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Browsing by Subject "Orthodontics, Corrective -- Adverse Effects"

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    Analysis of a TNFRSF11A Gene Polymorphism and External Apical Root Resorption During Orthodontic Treatment
    (2005-07) French, Michael; Hartsfield, James K., Jr.; Al-Qawasmi, Riyad A.; Foroud, Tatiana M.; Roberts, W. Eugene; Shanks, James
    External Apical Root Resorption (EARR) can be an undesirable side effect of orthodontic treatment. Several studies have already recognized a genetic predisposition to EARR, and some have suggested possible candidate genes that may be involved. The objective of this prospective study was to explore one possible candidate gene that may predispose individuals to EARR during orthodontic treatment. The TNFRSF11A gene encodes the receptor activator of nuclear factor-kappa β (RANK). Together with the RANK ligand, RANK mediates cell signaling that leads to osteoclastogenesis. A diallelic marker was used to investigate the possible relationship between a nonsynonymous TNFRSF11A (RANK) polymorphism and the individuals' development of EARR concurrent with orthodontic treatment. Buccal swab cells of 112 patients who had completed orthodontic treatment were collected for DNA isolation and analysis. EARR of the maxillary central incisors was calculated based on measurements from pre and post treatment occlusal radiographs. Linear regression analysis indicated that length of treatment, overjet, and molar classification are significant predictors of EARR (p=0.05). Other factors, including age, gender, and overbite, were not found to be significantly associated with EARR. An ANOVA was performed to examine the relationship of the genotyped TNFRSF11A marker with the dependent variable EARR. When individuals having at least one copy of allele 2 (1,2 and 2,3 genotypes) were pooled together, a marginally significant association was found between EARR and the marker. Further analysis using logistic regression revealed that individuals with a (1,1) genotype are 4.3 times more likely to be affected by EARR than a person with a (1,2) or (2,2) genotype. From these findings it was concluded that EARR is a complex condition influenced by several treatment variables with the TNFRSF11A gene and its product (RANK) contributing to the individuals' predisposition.
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    Evaluation of IL-1 B (+3954) Gene Polymorphism and External Apical Root Resporption Associated with Orthodontic Treatment
    (2005) Smith, Elizabeth Dockerty; Hartsfield, James K., Jr.; Al-Qawasmi, Riyad A.; Foroud, Tatiana M.; Roberts, W. Eugene; Shanks, James
    The purpose of this prospective study was to examine the external apical root resorption (EARR) status and genetic marker composition of 100 Caucasian patients (59 females and 41 males) who have undergone orthodontic treatment at the private practice office of Dr. James V. Macri. A diallelic polymorphism marker for IL-1B +3954 within the candidate gene IL-1B was used to investigate the difference in relative risk for EARR. EARR measurements taken on pre and post treatment occlusal radiographs were then used to determine any association with genotype. Using linear regression analysis, length of treatment, overjet and molar classification were found to be significant predictors of EARR (p<0.05). The findings indicated that increased length of treatment or overjet is associated with increased EARR. Furthermore, those subjects with a class II molar classification were less likely to experience EARR compared to those with either a class I or class III molar classification. An ANOV A test was performed to examine the relationship of the IL-1B marker with the dependent variable EARR. There was no statistically significant association between the IL-1B genotype and EARR (p=0.53). Finally, a chi-square test was used to evaluate the association of the IL-1B genotypes in the affected (>5mm EARR) and unaffected (<5mm EARR) groups. There was no significant association between affection status and the IL-1B genotype (p=0.87).
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    Evaluation of the IL-6 Gene in External Apical Root Resorption Associated with Orthodontic Treatment
    (2003) Harris, Nathan P.; Hartsfield, James K., Jr.; Everett, Eric T.; Foroud, Tatiana M.; Roberts, W. Eugene; Shanks, James
    The objective of this project is to investigate the possibility that a functional polymorphism of the interleukin-6 (IL-6) gene is associated with external apical root resorption (EARR) during orthodontic tooth movement. If genes that are involved in EARR could be identified and easily screened, the orthodontist could adjust the patient's treatment plan accordingly. Having information about a patient's susceptibility to EARR could help diagnose and treat a patient accordingly. This would allow orthodontists to monitor patients more closely or modify the treatment plan to minimize the amount EARR. The study sample consists of 60 subjects from 36 different families. The siblings had received orthodontic treatment at Indiana University School of Dentistry or in the private practice of Dr. James V. Macri. EARR was not a prerequisite to be included in this sample. Informed consent was obtained for sample collection. This study received Indiana University School of Dentistry Student Research Subcommittee Review and Indiana University Purdue University at Indianapolis Institutional Review Board approval. No significant difference between any of the IL-6 genotypes and EARR could be noted. The hypothesis that individuals with the IL-6 -174 C/C genotype would show a greater amount of EARR during orthodontic treatment could not be supported.
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    Genetic Factors in External Apical Root Resorption Associated with Orthodontic Treatment
    (2004-06) Al-Qawasmi, Riyad A.; Hartsfield, James K., Jr.; Everett, Eric T.; Roberts, W. Eugene; Foroud, Tatiana M.; Mah, James
    External apical root resorption (EARR) is a common sequela of orthodontic treatment, although it may also occur without orthodontic treatment. Despite rigorous investigation, no single factor or group of factors that directly causes root resorption has been identified. Experiment 1. A sample of 83 pairs of full siblings who had undergone orthodontic treatment was studied. Measurements were made of the longest maxillary central incisor, mandibular central incisor and mesial and distal roots of the mandibular first molars. Heritability estimates were generated by generalized liner models. Our results showed that the heritability estimate of the EARR was 64% on average. It was concluded that there was sufficient heritability for EARR to pursue genetic analysis. Experiment 2. Five polymorphic markers flanking or lying within the IL-IA , IL-JB, TNSALP, TNFA, and TNFRSFJ JA genes were used in a candidate gene approach to assess linkage and association with EARR in 38 pedigrees. Suggestive evidence for linkage between EARR and the polymorphic marker D18S64 was obtained with the analysis program MAPMAKER/SIBS (LOD score 2.51). The Q-TDT program showed highly significant (p = 0.0003) evidence of linkage disequilibrium of IL-1 B polymorphisms with EARR. Our analysis indicates that the JL -1 B polymorphism accounts for 15% of the total EARR variation. Experiment 3. Nine-week-old male mice were randomly selected as controls or for placement under anesthesia of an open coil spring ligated to the left maxillary first molar producing a force of approximately 25 g. The control (C) or treated (T) per strain were A/J (C=3,T=9), C57BL/6J (C=7,T=8), C3H/HeJ (C = 4,T=6), BALB/cJ (C=4,T=6), 129P3 /J (C=6,T=8), DBA/2J (C=8,T=9), SJL/J (C=8,T= 10), and AKR/J (C=9,T =8). Animals were sacrificed after nine days of treatment or control; maxillae were immediately removed, prepared, sectioned, mounted, stained with H&E, and observed microscopically at 1 OOX to determine root resorption. Mice were grouped into root resorption resistant (A/J, C57BL/6J and SJL/J); intermediate (C3H/HeJ and AKR/J); and susceptible (BALB/cJ, DBA/2J, and 129P3/J) strains. It was concluded that there were differential susceptibility or resistance to root resorption among inbred mouse strains, indicating that genotype is an influencing factor.
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    Root Damage in Mechanically Fatigued Teeth
    (2004) Altschul, Aaron S.; Katona, Thomas R.; Roberts, W. Eugene; Everett, Eric T.; Hohlt, William F.; Shanks, James C.
    According to one theory of root resorption, occlusal trauma during orthodontic tooth movement damages the cementum covering the root dentin. The body detects the exposed dentin and seeks to remove it, and the result is root resorption. This experiment will explore an aspect of this theory by quantifying the amount and location of damage in mechanically fatigued teeth. Nine dog mandibles were sectioned at the mandibular symphysis. Each half was mounted in orthodontic resin with the incisors upright and exposed. The block was inserted into a jig and placed into a servohydraulic mechanical testing machine. The left central incisor was fatigue loaded with a 2Hz, 10-90 N sinusoidal force for 100,000 cycles (approximately 14 hours). The right central incisor served as the control. Both specimens were scanned with a micro-CT unit, stained with basic fuchsin, and then sectioned along the sagittal plane. Because the experimental and control specimens were stained before sectioning, only microdamage due to the loading process would be evident in the sections. Microdamage which occurred during the sectioning process would not be stained. Central sections through the long axes of the samples were examined for the presence of microdamage with a light microscope and a micro-CT unit. Based on preliminary findings, two types of staining patterns were measured and recorded. The first was called "diffuse stain" and consisted of large stained areas in the dentinal tubules. Diffuse stain was not associated with any visible features at the dentinocemental junction. The second type of staining pattern was called "stained defects." Stained defects were stained irregularities at the dentinocemental junction. For statistical analysis, the roots were divided into buccal-cervical, buccal-middle, buccal-apical, lingual-cervical, lingual-middle, and lingual-apical regions. Comparisons between the fatigued and non-fatigued teeth for differences in area, length, and depth were made under the generalized estimating equation (GEE) framework applied to normally-distributed data. Because the measurements were not normally distributed, a rank transformation of the measurements was performed before conducting the analyses. Comparisons between the fatigued and non-fatigued teeth for differences in presence or absence of stain or defects were made using Cochran-Mantel-Haenszel tests. Repeatability of the measurements was assessed using intraclass correlation coefficients (ICCs), paired t-tests, and Bland-Altman plots. The ICC's ranged from 0 .85 to 1.00, thus making the repeatability of the measurements generally very good. The statistical analysis showed there were no significant differences between the experimental and control teeth for stained defects or diffuse staining for length, depth, or area measurements. However, analyses comparing the distribution of stained defects and diffuse stain within the control and experimental specimens showed significant differences in the distribution of stained defects within the experimental specimens. In the experimental specimens, the stained defects were distributed in a gradient, with the most in the apical region and progressing to the least amount in the cervical region. In the control specimens, there was only a difference in the stained defects between the cervical and apical regions. This distribution is consistent with the biomechanical model which shows increasing stress moving from the cervical region towards the apex. These results show that the test and control specimens differed in how the stained defects were distributed throughout the root, even though there were no differences in the amount of staining between the control and experimental specimens. Whole tooth and histologic slides were scanned with the micro-CT unit, but the dentinocemental junction could not be delineated enough to make any measurements. No data could be collected regarding microdamage in this area using the micro-CT unit. It was recommended that future studies use a tomography unit with better resolution, use a larger samples size, employ a contrast agent when trying to visualize microdamage with the micro-CT unit, and incorporate a way to measure the intensity of the staining in addition to the location and size.
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