Causal associations of osteoporosis with stroke: a bidirectional Mendelian randomization study.

ABSTRACT

This study employed bidirectional Mendelian randomization (MR) to investigate the causal relationship between osteoporosis (OP) and stroke. Utilizing large-scale genome-wide association data revealed a reciprocal relationship stroke increases the risk of OP, and vice versa. These findings underscore the importance of addressing both conditions for comprehensive patient care. INTRODUCTION: The correlation between OP and stroke is unclear. This study used a two-sample bidirectional MR study to determine the causal relationship between OP and stroke. METHODS: Summary data from genome-wide association studies (GWAS) were used to perform MR analyses. Summary data for OP (n = 300,147), OP with pathological fracture (n = 239,702), and postmenopausal OP with pathological fracture (n = 182,601) were extracted from large-scale GWAS and meta-analyses of European populations in the FinnGen consortium. Similarly, summary data for stroke (n = 446,696), ischemic stroke (IS, n = 440,328), small vessel stroke (SVS, n = 198,048), large artery atherosclerosis stroke (LAS, n = 150,765), and cardioembolic stroke (CES, n = 211,763) were extracted from the MEGASTROKE consortium. Methods such as inverse variance weighted, MR-Egger, and weighted median were applied to perform various outcome analyses for MR. RESULTS: The results demonstrated significant positive causality of stroke, IS, and LAS on OP (stroke odds ratio [OR] 1.39, 95% confidence interval [CI] 1.04-1.85, and P = 0.027; IS, OR 2.02, 95% CI 1.05-3.87, and P = 0.035; LAS OR 1.29, 95% CI 1.08-1.55, and P = 0.005), positive causality of LAS on OP with pathological fracture (LAS OR 1.69, 95% CI 1.18-2.42, and P = 0.004), and positive causality of stroke and LAS on postmenopausal OP with pathological fracture (stroke OR 2.02, 95% CI 1.05-3.87, and P = 0.035; LAS, OR 1.75, 95% CI 1.06-2.90, and P = 0.030). There was also a significant positive causal relationship between OP and SVS (OP, OR 1.08, 95% CI 1.01-1.14, and P = 0.021). CONCLUSION: In conclusion, there is a causal relationship between stroke and OP, suggesting that they may be potential risk factors for each other. Therefore, patients with stroke should receive timely prevention for OP, OP with pathological fracture, and postmenopausal OP with pathological fracture. Similarly, patients with OP may need to be evaluated for potential cardiovascular risks.