Variables Affecting Orthodontic Tooth Movement

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Title:
Variables Affecting Orthodontic Tooth Movement
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english
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Chisari, Justin
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University of Florida
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Thesis/Dissertation Information

Degree:
Master's ( M.S.)
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University of Florida
Degree Disciplines:
Dental Sciences, Dentistry
Committee Chair:
Wheeler, Timothy T
Committee Members:
Mcgorray, Susan P
Nair, Madhu
Dopazo, Leandra

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Subjects / Keywords:
age -- bone -- fractal -- movement -- orthodontic -- sex -- teeth -- tooth -- variables
Dentistry -- Dissertations, Academic -- UF
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Dental Sciences thesis, M.S.
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Abstract:
There are many variables that can affect the rate of orthodontic tooth movement. Both extrinsic and systemic factors, such as medication history, age, and metabolic bone diseases can alter key molecules that regulate bone remodeling. The purpose of this study is to gather data on the affect of age, sex, root length, bone levels and bone quality on the rate of orthodontic tooth movement. This is a prospective single center clinical trial comparing a group of 15 patients between the ages of 18-35 with a group of 15 patients 50 and older with an Invisalign tooth movement model of a single central incisor programmed to move 1mm facially over a course of 8 weeks. Cone Beam Computed Tomography (CBCT) was done to assess root length, bone levels and bone quality. Data from this study was combined with data from two other similar studies led by the same principal investigator, increasing the sample size to 82.20,21 The mean and median percentage of tooth movement achieved was 61.6 % (.62 mm) and 68% (.68mm) respectively. In males, there was a negative correlation with tooth movement and age while just the opposite trend was seen in females. The results suggest a quadratic relationship between tooth movement in females and a more linear relationship in males. Notably, a quadratic trend was found in tooth movement among females as age increased. Significant positive correlations (p<.05) between CT measurements and digital model analysis were noted for the following variables: ?U1 (x), ?U1(s), and Rotation angle. A significant negative correlation was found with tooth movement and the measurement apex to the center of rotation. When all three data sets were combined, the mean and median percentage of tooth movement achieved compared with the tooth movement goal was 56.9% and 61.8% respectively. Significant positive correlations between measurement methods were found for the variables ?U1 (x), ?U1(s), and Rotation angle, while a significant negative correlation was seen between tooth movement and the apex to center of rotation.
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by Justin Chisari.
Thesis:
Thesis (M.S.)--University of Florida, 2012.
Local:
Adviser: Wheeler, Timothy T.
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RESTRICTED TO UF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE UNTIL 2014-05-31

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1 VARIABLES AFFECTING ORTHODONTIC TOOTH MOVEMENT By JUSTIN R. CHISARI A THESIS PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE U NIVERSITY OF FLORIDA 2012

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2 2012 Justin R. Chisari

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3 To my wife and children, for your unwavering supp ort through this entire process

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4 ACKNOWLEDGMENTS First and foremost, I would like to thank my wife, Sherri, for being patient with me as I c omplete my education, for helping to support me during this time, for helping provide me with a beautiful family, and most importantly being there when I need her most. I would like to thank all of my family, especially my parents, for nurturing and suppo rting me in my endeavors over the years. I thank my research mentor, Dr. Wheeler, for providing me with the necessary instruments, guidance, and experience to conduct this project, as well as for giving me a chance to prove myself. I would like to thank my research committee, specifically Dr. Nair and Dr. McGorray, for their expert knowledge and contributions to this study, as well as Marie Taylor, Dr. Ju Han (Donna) Chang, Dr. Patrick Holmes, and Melissa Alfonso. I also would like to acknowledge financi al and/or logistical support from the University o f Florida, Department of Orthodontics, the University of Florida Graduate Student Council, the American Association of Orthodontists, the Southern Association of Orthodontists, the Florida Association of Or thodontists, and Align Technology. Above all, I thank God for all that he has given me, especially the strength to overcome challenges and persevere.

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5 TABLE OF CONTENTS page ACKNOWLEDGMENTS ................................ ................................ ................................ .. 4 LIST OF TABLES ................................ ................................ ................................ ............ 6 LIST OF FIGURES ................................ ................................ ................................ .......... 7 LIST OF ABBREVIATIONS ................................ ................................ ............................. 8 ABSTRACT ................................ ................................ ................................ ..................... 9 CHAPTER 1 INTRODUCTION ................................ ................................ ................................ .... 11 2 METHODS ................................ ................................ ................................ .............. 16 Study Design ................................ ................................ ................................ .......... 16 Enrollment ................................ ................................ ................................ ............... 18 Preliminary visit 1: Eligibility Visit ................................ ................................ ...... 18 Preliminary visit 2: Screening Visit ................................ ................................ ... 1 8 Study Visits ................................ ................................ ................................ ............. 19 Week 0 ................................ ................................ ................................ ............. 19 Weeks 1, 3, 5, and 7 ................................ ................................ ........................ 19 Weeks 2, 4, and 6 ................................ ................................ ............................ 19 Week 8 (Study Termination) ................................ ................................ ............. 19 Collection of Data ................................ ................................ ................................ ... 20 Statistical Analysis ................................ ................................ ................................ .. 20 3 RESULTS ................................ ................................ ................................ ............... 22 4 DISCUSSION ................................ ................................ ................................ ......... 30 5 CONCLUSION ................................ ................................ ................................ ........ 33 LIST OF REFERENCES ................................ ................................ ............................... 34 BIOGRAPHICAL SKETCH ................................ ................................ ............................ 36

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6 LIST OF TABLES Table page 3 1 Demographic characteristics and descriptive statistics ................................ ....... 27 3 2 Correlation of % of tooth movement achieved and age ................................ ...... 27 3 3 Tooth Movement and Age Relationship ................................ .............................. 28

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7 LIS T OF FIGURES Figure page 2 1 Superimposed CBCT measurements. ................................ ................................ 21 3 1 Mean % of Tooth Movement achieved compared with % of Tooth Movement Goal ................................ ................................ ................................ .................... 24 3 2 Correlation between tooth movement and apex to the center of rotation measurement ................................ ................................ ................................ ...... 25 3 3 Cubic age model representing age vs. the amount of tooth movement for the JC, CD and BAS data sets ................................ ................................ ................. 26

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8 LIST OF ABBREVIATION S AP Anterior Posterior BAS Previous study by same principal investigator, McGorray et al, AJDO 2012 CBCT Cone Beam Computed Tomography CD Previous study by same principal investigator, Thesis of Dr. Carl Drake IRB Institutional Review Board JC Present Study NSAID Non Steroidal Anti Inflammatory Drug OTM Orthodontic Tooth Movement PDL Periodon tal Ligament PVS Poly Vinyl Siloxane RANK L R eceptor A ctivator of N uclear F actor K appa B L igand

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9 Abstract of Thesis Presented to the Graduate School of the University of Florida in Partial Fulfillment of the Requirements for the Degr ee of Master of Science VARIABLES AFFECTING ORTHODONTIC TOOTH MOVEMENT By Justin R. Chisari May 201 2 Chair: Timothy Wheeler Major: Dental Sciences Orthodontics There are many variables that can affect the rate of orthodontic tooth movement. Both extr insic and systemic factors, such as medication history, age, and metabolic bone diseases can alter key molecules that regulate bone remodeling. The purpose of this study is t o gather data on the affect of age, sex, root length, bone levels and bone qualit y on the rate of orthodontic tooth movement. This is a prospective single center clinical trial comparing a group of 15 patients between the ages of 18 35 with a group of 15 patients 50 and older with an Invisalign tooth movement model of a single central incisor programmed to move 1mm facially over a course of 8 weeks Cone Beam C omputed T omography (CBCT) was done to assess root length, bone levels and bone quality. Data from this study was combined with data from two other similar studies led by the sam e principal investigator, increasing the sample size to 82. 20,21 The mean and median percentage of tooth movement achieved was 61.6 % (.62 mm) and 68% (.68mm) respectively. In males, there was a negative correlation with tooth movement and age while just the opposite trend was seen in females. The results suggest a quadratic relationship between tooth movement in females and a more linear relationship in males. Notably, a quadratic trend was found in tooth movement among

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10 females as age increased. Signif icant positive correlations (p<.05) between CT measurements and digital model analysis were noted for the following variables: and Rotation angle A significant negative correlation was found with tooth movement and the measurement a pex to the center of rotation. When all three data sets were combined, the mean and median percentage of tooth movement achieved compared with the tooth movement goal was 56.9% and 61.8% respectively. Significant positive correlations between measurement met hods were found for the variables while a significant negative correlation was seen between tooth movement and the apex to center of rotation.

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11 CHAPTER 1 INTRODUCTION It is clear that the broad principles of orthodontic tooth movement (OTM) are based largely on bone and tissue remodeling, specifically the resorption and deposition of alveolar bone as force is applied The biology of OTM has proven to be an extremely complex process involving an array o f coordinated biochemical reactions including cr itical cell signaling pathways and a wide range of cellular differentiation leading to bone remodeling. 1 As the science of bone biology continues to evolve, several theories of OTM have surfaced. The pressure tension theory has emerged as the most popul ar concept behind the movement of teeth. Simply stated, b one remodeling involves an intricate arrangement of coordinated cellular activity leading to bone resorption performed by osteoclasts, followed by bone formation carried out by osteoblasts 2 Speci fically, the process of osteoclastogenesis begins with the osteoblasts expressing receptor activator of nuclear factor kappa B ligand (RANK L) on their surface. Premature osteoclasts then bind to RANK L through expression of RANK on their surface. As a r esult of this interaction, a multitude of biochemical signaling cascades are initiated, and the osteoclast undergoes maturation and begins the resorptive process. 3 RANK L is a critical factor for the maturation of osteoclasts and bone turnover Dolce and Holliday 4 have reported that while the precise biological response to orthodontic force has not been identified, several hypotheses regarding the mechanisms by which osteoblasts and osteocytes sense this initial mechanical stimulus have been proposed. Som e of these hypotheses include strain sensitive ion channels, shear stress receptors, integrin activation, and cytoskeleton reorganization. 4

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12 Three phases of tooth movement have been described in the literature: 1) initial phase, 2) lag phase, and 3) seconda ry phase. 5,6 Briefly, t he initial phase of tooth movement begins as light force is applied to a tooth and gradual compression and tension of the periodontal ligament ( PDL ) occurs In the second phase, a significant decrease in the rate of tooth movement is seen as hyalinization of the PDL and the surrounding tissues occurs The secondary phase is the last stage of tooth movement in which the period of hyalinization has been reduced or eliminated and there is direct bone resorption. This stage accounts fo r most of the tooth movement and teeth during this period move at a faster, more continuous pace. 7 The magnitude and direction of force placed on teeth during OTM, in addition to the length of time these forces are placed, also plays a critical role in h ow teeth move. Forces applied to teeth cause various types of tooth movement depending on the location of the center of resistance of that tooth and the direction in which the force is applied. It is understood that the center of resistance for a given t ooth changes based on the tooth size, number of roots, and the amount of tooth root that is submerged in bone. Depending on the magnitude and direction that a force is applied in combination with the factors just listed above various moments and/or coup les can be cr eated resulting in OTM. In 2001, Konoo et al. 8 demonstrated in rats that one hour of force activation stimulates osteoclast activity but does not stimulate tooth movement. Clinical experience has suggested that tooth movement can be enhanced when forces are applied for a longer duration. Accordingly, the most efficient tooth movement is achieved from app lication of a continuous force.

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13 Variability among patients can affect OTM. Factors including age, gender, root length, bone levels, bone de nsity, medications and certain systemic conditions can have inhibitory, synergistic, or additive effects on OTM. 9 The majority of literature on the affects of age on OTM has been completed using animal models. Bridges 10 et al reported that a significant ly greater amount and rate of tooth movement occurred in younger rats compared with their older counterparts in all three phases of tooth movement described earlier. Similar findings of the effects of increasing age on the rate and amount of tooth movemen t has been reported by Misawa Kageyama et al 11 and Harris 12 There has also been some indication that, while there is a delay in the onset of tooth movement in adult rats, once the secondary phase of tooth movement is reached, the movement becomes equally efficient among the two age groups. 13 The effect of age on OTM clearly exists and is likely due in part to a decreased biological response. While individual variability exists from patient to patient, a direct difference in OTM between males and females has not been shown in the literature. Furthermore, w hile patients of any age may be taking medications, particularly older patients are more likely to be taking medications with pharmacologic effects that can impact the cells targeted in OTM. Some of the se medication classes include bisphosphonates, estrogens, NSAIDS and other analgesics, corticosteroids, calcium regulators and supplements. 9,14,15 A considerable portion of the literature has not demonstrated experimental data on the effects of medication on OTM and many are limited to animal models. However, knowing the biochemical action of these medications has led to some concern regarding how they may affect orthodontic

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14 treatment. 15 It can be reasoned that any medication that interferes with or alte rs bone biology may impact the rate of tooth movement. Additionally, c ertain systemic factors or nutritional deficiencies affecting bone metabolism have also been found to alter OTM. Specifically, d iseases of bone can have a significant impact in the ra te of tooth movement as well Reduced or complete lack of osteoclast function can lead to a condition known as osteopetrosis, characterized by sclerosis of the skeleton and inhibited tooth movement and eruption. ntrollable bone turnover occurs due to the over activity of osteoclasts. 16 Since OTM stimulates an inflammatory process in the PDL and surrounding tissues, it is thought that any chronic inflammatory disease such as thyroiditis, asthma, and even allergies may affect the movement of teeth. 17 Other variables among patients that can be of great significance in OTM are root length, bone levels and the density or quality of bone. A ge related decreases in bone turnover as well as a relatively higher level of bo ne density have been documented. 10,15 Alveolar bone levels, on average, decrease over time impacting OTM by changing the center of resistance. The center o f resistance of a tooth is largely influenced by its surroundings particularly in regard s to root morphology, bone levels, and bone quality. 18 One can reason from this data that patients with alveolar bone loss or abnormally long roots will have centers of resistance further from the point of force application (more apically). On the other hand, the more the root tapers, the more the center of resistance moves coronally. 19 The effect of bone quality/density and of root volume on the location of centers of resistance is unknown. The purpose of this study is t o gather

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15 data on the affect of age, sex, r oot length, bone levels and bone quality on the rate of orthodontic tooth movement.

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16 CHAPTER 2 METHODS Study Design The design for this study is patterned off of a previous study (Drake, et al.) designed by the same principal investigator (Wheeler TT) 2 0 Approval for this study was obtained by the University of Florida IRB. This project consists of a prospective single center clinical trial involving subjects of two different age groups with minor incisor malalignment, who are otherwise healthy, and wh o will be undergoing orthodontic procedures. The first group consisted of 7 males and 8 females between the ages of 18 35 years old inclusive. The second group consisted of 5 males and 10 females 50 years old and older. Fifteen subjects were enrolled in e ach of the two age groups for a total of 30 subjects. For statistical purposes, data from this study was combined with that from two similar previous studies by the same principal investigator. Throughout this paper, the present study will be denoted as JC, and the two additional studies will be denoted as CD 2 0 and BAS 21 Combined, the total number of subjects was 82. All subjects were in good health and have acceptable malocclusions as defined in the inclusion criteria, which has been thoroughly descri bed in a previous study. 20 Once a subject was accepted into the trial the right or left maxillary central incisor was selected as the target tooth. The selection was based on the target tooth not being blocked out by the adjacent teeth to allow a total AP movement of 1 mm. Tooth movement was accomplished using a series of 4 maxillary aligners each programmed in increments of 0.25 mm of anterior movement of the central incisor being studied as described above. Aligners were collected every 2 weeks from each subject and new aligners were dispensed. The study termination visit and final time point for data

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17 collection was at week 8. Poly vinyl siloxane (PVS) impressions were taken weekly and submitted to Align Technology (San Jose, CA) for scanning to create 3D models. Tooth movement measurements from baseline through week 8 were made from each scanned model using ToothMeasure software (proprietary software Align Technology). CT measurements and fractal analysis was completed using a combination of software including Anatomage InVivo(San Francisco, CA), Image J (NIH, Bethesda, MD), and Tact Workbench (Wake Forest University, Winston Salem, NC). The following are definitions of the measurements used in the CT superimposition the incisal edges of the superimposed target tooth perpendicular to the A P axis (the U1 (s) is the length of the line connecting the length of a line connecting the change in apex of the superimposed target tooth. Rotation angle is the angle created by the intersection of lines dr awn from the midpoint of the incisal edge to the apex of the target tooth. The apex of this angle is considered the center of rotation. Tooth length refers to the distance from the midpoint of the incisal edge to the apex of the target tooth from the ini tial CT image. Crown length is the portion of the tooth length that is coronal to the bone. Bone to C rot. is the section of tooth length between the center of rotation and a line connecting the most coronal aspect of the faciolingual crestal bone. From these measurements, additional ratios and measurements were calculated. These variables are depicted in Figure 2 1. All study subjects were instructed to wear the aligner appliance full time. They were allowed to remove the appliance when eating, drink ing, or brushing their teeth.

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18 Compliance with use of the aligners, in addition to medication use, was monitored using a daily diary. A medication and medical history were taken initially. Medication use was monitored throughout the study. At the conclu sion of the study, patients were routinely treated orthodontically using the Invisalign appliance. Enrollment To determine subject eligibility, two preliminary visits were required Preliminary visit 1: Eligibility Visit The first visit was designed to identify potential subjects with malocclusions needing minor incisor alignment of at least the upper incisors and to eliminate those with medical conditions or intraoral problems that are exclusionary. Subjects who were determined eligible based on the re sults of these procedures proceed ed with the Screening Visit. Preliminary visit 2: Screening Visit initial records. The following procedures were performed at this visit: i mpressions were taken using PVS for preparat ion of Invisalign appliances, im pressions were sent to ALIGN Technology, Inc. follow ing confirmation of eligibility, i ntra oral and extraoral photographs, and c one beam imaging was performed For women, a nega tive urine pregnancy test immediately prior to this procedure was required. After the investigator reviewed all subject information to confirm eligibility, subjects were enrolled into the study and assigned a unique study number.

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19 Study Visits Week 0 At the first study visit (Week 0) the first aligner was delivered to each subject. The acceptable visit window for Weeks 0 8 was one day, and all 30 treatment subjects successfully satisfied this requirement. A diary was provided to all subjects to rec ord the amount of time they do not wear their appliance each day and of any medications taken. Weeks 1, 3, 5, and 7 During the study visit of Weeks 1, 3, 5, and 7, the follo wing procedures were performed: intraoral clinical examination, maxillary occlusal and frontal photograph, medications taken from the previous week and dispensed the diary for the next week. Weeks 2, 4, and 6 During the study visit of Weeks 2, 4, and 6, t he following procedures were performed: intraoral clinical examination, maxillary occlusal and frontal photograph, PVS medications taken from the previous week and dispensed the diary for the next week. The aligner (used during the previous 2 weeks was collected and the next aligner was dispensed. Week 8 (Study Termination) At the study termination visit, week 8, the following procedures were performed: intraoral clinical examina tion, PVS impression, intraoral photographs, cone beam use and medications taken from the previous week.

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20 Collection of Data Weekly anterior posterior movement of t he target tooth was recorded with PVS impressions. These impressions were sent to Align Technology and digital models software. The digitized model fabricated each week was supe rimposed on the baseline digital model, taken at week 0, according to the best fit of unmoved teeth, particularly the posterior dentition. The most central portion on the facial surface of the clinical crown of the target tooth, referred to as the centroi d, was determined and subsequent tooth movement in all dimensions was measured from this point for each study visit. The same investigator measured the digital models for all 30 subjects. Cone beam CT scans of each subject was performed at the screenin g visit and were superimposed on each other and registered at the curvature of the palate in addition to other stable maxillary structures. A series of measurements were recorded from these superimpositions and can be found in Table 1. These measurements, in addition to fractal analysis, were modeled from and described thoroughly in a previous study. 20 Statistical Analysis Orthodontic tooth movement was quantified using d escriptive statistics for the digital model analysis. Demographic characteristics were evaluated for differences between the three studies using Chi square tests. Linear r egression m odeling was used to examine the relationship between percent of tooth mo vement achieved and covariates. Statistical analysis was completed and the best one two and three variable models were determined. Interaction was also assessed in the two and three

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21 variable models. Pearson and Spearman correlation coefficients we re calculated to determine if correlations existed between tooth movement and CT measurements. Both parametric and nonparametric approaches were used to aid in identification of non normality or outliers. Figure 2 1. Superimposed CBCT measurements. B lue is initial and red is final. Figure taken from M.S. Thesis of Dr. Carl Drake, 2010

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22 CHAPTER 3 RESULTS The demographic characteristics of study subjects can be found in Table 3 1. No significant differences were found among sex, race and percentage of tooth movement goal achieved. Again, the current study is denoted as JC in the tables and the other two studies will be denoted as CD and BAS. For the present study, the mean age of the study subjects in both age groups was 40.3 years. By design, thi s was higher than the previous two studies. The mean and median percentage of tooth movement achieved compared with the goal of 1mm was 61.6 % (.62 mm) and 68% (.68mm) respectively. Comparatively, when all three data sets (JC, CD, BAS) were combined, the mean and median percentage of tooth movement achieved compared with the tooth movement goal was 56.9% and 61.8% respectively (Figure 3 1). Most tooth movement occurred in the first week of the two week wear cycle. As shown in Table 3 2, there was a stat istically significant negative correlation between tooth movement and age in males. I n females, no significant correlation was found. Table 3 3 shows a summary of the correlations for CT superimposition measurements and the tooth movement measurements obtain from the PVS impression analysis using ToothMeasure software. Significant positive correlations (p<.05) were and CD data sets were combined, a significant negativ e correlation was found for the variable Apex to the Center of Rotation, in addition to the three positive correlations noted above (Figure 3 2). Note that no significant correlations were noted in the fractal dimension. Exploratory analysis was complete d modeling percent of tooth movement achieved as a function of covariates. Covariates considered included sex, age, age 2

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23 race, study, and tooth movement goal. A cubic age model was identified as the best three variable model (R 2 = 0.14). A plot showin g the relationship between age and the amount of tooth movement achieved, for the JC, CD and BAS data sets is depicted in figure 3 3 This plot also includes model results based on separate fits for males and females. This exploratory analysis suggest s that a quadratic fit may be appropriate for females, while the cubic model appears adequate for males.

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24 Figure 3 1. Mean % of Tooth Movement achieved compared with % of Tooth Movement Goa l

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25 Figure 3 2. Correlation between tooth mo vement and apex to the center of rotation measurement

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26 Figure 3 3. Cubic age model representing age vs. the amount of tooth movement for the JC, CD and BAS data sets Lines: Solid Line (indicated by green arrow) = Overall Cubic Model; Dotted Line (ind icated by orange arrow) = Females; Dashed Line (indicated by blue arrow) = Males. Diamonds: Solid Black Diamond: Males (example with blue circle); Open Diamond = Females (example with orange circle).

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27 Table 3 1. Demographic characteristics a nd descriptive statistics Table 3 2. Correlation of % of tooth movement achieved and age

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28 Table 3 3. Tooth Movement and Age Relationship Variable Mean SD Min Max Pearson correlation with % goal Spearman correlation with % goal % goal 55.40 61.62 59.54 14.87 20.00 18.52 17.50 11.00 11.00 73.00 93.00 93.00 Movement* 1.11 0.60 0.30 0.20 0.35 0.11 1.46 0.93 Age 25.50 40.33 35.27 4.80 14.91 18.71 20.50 19.00 19.00 35.90 64.00 64.00 0.00 0.46 0.10 0.09 1.56 0.85 1.09 0.38 0.37 0.50 0.80 0.22 0.22 2.02 1.96 2.02 0.40 0.90 0.69 0.37 1.63 1.17 1.33 0.40 0.49 0.51 0.80 0.34 0.34 2.09 2.32 2.32 0.49 0.86 0.56 0.44 0.73 0.41 0.52 0.26 0.14 0.24 1.32 0.67 1.32 0.39 0.09 0.09 0.21 0.72 0.21 0.09 Rotation 5.31 4.08 4.49 1.32 1.63 1.63 2.70 1.60 1.60 7.50 8.90 8.90 0.52 0.86 0.59 0.47 Tooth Length 24.87 22.84 23.52 2.02 2.09 2.26 21.67 17.90 17.90 30.32 26.90 30.32 0.15 0.42 0.08 0.17 Crown len gth 12.27 11.51 11.76 0.74 0.93 0.94 10.84 9.82 9.82 13.27 13.79 13.79 0.14 0.17 0.07 0.07 Root length 12.60 11.33 11.76 1.74 1.87 1.90 10.56 6.44 6.44 17.74 14.95 17.74 0.11 0.40 0.12 0.16 Crown/root ratio 0.99 1.05 1.03 0.12 0.22 0.19 0.71 0 .75 0.71 1.23 1.78 1.78 0.14 0.12 0.13 0.12 Bone to C rot 5.14 5.64 5.47 1.25 2.24 1.96 2.89 1.90 1.90 7.70 10.19 10.18 0.19 0.10 0.13 0.15 0.28 0.16 0.52 0.00 0.25 1.85 0.36 1.08 2.40 0.70*

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29 Table 3 3. Continued Apex t o C rot 7.46 5.70 6.29 2.01 1.57 1.90 4.59 1.18 1.18 12.82 9.26 12.82 0.31 0.18 0.27 0.35 Crot= Bone C rot/ Apex C rot 0.41 0.49 0.46 0.11 0.16 0.14 0.25 0.20 0.20 0.63 0.87 0.87 0.25 0.08 0.19 0.24 Fractal dimension 1.71 2.11 1.98 0.20 0.05 0. 23 1.37 1.99 1.37 2.00 2.21 2.21 0.23 0.25 0.00 0.13 ABL wi dth at max width of root (pix) 45.76 8.23 4.33 0.90 38.33 6.77 53.85 10.08 0.43 0.09 0.31 0.12 D istance root tip to BCP (pix) 10.79 1.92 4.74 0.78 4.12 0.15 18.03 3.07 0.56 0.19 0.55 0.19 = Significant correlations (p<.05) = Data not obtained for all three studies Listed are: 3rd Row: Total n=45

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30 CHAPTER 4 DISCUSSION The data has shown that despite ha ving aligners programmed to bodily move a single central incisor 1mm labially (0.25mm/aligner), on average only 61.6% of that movement was achieved. This discrepancy of not attaining 100% programmed movement may be due to a number of reasons. It has been postulated that a greater percentage of tooth movement would occur if the prescription in each aligner was decreased from 0.5mm to 0.25mm. In study CD 20 where each set of aligners were programmed for 0.5mm of tooth movement, only 55.4% of tooth movement was achieved and no statistical difference existed between the amount of tooth movement in each study. As mentioned earlier, t he magnitude and direction of force placed on teeth during OTM, in addition to the length of time these forces are placed, can play a critical role in how teeth move. In the aligner tooth movement model, patient compliance in wearing their aligners is a critical factor in achieving the prescribed tooth movement. There have been an increasing number of older patients seeking ortho dontic treatment in recent years, raising concerns regarding the efficiency of tooth movement in this population compared with that of a younger population. Conventional thinking and clinical experience, likely founded from multiple studies, 10,11,12 has l ed to the belief that the rate of tooth movement decreases with age. Additional f actors including sex, root length, bone levels, and bone density, can have various effects on tooth movement as well. 9 In our study, combined with data sets CD and BAS, a s tatistically significant negative correlation was seen between age and tooth movement in males (Table 3 2). While this correlation was not significant in females, an interesting trend was noted. The results of our regression modeling suggest an overall c ubic relationship between

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31 OTM and age, represented by an s shaped curve. Further exploratory analysis revealed a quadratic (u shaped) relationship for females and a more linear or cubic relationship for males. These relationships are depicted in Figure 3 3. One may conclude that these trends are the consequence of decreased quality of bone (osteoporosis) typically seen in this older female population. However, the individual data, as well as the combined data (JC, CD), has shown no statistical correlati on between age and fractal dimension, a bone complexity and quality indicator. Of the multiple CT and digital model measurements obtained (Table 3 3), significant positive correlations were noted with That is, as to oth movement increased, these measurements increased in both the CT difference between JC and CD studies implies more uncontrolled tipping in CD study was noted, likely d ue to the higher programmed tooth movement in that study. 20 These significant positive correlations were noted for each study separately and when the data was combined. A significant negative correlation existed for the measurement apex to center of rotat ion, indicating that as tooth movement increased the apex to center of rotation measurement decrease (Figure 3 2). This could be the result of root resorption, but more likely due to decreased alveolar bone levels. 22,23 The advantages of using this al igner model for tooth movement include: ease of patient wear and patient recruitment, reliable outcome measures, and the benefit of having a human model. On the contrary, there are several limiting factors of studying tooth movement using this model. As mentioned previously, patient compliance is the single most important factor contributing to the amount of tooth movement seen.

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32 Unfortunately, even recording wear time on a daily basis has limited value. Clinical experience has suggested that a more cont inuous force enhances tooth movement. Taking the aligners out for eating and brushing results in an interrupted force. Another factor, addressed by other similar studies, is the loss of anchorage of adjacent teeth during tooth movement. While only one t arget tooth was programmed for tooth movement, movement of adjacent teeth is expected and can falsely minimize the amount of tooth movement of the target tooth. Lastly, PVS impressions may have inaccuracies due to operator error or patient movement. Being able to make an accurate prediction regarding how teeth will move when a force is applied has long been a challenge for orthodontists. Contributing to this factor is the large degree of variability of OTM seen among patients of the same age group, not to mention those of across all age groups. Different types of tooth movement, combined with varying biological responses make this prediction difficult. While variability will always exist in our patients, the results of these studies combined have allowed us to predict, with more certainty, how teeth will move in different age groups considering a mixture of patient factors such a bone quality and root length.

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33 CHAPTER 5 CONCLUSION This single center prospective clinical trial examined the variables affec ting tooth movement using an Invisalign model. When all three data sets (BAS, CD, JC) were combined, the mean and median percentage of tooth movement achieved compared with the tooth movement goal was 56.9% and 61.8% respectively. In males, there was a negative correlation between tooth movement and age while just the opposite trend was seen in females. The results of our regression modeling suggest an overall cubic relationship between OTM and age, represented by and s shaped curve. Further explorator y analysis revealed a quadratic (u shaped) relationship for females, indicating an increase in tooth movement in females as age increased, and a more linear relationship for males. Significant positive correlations were found between CT superimposition me and Rotation angle variables, while a significant negative correlation was seen with tooth movement and the apex to center of rotation.

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34 LIST OF REFERENCES 1. Masella RS, Meister M. Current Conc epts in the Biology of Orthodontic Tooth Movement. Am J Orthod Dentofacial Orthop l 2006 ; 129 : 458 468. 2. Proff P Romer P. The molecular mechanism behind bone remodeling: a review. Clin Oral Invest 2009 ;13 : 355 62. 3. Meikle M. The tissue, cellular, and molecula r regulation of orthodontic tooth movement: 100 years after Carl Sandstedt. Eur J of Ortho d 2006 ; 2 8: 221 240 4. Dolce C., Holliday L.S. Toward Molecular Orthodontics. In Essentials for Orthodontic Practice (Riolo and Avery, ed), Sec II, Ch. 10. EFOP Press, Inc., Ann Arbor and Grand Haven, MI. 5. Kohno T., Matsumoto Y., Kanno Z., Warita H., Soma K. Experimental tooth movement under light orthodontic forces: rates of tooth movement and changes of the periodontium. J of O rt ho d 2002 ;2 9 : 129 35. 6. D. Cellular, molecular, and tissue level reactions to orthodontic force. Am J Ortho d Dentofacial Orthop 2006 ;129 : 469.e1 32 7. Iwasaki LR, Haack JE, Nickel JC, Morton J. Human tooth movement in response to continuous stress of low Magnitude. A m J Ortho d Dent ofacial Orthop 2000; 117 : 175 183 8. Konoo T., Kim YJ, Gu GM, King GJ. Intermittent force in orthodontic tooth movement. J Dent Res 2001 ; 80:457 60 9. Krishnan V, Davidovitch Z. The effect of drugs on orthodontic tooth movement. Ortho d Craniofac Res 2006 ;9:63 7 1. 10. Bridges T, King GJ, Mohammed A. The effect of age on tooth movement and mineral density in the alveolar tissues of the rat. Am J Ortho d Dentofacial Orthop 1988 ; 93 : 245 248. 11. Misawa Kageyama Y, Kageyama T, Moriyama K, Kurihara S, Yagasaki H, Deguchi T, Ozawa H, Sahara N. Histomorphometric study on the effects of age on orthodontic tooth movement and alveolar bone turnover in rats. Eur J Oral Sci 2007; 1 15: 1 24 30. 12. Harris E., Effects of patient age and sex on treatment: correction of class II malocclusion with the Begg Technique. Angle Orthod 2001;71:433 41 13. Jagtman A. Age effect on orthodontic tooth movement in r ats. J of Dent Res 2003 ; 82:38 42. 14. Rinchuse DJ, Rinchuse DJ, Sosovicka MF, Robison JM, Pendleton R. Or thodontic treatment of patients using bisphosphonates: A report of 2 cases. Am J Orthod Dentofacial Orthop 2007;131:321 326. 15. Bartzela T, Trp JC, Motschall E, Maltha JC. Medication effects on the rate of orthodontic tooth movement: A systematic literatu re review. Am J of Orthod Dentofacial Orthop 2009; 1 35 : 16 26

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35 16. Helfrich M. Osteoclast diseases and dental abnormalities. Arch of Oral Bio 2005 ;50:115 22 17. Davidovitch Z, and Krishnan V., Role of basic biological sciences in clinical orthodontics: a case series. Am J Ortho d Dentofacial Orthop 2009; 135:222 231 18. Proffit WR. Biologic basis of orthodontic therapy/Mechanical Principles of Orthodontic Force Control. In: Proffit WR, Fields HW, Sa rver DM editors. Contemporary orthodontics. 4 th ed. St Louis: Mosby; 2007. Ch s 9, 10. 19. Choy K, Pae E, Park Y, Kim K, Burstone CJ. Effect of root and bone morphology on the stress distribution in the periodontal ligament. Am J of Orthod Dentofacial Orthop 2000;117 : 98 105 20. Drake CT, McGorray SP, Dolce C, Wheeler TT, Nair M. Orthodontic tooth movement with clear aligners. Orthodontics and Craniofacial Research. Submitted for publishing as of 2/2012 21. McGorray SP, Dolce C, Kramer S, Stewart D, Wheeler TT. A randomized, placebo controlled clinical trial on the effects of recombinant human relaxin on tooth movement and short term stability. Am J Orthod Dentofacial Orthop 2012;141:196 203. 22. Liang S Hosur KB Domon H Hajishengallis G Periodontal inflammation and bone loss in aged mice. J Perio Res 2010;45:574 80. 23. Renvert S Persson RE P ersson GR A history of frequent dental care reduces the risk of tooth loss but not periodontitis in older subjects. Swed Dent J 2011;35: 69 75.

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36 BIOGRAPHICAL SKETCH Ju stin R. Chisari was born in Plantation, Florida and raised in Coconut Creek, Florida where he graduated from Coconut Creek High School in 1998. He received a Bachelor of Science degree in food science and human nutrition from the University of Florida in 2002. He continued his education at the University of Florida and earned a Doctor of Dental Medicine degree in 2006. He received a Master of Science in dental sciences as well as a certificate in orthodontics from the University of Florida in the spring of 2012. Justin plans on living and working in South Florida following graduation. He has been married to his wife, Sherri, since 2007, and they have two children, Addison and Grayson.