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The present study aimed to determine the association between single nucleotide polymorphisms (SNPs) in RUNX2, SMAD6, BMP2, and BMP4 genes in relation to tooth-size discrepancy (TSD). A cross-sectional study of patients undergoing orthodontic treatment measured the mesiodistal width of permanent teeth from pretreatment dental casts. Sixty-two patients were included in the study and TSD was assessed according to the Bolton analysis. The patients were allocated into a control group (without a TSD), an anterior excess group and an overall excess group. Genomic DNA was extracted from saliva samples, and SNPs previously associated with tooth size were evaluated using a real-time polymerase chain reaction (PCR) system. The Fisher exact test was performed to compare genotype and allele frequencies at an α = 0.05. An Odds Ratio (OR) and 95% Confidence Interval (95% CI) were calculated. The rs59983488 SNP in the RUNX2 gene was significantly related to the presence of anterior mandibular tooth-size excess in allele (T allele: <0.001; OR = 11.74; 95% CI =2.61–55.80), and genotype models (GT genotype: = 0.002; OR = 12.69; 95% CI = 2.47–64.83). The rs3934908 SNP in the SMAD6 gene was significantly associated with the presence of an overall maxillary tooth-size excess in allele (T allele: < 0.001) and genotype models (TT genotype: = 0.010). The present results suggest that SNPs in RUNX2 (rs59983488) and SMAD6 (rs3934908) genes may be associated with the presence of tooth-size excess.

ABSTRACT Objective: This study aimed to compare the insertion torque (IT), flexural strength (FS) and surface alterations between stainless steel (SS-MIs) and titanium alloy (Ti-MIs) orthodontic mini-implants. Methods: Twenty-four MIs (2 x 10 mm; SS-MIs, n = 12; Ti-MIs, n = 12) were inserted on artificial bone blocks of 20 lb/ft3 (20 PCF) and 40 lb/ft3 (40 PCF) density. The maximum IT was recorded using a digital torque meter. FS was evaluated at 2, 3 and 4 mm-deflection. Surface topography and chemical composition of MIs were assessed by scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS). General linear and mixed models were used to assess the effect of the MI type, bone density and deflection on the evaluated outcomes. Results: The IT of Ti-MIs was 1.1 Ncm greater than that obtained for the SS-MIs (p= 0.018). The IT for MIs inserted in 40 PCF test blocks was 5.4 Ncm greater than that for those inserted in 20 PCF test blocks (p < 0.001). SS-MIs inserted in higher density bone (40 PCF) had significantly higher flexural strength than the other groups, at 2 mm (98.7 ± 5.1 Ncm), 3 mm (112.0 ± 3.9 Ncm) and 4 mm (120.0 ± 3.4 Ncm) of deflection (p< 0.001). SEM evidenced fractures in the Ti-MIs. EDS revealed incorporation of 18% of C and 2.06% of O in the loaded SS-MIs, and 3.91% of C in the loaded Ti-MIs. Conclusions: Based on the findings of this in vitro study, it seems that SS-MIs offer sufficient stability and exhibit greater mechanical strength, compared to Ti-MIs when inserted into higher density bone. RESUMO Objetivo: O objetivo deste estudo foi comparar o torque de inserção (TI), a resistência flexural (RF) e as alterações de superfície em mini-implantes ortodônticos de aço inoxidável (MIs-Ai) e de liga de titânio (MIs-Ti). Métodos: Vinte e quatro MIs (2 x 10 mm; MIs-Ai, n = 12; MIs-Ti, n = 12) foram inseridos em blocos de osso artificial de densidades de 20 lb/ft3 (20 PCF) e 40 lb/ft3 (40 PCF). O torque máximo de inserção foi registrado por meio de um torquímetro digital. A resistência flexural foi avaliada nas deflexões de 2, 3 e 4 mm. Topografia de superfície e composição química dos MIs foram avaliadas por Microscopia Eletrônica de Varredura (MEV) e Espectroscopia de Energia Dispersiva de Raios X (EDS). Modelos lineares gerais e mistos foram utilizados para avaliar o efeito do tipo de MI, da densidade óssea e da deflexão nos desfechos avaliados. Resultados: O TI dos MIs-Ti foi 1,1 Ncm maior do que o obtido para os MIs-Ai (P = 0,018). O TI para MIs inseridos em blocos de teste de 40 PCF foi 5,4 Ncm maior do que para aqueles inseridos em blocos de teste 20 PCF (p < 0,001). MIs-Ai inseridos em osso de maior densidade (40 PCF) apresentaram resistência flexural significativamente maior do que outros grupos, em deflexões de 2 mm (98,7 ± 5,1 Ncm), 3 mm (112,0 ± 3,9 Ncm) e 4 mm (120,0 ± 3,4 Ncm) (p < 0,001). A MEV evidenciou fraturas nos MIs-Ti. A EDS revelou incorporação de 18% de C e 2,06% de O nos MIs-Ai e 3,91% de C nos MIs-Ti, ambos submetidos a testes mecânicos. Conclusões: Com base nos resultados desse estudo in vitro, os MIs-Ai aparentam oferecer adequada estabilidade e maior resistência mecânica, em comparação aos MIs-Ti, quando inseridos em osso de maior densidade.

The vertical facial profile is a crucial factor for facial harmony with significant implications for both aesthetic satisfaction and orthodontic treatment planning. However, the role of single nucleotide polymorphisms (SNPs) in the development of vertical facial proportions is still poorly understood. This study aimed to investigate the potential impact of some SNPs in genes associated with craniofacial bone development on the establishment of different vertical facial profiles. Vertical facial profiles were assessed by two senior orthodontists through pre-treatment digital lateral cephalograms. The vertical facial profile type was determined by recommended measurement according to the American Board of Orthodontics. Healthy orthodontic patients were divided into the following groups: “Normodivergent” (control group), “Hyperdivergent” and “Hypodivergent”. Patients with a history of orthodontic or facial surgical intervention were excluded. Genomic DNA extracted from saliva samples was used for the genotyping of 7 SNPs in RUNX2 , BMP2 , BMP4 and SMAD6 genes using real-time polymerase chain reactions (PCR). The genotype distribution between groups was evaluated by uni- and multivariate analysis adjusted by age (alpha = 5%). A total of 272 patients were included, 158 (58.1%) were “Normodivergent”, 68 (25.0%) were “Hyperdivergent”, and 46 (16.9%) were “Hypodivergent”. The SNPs rs1200425 ( RUNX2 ) and rs1005464 ( BMP2 ) were associated with a hyperdivergent vertical profile in uni- and multivariate analysis (p-value < 0.05). Synergistic effect was observed when evaluating both SNPs rs1200425- rs1005464 simultaneously (Prevalence Ratio = 4.0; 95% Confidence Interval = 1.2–13.4; p-value = 0.022). In conclusion, this study supports a link between genetic factors and the establishment of vertical facial profiles. SNPs in RUNX2 and BMP2 genes were identified as potential contributors to hyperdivergent facial profiles.

Skeletal malocclusions are common phenotypes in humans and have a strong influence on genetic factors. Transforming growth factor beta (TGFβ) 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.

Introduction This study aimed to investigate if the mandibular trabecular bone structure of children and teenagers with cleft lip and/or cleft palate (CL/P) differs from non-cleft children using fractal analysis. Methods Children aged between 5 and 15 years with CL/P (cleft group) and a control group were recruited. Syndromic cases of CL/P and isolated cleft palate (CP) were excluded. To obtain the fractal dimension (FD) of the mandibular bone, regions of interest (ROI) were first delineated within the condyle and body of the mandible on panoramic radiographs. Subsequently, the FD was calculated using the box-counting algorithm on these defined ROIs. The results were adjusted by sex and age in a generalized linear model (GLM) with alpha error tolerance of 5%. Results A total of 205 patients were included. One hundred patients were allocated into the control group and 105 into the cleft group (37 CL and 68 CLP). The fractal dimension (FD) was statistically higher in the control group compared to the study group for both regions of interest (ROIs) ( p  < 0.001). In the GLMs, cleft was associated with low FD in the condyle (Beta=-0.132; p  < 0.001). In the body of the mandible, cleft was also associated with decreased FD values (Beta=-0.154; p  < 0.001). CLP presented decreased FD values in the condyle (Beta=-0.016; p  = 0.004). Conclusion Children with CL/P had lower FD values in the mandible compared to the control children, which may indicate that patients born with CL/P present a less complex bone structure.

During orthodontic tooth movement (OTM), there is the release of cytokines in the gingival crevicular fluid (GCF) that are supposed to participate in the bone remodeling. This systematic review aimed at assessing the effects of photobiomodulation (PBM) on the levels of these cytokines during OTM. This systematic review according to Cochrane Collaboration guidelines aimed to answer the clinical question following the PICOS strategy. The broad search in the literature was performed before 05 April, 2021 in six electronic databases (Pubmed, Web of Science, Scopus, Embase, Cochrane, Biblioteca Virtual de Saúde) and supplemented by the grey literature. The risk of bias of randomized and non-randomized clinical trials was evaluated by two tools: RoB 2 and ROBINS-I. Mean and standard deviation of cytokine levels was extracted to meta-analysis, and the GRADE system was applied to assess the quality of the evidence. Nine studies were included in this review. Low-level laser therapy (LLLT) was the photobiomodulation type used in most of the studies (n = 8). The wavelengths used varied from 618 to 980 nm and also differed concerning the light emission pattern. LLLT increased the levels of IL-1β, IL-8, OPN, and PGE2, but not TNF-α1, TGF-β1. The levels of IL6, RANKL, and OPG presented conflicting results. LLLT was statistically associated with an increase of IL-1β levels (standard mean difference [SMD] = 1.99; 95% confidence interval = 0.66 to 3.33; p < 0.001) with low certainty of evidence. LLLT may increase the levels of IL-1β and other cytokines; however, the results should be interpreted with caution due to protocol variations between studies, and the few studies added in the meta-analysis.

Introduction: dental development assessment may help in diagnosis of development disruptions and in orthodontic treatment planning. Disturbances of dental and craniofacial development share similar risk factors. In this way, dental development assessment may be a useful method to also predict skeletal malocclusion. Objective: This study investigated the relationship between dental development and skeletal patterns. Methods: patients of both genders, aged 7 to 16 years old, who presented cephalometric and panoramic radiographs before orthodontic treatment were included. Calibrated examiners blinded for sex and age defined the dental age by analyzing the radiographs using the Demirjian method (1973). ANB, SNA and SNB angles were obtained by cephalometric tracing. The dependent variable of the study was the subtraction of dental age (DA) by chronological age (CA) (DA-CA). The agreement between dental age and chronological age was determined by the Bland-Altman method. The relationship between CI-ID and skeletal patterns was analyzed by Spearman’s correlation tests and the Generalized Linear Model adjusted for age and sex. Results: 145 patients were included in the study and the Bland-Altman test showed agreement between dental and chronological ages. In the correlation test, no association was found between DA-CA and skeletal patterns (p>0.05). In the multivariate analysis adjusted for sex and age, it was also not found a significant association. Conclusion: our results suggest that there is no relationship between dental development and skeletal patterns. Introdução: a análise de desenvolvimento dentário pode auxiliar no diagnóstico de desequilíbrios de desenvolvimento e no planejamento do tratamento ortodôntico. Distúrbios de desenvolvimento dentário e craniofacial compartilham fatores de risco similares. Dessa forma, a análise de desenvolvimento dentário pode prever o estabelecimento de más oclusões. Objetivo: este estudo investigou a relação entre o desenvolvimento dental e os padrões esqueléticos. Método: foram incluídos pacientes de ambos os sexos, com idades entre 7 e 16 anos, que apresentaram radiografias cefalométricas e panorâmicas antes do tratamento ortodôntico. Examinadores calibrados, cegos quanto ao sexo e à idade, definiram a idade dental analisando as radiografias pelo método de Demirjian (1973). Os ângulos ANB, SNA e SNB foram obtidos por traçado cefalométrico. A variável dependente do estudo foi a subtração da idade dental (ID) pela idade cronológica (ID) (ID-IC). A concordância entre a idade dental e a idade cronológica foi determinada pelo método de Bland-Altman. A relação entre a ID-IC e os padrões esqueléticos foi analisada por testes de correlação de Spearman e pelo Modelo Linear Generalizado ajustado para idade e sexo. Resultados: 145 pacientes foram incluídos no estudo e o teste de Bland-Altman mostrou concordância entre as idades dentais e cronológicas. No teste de correlação, não foi encontrada nenhuma associação entre ID-IC e padrões esqueléticos (p>0.05). Na análise multivariada ajustada para sexo e idade, também não foi encontrada uma associação significativa. Conclusão: nossos resultados sugerem que não há relação entre o desenvolvimento dental e os padrões esqueléticos.

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.

In this study we evaluated whether single nucleotide polymorphisms (SNPs) in the genes encoding PTH, VDR, CYP24A1, and CYP27B1 were associated with mandibular retrognathism (MR). Samples from biologically-unrelated Brazilian patients receiving orthodontic treatment were included in this study. Pre-orthodontic lateral cephalograms were used to determine the phenotype. Patients with a retrognathic mandible were selected as cases and those with an orthognathic mandible were selected as controls. Genomic DNA was used for genotyping analysis of SNPs in PTH (rs694, rs6256, and rs307247), VDR (rs7975232), CYP24A1 (rs464653), and CYP27B1 (rs927650). Chi-squared or Fisher’s tests were used to compare genotype and allele distribution among groups. Haplotype analysis was performed for the SNPs in PTH. The established alpha was p < 0.05. Multifactor dimensionality reduction (MDR) was used to identify SNP–SNP interactions. A total of 48 (22 males and 26 females) MR and 43 (17 males and 26 females) controls were included. The linear mandibular and the angular measurements were statistically different between MR and controls (p < 0.05). In the genotype and allele distribution analysis, the SNPs rs694, rs307247, and rs464653 were associated with MR (p < 0.05). MDR analyses predicted the best interaction model for MR was rs694–rs927650, followed by rs307247–rs464653–rs927650. Some haplotypes in the PTH gene presented statistical significance. Our results suggest that SNPs in PTH, VDR, CYP24A1, and CYP27B1 genes are associated with the presence of mandibular retrognathism.

Single nucleotide polymorphisms (SNPs) play a crucial role in regulating vitamin D, parathyroid hormone (PTH), and calcitonin concentrations, which are involved in bone health. Some reports suggested that fractal analysis is useful in the morphometric analysis of the mandible trabecular bone in panoramic radiographs. Therefore, we investigated if SNPs in genes that influence vitamin D, calcitonin, and PTH levels are involved in condylar bone quality during the active growing phase of the mandible. Fractal dimension was obtained from the condyle region of interest (ROI) using panoramic radiographs and used to measure the complexity and the microarchitecture of the bone. Fractal dimension using the box‐counting algorithm was then calculated. In order to avoid information bias, a script to automate the commands in the software ImageJ was generated to ensure consistency and minimize the potential for human error during the data analysis process. SNPs in vitamin D receptor ( VDR ), cytochrome P450 family 27 subfamily B member 1 ( CYP27B1 ), cytochrome P450 family 24 subfamily A member 1 ( CYP24A1 ), vitamin D binding protein ( VDBP ), SEC23 homolog A ( SEC23A ), calcitonin receptor ( CALCR ), and parathyroid hormone ( PTH ) were analyzed. DNA extracted from saliva was used for genotyping analysis of VDR (rs7975232, rs2228570, and rs1544410), CYP27B1 (rs4646536), CYP24A1 (rs927650), VDBP (rs4588), SEC23A (rs8018720), CALCR (rs1801197), and PTH (rs6256, rs307247, and rs694). A statistical analysis was performed with an alpha error tolerance of 5%. A total of 100 children were included; 50 (50%) were boys and the age ranged from 5 to 14 years old. Fractal dimensions were compared among genotypes. The GT (mean = 1.20 and standard error = 0.03, p = 0.024) and TT genotypes (mean = 1.16 and standard error = 0.06, p = 0.047) in the gene VDBP (rs4588) presented lower fractal dimension. The GG genotype in SEC23A (rs8018720) (mean = 1.34 and standard error = 0.03, p = 0.011) and the TC genotype in PTH (rs694) showed an increased fractal dimension (mean = 1.29 and standard error = 0.03, p = 0.020). In conclusion, SNPs in VDBP, SEC23A, and PTH encoding genes are associated with mandibular condylar trabecular bone structure in children.