Genetic and Epidemiologic Assessment of Mandibular Cortical Indices and Bone Mineral Density in Peripubertal Children: The Generation R Study

ObjectiveThe panoramic mandibular index (PMI) and mental index (MI) assessed on dental panoramic radiographs (DPRs) have been postulated as useful for the assessment of adult bone health. However, their utility in children remains to be determined. Our objective was to establish genetic determinants of the PMI/MI and to evaluate the relationship between these indices and total body less-head bone mineral density (TBLH-BMD) by leveraging data from medical records and genetic profiles of Dutch children. Study designThis study was embedded in the Generation R Study including 3,518 participants at a mean age of 13 years. BMD was obtained from dual-energy X-ray (DXA) scans, while radiomorphometric measurements of the mandibular bone were obtained from DPRs. Genome-wide association studies (GWAS) on PMI/MI were performed using individual genotyped data imputed to the 1000 Genomes reference panel. The association between PMI/MI and BMD was comprehensively assessed following a combined observational and genetic analysis, both corrected for biological covariates such as sex, age, and others, using a BMD polygenic risk score (PGS) in pubescent children. ResultsThe PMI and MI GWAS identified an associated signal (p=2.53x10-9) mapping to the ODF3/BET1L/RIC8A/SIRT3 locus, previously associated with BMD. Moreover, significant differences in PMI and MI were observed across the extremes of the TBLH-BMD PGS distribution. Our results also show that a standard deviation (SD) increase in measured TBLH-BMD was associated with 0.244 SD increase [95% CI 0.211 - 0.277, p<0.001] in PMI and 0.426 SD increase in MI (95% CI 0.395 - 0.457, p<0.001). ConclusionAltogether, our results suggest that PMI/MI and BMD partially share common biological pathways, and the former may constitute a relevant marker if screening for children with impaired bone health using DPRs.