Causal Association between Bone Mineral Density and Osteoarthritis: A Mendelian Randomization Study

Objective. To examine whether bone mineral density (BMD) is causally associated with osteoarthritis (OA). Methods. We performed a two-sample Mendelian randomization (MR) analysis using the inverse-variance weighting (IVW), weighted median, and MR-Egger regression methods. We used publicly available summary statistics datasets of a genome-wide association study (GWAS) on femur neck (FN) BMD of individuals of European ancestry as the exposure and a GWAS for non-cancer illness code self-reported: OA from the individuals included in the UK Biobank as the outcome. Results. We selected 21 independent single-nucleotide polymorphisms with genome-wide significance (p<5.00E-08) from GWAS on FN BMD as the instrumental variables. The IVW method (beta=0.010, standard error [ SE]=0.003, p=0.002) and the weighted median approach (beta=0.011, SE=0.004, p=0.006) yielded evidence of a causal association between FN BMD and OA. However, the MR-Egger analysis showed no causal association between FN BMD and OA (beta=0.005, SE=0.017, p=0.753). Since MR-Egger regression suffers from a lack of power and a susceptibility to weak instrument bias, the MR analysis results may support a causal association between FN BMD and OA. Conclusion. The results of MR analysis by IVW and weighted median, but not MR-Egger regression indicate that FN BMD is likely to be causally associated with an increased risk of OA incidence The current findings may provide an opportunity to elucidate the underlying mechanisms of the effects of BMD on the OA incidence.