Depression and Osteoporosis: A Mendelian Randomization Study

Observational studies suggest a link between depression and osteoporosis, but these may be subject to confounding and reverse causality. In this two-sample Mendelian randomization analysis, we included the large meta-analysis of genome-wide association studies for depression among 807,553 individuals (246,363 cases and 561,190 controls) of European descent, the large meta-analysis to identify genetic variants associated with femoral neck bone mineral density (FN-BMD), forearm BMD (FA-BMD) and lumbar spine BMD (LS-BMD) among 53,236 individuals of European ancestry, and the GWAS summary data of heel BMD (HE-BMD) and fracture among 426,824 individuals of European ancestry. The results revealed that genetic predisposition towards depression showed no causal effect on FA-BMD (beta-estimate: 0.091, 95% confidence interval [CI] - 0.088 to 0.269, SE:0.091, P value = 0.320), FN-BMD (beta-estimate: 0.066, 95% CI - 0.016 to 0.148, SE:0.042, P value = 0.113), LS-BMD (beta-estimate: 0.074, 95% CI - 0.029 to 0.177, SE:0.052, P value = 0.159), HE-BMD (beta-estimate: 0.009, 95% CI - 0.043 to 0.061, SE:0.027, P value = 0.727), or fracture (beta-estimate: 0.008, 95% CI - 0.071 to 0.087, SE:0.041, P value = 0.844). These results were also confirmed by multiple sensitivity analyses. Contrary to the findings of observational studies, our results do not reveal a causal role of depression in osteoporosis or fracture.