Abstract

Objective 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) by leveraging data from medical records and genetic profiles of Dutch children.

Study design This 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.

Results The PMI and MI GWAS identified an associated signal (p=2.53×10-9) 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).

Conclusion Altogether, 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.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

Funding sources: The general design of Generation R Study is made possible by financial support from the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam, the Netherlands Organisation for Health Research and Development (ZonMw), the Netherlands Organisation for Scientific Research (NWO), the Dutch Ministry of Health, Welfare and Sport. Additional grants from the Netherlands Organisation for Health Research and Development supported this study (ZonMw 907.00303, ZonMw 916.10159, ZonMw VIDI 016.136.361 and ZonMw VIDI 016.136.367 to F.R. and C.M-G). F.R. was also sponsored by the European Research Council (ERC) Advanced Grant No. 101021500 LEGENDARE.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Medical Ethical Committee of the Erasmus Medical Centre, Rotterdam, the Netherlands gave ethical approval for this work (MEC-2015-749)

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

AbbreviationsPMIPanoramic mandibular indexMIMental indexDPRdental panoramic radiographTBLH-BMDtotal body-less head bone mineral densityDXAdual-energy X-ray absorptiometryGWASgenome-wide association studyPGSpolygenic scoreSDstandard deviation