with growth and

development, with both the glenoid fossa and mandibular condyle moving

posterior.

3. On cephalometric evaluation the center of the mandibular condyle was located in

a more inferior position in relation to Frankfort horizontal after treatment with the

MARA appliance.

4. The metric analysis of CBCT images demonstrated increase in size of the condyle

in the width and depth. These changes appeared to be consistent with normal

growth and development when compared to age matched controls.

5. The increase in mandibular length was the same for both treatment and control

patients.

6. The treated class II patients had larger condylar volumes both before and after

treatment when compared to the age match control class I.

CHAPTER THREE

EXTENDED DISCUSSION

Study Improvements and Future Discussion

This study was limited by the small sample size of patients in the Loma Linda

University Orthodontics Clinic that have been treated with the MARA appliance. One of the directions for future study would be to increase the sample size and to include separate groups for male and female patients. A similar study could also be done for growing and non-growing patients, since use of the MARA appliance is advocated for all ages. Due to the differences between the NewTom 3G and 5G units, future studies could utilize only the NewTom 5G images.

The majority of research in functional appliances has centered around the use of the Herbst appliance, Twin-Block, Jasper Jumper, and Forsus. Since the MARA appliance is relatively new future study could evaluate the effects of the MARA appliance in relation to the other functional appliances.

With the advent of 3D printing a future topic of investigation could be to print the condyle and glenoid fossa from the CBCT and to make direct measurements on the printings to evaluate the potential change within the TMJ complex that we are seeing in digital form when viewing CBCT.

Utilizing superimposition of the CBCT scans on the cranial base could provide a representation of the final treatment outcome in comparison to the starting image.

Superimpositions of CBCT images with detailed heat mapping could provide a qualitative representation of the treatment effects.

As more patients are treated with this appliance a ten year follow-up CBCT study of the TMJ complex would give insight into the long-term possible post treatment effects on the TMJ complex.

REFERENCES

1. Proffit, William R., Henry w. Fields, and David M. Sarver. Contemporary Orthodontics Fifth Edition. St. Louis, Mo: Mosby Elsevier, 2013.

2. Moyers RE, Riolo ML, Guire KE, Wainright RL, Bookstein FL. Differential diagnosis of class II malocclusions. Part 1. Facial types associated with class II malocclusions. Am J Orthod 1980;78:477-94.

3. Baccetti T, Franchi L, McNamara JA Jr, Tollaro I. Early dentofacial features of Class II malocclusion: a longitudinal study from the deciduous through the mixed dentition. Am J Orthod Dentofacial Orthop. 1997;111:502-9.

4. Proffit WR, Fields HW Jr, Moray LJ. Prevalence of malocclusion and orthodontic treatment need in the United States: estimates from the NHANES III survey. Int J Adult OrthodonOrthognathSurg 1998;13:97-106.

5. Tangugsorn V, Krogstad O, Espeland L, Lyberg T. Obstructive sleep apnea (OSA): a cephalometric analysis of severe and non-severe OSA patients. Part I: Multiple comparison of cephalometric variables. Int J Adult Orthodon Orthognath Surg 2000;15:139-52.

6. Zhou D, Hu M, Liang D, Zhao G, Liu A. Relationship between fossa-condylar position, meniscus position, and morphologic change in patients with Class II and III malocclusion. Chin J Dent Res 1999;2:45-9.

7. Jolley CJ, Huang GJ, Greenlee GM, Spiekerman C, Kiyak HA, King GJ. Dental effects of interceptive orthodontic treatment in a Medicaid population: interim results from a randomized clinical trial. Am J Orthod Dentofacial Orthop 2010;137:324-33.

8. Taylor KR, Kiyak A, Huang GJ, Greenlee GM, Jolley CJ, King GJ. Effects of malocclusion and its treatment on the quality of life of adolescents. Am J Orthod Dentofacial Orthop 2009;136:382-92.

9. Bishara SE, Ziaja RR. Functional appliances: a review. Am J Orthod Dentofacial Orthop 1989;95:250-8.

10. Eckhart, James, and Toll, Douglas."Appliance and method for assisting a patient in maintaining a forward-moving force on the patient's mandibular jaw." US Patent 5,848,891. 15 Dec. 1998.

11. Gönner U, Ozkan V, Jahn E, Toll DE. Effect of the MARA appliance on the position of the lower anteriors in children, adolescents and adults with Class II malocclusion. J OrofacOrthop 2007;68:397-412.

12. Kinzinger G, Diedrich P. Skeletal effects in class II treatment with the Functional Mandibular Advancer(FMA)? J OrofacOrthop 2005;66:469-90

13. Kinzinger G, Kober C, Diedrich P. Topography and morphology of the mandibular condyle during fixed functional orthopedic treatment -- a magnetic resonance imaging study. J OrofacOrthop 2007;68:124-47.

14. Ghislanzoni LT, Toll DE, Defraia E, Baccetti T, Franchi L. Treatment and posttreatment outcomes induced by the Mandibular Advancement Repositioning Appliance; a controlled clinical study. Angle Orthod 2011;81:684-91.

15. McSherry PF, Bradley H. Class II correction-reducing patient compliance: a review of the available techniques. J Orthod 2000;27:219-25

16. Pangrazio MN, Pangrazio-Kulbersh V, Berger JL, Bayirli B, Movahhedian A. Treatment effects of the mandibular anterior repositioning appliance in patients with Class II skeletal malocclusions. Angle Orthod 2012;82:971-7.

17. Güner DD, Oztürk Y, Sayman HB. Evaluation of the effects of functional orthopaedic treatment on temporomandibular joints with single-photon emission computerized tomography. Eur J Orthod 2003;25:9-12.

18. Siara-Olds NJ, Pangrazio-Kulbersh V, Berger J, Bayirli B. Long-term dentoskeletal changes with the Bionator, Herbst, Twin Block, and MARA functional appliances . Angle Orthod 2010;80:18-29.

19. Voudouris JC, Woodside DG, Altuna G, Kuftinec MM, Angelopoulos G, Bourque PJ. Condyle-fossa modifications and muscle interactions during herbst treatment, part 1. New technological methods. Am J Orthod Dentofacial Orthop 2003;123:604-13.

20. Voudouris JC, Woodside DG, Altuna G, Angelopoulos G, Bourque PJ, Lacouture CY, Kuftinec MM. Condyle-fossa modifications and muscle interactions during Herbst treatment, Part 2. Results and conclusions. Am J Orthod Dentofacial Orthop 2003;124:13-29

21. Arici S, Akan H, Yakubov K, Arici N. Effects of fixed functional appliance treatment on the temporomandibular joint. Am J Orthod Dentofacial Orthop 2008;133:809-14.

22. Rabie B, Zhao Z, Shen G, Hägg U, Robinson W, Ed D. Osteogenesis in the glenoid fossa in response to mandibular advancement. Am J Orthod Dentofacial Orthop 2001;119:390-400

23. Hägg U, Rabie B, Bendeus M, Wong R, Wey M, Du X, Peng J. Condylar growth

and mandibular positioning with stepwise vs maximum advancement. Am J Orthod Dentofacial Orthop 2008;134:525-36

24. Pancherz H, Michailidou C. Temporomandibular joint growth changes in hyperdivergent and hypodivergent Herbst subjects. A long-term roentgenographic cephalometric study. Am J Orthod Dentofacial Orthop 2004;126:153-61

25. Ruf S, Pancherz H. Long-term TMJ effects of Herbst treatment: a clinical and MRI study.Am J Orthod Dentofacial Orthop 1998;114:475-83.

26. Ruf S, Pancherz H. Temporomandibular joint remodeling in adolescents and young adults during Herbst treatment: A prospective longitudinal magnetic resonance imaging and cephalometric radiographic investigation. Am J Orthod Dentofacial Orthop 1999;115:607-18.

27. Berco M, Rigali PH Jr, Miner RM, DeLuca S, Anderson NK, Will LA. Accuracy and reliability of linear cephalometric measurements from cone-beam computed tomography scans of a dry human skull. Am J Orthod Dentofacial Orthop 2009;136:17.e1-9.

28. Bayram M, Kayipmaz S, Sezgin OS, Küçük M. Volumetric analysis of the mandibular condyle using cone beam computed tomography. Eur J Radiol 2012;81:1812-6.

29. Gribel B F, Gribel M N, Frazao D C, McNamara J A, Manzi F R. Accuracy and reliability of craniometric measurements on lateral cephalometry and 3D measurements on CBCT scans. Angle Orthod. 2011;81:26–35

30. Lascala C, Panella J, Marques M. Analysis of the accuracy of linear measurements obtained by cone beam computerized tomography (CBCT-NewTom). Dentomaxillofacial Radiology 2004;33:291-294

31. Kumar V, Ludlow J, Soares L H, Mol A. Invivo comparison of conventional and cone beam synthesized CT cephalograms. Angle Orthod 2008;78(5):873-879

32. Oz U, Orhan K, Abe N. Comparison of linear and angular measurements using two- dimensional conventional methods and three-dimensional cone beam CT images reconstructed from a volumetric rendering program in vivo. Dentomaxillofacial Radiology (2011) 40, 492–500

33. Ludlow JB, Laster WS, See M, Bailey LJ, Hershey HG. Accuracy of measurements of mandibular anatomy in cone beam computed tomography images. Oral Surg Oral Med Oral Pathol Oral Radio Endod 2007;103(4):534-42

34. Grauer D, Cevidanes L, Proffitt W. Working with DICOM craniofacial images. AM J Orthod. 2009;136:460-470

35. Cattaneo P, Borgkvist Bloch C, Calmar D, Hjortshøj M, Melsen B. Comparison between conventional and cone-beam computed tomography–generated cephalograms. Am J Orthod. 2008;34:798-802

36. Karacay S, Akin E, Olmez H, Gurton AU, Sagdic D. Forsus Nitinol Flat Spring and Jasper Jumper corrections of Class II division 1 malocclusions. Angle Orthod 2006;76:666-72.

37. Küçükkeleş N, Ilhan I, Orgun IA. Treatment efficiency in skeletal Class II patients treated with the jasper jumper. Angle Orthod 2007;77:449-56.

38. de Oliveira JN Jr, Rodrigues de Almeida R, Rodrigues de Almeida M, de Oliveira JN. Dentoskeletal changes induced by the Jasper jumper and cervical headgear appliances followed by fixed orthodontic treatment. Am J Orthod Dentofacial Orthop 2007;132:54-62.

39. Jones G, Buschang PH, Kim KB, Oliver DR. Class II non-extraction patients treated with the Forsus Fatigue Resistant Device versus intermaxillary elastics. Angle Orthod 2008;78:332-8.

40. Ricketts RM, Bench RW, Gugino CF, Hilgers JJ, Schulhof RJ: Bioprogressive therapy, Book I, Denver, 1979, Rocky Mountain Orthodontics.

41. Ikeda K, Kawamura A. Assessment of optimal condylar position with limited cone- beam computed tomography. Am J Orthod Dentofacial Orthop2009;135:495-501.

42. Chang, BC. Treatment effects of the edgewise bioprogressive herbst appliance. Loma Linda (CA): Loma Linda University; 1996

43. Hoppenreijs TJ, Freihofer HP, Stoelinga PJ, Tuinzing DB, van't Hof MA. Condylar remodelling and resorption after Le Fort I and bimaxillary osteotomies in patients with anterior open bite. A clinical and radiological study. Int J Oral Maxillofac Surg. 1998;27:81-91.

44. Emmerson W. Activator growth augmentation-A long-term perspective. Loma Linda (CA): Loma Linda University 1982

45. NEWTOM, www. Newtom.it

46. Langlais R. Exercises in Oral Radiology and Interpretation, 4th Edition. W.B. Saunders Company, 2009

47. Jacobson A, Jacobson R. Radiographic Cephalometry From Basics to 3-D Imaging, 2nd Edition. Quintessence Publishing, 2006

48. Paulsen HU, Karle A, Bakkle M, Herskind A. CT-scanning and radiographic analysis of temporomandibular joints and cephalometric analysis in a case of Herbst treatment in late puberty. Eur J Orthod 1995;17:165-7

49. Saccucci M, D’Attilio M, Rodolfino D, Festa F, Polimeni A, Tecco S. Condylar volume and condylar area in class I, class II and class III young adult subjects. Head & Face Medicine 2012 8:34

50. Mah P, Reeves TE, McDavid WD. Deriving Hounsfield units using grey levels in cone beam computed tomography. Dentomaxillofac Radiol. 2010;39:323-35

51. Park HS, Lee YJ, Jeong SH, Kwon TG. Density of the alveolar bones of the maxilla and the mandible. Am J Orthod Dentofacial Orthop 2008;133:30-37

52. Herford A, Mei L, Buxton A, Kim J, Henkin J. Recombinant Human Bone Morphogenetic Protein 2 Combined With an Osteoconductive Bulking Agent for Mandibular Continuity Defects in Nonhuman Primates. J Oral Maxillofac Surg 2012;70:703-716