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Introduction: In this study, we examined the impacts of age, sex, root length, bone levels, and bone quality on
orthodontic tooth movement. Methods: Clear aligners were programmed to move 1 central incisor 1 mm over the
course of 8 weeks. Thirty subjects, ages 19 to 64, were enrolled, and measurements were made on digital
models (percentage of tooth movement goal achieved). Morphometric features and bone quality were assessed
with cone-beam computed tomography. Data from this study were combined with data from 2 similar studies to
increase the power for some analyses. Results: The mean percentage of tooth movement goal achieved was
57% overall. Linear regression modeling indicated a cubic relationship between age and tooth movement, with a
decreasing rate of movement from ages 18 to 35 years, a slightly increasing rate from ages 35 to 50, and a
decreasing rate from ages 50 to 70. The final decreasing trend was not apparent for women. As would be ex-
pected, the correlation was significant between the percentage of the goal achieved and the cone-beam
computed tomography superimposed linear measures of tooth movement. A significant negative correlation
was found between tooth movement and the measurement apex to the center of rotation, but bone quality, as
measured by fractal dimension, was not correlated with movement. Conclusions: The relationship between
age and tooth movement is complex and might differ for male and female patients. Limited correlations with
cone-beam computed tomography morphology and rate of tooth movement were detected. (Am J Orthod
Dentofacial Orthop 2014;145:S82-91)
T
he use of clear aligners to produce orthodontic pressure-tension theory has emerged as the most
tooth movement (OTM) provides an opportunity popular concept behind the movement of teeth.
to measure incremental movement and investigate Bone remodeling involves an intricate arrangement
factors that might affect the rate of movement. The of coordinated cellular activity leading to bone resorp-
broad principles of OTM are based largely on bone and tion performed by osteoclasts, followed by bone forma-
tissue remodeling, specifically the resorption and depo- tion carried out by osteoblasts.2 Dolce and Holliday3
sition of alveolar bone as force is applied. The biology of have reported that although the precise biologic
OTM has proven to be an extremely complex process response to orthodontic force has not been identified,
involving an array of coordinated biochemical reactions, several hypotheses regarding the mechanisms by which
including critical cell signaling pathways and a wide osteoblasts and osteocytes sense this initial mechanical
range of cellular differentiation, leading to bone remod- stimulus have been proposed, including strain-
eling.1 As the science of bone biology continues to sensitive ion channels, shear stress receptors, integrin
evolve, several theories of OTM have surfaced. The activation, and cytoskeleton reorganization. Three
phases of tooth movement have been described in the
a
b
Private practice, West Palm Beach, Fla. literature: initial phase, lag phase, and secondary
Assistant professor, Department of Biostatistics, University of Florida,
Gainesville.
phase.4,5 The secondary stage accounts for most of the
c
Chairman and professor, Department of Oral & Maxillofacial Diagnostic tooth movement, and teeth during this period move at
Sciences, University of Florida, Gainesville.
d
a faster, more continuous pace.6
Professor, Department of Orthodontics, University of Florida, Gainesville.
All authors have completed and submitted the ICMJE Form for Disclosure of
The magnitude and direction of force placed on teeth
Potential Conflicts of Interest, and none were reported. during OTM, in addition to the length of time these
Supported by Align Technology, San Jose, Calif, and the Southern Association of forces are in place, also play critical roles in how teeth
Orthodontists.
Address correspondence to: Susan P. McGorray, Department of Biostatistics, Box
move. Forces applied to teeth cause various types of
117450, Gainesville, FL 32611; e-mail, spmcg@ufl.edu. tooth movement depending on the location of the center
Submitted, June 2012; revised and accepted, October 2013. of resistance of that tooth and the direction in which the
0889-5406/$36.00
Copyright Ó 2014 by the American Association of Orthodontists.
force is applied. It is understood that the center of resis-
http://dx.doi.org/10.1016/j.ajodo.2013.10.022 tance for a given tooth changes based on tooth size,
S82
Chisari et al S83
number of roots, and amount of tooth root that is relatively higher level of bone density have been
submerged in bone. documented.8,13 Alveolar bone levels, on average,
Variability among patients can affect OTM. Factors decrease over time, impacting OTM by changing the
including age, sex, root length, bone levels, bone center of resistance. The center of resistance of a tooth
density, medications, and certain systemic conditions is largely influenced by its surroundings, particularly in
can have inhibitory, synergistic, or additive effects on regard to root morphology, bone levels, and bone
OTM.7 The majority of literature on the effects of age quality.16 Thus, patients with alveolar bone loss or
on OTM has been completed using animal models. abnormally long roots will have centers of resistance
Bridges et al8 reported that a significantly greater farther from the point of force application (more
amount and rate of tooth movement occurred in apically). Alternatively, the more the root tapers, the
younger rats compared with their older counterparts in more the center of resistance moves coronally.17
all 3 phases of tooth movement. Similar findings of Clear aligners with sequentially programmed
the effects of increasing age on the rate and amount movement provide an excellent model for investigating
of tooth movement have been reported by Misawa- tooth movement. A single tooth can be isolated, and
Kageyama et al9 and Harris.10 There has also been frequent measurements made with polyvinyl siloxane
some indication that whereas there is a delay in the onset or digital impressions provide incremental information
of tooth movement in adult rats, once the secondary regarding the pattern of movement. For example,
phase of tooth movement is reached, the movement McGorray et al18 characterized the weekly pattern of
becomes equally efficient among the 2 age groups.11 tooth movement using this model over 8 weeks, along
The effect of age on OTM clearly exists and is likely with subsequent relapse. Kravitz et al19 compared actual
due in part to a decreased biologic response. Although tooth movement with aligners with predicted movement
there is individual variability from patient to patient, a over the course of treatment. Aligner treatment is now a
direct difference in OTM between the sexes has not commonly prescribed modality for OTM in adolescents
been shown in the literature. and adults, and a better understanding of the pattern
Medications with pharmacologic effects can impact of movement and factors that influence movement
the cells targeted in OTM. Some of these medication could lead to more efficient treatment.
classes include bisphosphonates, estrogens, NSAIDS The purposes of this study were to better characterize
and other analgesics, corticosteroids, calcium regulators, the pattern of tooth movement with clear aligners with
and supplements.7,12,13 There is little human programmed movement over 8 weeks and to examine
experimental data on the effects of medications on the influence of age, sex, root length, morphometric
OTM and limited information from animal models. measurements, and bone quality on the rate of OTM.
However, knowing the biochemical action of these
medications has led to concerns regarding how they MATERIAL AND METHODS
can affect orthodontic treatment.13 Any medication The design for this study was similar to 2 previous
that interferes with or alters bone biology might impact studies that investigated specific aspects of tooth move-
the rate of tooth movement. ment with clear aligners.18,20 Approval was obtained
Systemic factors or nutritional deficiencies affecting from the University of Florida Institutional Review
bone metabolism have also been found to alter OTM. Board for the Protection of Human Subjects. This
Specifically, diseases of bone can have a significant project was a prospective single-center clinical trial
impact on the rate of tooth movement as well. Reduced involving subjects of 2 age groups with minor incisor
or complete lack of osteoclast function can lead to a malalignments, who were otherwise healthy and would
condition known as osteopetrosis, characterized by be undergoing orthodontic treatment. The first group
sclerosis of the skeleton and inhibited tooth movement included 7 men and 8 women between the ages of 18
and eruption. On the other hand, in Paget's disease, and 35 years, inclusive. The second group consisted of
uncontrollable bone turnover occurs because of the 5 men and 10 women 50 years of age and older.
overactivity of osteoclasts.14 Since OTM stimulates an Throughout this article, this study will be called Study
inflammatory process in the periodontal ligament and 3. Study 1 investigated the role of relaxin in tooth move-
surrounding tissues, it is thought that any chronic ment and relapse, and has been previously described.18
inflammatory disease such as thyroiditis, asthma, and No difference in tooth movement was detected when
even allergies can affect the movement of teeth.15 comparing those who received relaxin injections with
Other variables that might be of significance in OTM those who received placebo injections; thus, data from
are root length, bone levels, and the density or quality of both groups in this study were combined, yielding a
bone. Age-related decreases in bone turnover as well as a sample size of 37 subjects. Cone-beam computed
American Journal of Orthodontics and Dentofacial Orthopedics April 2014 Vol 145 Issue 4 Supplement 1
S84 Chisari et al
tomography (CBCT) imaging was not performed in of rotation. Tooth length refers to the distance from
Study 1. Study 2 was similarly designed but included the midpoint of the incisal edge to the apex of the target
CBCT imaging and examined the role of aligner material tooth from the initial computed tomography image.
fatigue in tooth movement.20 Subjects in this study Crown length is the portion of the tooth length that is
received a new aligner every week rather than every 2 coronal to the bone. Bone to C-rot is the section of tooth
weeks as in Study 1. No difference was detected in total length between the center of rotation and a line con-
tooth movement when comparing the weekly aligner necting the most coronal aspect of the faciolingual
and the biweekly aligner groups. For studies 1 and 2, crestal bone. These variables are illustrated in Figure 1.
the biweekly tooth movement goal was 0.50 mm, for a All study subjects were instructed to wear the aligner
total 8-week goal of 2 mm. Study 3 was designed to appliance full time. They were allowed to remove the appli-
broaden the age range and to be used in conjunction ance when eating, drinking, or brushing their teeth. Their
with the previous studies to examine the role of age medication and medical histories were taken initially. Each
and other factors in tooth movement. In the 3 studies subject recorded aligner wear time in a diary format. At the
combined, the total number of subjects was 82. All conclusion of the study, the participants were routinely
subjects were in good health and had acceptable maloc- treated orthodontically with clear aligners.
clusions as defined in the inclusion criteria, which have To determine subject eligibility, 2 visits were
been described in a previous study.18 required. The first visit was designed to identify potential
Once a subject was accepted into the trial, the right or subjects with malocclusions needing minor incisor
left maxillary central incisor was selected as the target alignment of at least the maxillary incisors. Those with
tooth. The selection was based on the target tooth's medical conditions or intraoral problems, including
not being blocked out by the adjacent teeth to allow a significant periodontal disease, chronic daily use of
total anteroposterior movement of 1 mm. Tooth move- any nonsteroidal or anti-inflammatory medication,
ment was accomplished using a series of 4 maxillary current smokers, or history of significant cardiac disease,
aligners (Invisalign; Align Technology, San Jose, Calif), uncontrolled hypertension, bleeding disorders, or renal
each programmed in increments of 0.25 mm of anterior disease, were also excluded. Subjects who were deter-
movement of the central incisor being studied, as mined to be eligible based on these procedures
described above. Aligners were collected every 2 weeks proceeded to the next visit.
from each subject, and new aligners were dispensed. The screening visit was designed to finalize the
The study termination visit and final time point for subject's eligibility and collect initial records. The
data collection was at week 8. Polyvinyl siloxane impres- following procedures were performed at this visit:
sions were taken weekly and sent to Align Technology impressions were taken with polyvinyl siloxane for prep-
for scanning to create 3-dimensional models. Tooth aration of the Invisalign appliances, impressions were
movement measurements from baseline through week sent to Align Technology after confirmation of
8 were made from each scanned model using Tooth- eligibility, and intraoral and extraoral photographs and
Measure proprietary software (Align Technology). CBCT imaging were done. For women, a negative urine
CBCT measurements and fractal analysis were pregnancy test immediately before this procedure was
completed using a combination of software including required. After the investigator (T.T.W.) reviewed all sub-
InVivo (Anatomage, San Jose, Calif), ImageJ (National ject information to confirm eligibility, the subjects were
Institutes of Health, Bethesda, MD), and Tact Work- enrolled into the study and assigned a unique number.
bench (Wake Forest University, Winston-Salem, NC). At the first study visit (week 0), the first aligner was
The following are definitions of the measurements delivered to each subject. The acceptable visit window
used in the CBCT superimposition analysis. D U1 (x) for weeks 1 through 8 was 6 1 day, and all 30 treatment
refers to the distance between lines drawn through the subjects successfully satisfied this requirement.
midpoint of the incisal edges of the superimposed target During the study visits of weeks 1 through 8, the
tooth perpendicular to the anteroposterior axis (the following procedures were performed: intraoral clinical
plane of prescribed tooth movement). D U1 (s) is the examination, maxillary occlusal and frontal photo-
length of the line connecting the midpoint of the incisal graphs, and polyvinyl siloxane impressions. In addition,
edges of the superimposed target tooth. D Apex refers to during the study visits of weeks 2, 4, and 6, the aligner
the length of a line connecting the change in apex of the (used during the previous 2 weeks) and the wear diary
superimposed target tooth. Rotation angle is the angle were collected, and the next aligner and diary were
created by the intersection of lines drawn from the dispensed. At the study termination visit, week 8, the
midpoint of the incisal edge to the apex of the target same procedures were performed, and CBCT imaging
tooth. The apex of this angle is considered the center of the maxilla took place.
April 2014 Vol 145 Issue 4 Supplement 1 American Journal of Orthodontics and Dentofacial Orthopedics
Chisari et al S85
Statistical analysis
Orthodontic tooth movement was quantified using
descriptive statistics for the digital model analysis.
Chi-square tests of equality of proportions and analysis
of variance (ANOVA) were used to compare subject char-
acteristics and results over the 3 studies. To standardize
the studies, the primary outcome was the percentage of
tooth movement goal achieved over 8 weeks. Spearman
correlation coefficients were estimated to examine the
relationship between that outcome variable and age,
morphometric measurements, and compliance. Median
weekly hours of wear were used to represent compliance
during the study, and this would not be overly influ-
enced by a week of limited wear or excessive wear and
would better represent typical weekly compliance. Linear
regression modeling was used to examine the relation-
ship between the percentage of tooth movement goal
achieved and multiple covariates. Based on the R2 value
Fig 1. Superimposed CBCT measurements. Blue is (percentage of variability in the outcome explained by
initial tooth position, and red is final tooth position (figure the model), the best 1, 2, 3, and so on variable models
from thesis of Carl Drake; Gainesville: University of Flor- were determined. Model building was concluded when
ida; 2010). additional variables did not significantly improve the
previous model. Potential interactions between covari-
Weekly anteroposterior movement of the target ates and the influence of outliers were also examined.
tooth was recorded with polyvinyl siloxane impressions. A P value less than 0.05 was considered statistically
These impressions were sent to Align Technology, and significant, and analyses were performed using SAS
digital models were created so that OTM could be software (version 9.1.3; SAS Institute, Cary, NC) and R
measured using Align Technology's ToothMeasure software (version 2.15; R Foundation for Statistical
software. The digitized model fabricated each week Computing, Vienna, Austria).
was superimposed on the baseline digital model, taken
at week 0, according to the best fit of unmoved teeth,
RESULTS
particularly the posterior dentition. The most central
portion on the facial surface of the clinical crown of The demographic characteristics of the subjects for
the target tooth, referred to as the centroid, was deter- the 3 studies can be found in Table I. No significant
mined, and subsequent tooth movements in all dimen- differences were detected when comparing the studies
sions were measured from this point at each study visit. for sex, race, compliance, and percentage of tooth
The same investigator (J.R.C.) measured the digital movement goal achieved. Tooth movement goal and
models for all 30 subjects. age were not compared because they differed in the
CBCT scans of each subject were performed at the designs of the studies. The pattern of tooth movement
screening visit and at the study termination visit over 8 weeks is shown in Figure 2. Most tooth movement
(week 8). Using the InVivo software, the images were occurred in the first week of the 2-week wear cycle.
superimposed on each other and registered at the Table II presents summary statistics and group com-
curvature of the palate in addition to other stable parisons for the demographic variables and planned
maxillary structures. Measurements recorded from biweekly tooth movement. The percentage of the goal
these superimpositions are shown in Figure 1. A fractal achieved did not differ significantly by sex or race.
dimension score was calculated for each subject, Although it was not statistically significant (P 5 0.06),
representing the quality of the bone.21 Higher fractal subjects with a smaller goal had a higher mean percent-
dimensions correspond to greater morphologic age of goal achieved, 62%, compared with 54% for those
complexity of the bone. with a planned movement of .50 mm. There was no sig-
Weekly wear time was calculated for each subject, nificant correlation with age, according to the Pearson
with mean, median, and standard deviation of weekly correlation coefficient estimate of 0.021 (P 5 0.90).
wear time used to characterize each participant's wear However, examining this correlation separately for men
patterns. and women, different patterns were suggested, with
American Journal of Orthodontics and Dentofacial Orthopedics April 2014 Vol 145 Issue 4 Supplement 1
S86 Chisari et al
*Chi-square test of equality of proportions; ynot tested because of different study designs; zANOVA.
Fig 2. Mean percentage of tooth movement goal achieved for the 3 studies. Solid line indicates tooth
movement goal (assuming linear movement) over the 8 weeks.
the women having a positive correlation coefficient esti- between percentage of goal achieved and DU1(x),
mate, 0.09 (P 5 0.52), whereas the men had a negative DU1(s), and rotation angle, since these should corre-
correlation coefficient estimate, 0.23 (P 5 0.25). We spond well with the model-based tooth movement per-
also did not detect a significant correlation between centage of goal achieved measurement. Significant
compliance (measured by median weekly hours worn) correlations were not noted for most morphometric
and percentage of goal achieved, with the Pearson cor- measures. A negative correlation with percentage of
relation coefficient estimate of 0.06 (P 5 0.59). This goal achieved was identified for the apex to center of
relationship is displayed in Figure 3. rotation measurement; this is illustrated in Figure 4.
Summary statistics for the CBCT measurements and Linear regression modeling was used to examine the
their correlations with percentage of goal achieved are relationship between percentage of tooth movement
given in Table III. High correlation would be expected goal achieved and covariates. Covariates considered for
April 2014 Vol 145 Issue 4 Supplement 1 American Journal of Orthodontics and Dentofacial Orthopedics
Chisari et al S87
American Journal of Orthodontics and Dentofacial Orthopedics April 2014 Vol 145 Issue 4 Supplement 1
S88 Chisari et al
April 2014 Vol 145 Issue 4 Supplement 1 American Journal of Orthodontics and Dentofacial Orthopedics
Chisari et al S89
Fig 4. Correlation between tooth movement and apex to the center of rotation measurement. Dots repre-
sent observed data, and line indicates best linear fit (Pearson correlation coefficient estimate 5 0.35;
P 5 0.0184).
American Journal of Orthodontics and Dentofacial Orthopedics April 2014 Vol 145 Issue 4 Supplement 1
S90 Chisari et al
Table IV. Linear regression model fit and parameter estimates (parameter estimates and P values)
Variables in the model
Model R2
Overall fit (P value) Intercept Age Age2 Age3
Overall 0.20 0.0006 252.9 (\0.0001) 16.23 (\0.0001) 0.41 (\0.0001) 0.0033 (0.0001)
Women 0.20 0.0116 145.7 (0.18) 15.49 (0.59) 0.079 (0.80) 0.0001 (0.98)
Men 0.24 0.07 235.7 (0.0041) 9.92 (0.0229) 0.37 (0.0234) 0.0030 (0.0232)
compliance is the single most important factor contrib- relationship for men, with decreased movement at older
uting to the amount of tooth movement seen. Unfortu- ages. Significant positive correlations were found be-
nately, even recording wear time on a daily basis has tween CBCT superimposition measurements and digital
limited value. Clinical experience has suggested that a model measurements of the percentage of goal achieved
more continuous force enhances tooth movement. for the DU1 (x), DU1(s), and rotation angle variables,
Removing the aligners for eating and brushing results whereas a significant negative correlation was seen
in an interrupted force. Another factor, addressed by with the percentage of goal achieved and the apex to
other studies, is the loss of anchorage of adjacent teeth center of rotation measurement.
during tooth movement. Whereas only 1 target tooth
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