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

Objectives The 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). Methods This study was embedded in the Generation R Study 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. The association between PMI/MI and BMD was assessed following a combined observational and genetic analysis using a polygenic risk score (PGS). Results The PMI and MI GWAS identified an association signal (p=2.53x10 ^-9 ) mapping to the ODF3/BET1L/RIC8A/SIRT3 locus, previously associated with BMD. Significant differences in PMI and MI were observed across the extremes of the TBLH-BMD PGS distribution. One standard deviation (SD) increase in measured TBLH-BMD was associated with 0.244 SD increase in PMI and 0.426 SD increase in MI. Conclusions Our results suggest that PMI/MI and BMD share common biological pathways, and the former may be considered as relevant markers if screening for children with impaired bone health using DPRs. Clinical Relevance This study demonstrates that mandibular indices measured from panoramic radiographs can help clinicians identify pediatric patients who may have reduced bone mineral density. Both traits share a shared genetic and the association is not due to confounding factors. These findings highlight the potential of panoramic radiography as a valuable tool in assessing pediatric skeletal health.