The Complexity of Skeletal Transverse Dimension: From Diagnosis, Management, and Treatment Strategies to the Application of Collaborative Cross (CC) Mouse Model.

This study investigates the significance of skeletal transverse dimension (STD) in orthodontic therapy and its impact on occlusal relationships. The primary goal is to enhance understanding and promote the integration of transverse skeletal diagnostics into routine orthodontic assessments. To achieve this aim, the study employs a comprehensive approach, utilizing model analysis, clinical assessments, radiographic measurements, and occlusograms. The initial step involves a meticulous assessment of deficiencies in the maxilla, mainly focusing on transverse dimension issues. Various successful diagnostic methods are employed to ascertain the type and presence of these deficiencies. Furthermore, the study compares surgically assisted maxillary expansion (SARME) and orthopedic maxillary expansion (OME) in addressing skeletal transverse issues. Stability assessments and efficacy analyses are conducted to provide valuable insights into the superiority of SARME over OME. The findings reveal that proper evaluation of STD is crucial in orthodontic diagnosis, as overlooking transverse dimension issues can lead to complications such as increased masticatory muscle activity, occlusal interferences, and an elevated risk of gingival recession. Surgically assisted maxillary expansion emerges as a more stable solution than orthopedic methods. In conclusion, incorporating skeletal transverse diagnostics into routine orthodontic assessments is imperative for achieving optimal occlusal relationships and minimizing negative consequences on dentition, periodontium, and joints. The study emphasizes the significance of accurate three-dimensional assessments and recommends the consideration of SARME over OME for addressing skeletal transverse deficiencies. Finally, the Collaborative Cross (CC) mouse model is also a novel mouse model for studying complex traits. Exploring the Collaborative Cross mouse model opens avenues for future research, promising further insights into transverse skeletal issues in orthodontics.

Impact of Mechanical Strain and Nicotinamide on RUNX2-Deficient Osteoblast Mimicking Cleidocranial Dysplasia.

Cleidocranial dysplasia (CCD) is a rare genetic defect caused by a heterozygous mutation of runt-related transcription factor 2 (RUNX2), which is important for osteoblast and skeletal development. RUNX2-deficiency causes extra- and intra-oral malformations that often require orthodontic treatment. Nicotinamide (NAM) affects bone remodelling processes. As these are crucial for orthodontic therapy, NAM could improve orthodontic treatment in CCD patients. This study investigates the effect of NAM in control and RUNX2-deficient osteoblasts under mechanical strain mimicking orthodontic treatment. First, the optimal NAM concentration and the differences in the expression profile of control and RUNX2-deficient osteoblasts were determined. Subsequently, osteoblasts were exposed to tensile and compressive strain with and without NAM, and the expression of genes critically involved in bone remodelling was investigated. NAM increased the expression of bone remodelling genes. RUNX2-deficient osteoblasts expressed more receptor activator of NFkB ligand (RANKL) and interleukin-6 (IL6), but less colony-stimulating factor-1 (CSF1). Most of the positive effects of NAM on bone remodelling genes were impaired by mechanical loading. In conclusion, NAM stimulated osteoblast differentiation by increasing the expression of RUNX2 and regulated the expression of osteoclastogenic factors. However, the positive effects of NAM on bone metabolism were impaired by mechanical loading and RUNX2 deficiency.

Anterior Open Bite Malocclusion: From Clinical Treatment Strategies towards the Dissection of the Genetic Bases of the Disease Using Human and Collaborative Cross Mice Cohorts.

Anterior open bite malocclusion is a complex dental condition characterized by a lack of contact or overlap between the upper and lower front teeth. It can lead to difficulties with speech, chewing, and biting. Its etiology is multifactorial, involving a combination of genetic, environmental, and developmental factors. Genetic studies have identified specific genes and signaling pathways involved in jaw growth, tooth eruption, and dental occlusion that may contribute to open bite development. Understanding the genetic and epigenetic factors contributing to skeletal open bite is crucial for developing effective prevention and treatment strategies. A thorough manual search was undertaken along with searches on PubMed, Scopus, Science Direct, and Web of Science for relevant studies published before June 2022. RCTs (clinical trials) and subsequent observational studies comprised the included studies. Orthodontic treatment is the primary approach for managing open bites, often involving braces, clear aligners, or other orthodontic appliances. In addition to orthodontic interventions, adjuvant therapies such as speech therapy and/or physiotherapy may be necessary. In some cases, surgical interventions may be necessary to correct underlying skeletal issues. Advancements in technology, such as 3D printing and computer-assisted design and manufacturing, have improved treatment precision and efficiency. Genetic research using animal models, such as the Collaborative Cross mouse population, offers insights into the genetic components of open bite and potential therapeutic targets. Identifying the underlying genetic factors and understanding their mechanisms can lead to the development of more precise treatments and preventive strategies for open bite. Here, we propose to perform human research using mouse models to generate debatable results. We anticipate that a genome-wide association study (GWAS) search for significant genes and their modifiers, an epigenetics-wide association study (EWAS), RNA-seq analysis, the integration of GWAS and expression-quantitative trait loci (eQTL), and micro-, small-, and long noncoding RNA analysis in tissues associated with open bite in humans and mice will uncover novel genes and genetic factors influencing this phenotype.

Validation of a mathematical-geometrical model to calculate the length of an individual anterior arch.

PURPOSE: For resolving anterior dental crowding or spacing, it is of key interest in personalised orthodontic diagnostics and treatment planning to predict the extent of space gained or lost in the anterior dental arch by changing incisor inclination or position. To facilitate the determination of anterior arch length (AL) and to predict its alterations following tooth movements, a mathematical-geometrical model, based on a third-degree parabola, was established. The aim of this study was to validate this model and assess its diagnostic precision. METHODS: This retrospective diagnostic study evaluated 50 randomly chosen dental casts taken before (T0) and after (T1) orthodontic treatment with fixed appliances. Plaster models were digitally photographed, allowing two-dimensional digital measurements of arch width, depth and length. A computer programme based on the mathematical-geometrical model to be validated was created to calculate AL for any given arch width and depth. Mean differences and correlation coefficients as well as Bland-Altman plots were used to compare the measured and the calculated (predicted) AL, evaluating the precision of the model. RESULTS: Inter- and intrarater reliability tests showed reliable measurements of arch width, depth and length. Measured and calculated (predicted) AL revealed high concordance according to concordance correlation coefficient (CCC), intraclass correlation coefficient (ICC), and Bland-Altman analyses and negligible differences between the mean values. CONCLUSIONS: The mathematical-geometrical model calculated anterior AL without significant difference to the measured AL, indicating its validity. The model can thus be used clinically for predicting alterations of AL following therapeutic changes of incisor inclination/position.

Association between craniofacial patterns and third molar agenesis in orthodontic patients.

PURPOSE: Third molar agenesis (TMA) is the most common craniofacial anomaly and has been associated with craniofacial patterns in different populations. Therefore, the aim of this retrospective cross-sectional study was to assess a possible association between craniofacial patterns and TMA in German orthodontic patients. METHODS: Patients undergoing orthodontic treatment with dental records including anamnesis, pretreatment lateral cephalograms and orthopantomograms were evaluated. Cephalometric analyses were conducted digitally and lines, angles and proportions were measured to investigate craniofacial morphology. Skeletal classes were determined by the individualised Wits appraisal and ANB angle. The TMA was identified with the help of orthopantomograms. Patients showing agenesis of at least one third molar were included in the TMA group. Statistical analysis was performed to assess the association between TMA and craniofacial patterns (α of p ≤ 0.05). RESULTS: A total of 148 patients were included, 40 (27.0%) presented at least one missing tooth (TMA group) and 108 (73.0%) showed full dentition (control group). Skeletal class determined by the individualised Wits appraisal revealed statistical significance between the TMA and control groups (p = 0.022), in which TMA patients were 11 times more likely to present with an individualised skeletal class III (odds ratio 11.3, 95% confidence interval 1.7-139.5). Skeletal cephalometric analysis revealed no statistical differences between TMA and control groups for any further angular, linear and proportional parameters. CONCLUSION: Third molar agenesis was associated with skeletal class III determined by the individualised Wits appraisal.

Comparative treatment outcomes after bilateral extractions of maxillary second molars or first premolars in patients with class II malocclusion: a retrospective study.

BACKGROUND: This retrospective cohort study aimed to compare treatment results between bilateral extraction of upper second molars (M2) and first premolars (P1) in terms of treatment timing, cephalometry, upper third molar alignment and relapse in the long-term. METHODS: Fifty-three consecutively treated Caucasian patients with a brachyfacial pattern, skeletal class I and dental class II requiring extraction in the maxilla due to crowding were retrospectively divided into group I (M2 extracted; N = 31) and II (P1 extracted; N = 22). Fixed appliances were inserted after extraction and after distalisation of the first molars in group I. Post-treatment lateral cephalograms were digitally analysed and compared between groups. Six to seven years later relapse and success of upper third molar alignment were clinically evaluated as well as orthodontic treatment duration, pre-treatment age and gender recorded. RESULTS: After debonding patients with second molar extraction showed significantly smaller values for the Wits-appraisal, but higher values for index and facial axis. Extracting first premolars caused significantly more retroinclination/-position of anterior teeth and an increased profile concavity, more relapse and less successful alignment of upper third molars. Orthodontic treatment duration, pre-treatment age and gender were not significantly different between groups. CONCLUSIONS: Bilateral extraction of upper first premolars or second molars may solve dental crowding in skeletal class I dental class II patients with a brachyfacial growth pattern. Upper second molar extraction seems to affect maxillary third molar alignment, long-term stability and dental and soft-tissue cephalometric parameters positively, but no intervention proved to be clearly superior.

Impact of PIEZO1-channel on inflammation and osteoclastogenesis mediated via periodontal ligament fibroblasts during mechanical loading.

The identification of mechanosensitive ion channels and their importance in innate immunity provides new starting points to elucidate the molecular mechanisms of orthodontic tooth movement. The mechanosensitive electron channel PIEZO1 (Piezo Type Mechanosensitive Ion Channel Component 1) may play a crucial role in orthodontic tooth movement. To investigate the role of the PIEZO1 channel, periodontal ligament fibroblasts (PDLF) were subsequently treated with a PIEZO1 inhibitor (GsMTx) with simultaneous pressure application or with an activator (JEDI2) without mechanical strain. The expression of genes and proteins involved in orthodontic tooth movement was examined by RT-qPCR, Western blot and ELISA. In addition, the effect on PDLF-mediated osteoclastogenesis was investigated in a coculture model using human monocytes. Inhibition of PIEZO1 under pressure application caused a reduction in RANKL (receptor activator of NF-kB ligand) expression, resulting in decreased osteoclastogenesis. On the other hand, activation of PIEZO1 without mechanical strain downregulated OPG (osteoprotegerin), resulting in increased osteoclastogenesis. PIEZO1 appears to play a role in the induction of inflammatory genes. It was also shown to influence osteoclastogenesis.

Floating norms for individualising the ANB angle and the WITS appraisal in orthodontic cephalometric analysis based on guiding variables.

PURPOSE: The sagittal skeletal relationship of maxilla and mandible (skeletal class) can generally be determined via lateral cephalograms (ANB angle or Wits appraisal) by comparing measurements to empirical norms based on the respective population mean. However, values differing from these empirical norms also enable a therapeutically desired, normal class I occlusion depending on individual craniofacial pattern, thus requiring floating norms based on guiding variables. As available regression equations consider only few predictor variables and are not up-to-date regarding a contemporary patient collective, the aim of this study was to establish improved and extended regression equations for individualising the ANB angle and Wits appraisal. METHODS: This retrospective, cross-sectional multicentre study was based on 71 Caucasian male and female subjects of any age with normal dental occlusion. We cephalometrically analysed digitised pretreatment lateral radiographs and performed multiple linear regression analyses to identify suitable skeletal predictor variables for individualising the ANB angle and Wits appraisal. RESULTS: Inter- and intrarater reliability tests showed mostly perfect measurement concordance. Both original regression equations by Panagiotidis/Witt and Järvinen could be updated for a contemporary population with new regression coefficients. The equation for individualising the ANB could be further optimised in its prediction reliability by adding the skeletal predictor variables NL-NSL, NSBa, facial axis (Ricketts) and index (Hasund), whereas the recalculated Wits equation could not be further improved by additional guiding variables. CONCLUSIONS: The improved regression formulae for individualising the ANB angle and Wits appraisal should help to improve the assessment of sagittal skeletal class in clinical orthodontic practice.

Relapse in class II orthognathic surgery: a systematic review.

OBJECTIVES: Relapse after orthognathic surgery seems to depend on diverse factors. Proffit et al. postulated in 2007 a "hierarchy of stability" (Head Face Med 6:66, 2007), ranking posttreatment stability after various orthognathic procedures, but no systematically reviewed evidence was provided. Therefore, the aim of this review was to investigate the extent of class II relapse in orthognathic surgery of Angle class II patients depending on the surgical procedure used. MATERIALS AND METHODS: Seven databases were searched for randomized and controlled clinical trials to compare relapse in surgical procedures for Angle class II patients. After duplicate study selection, data extraction and risk of bias assessment were performed with the ROBINS-I tool as well as data synthesis by frequency distribution, followed by assessment of the quality of evidence with GRADE. RESULTS: Four non-randomized cohort-studies with a total of 132 patients were included. Bimaxillary procedures as well mandibular advancement procedures proved to be highly stable. Single jaw interventions at the maxilla achieved mostly stable results at sagittal dimension and problematic stability in the vertical dimension. However, there were only limited data available with low quality of evidence. CONCLUSIONS: Limited existing evidence of low quality partly support the postulated hierarchy of stability of Proffit et al. (Head Face Med 6:66, 2007) and indicates that a surgical correction of class II dysgnathia with bimaxillary procedures and mandibular advancement seems to be highly stable. However, additional studies are needed to address the relation between relapse and surgical orthognathic intervention. Trial registration PROSPERO 2019 CRD42019144873.

Impact of Melatonin on RAW264.7 Macrophages during Mechanical Strain.

The concentration of melatonin is elevated during the night when patients mainly wear removable orthodontic appliances. Next to periodontal ligament fibroblasts and osteoblasts, macrophages react to mechanical strain with an increased expression of inflammatory mediators. Here, we investigated the impact of melatonin on RAW264.7 macrophages exposed to tensile or compressive strain occurring during orthodontic tooth movement in the periodontal ligament. Before exposure to mechanical strain for 4 h, macrophages were pre-incubated with different melatonin concentrations for 24 h, to determine the dependence of melatonin concentration. Afterwards, we performed experiments with and without mechanical strain, the most effective melatonin concentration (25 µM), and the melatonin receptor 2 (MT2) specific antagonist 4P-PDOT. The expression of inflammatory genes and proteins was investigated by RT-qPCR, ELISAs, and immunoblot. Both tensile and compressive strain increased the expression of the investigated inflammatory factors interleukin-1-beta, interleukin-6, tumor necrosis factor alpha, and prostaglandin endoperoxide synthase-2. This effect was inhibited by the addition of melatonin. Incubation with 4P-PDOT blocked this anti-inflammatory effect of melatonin. Melatonin had an anti-inflammatory effect on macrophages exposed to mechanical strain, independent of the type of mechanical strain. As inhibition was possible with 4P-PDOT, the MT2 receptor might be involved in the regulation of the observed effects.

Individual dental and skeletal age assessment according to Demirjian and Baccetti: Updated norm values for Central-European patients.

PURPOSE: Chronological age often differs from dental and skeletal age. With orthopantomograms and lateral cephalograms, dental and skeletal development can be determined according to the methods published by Demirjian et al. and Baccetti et al. However, gender and skeletal class as possible confounders were frequently not considered and available norm values are not up-to-date. This retrospective cross-sectional study thus aimed to evaluate effects of skeletal class and gender on dental and skeletal age of growing patients and to generate updated norm values for contemporary Central-European patients. METHODS: A total of 551 patients were included in the dental and 733 in the skeletal age assessment, respectively. Dental analysis was based on tooth mineralisation stages in orthopantomograms (Demirjian) and skeletal age was defined by cervical vertebrae maturation stages (CVMS) in lateral cephalograms (Baccetti). Skeletal class was determined by the individualised ANB angle of Panagiotidis/Witt. With nonlinear regression analysis a formula for determining dental age was established. Effects of gender and skeletal class were evaluated and updated norm values generated. RESULTS: Inter- and intrarater reliability tests revealed at least substantial measurement concordance for tooth mineralisation and CVMS. Demirjian stages and CVMS significantly depended on gender with girls developing earlier. Skeletal class significantly affected skeletal age only, but without clinical relevance. Updated norm values for dental age differed significantly from the original values of Demirjian and the values for skeletal age differed from those published by Baccetti. CONCLUSION: Optimised norms, separated by gender, increase precision in determining individual dental and skeletal age during orthodontic treatment planning. Further studies analysing the effect of skeletal class on dental and skeletal development are needed.

Impact of Leptin on the Expression Profile of Macrophages during Mechanical Strain In Vitro.

Childhood obesity is a growing problem in industrial societies and associated with increased leptin levels in serum and salvia. Orthodontic treatment provokes pressure and tension zones within the periodontal ligament, where, in addition to fibroblasts, macrophages are exposed to these mechanical loadings. Given the increasing number of orthodontic patients with these conditions, insights into the effects of elevated leptin levels on the expression profile of macrophages during mechanical strain are of clinical interest. Therefore, the aim of this in vitro study was to assess the influence of leptin on the expression profile of macrophages during simulated orthodontic treatment. RAW264.7 macrophages were incubated with leptin and lipopolysaccharides (LPS) from Porphyromonas gingivalis (P. gingivalis) or with leptin and different types of mechanical strain (tensile, compressive strain). Expression of inflammatory mediators including tumor necrosis factor (TNF), Interleukin-1-B (IL1B), IL6, and prostaglandin endoperoxide synthase (PTGS2) was assessed by RT-qPCR, ELISAs, and immunoblot. Without additional mechanical loading, leptin increased Tnf, Il1b, Il6, and Ptgs2 mRNA in RAW264.7 macrophages by itself and after stimulation with LPS. However, in combination with tensile or compressive strain, leptin reduced the expression and secretion of these inflammatory factors. By itself and in combination with LPS from P. gingivalis, leptin has a pro-inflammatory effect. Both tensile and compressive strain lead to increased expression of inflammatory genes. In contrast to its effect under control conditions or after LPS treatment, leptin showed an anti-inflammatory phenotype after mechanical stress.

Single Nucleotide Polymorphisms in COX2 Is Associated with Persistent Primary Tooth and Delayed Permanent Tooth Eruption.

Persistent primary tooth (PPT) is a prevalent clinical condition that occurs when a primary tooth is over-retained beyond the established period of its normal exfoliation time, remaining in the oral cavity. Many factors could be involved in the risk of PPT; therefore, the aim of this study was to evaluate if single nucleotide polymorphisms (SNPs) in the COX2 gene are associated with PPT. Children undergoing orthodontic treatment were screened. Orthopantomographs were assessed to evaluate PPT according to the Nolla stage of its permanent successor. The primary tooth was considered retained when its successor permanent tooth was in Nolla stage 8 and below the alveolar crypt, Nolla stage 9, or Nolla stage 10. A saliva sample from each child was collected and used for DNA extraction. A real-time PCR of two SNPs, rs689466 (-1195 G/A) and rs5275 (+665 T/C), was performed. A chi-square test was used to compare the allele and genotype distribution. Haplotype analysis was also performed. A total of 100 children were included in the study. Fifty-one had at least one PPT, while 49 children were classified as a control. The number of teeth persistent in the oral cavity ranged from 1 to 8. The genotype distribution was associated with PPT in the co-dominant model (p = 0.006) for SNP rs5275. The individuals that carry two T alleles (TT) compared with the individuals that carry at least one C allele (C + TC) had an almost three times higher chance of presenting with PPT (p = 0.012; OR = 2.99, CI95% 1.28 to 6.95-recessive model). The haplotype C-A for the SNPs rs5275 and rs689466, respectively, was significantly associated (p = 0.042). In conclusion, single nucleotide polymorphisms in the gene encoding for COX2 are associated with persistent primary tooth and may delay permanent tooth eruption.

Dietary salt and myeloid NFAT5 (nuclear factor of activated T cells 5) impact on the number of bone-remodelling cells and frequency of root resorption during orthodontic tooth movement.

PURPOSE: The aim of the study was to investigate the impact of dietary salt and the osmoprotective transcription factor nuclear factor of activated T cells 5 (NFAT5) in myeloid cells on bone remodelling cells as osteocytes, osteoblasts and osteoclasts and on force-induced dental root resorptions in a mouse model. METHODS: Control mice and mice lacking myeloid NFAT5 (nuclear factor of activated T cells 5) were either kept on low, normal or high salt diets. After one week on the specified diet an elastic band was inserted between the first and second molar to induce orthodontic tooth movement. One week later the mice were euthanised and jaws were fixed for histological analysis. Osteocyte, osteoblast and osteoclast numbers as well as extent of root resorptions were assessed histologically. RESULTS: Osteocyte number was diminished with high salt diet in wildtype mice. Osteoblast numbers increased with low salt diet in control mice and reduced with high salt diet in mice without NFAT5 in myeloid cells. High salt diet tended to increase osteoclast number in control mice. In mice without myeloid NFAT5, numbers of osteoclasts were reduced under high salt diet. Frequency of force-induced root resorptions tended to be dependent on dietary salt content in control mice. CONCLUSION: During orthodontic tooth movement dietary salt impacts on the frequency of root resorptions and the number of osteoclasts and osteoblasts in alveolar bone of mice. This can affect bone remodelling during orthodontic treatment. Myeloid NFAT5 impacts on this salt-dependent reaction.

Transforming Growth Factor Beta Receptor 2 (TGFBR2) Promoter Region Polymorphisms May Be Involved in Mandibular Retrognathism.

Skeletal malocclusions are common phenotypes in humans and have a strong influence on genetic factors. Transforming growth factor beta (TGFß) controls numerous functions of the human body, including cell proliferation, differentiation, and migration. Thus, this study is aimed at evaluating whether genetic polymorphisms in TGFB1 and its receptor TGFBR2 are associated with mandibular retrognathism in German children and adolescents. Children and teenagers older than 8 years in the mixed or permanent dentition were included in this study. Patients with syndromes and facial trauma and patients with congenital alterations were excluded. Digital cephalometric tracings were performed using the anatomical landmarks point A, point B, sella (S), and nasion (N). Patients that have a retrognathic mandible (SNB < 78°) were selected as case group, and the patients with an orthognathic mandible (SNB = 78°- 82°) were selected as the control group. Genomic deoxyribonucleic acid (DNA) from saliva was used to evaluate four genetic polymorphisms in TGFB1 (rs1800469 and rs4803455) and TGBR2 (rs3087465 and rs764522) using real-time PCR. Chi-square or Fisher exact tests were used to compare gender, genotype, and allele distribution among groups. Genotype distribution was calculated in an additive and recessive model. Haplotype analysis was also performed. The established alpha of this study was 5%. A total of 146 patients (age ranging from 8 to 18 years) were included in this epidemiological genetic study. The genetic polymorphism rs3087465 in TGFBR2 was associated with mandibular retrognathism. Carrying the AA genotype in the rs3087465 polymorphism decreased the chance of having mandibular retrognathism (odds ratio = 0.25, confidence interval 95% = 0.06 to 0.94, p = 0.045). None of the haplotypes was associated with mandibular retrognathism (p > 0.05). In conclusion, we found that the genetic polymorphism rs3087465 in the promoter region of the TGFBR2 was associated with mandibular retrognathism in Germans.

Association of third molar agenesis and microdontia with genetic polymorphisms in vitamin-D-related genes.

The present study aimed to evaluate if functional genetic polymorphisms in vitamin-D-related genes are associated with third molar agenesis and third molar microdontia in German orthodontic patients. Pre-orthodontic and follow-up treatment records were evaluated for phenotype definition. Saliva samples were collected for DNA extraction. Eight potential functional genetic polymorphisms in VDR [rs731236 (TaqI), rs7975232 (ApaI), rs2228570 (FokI), and rs1544410 (BsmI)], CYP27B1 (rs4646536), CYP24A1 (rs927650), GC (rs4588), and SEC23A (rs8018720) were evaluated using real-time PCR. Comparison among the groups were performed (third molar anomaly vs. control; third molar agenesis vs. control; and third molar microdontia vs. control) with an alpha of 5%. A total of 164 patients were analyzed. Forty-nine (29.9%) patients had at least one third molar anomaly. In the haplotype analysis, genetic polymorphisms in VDR and CYP27B1 were associated with third molar anomalies (p < 0.05). The G allele in rs8018720 (SEC23A) was more frequent in microdontia cases. In the genotype distribution analysis, rs8018720 in SEC23A was associated with third molar microdontia in the co-dominant (p = 0.034; Prevalence Ratio [PR]=5.91, 95% Confidence Interval [CI]= 1.14-30.66) and in the recessive (p = 0.038; PR=5.29; 95% CI= 1.09-25.65) models. In conclusion, vitamin D-related genes could be involved in third molar anomalies.

Ideal transverse position of mandibular first molars based on CBCT-derived alveolar bone coverage.

BACKGROUND: In orthodontic treatment, transverse arch width often needs to be adjusted to correct anomalies such as posterior crossbite. Ideal transverse arch width at the first molars enabling long-term stability and periodontal health, however, requires sufficient posttreatment bony coverage buccally and orally of the tooth roots. Thus, the aim of this retrospective study was to determine the physiological alveolar bone thickness at the buccal and oral roots of the first mandibular molars in the general population using human CBCT scans assessing local and gender-specific differences. METHODS: CBCTs of 124 random 11- to 55-year old patients (46 female, 78 male) were analysed retrospectively. Alveolar bone thickness was measured digitally at mesial and distal tooth roots of the first mandibular molars buccally and orally at different vertical positions (4 and 8 mm apically of the cement-enamel-junction CEJ). For each patient, the mean of corresponding measurements from left and right molars was used for analysis. RESULTS: All measurements were reliable, as proven by intrarater- and interrater-reliability-testing. On average, bone thickness increased from the mesial to the distal tooth root, as well as in apical and oral direction. These local differences in alveolar bone thickness were all highly significant at p < 0.0001. Women showed thicker bone buccally at the distal tooth root at 8 mm apically of the CEJ, as well as orally at both mesial and distal tooth roots 4 mm apically of the CEJ. CONCLUSIONS: The results of this study suggest that especially in buccal, mesial and gingival direction alveolar bone around mandibular first molars becomes thinner and hence the scope for orthodontic tooth movements is limited. Our results should aid assessing ideal transverse molar position based on alveolar bone coverage, although variations due to age may occur.

Assessing the association between vitamin D receptor and dental age variability.

OBJECTIVES: To explore the association between genetic polymorphisms in vitamin D receptor (VDR), vitamin D serum levels, and variability in dental age. MATERIAL AND METHODS: This cross-sectional study was based on an oral examination, panoramic radiograph analysis, and genotype analysis from biological samples. Dental age was evaluated using two different methods: Demirjian et al. (Hum Biol 45:211-227, 1973) and Hofmann et al. (J Orofac Orthop.78:97-111, 2017). The genetic polymorphisms BglI (rs739837) and FokI (rs2228570) in VDR were genotyped through real-time PCR. The vitamin D level was also measured in the serum. Delta (dental age-chronological age) was compared among genotypes in VDR in the co-dominant model. Multiple linear regression analysis was also performed. An established alpha of 5% was used. RESULTS: Genotype distributions of BglI and FokI were not associated with dental maturity (p > 0.05). In the logistic regression analyses, genotypes in BglI and FokI and vitamin D levels were not associated with variability in dental age (p > 0.05). CONCLUSIONS: The genetic polymorphisms BglI and FokI in VDR and the vitamin D levels were not associated with variability in dental age. CLINICAL RELEVANCE: To unravel the factors involved in dental maturity can improve dental treatment planning in pediatric and orthodontic practice.

Exploring the Association Between Genetic Polymorphisms in Genes Involved in Craniofacial Development and Isolated Tooth Agenesis.

Tooth agenesis is a common congenital anomaly in humans and is more common in oral cleft patients than in the general population. Many previous studies suggested that oral cleft and tooth agenesis share a similar genetic background. Therefore, this study explored the association between isolated tooth agenesis and genetic polymorphisms in genes that are crucial for craniofacial and tooth development. Panoramic radiographs, anamnesis, and genomic DNA from 273 patients were included. Patients were classified as tooth agenesis present, when at least one permanent tooth was congenitally missing. Patients with syndromes and oral cleft were excluded. Only unrelated patients were included. The genetic polymorphisms in BMP2 (rs235768 and rs1005464), BMP4 (rs17563), RUNX2 (rs59983488 and rs1200425), and SMAD6 (rs3934908 and rs2119261) were genotyped by real-time polymerase chain reaction. Genotype and allele distributions were compared between the tooth agenesis phenotypes and controls by Chi-square test. Haplotype and diplotype analysis were also performed, in addition to multivariate analysis (alpha of 0.05). A total of 86 tooth agenesis cases and 187 controls were evaluated. For the rs235768 in BMP2, patients carrying TT genotype have higher chance to present tooth agenesis [p < 0.001; prevalence ratio (PR) = 8.29; 95% confidence interval (CI) = 4.26-16.10]. The TT genotype in rs3934908 (SMAD6) was associated with higher chance to present third molar agenesis (p = 0.023; PR = 3.25; 95% CI = 1.17-8.99). BMP2 was also associated in haplotype and diplotype analysis with tooth agenesis. In conclusion, genetic polymorphisms in BMP2 and SMAD6 were associated with isolated tooth agenesis.

Myeloid HIF1α Is Involved in the Extent of Orthodontically Induced Tooth Movement.

During orthodontic tooth movement, transcription factor hypoxia-inducible factor 1α (HIF1α) is stabilised in the periodontal ligament. While HIF1α in periodontal ligament fibroblasts can be stabilised by mechanical compression, in macrophages pressure application alone is not sufficient to stabilise HIF1α. The present study was conducted to investigate the role of myeloid HIF1α during orthodontic tooth movement. Orthodontic tooth movement was performed in wildtype and Hif1αΔmyel mice lacking HIF1α expression in myeloid cells. Subsequently, µCT images were obtained to determine periodontal bone loss, extent of orthodontic tooth movement and bone density. RNA was isolated from the periodontal ligament of the control side and the orthodontically treated side, and the expression of genes involved in bone remodelling was investigated. The extent of tooth movement was increased in Hif1αΔmyel mice. This may be due to the lower bone density of the Hif1αΔmyel mice. Deletion of myeloid Hif1α was associated with increased expression of Ctsk and Acp5, while both Rankl and its decoy receptor Opg were increased. HIF1α from myeloid cells thus appears to play a regulatory role in orthodontic tooth movement.