Download External apical root resorption caused by orthodontic treatment: a

A. Topkara
Herein, we review prevalence, diagnosis and aetiology of
ARR with an emphasis on the effect of genetics and
orthodontic forces, as well as discuss prevention
strategies.
Private Practice, Alanya, Antalya, Turkey
e-mail: [email protected]
Classification and prevalence of ARR
External apical root
resorption caused by
orthodontic treatment:
a review of the
literature
ABSTRACT
Aim External apical root resorption is a common
consequence of orthodontic treatment. A number of
treatment-related factors have been implicated in the
pathogenesis of root resorption in orthodontic patients;
however recent evidence suggests that genetic factors also
play a major role in the development of this condition. Herein,
we review prevalence, diagnosis and aetiology of root
resorption with a particular emphasis on the effect of genetic
variation and orthodontic forces, as well as discuss effective
prevention strategies.
Keywords Root resorption; Orthodontic treatment; Genetic
predisposition; Review.
Introduction
External apical root resorption (ARR) is an undesirable
complication of orthodontic treatment, which results in
permanent loss of tooth structure from the root apex
[Mohendesan et al., 2007]. Previous studies have
demonstrated a number of treatment-related factors that
are significantly associated with the development of ARR
in orthodontic patients, and led to the use of the term
iatrogenic consequence [Brezniak and Wasserstein, 2002].
However, a growing body of evidence suggests that single
nucleotide variations in human genome are also
associated with development of ARR, suggesting that
orthodontic treatment is not the only culprit [Al-Qawasmi
et al., 2003]. Even though there is no clinical practice
guidelines on diagnosis, monitoring and management of
root resorption, understanding patient- and treatmentrelated risk factors of this unwanted complication is of
utmost importance to general dentists and orthodontists
in the care of these patients.
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Levander and Malmgren presented a classification
system for root resorption which is widely accepted in the
orthodontic literature [1988]. According to this index,
severity of root resorption increases from grade 1, defined
as presence of irregular root contour, to grade 4, where
root resorption is greater than 1/3 of the original root
length (Table 1).
Previous studies reported a prevalence of root resorption
greater than 2 mm (grades 3 and 4) of 10-18% [Linge
and Linge, 1983; Levander and Malmgren, 1988].
However, it is important to note that plain radiography is
a crude method of assessing root resorption, which may
underestimate the true prevalence of this condition.
Indeed, experimental and human histological studies have
shown that root resorption occurs in over 90% of patients
undergoing orthodontic treatment [Kural and OwmanMoll, 1998].
Diagnosis of ARR
The most widely used diagnostic technique for root
resorption remains conventional radiography including
panoramic and periapical views. Newer imaging
modalities, including 3-D Cone Beam Computed
Tomography (CBCT), were recently introduced into clinical
use and serve as attractive alternatives to conventional
radiotherapy in diagnosis of ARR. Dudic and colleagues
[2009] assessed the effectiveness of CBCT compared to
panaromic radiographs in 22 patients near the end of their
orthodontic treatment and demonstrated that detection
of root resorption was significantly higher in CBCT
compared to panaromic radiographs (69.0% vs. 43.5%,
respectively). Similarly, Alqerban et al. [2011]
demonstrated, in 60 patients with impacted or ectopically
erupting maxillary canines seeking orthodontic treatment,
that there was a significant difference in root resorption
rates obtained by CBCT versus panagromic radiograph in
favor of CBCT. Taken together, these studies suggest that
CBCT may be a more sensitive imaging modality for
diagnostic and prognostic assessment of ARR. However,
further studies are needed to assess safety and costeffectiveness of CBCT in the management of orthodontic
patients with ARR.
Grade
Definition
0
1
2
3
4
No evidence for resorption
Irregular root contour
Apical root resorption less than 2 mm
Apical root resoption > 2mm and < 1/3 of original root length
Root resorption exceeding 1/3 of original root length
TABLE 1 - Levander-Malmgren classification for root resorption.
163
TOPKARA A.
Aetiology of ARR
Identification of risk factors responsible for ARR has
been the focus of numerous research studies in an effort
to understand underlying mechanisms and develop
prevention strageties and treatment methods.
Collectively, these studies suggest that the aetiology of
ARR is complex and multifactorial including patient-related
and treatment-related risk factors [Weltman et al., 2010].
Patient-related risk factors implicated in the pathogenesis
of ARR include age, gender, genetic predisposition,
severity of malocclusion, tooth and root morphology, as
well as systemic conditions such as allergy, asthma, and
alcoholism. Treatment-related risk factors implicated in the
pathogenesis of ARR include magnitude of orthodontic
force, direction of tooth movement, amount of apical
displacement, and duration of treatment.
Genetic predisposition to ARR
Growing lines of evidence suggest that genetic factors
play a major role in the development of root resorption.
Genetic aepidemiology defines heritability as the ratio of
genetic variance to total variance for a given trait, which
represents the proportion of the phenotypic variance
attributable to genetic factors. In a sibling pair study design,
Harris et al. [1997] estimated heritability for root resorption
to be 80% for the maxillary incisors. In a separate
retrospective twin study, phenotypic concordance for
quantitative detection of root resorption was 49.2% in
monozygotic twins compared to 28.3% in dizygotic twins
with an estimated heritability of 34% [Ngan et al., 2004].
Taken together, these findings suggest that there is a strong
genetic component of root resorption trait. Interestingly, in
the latter study, concordance for monozygotic twins was
less than 100% suggesting that environmental factors also
play a role in the development of ARR.
Al-Qawasmi and colleagues [2003a] performed a family
study to assess the potential effect of single nucleotide
polymorphisms (SNPs) in two closely-located proinflammatory candidate genes (IL-1A and IL-B) on root
resorption. These genes have been selected for their
potential involvement/activation in periodontitis as well as
tooth movement process. Interestingly, the transmission
disequilibrium test identified evidence for significant
linkage disequilibrium of IL-1B SNP (+3954) with clinical
ARR. Patients who were homozygous for IL-1B allele 1
have a 5.6 fold (95% CI 1.9-21.2) increased risk of ARR
compared with those who were not homozygous for the
IL-1B (+3954) allele 1. Allele 1, which was shown to
decrease the production of IL-1 cytokine in vivo,
significantly increases risk of ARR in this patient group. An
independent verification study for this SNP trait
association was published by a group of investigators from
Brazil [Bastos Lages, 2009]. In this case-control study of 61
patients, the authors demonstrated that carrying patients
who were homozygous for IL-1B allele 1 have a 4.0 fold
(95% CI 1.23-12.9) increased risk of ARR compared with
those who were not homozygous for the IL-1B (+3954)
allele 1. However, Gulden et al. [2009] from Germany
failed to demonstrate such relationship in a study of 96
ARR cases and 162 controls. Indeed, IL-1B (+3954) allele 1
was observed more commonly in the control group.
Conversely, this study demonstrated a significant
association between IL-1A (-899) genotype and root
resorption. Reasons for this discrepancy remains
unknown, however it might be related to differences in
genetic background of the populations, analytical
methods, as well as Type I and/or Type II statistical errors.
Another candidate locus implicated for the development
of ARR is located on chromosome 18 [Al-Qawasmi et al.,
2003b]. Using a sibling correlation design by calculating
shared IBD (identical by descent) for candidate markers,
Al-Qawasmi and colleagues identified evidence for linkage
(LOD score of 2.5) between a microsatellite marker
D18S64 which lies close to the candidate gene TNFRSF11A
and root resorption trait. The TNFRSF11A gene encodes
the receptor activator of nuclear factor-kappa B (RANK),
an essential signaling molecule in osteoclast formation
and activation as a potential mechanism in pathogenesis
of root resorption.
Although the aforementioned preliminary studies are
promising, their results need to be carefully evaluated. First
of all, it is important to remember that SNP-trait
association may not necessarily represent a causal
relationship, and the marker SNP may in fact be in LD with
the causal SNP. Secondly, sample sizes of these studies are
extremely small and subject to Type II error. Lastly,
candidate gene approach is subject to selection bias and
limits analysis to a few markers compared to millions of
different variations present in the human genome.
Genomewide association studies or next-generation
sequencing techniques in a large group of patients with
case-control design may provide an unbiased approach to
detect candidate genes and/or markers in this complex
genetic disease. Nevertheless, these studies provide the
basis for evidence that genetic markers of root resorption
Study
SNP
n (cases)
n (controls)
Odds Ratio
*95% CI
p value
Al-Qawasmi et al.
IL-1A (-899)
IL-1B (+3954)
IL-1B (+3954)
IL-1A (-899)
IL-1B (+3954)
33
33
23
45
45
40
40
38
44
49
NR
5.6
4.0
9.3
0.5
NR
1.9 - 21.2
1.2 - 12.9
1.1 - 77.8
0.2 - 1.0
NS
0.004
0.014
0.040
0.062
Bastos-Lages et al.
Gulden et al.
*Odds Ratio calculation based on 2/2 genotype vs. 1/1 and 1/2 genotypes for IL-1A SNP and 1/1 genotype vs. 1/2 and 2/2 genotypes for IL-1B SNP.
NR= not reported, NS= non-significant.
TABLE 2 - Candidate gene studies of root resorption.
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ROOT RESORPTION CAUSED BY ORTHODONTIC TREATMENT
do exist, and in the future may serve to identify patients at
risk prior to initiation of treatment.
Role of orthodontic forces
Previous studies have shown that teeth subjected to
orthodontic forces had significantly more ARR than the
control teeth from the same subjects, suggesting that
orthodontic forces have a signifcant role on the
development of ARR, irrespective of patient-related factors
[Harris et al., 2006; Barbagallo et al., 2008]. It has also
been demonstrated that heavy forces induce significantly
more ARR compared to light forces factors [Harris et al.,
2006; Barbagallo et al., 2008; Chan et al., 2005]. This
may be attributed, at least in part, to rapid lacuna
development as well as compromised repair process
observed with heavy force application.
The direction of force has also been implicated in the
aetiology of ARR. Chan et al. [2005] indicated that
compressive forces on the periodontal ligament cause
more root resorption than tensile forces. Han et al. [2005]
suggested that the intrusion of teeth causes about four
times more ARR than extrusion, however it should be
noted that extrusion of teeth may also cause ARR in
susceptible individuals. Several reports indicated that
jiggling and movement caused by application of
intermaxillary elastics are likely to increase the risk of ARR
[Baumrind, 1996; Mirabella, 1995; Weltman, 2010]. Taken
together, intrusive forces with and lingual root torque
appear to be strongly associated with ARR following
orthodontic treatment.
One of the other established treatment-related risk
factors for ARR is duration of treatment. In a meta-analysis
of 8 independent studies, Segal et al. [2004]
demonstrated that mean apical root resorption was
strongly correlated with total apical displacement (r =
0.822) and treatment duration (r = 0.852). Apical root
resorption and duration of treatment reported from these
8 trials were a scatterplot (Fig. 1). Given that duration of
treatment is proportional to severity of root resorption,
investigators have explored whether treatment pause
would have a favourable effect on root resorption.
Levander et al. [1994] studied 40 patients with evidence of
root resorption after 6 months of orthodontic treatment,
and randomised these patients to either continuation of
treatment or a treatment pause of 2 to 3 months after
which the treatment was resumed. They observed that the
amount of root resorption was significantly less in patients
who underwent treatment interruption. Acar et al. [1999]
indicated that the application of discontinuous force
results in less ARR than does the application of continuous
force.
Rudolf et al. [2001] investigated the effect of different
types of orthodontic tooth movement on stress
distribution using a three-dimensional finite element
model of maxillary incisor. In this single-tooth model,
authors have demonstrated that the greatest amount of
relative stress at tooth apex occured with tipping,
intrusion, and extrusion forces. Field et. al. [2009]
extended these observations into a multi-tooth finite
element model with tipping forces and suggested that the
disto-cervical region of tooth experiences the greatest
stress. An important message of these preliminary studies
is that, in parellel with the advances in imaging
techniques, it might be possible to mathematically model
stress distributions based on different treatment
approaches in orthodontic patients prior to initiation of
treatment, therefore tailoring treatments in susceptible
individuals.
Long-term outcomes of ARR
Remington et al. [1989] have first reported long-term
outcomes of 100 orthodontic patients who had
undergone active orthodontic treatment and subsequently
exhibited root resorption. In their analysis, maxillary
incisors seemed to be affected more frequently and to a
more severe extent than the rest of the dentition. They
also reported that ARR associated with orthodontic forces
did not progress radiologically following the termination
of active orthodontic treatment, and reparative processes
took place including smoothing and remodeling of sharp
edges. There was no evidence of tooth loss, however
hypermobility was observed in 2 cases. This finding is
inconsistent with the reports indicating that the apical part
of the root has relatively minor importance for total
periodontal support [Weltman et al., 2010]. In a recent
long-term study by Jonnson et al. [2007], patients who
had experienced moderate, severe, and extreme ARR were
recalled 5 to 15 years following orthodontic treatment for
quantitative assessment of tooth mobility by periotest
method. They noticed increased mobility only in teeth with
extremely resorbed roots (root length less than 1 mm). The
increase in mobility was minimal and non-significant in
teeth with longer root lengths. The length of the followup period did not influence severity of root resorption,
again suggesting that root resorption process does not
progress following termination of the treatment.
Prevention and management
strategies
FIG. 1 - Association of Root Resorption and Duration of
Therapy. Trial level data obtained from Segal et al. [2004].
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Several points merit consideration prior to initiation of
orthodontic treatment. First of all, patient and parents
should be informed about root resorption as a potential
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TOPKARA A.
consequence of orthodontic treatment and long-term
outcomes. Collecting a good medical history particularly
focusing on the presence of potentially predisposing
clinical conditions, such as allergy or asthma, is of utmost
importance. Patients with positive family history of root
resorption should be carefully investigated, and records of
siblings and/or parents with root resorption should be
reviewed. Currently, there is not enough evidence to
support screening individuals for genetic susceptibility on
a routine basis.
As discussed above, heavy forces are particularly
harmful, and until more evidence is obtained, it is
recommended to apply light forces particularly for
intrusive movements. Following initial 6 months of
treatment, periapical radiographs should be obtained to
assess the early development of root resorption. Whenever
tooth resorption is identified, patient and parents should
be informed of the finding. Interruption of treatment with
a passive archwire may be considered to reduce root
resorption. In cases of severe root resorption, the
treatment plan should be reassessed with the patient.
Upon completion or termination of the treatment, final
radiographs should be obtained. Fixed appliances for
retention should be carefully designed to prevent further
root resorption. Patients should be informed about the
importance of mainintaining a proper oral hygiene to
prevent periodontitis. Serial radiographs should be
obtained in patients with severe root resorption until
evidence for progression is no longer present. In cases of
extreme resorption, endodontic treatment and calcium
hydroxide may be considered.
Conclusion
The fundamental principle of medicine primum non
nocere (first do no harm) by Hippocrates also applies to
the field of orthodontics. Orthodontists should be well
aware of the risks and benefits of orthodontic treatment,
specific to each case. Despite recent advances in molecular
biology, imaging modalities and clinical care of patients,
our understanding of root resorption remains limited.
Large clinical and genetic association studies are needed
to further understand biology, detection, and treatment of
this undesired complication.
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