Osteoporosis and Stroke: A Bidirectional Mendelian Randomization Study

Abstract Objective: Numerous observational studies have identified a link between osteoporosis and stroke. However, the causal genetic relationship between these conditions remains unclear. This study employs a two-sample bidirectional Mendelian randomization (MR) approach to ascertain the causal relationship between osteoporosis and stroke. Design: We conducted a two-sample Mendelian randomization (MR) study to investigate the potential causal relationship between osteoporosis and stroke, including its subtypes. Genetic data for osteoporosis and stroke, along with their subtypes, were sourced from published genome-wide association studies (GWAS). Single nucleotide polymorphisms (SNPs) demonstrating genome-wide significance (p < 5×10^−8) and independence (r^2 < 0.001) were selected for further analysis, provided they had an F-statistic ≥10. The inverse-variance weighted (IVW) method was employed to evaluate causality, with results reported as odds ratios (ORs). Heterogeneity was assessed using Cochran’s Q test, while pleiotropy was tested using the MR-Egger intercept test. A leave-one-out sensitivity analysis was performed to ensure the robustness of the results. Results: Employing the IVW method, MR Egger method, and median-weighted method, we found no significant bidirectional causal relationship between osteoporosis and stroke or its subtypes, irrespective of the inclusion of potential pleiotropic SNPs. Sensitivity analyses affirmed the reliability and stability of these findings. Conclusion: This study indicates that there is no bidirectional causal relationship between osteoporosis and stroke or its subtypes. Nevertheless, these conditions share similar pathophysiological mechanisms and pathways.