Exploring the sex-associated differences in molars fused roots.

BACKGROUND: Human sexual dimorphism is associated with many biological characteristics, including dental variables. OBJECTIVES: To investigate if molars fused roots present sex-associated differences. METHODS: Panoramic radiographs were used to investigate the frequency and distribution of permanent molars fused roots. Only patients with all first and second permanent molars were included. Third molars were not investigated. Any molar with roots fused apical to the usual furcal position were considered molar fused roots. Comparisons between males and females were performed using chi-square or Fisher's and Mann-Whitney tests and the established alpha was 5% (p<0.05). Sex-differential liability models were also proposed. RESULTS: A total of 84 males and 86 females were included and 1360 molars were analyzed. Among them, 46 (26.06%) present at least one molar with fused root. Second maxillary molars were the most affected teeth. There was an association between sex and molars with fused roots. Females had a 3.4 higher chance to present fused roots than males (OR=3.4, CI 95% 1.6-6.8; p=0.0008). The female: male ratio of molars with fused roots was 2.5:1. The number of molars with fused roots ranged from 1 to 6 per patient, and the mean number of Females presented more molars with fused roots (mean = 1.01; standard deviation = 1.52) than males (mean = 0.31; standard deviation = 0.85) (p<0.05). CONCLUSIONS: Molar fused root of permanent teeth presents sex-associated differences, in which females are more affected than males. Our results support sex-differential liability models for molars fused roots.

Association between dental age and malocclusions: a systematic review.

BACKGROUND: The evidence in the literature suggests that some skeletal or dental malocclusions are involved with dental development, resulting in advanced or delayed dental age (DA). The purpose of this systematic review was to investigate the association between DA and different types of malocclusions. METHODS: The search was carried out on PubMed, Scopus, Web of Science, Virtual Health Library, and in the gray literature. Observational studies that evaluated the association between DA and sagittal, vertical, or transversal malocclusions were included. The quality assessment was performed using the Newcastle-Ottawa Scale (NOS). The data from primary studies were narratively synthesized. The certainty of evidence was evaluated using the GRADE approach. The study was conducted from August 2023 to October 2023. RESULTS: One Thousand Nine Hundred Ninety-One records were identified in the initial search. Twenty (n = 20) studies were included. Most of the studies (n=15) presented a moderate quality according to NOS. Twelve studies evaluated the association between DA and sagittal discrepancies; eight studies evaluated vertical discrepancies, and only one study analyzed a transversal discrepancy. Demirjian's method for DA assessment was the most used among the studies. The primary studies observed that patients of both sexes presenting a vertical growth pattern and males with skeletal Class III malocclusion tend to have advanced DA. The study that investigated transversal malocclusion found that unilateral posterior cross-bite is associated with delayed DA. The certainty of evidence was very low for all outcomes evaluated. CONCLUSION: DA may be associated with the type of malocclusion. It is suggested that DA can be used as an initial diagnostic tool in orthodontics. Future well-designed studies should be performed in order to investigate the association between DA and different types of malocclusions in more detail. TRIAL REGISTRATION: This study was registered in the PROSPERO database (CRD42023454207).

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.

BMP2 rs1005464 is associated with mandibular condyle size variation.

This study aimed to evaluate the association between single nucleotide polymorphisms (SNPs) in endochondral development-related genes and mandibular condyle shape, size, volume, and symmetry traits. Cone-beam Computed Tomographies and genomic DNA from 118 individuals were evaluated (age range: 15-66 years). Data from twelve 3D landmarks on mandibular condyles were submitted to morphometric analyses including Procrustes fit, principal component analysis, and estimation of centroid sizes and fluctuating asymmetry scores. Condylar volumes were additionally measured. Seven SNPs across BMP2, BMP4, RUNX2 and SMAD6 were genotyped. Linear models were fit to evaluate the effect of the SNPs on the mandibular condyles' quantitative traits. Only the association between BMP2 rs1005464 and centroid size remained significant after adjusting to account for the false discovery rate due to multiple testing. Individuals carrying at least one A allele for this SNP showed larger condylar size than common homozygotes GG (ß = 0.043; 95% CI: 0.014-0.071; P value = 0.028). The model including BMP2 rs1005464, age and sex of the participants explained 17% of the variation in condylar size. Shape, volume, and symmetry were not associated with the evaluated SNPs. These results suggest that BMP2 rs1005464 might be associated with variation in the mandibular condyles size.

Calcification patterns and morphology of Sella turcica are related to anteroposterior skeletal malocclusions: A cross-sectional study.

BACKGROUND: The sphenoid bone is an irregular, unpaired, symmetrical bone located in the middle of the anterior skull and is involved in craniofacial growth and development. Since the morphology of Sella turcica (ST) is associated with different craniofacial patterns, this study aimed to investigate if there is a correlation between ST morphology on the one hand and sagittal craniofacial patterns on the other hand. METHODS: This study was conducted with a convenience sample that included Brazilian individuals undergoing orthodontic treatment. Lateral cephalograms were used to evaluate the calcification pattern and morphology of ST, as well as skeletal class by analyzing the ANB angle. Pearson's chi-square test with Bonferroni post-hoc test was performed to evaluate the association between ST calcification pattern and morphology, and anteroposterior skeletal malocclusion. The established significance level was 0.05. RESULTS: The study collective was comprised of 305 orthodontic patients (178 (58.4 %) female, 127 (41.6 %) male), who had a mean age of 23.2 (±10.6) years. 131 participants (42.9 %) presented skeletal class I, 142 (46.6%) skeletal Class II, and 32 (10.5%) had a skeletal class III. The degree of prognathism of the mandible showed a homogenous distribution within the study collective (91 (29.9 %) orthognathic, 100 (32.9 %) retrognathic, 113 (37.2 %) prognathic mandible). Concerning the maxilla, 92 (30.2%) individuals presented an orthognathic upper jaw, whereas 60 (19.7%) showed maxillary retrognathism and 153 (50.2%) maxillary prognathism. Compared to patients with skeletal class I, skeletal class III individuals presented significantly more hypertrophic posterior clinoid process (p<0.007) and pyramidal shape of the dorsum of the ST (p<0.038). CONCLUSIONS: Our results suggest that the hypertrophic posterior clinoid process and pyramidal shape of the ST dorsum are more prevalent in individuals with skeletal class III malocclusion.

Exploring the association between PITX2, third molars agenesis and sella turcica morphology : PITX2, third molars agenesis and sella turcica morphology.

OBJECTIVES: PITX2 is required for mammalian development and single nucleotide polymorphisms (SNPs) in this gene could be involved in dental agenesis and sella turcica patterns. Thus, the present study evaluated the association between SNPs in PITX2, third molars agenesis and sella turcica phenotypes. MATERIALS AND METHODS: The sample consisted of healthy orthodontic German patients with lateral cephalometric radiographs with clearly visualization of the sella turcica, and dental orthopantomograms. The morphological variations of the sella turcica were evaluated using the lateral cephalograms, while third molar agenesis was evaluated using orthopantomograms. DNA isolated from buccal cells was used for genotyping three SNPs in PITX2 (rs3796902, rs1947187, and rs2595110). The analyzes were performed using a significance of 5%. There was no association between third molar agenesis and sella turcica phenotypes (p > 0.05). SNPs in PITX2 were also not associated with third molars agenesis (p > 0.05). RESULTS: SNPs in PITX2 were associated with sella turcica phenotypes. The rs3796902 was associated with hypertrophic posterior clinoid process (p = 0.013). The rs1947187 and rs2595110 were associated with sella turcica bridge type A (p = 0.013 and p = 0.011, respectively for genotype distribution). Patients that carry the genotypes GG-CC-AG (rs3796902- rs1947187- rs2595110) had 7.2 higher chance to present sella turcica bridge type A (p = 0.002; Odds ratio = 7.2, Confidence interval 95% 2.04-27.04). CONCLUSIONS: Third molar agenesis was not associated with SNPs in PITX2 and sella turcica phenotypes. SNPs in PITX2 may have an important role in sella turcica pattern.

New insights into the genetics of mandibular retrognathism: novel candidate genes.

PURPOSE: Mandibular retrognathism (MR) is a common skeletal malocclusion in humans with a strong genetic component. Single nucleotide polymorphisms (SNPs) in genes encoding epidermal growth factor (EGF) and EGF receptor (EGFR) could be involved in the etiology of mandibular retrognathism. Therefore, in this study, we investigated whether SNPs in the genes encoding for EGF and EGFR are associated with MR in German teenagers. METHODS: This nested case-control study evaluated German orthodontic patients, aged 10-18 years. DNA, which was isolated from buccal epithelial cells using two cytobrushes, was used for genotyping analysis and digital pretreatment lateral cephalograms were examined to calculate SNB and ANB. Patients with a retrognathic mandible (SNB < 78°) were included as cases, while patients with an orthognathic mandible (SNB = 78-82°) were included as controls. Four SNPs in the genes encoding for EGF and EGFR were chosen and genotyped using real-time PCR. Allele, genotype, and haplotype frequency were compared across groups (α = 5%). RESULTS: Finally, 119 patients were included in this study (45 orthognathic mandible, 74 retrognathic mandible). The minor allele G in rs4444903 (EGF) was statistically more frequent in individuals with an orthognathic mandible (p = 0.008). The haplotype formed by the mutant alleles for rs4444903|rs2237051 (EGF; G|A) was statistically more frequent in the orthognathic mandible group (p = 0.007). The SNPs rs4444903 and rs2237051 in EGF, and rs2227983 in EGFR were statistically associated with a decreasing risk of developing a retrognathic mandible according to univariate and multivariate statistical analysis (p < 0.05). CONCLUSION: SNPs in EGF (rs4444903 and rs2237051) and EGFR (rs2227983) were associated with MR in our German sample and could be genetic biomarkers for early and individualized diagnostic identification of retrognathic mandibular development by means of genetic screening tests.

Non-syndromic supernumerary teeth and association with a self-reported family history of cancer.

BACKGROUND: Supernumerary teeth are an alteration of dental developmental and result in the formation of teeth above the usual number. Epidemiologic studies suggested that patients with dentofacial anomalies and their family members may present an increased risk of developing cancer, including female breast cancer and gynecologic cancers. These observations indicate that genetic alterations that result in dental anomalies may be related to cancer development. Thus, the aim of the present study was to evaluate the association between supernumerary teeth and a family history of female breast cancer and gynecologic cancers. METHODS: The diagnosis of supernumerary teeth was based on clinical and radiographic examinations. For data collection, a questionnaire asking for information regarding ethnicity, age, gender, and self-reported family history of cancer up to the second generation was used. Statistical analysis was performed using the Χ2 test and Fisher's exact test with an established α of 5%. RESULTS: A total of 344 patients were included; 47 of them had one or more non-syndromic supernumerary teeth (not associated with any syndrome or cleft lip and palate) and 297 were control patients. Age, ethnicity, and gender distribution were not statistically different between the group with supernumerary teeth and the control group (p > 0.05). The supernumerary teeth were most commonly observed in the incisors area. Breast cancer (n = 17) was the most commonly self-reported type of cancer, followed by uterine cervical (n = 10), endometrial (n = 2), and ovarian (n = 1) cancers. Endometrial cancer was significantly associated with the diagnosis of supernumerary teeth (p = 0.017). CONCLUSION: This study suggests that patients with supernumerary teeth possess a higher risk of having family members with endometrial cancer.

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.

Narrating the Genetic Landscape of Human Class I Occlusion: A Perspective-Infused Review.

This review examines a prevalent condition with multifaceted etiology encompassing genetic, environmental, and oral behavioral factors. It stands as a significant ailment impacting oral functionality, aesthetics, and quality of life. Longitudinal studies indicate that malocclusion in primary dentition may progress to permanent malocclusion. Recognizing and managing malocclusion in primary dentition is gaining prominence. The World Health Organization ranks malocclusions as the third most widespread oral health issue globally. Angle's classification system is widely used to categorize malocclusions, with Class I occlusion considered the norm. However, its prevalence varies across populations due to genetic and examination disparities. Genetic factors, including variants in genes like MSX1, PAX9, and AXIN2, have been associated with an increased risk of Class I occlusion. This review aims to provide a comprehensive overview of clinical strategies for managing Class I occlusion and consolidate genetic insights from both human and murine populations. Additionally, genomic relationships among craniofacial genes will be assessed in individuals with Class I occlusion, along with a murine model, shedding light on phenotype-genotype associations of clinical relevance. The prevalence of Class I occlusion, its impact, and treatment approaches will be discussed, emphasizing the importance of early intervention. Additionally, the role of RNA alterations in skeletal Class I occlusion will be explored, focusing on variations in expression or structure that influence craniofacial development. Mouse models will be highlighted as crucial tools for investigating mandible size and prognathism and conducting QTL analysis to gain deeper genetic insights. This review amalgamates cellular, molecular, and clinical trait data to unravel correlations between malocclusion and Class I phenotypes.

Association between nutritional status and children and adolescents' dental caries experiences: an overview of systematic reviews.

An increasing number of systematic reviews (SR) has investigated the association between dental caries and nutritional status in children and adolescents, thus requiring an overview to compile the information in a single piece of evidence. Therefore, this study aimed to evaluate and summarize evidence from published SR on the association between dental caries and nutritional status in children and adolescents. A wide search was conducted on May 29, 2023, in six databases (Medline via PubMed, Scopus, Web of Science, Cochrane library, Embase, and the Virtual Health Library - VHL). An additional search was performed in the gray literature (Open grey and Google Scholar), SR registration databases, and the list of references of the included SR. Our inclusion criteria were based on acronym PECOS. Overall, two reviewers independently extracted the data, evaluated the risk of bias (ROBIS), and assessed the quality of the chosen studies (AMSTAR-2). Data from the included meta-analysis were summarized and certainty of evidence using the GRADE approach was performed. After removing duplicates and applying our eligibility criteria, 19 SR from 2006-2022 were included. We found that 17 SR showed high risk of bias and critically low methodological quality. We observed an association between dental caries experiences and nutritional status since seven SR found an association between obesity/overweight and dental caries; one, an association between underweight and dental caries; and eleven, no associations. The meta-analysis showed divergent results according to the study designs, used indices, and participants' age group, and were scored as having a very low certainty of evidence. Therefore, based on the high risk of bias, low methodological quality, and very low certainty of evidence of the chosen SR, most studies found no association between children and adolescents' nutritional status and dental caries experience.

The investigation of WNT6 and WNT10A single nucleotide polymorphisms as potential biomarkers for dental pulp calcification in orthodontic patients.

The aim of this study is to evaluate if single nucleotide polymorphisms (SNPs) in WNT6 and WNT10A are associated with the risk of dental pulp calcification in orthodontic patients. This cross-sectional study followed the "Strengthening the Reporting of Genetic Association Studies" (STREGA) guidelines. Panoramic radiographs (pre- and post-orthodontic treatment) and genomic DNA from 132 orthodontic patients were studied. Dental pulp calcification (pulp stones and/or pulp space narrowing) was recorded in upper and lower first molars. The SNPs in WNT6 and WNT10A (rs7349332, rs3806557, rs10177996, and rs6754599) were assessed through genotyping analysis using DNA extracted from buccal epithelial cells. The association between pulp calcification and SNPs were analyzed using allelic and genotypic distributions and haplotype frequencies (p<0.05). Prevalence of dental pulp calcification was 42.4% in the 490 studied molars. In the genotypic analysis, the SNPs in WNT10A showed a statistically significant value for molar calcification (p = 0.027 for rs1017799), upper molar calcification (p = 0.040 for rs1017799) (recessive model), and molar calcification (p = 0.046 for rs3806557) (recessive model). In the allelic distribution, the allele C of the SNP rs10177996 in WNT10A was associated with molar calcifications (p = 0.042) and with upper first molar calcification (p = 0.035). Nine combinations of haplotypes showed statistically significant value (p<0.05). The findings of this study indicates that SNPs in WNT10A and WNT6 are associated with dental pulp calcification in molars after orthodontic treatment and may be considered as biomarkers for dental pulp calcification.

Controversial Aspects of Diagnostics and Therapy of Idiopathic Condylar Resorption: An Analysis of Evidence- and Consensus-Based Recommendations Based on an Interdisciplinary Guideline Project.

Idiopathic condylar resorption (ICR), though a rare event, is associated with severe detrimental sequelae for the patient. To date, the etiology remains unknown, and treatment strategies are highly controversial. Therefore, the aim of this study is to present an analysis of the consensus- and evidence-based approach to ICR by a German interdisciplinary guideline project of the AWMF (Association of the Scientific Medical Societies in Germany). Following a systematic literature search, including 56 (out of an initial 97) publications, with a predominantly low level of evidence (LoE), two independent working groups (oral and maxillofacial surgery and interdisciplinary, respectively) voted on a draft comprising 25 recommendations in a standardized anonymized and blinded Delphi procedure. While the results of the votes were relatively homogeneous, the interdisciplinary phase required a significantly higher number of rounds (p < 0.001). Most of the controversial recommendations were related to initial imaging (with consensus on CT/CBCT as the current diagnostic standard for imaging), pharmacotherapy (no recommendation due to lack of evidence), discopexy (no recommendation possible due to low LoE) and timing of orthognathic surgery (with consensus on two-staged procedures after invasive TMJ surgery, except for single-stage procedures if combined with total joint reconstruction). Overall, the Delphi procedure resulted in an interdisciplinary guideline offering the best possible evidence- and consensus-based expertise to date in the diagnosis and treatment of ICR.

Prevalence and local causes for retention of primary teeth and the associated delayed permanent tooth eruption.

BACKGROUND: This study aimed to evaluate the prevalence of retained primary teeth (RPT) associated with delayed permanent tooth eruption and the factors associated with this condition in German children. METHODS: This is a cross-sectional retrospective study that evaluated panoramic radiographs from orthodontic patients. The diagnosis of RPT was established according to Nolla developmental stage. The primary tooth was considered retained when its successor permanent tooth was in Nolla stage 8, 9, or 10. Statistical analysis was performed with an α of 5% (p < 0.05). RESULTS: A total of 102 children (48 girls and 54 boys), and 574 primary teeth and their respective permanent successor teeth were evaluated. We classified 192 teeth as RPT. Sixty-one (59.8%) children presented one or more RPT. Gender was not significantly different between RPT and control teeth (p = 0.838; odds ratio 0.95, confidence interval 95% 0.44-2.16). In the majority of the RPT cases (68.7%), no clear cause to explain the prolonged retention was identified. The pathological problems most commonly observed with RPT were dental fillings (19.3%), followed by dental caries (4.6%), and ectopic tooth eruption (2.1%). CONCLUSIONS: The incidence of RPT associated with delayed permanent tooth eruption in German children was high and the most common pathological condition associated with RPT was dental caries.

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.

Impact of genetic variations in the WNT family members and RUNX2 on dental and skeletal maturation: a cross-sectional study.

BACKGROUND: This study evaluated if genetic variations in the WNT family members and RUNX2 are associated with craniofacial maturation, investigating dental and skeletal maturity in children and teenagers. METHODS: Radiographs from pre-orthodontic treatment of Brazilian patients (7 to 17 years-old) were used to assess dental (panoramic radiographs) and skeletal maturity (cephalometric radiographs). The chronological age (CA) was calculated based on the date of birth and the time the radiographs were performed. For the dental maturity analysis, the Demirjian (1973) method was used and a delta [dental age - chronological age (DA-CA)] was calculated. For the skeletal maturity analysis, the Baccetti et al. (2005) method was used and the patients were classified as "delayed skeletal maturation", "advanced skeletal maturation" or "normal skeletal maturation". DNA isolated from buccal cells was used for genotyping of two genetic variations in WNT family genes: rs708111 (G > A) in WNT3A and rs1533767 (G > A) in WNT11; and two genetic variations in RUNX2: rs1200425 (G > A) and rs59983488 (G > T). A statistical analysis was performed and values of p < 0.05 indicated a significant difference. RESULTS: There were no associations between dental maturity and genotypes (p > 0.05). In the skeletal maturity analysis, the allele A in the rs708111 (WNT3A) was statistically more frequent in patients with delayed skeletal maturation (Prevalence Ratio = 1.6; 95% Confidence Interval = 1.00 to 2.54; p-value = 0.042). CONCLUSIONS: The rs708111 in the WNT3A gene impacts on skeletal maturation.

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.

Advancing oral immunology for improving oral health.

Although substantial progress has been made in dentistry in terms of diagnosis and therapy, current treatment methods in periodontology, orthodontics, endodontics, and oral and maxillofacial surgery, nevertheless, suffer from numerous limitations, some of which are associated with a dramatic reduction in the quality of life. Many general mechanisms of inflammation and immunity also apply to the oral cavity and oral diseases. Nonetheless, there are special features here that are attributable, on the one hand, to developmental biology and, on the other hand, to the specific anatomical situation, which is characterized by a close spatial relationship of soft and hard tissues, exposure to oral microbiota, and to a rapid changing external environment. Currently, a comprehensive and overarching understanding is lacking about how the immune system functions in oral tissues (oral immunology) and how oral immune responses contribute to oral health and disease. Since advances in translational immunology have created a game-changing shift in therapy in rheumatology, allergic diseases, inflammatory bowel disease, and oncology in recent years, it is reasonable to assume that a better understanding of oral immunology might lead to practice-changing diagnostic procedures and therapies in dentistry and thereby also profoundly improve oral health in general.

Towards Genetic Dissection of Skeletal Class III Malocclusion: A Review of Genetic Variations Underlying the Phenotype in Humans and Future Directions.

INTRODUCTION: Skeletal abnormalities and malocclusions have varied features that impact populations globally, impairing aesthetics and lowering life quality. The prevalence of the Skeletal Class III disease is the lowest among all angle malocclusions, with varied prevalence across nations. Environmental, genetic, and societal factors play a role in its numerous etiologies. In this study, we conducted a thorough search across the published data relating to quantitative trait loci (QTL) and the genes associated with Class III progression in humans, discussed these findings and their limitations, and proposed future directions and strategies for studying this phenotype. METHODS: An inclusive search of published papers in the PubMed and Google Scholar search engines using the following terms: 1. Human skeletal Class III; 2. Genetics of Human skeletal Class III; 3. QTL mapping and gene associated with human skeletal Class III; 4. enriched skeletal Class-III-malocclusion-associated pathways. RESULTS: Our search has found 53 genes linked with skeletal Class III malocclusion reported in humans, genes associated with epigenetics and phenomena, and the top 20 enriched pathways associated with skeletal Class III malocclusion. CONCLUSIONS: The human investigations yielded some contentious conclusions. We conducted a genome-wide association study (GWAS), an epigenetics-wide association study (EWAS), RNA-seq analysis, integrating GWAS and expression quantitative trait loci (eQTL), micro- and small-RNA, and long non-coding RNA analysis in tissues connected to skeletal Class III malocclusion phenotype in tissues connected with the skeletal phenotype. Finally, we invite regional, national, and international orthodontists and surgeons to join this effort by contributing human samples with skeletal Class III malocclusion following the accepted Helsinki ethical protocol to challenge these phenomena jointly.