| Objective Bidirectional and multivariable Mendelian randomization (MR) methods were employed to investigate the causal association between bone mineral density (BMD) and intervertebral disc degeneration (IVDD) at different sites. Methods Genetic instrumental variables for IVDD were sourced from the FinnGen database. Five independent genetic instrumental variables for osteoporosis, including lumbar spine BMD, femoral neck BMD, total body BMD, and heel BMD, were acquired from the GEFOS consortium and the UK Biobank. Our primary analytical approach was based on inverse-variance weighted, and we adhered to a robust framework that encompassed bidirectional, multivariable, and multiple sensitivity analyses to mitigate the risk of potential confounding biases. Results The occurrence of IVDD was negatively influenced by genetically predicted osteoporosis (OR=0.017, P=1.718E-02). Univariable MR analyses revealed significant positive associations between lumbar spine BMD (OR=1.131, 95% CI: 1.053–1.214, P=6.915E-04), total body BMD (OR=1.148, 95% CI: 1.093–1.206, P=4.221E-08), heel BMD (OR=1.061, 95% CI: 1.016–1.109, P=7.871E-03), and the occurrence of IVDD. However, in the multivariable model, only genetically predicted lumbar spine BMD demonstrated a positive causal effect on the risk of IVDD (OR=1.120, 95% CI: 1.003–1.250, P=4.493E-02). Results from the reverse causality study suggested a potential reverse causal association between lumbar spine BMD and IVDD (Beta=0.142, 95% CI: 0.052–0.233, P=2.078E-03), with no similar associations found for BMD at other sites. Sensitivity analysis affirmed the robustness of our findings. Conclusion Genetically predicted osteoporosis is a negative influence on the occurrence of IVDD. In addition, this study emphasizes a bidirectional causal association between lumbar spine BMD and IVDD. |