Exploring the causal relationship between osteoporosis and age-related macular degeneration: Evidence from observational studies and mendelian randomization

OBJECTIVE: This study aimed to systematically investigate the association between osteoporosis (OP) and age-related macular degeneration (AMD), including its subtypes, by integrating observational evidence with causal inference approaches. METHODS: We first conducted a systematic literature search and meta-analysis of relevant observational studies up to August 2025 to evaluate the observational association between OP and AMD. Subsequently, using summary data from genome-wide association studies, we performed a bidirectional two-sample Mendelian randomization (MR) analysis to examine the causal relationship between OP and four AMD subtypes. The primary causal estimates were derived using the inverse variance weighted method, and multiple sensitivity analyses were conducted to verify the robustness of the results. RESULTS: The meta-analysis, which included three studies, indicated that osteoporosis increases the risk of AMD in women (OR: 1.46; 95% CI: 1.12-1.91, P = 0.0049). Under Bonferroni correction, the MR analysis showed that genetically predicted osteoporosis significantly increased the risk of dry AMD (IVW OR: 1.26; 95% CI: 1.10-1.44, P = 0.00087. Bayesian weighted MR OR: 1.25; 95% CI: 1.05-1.49, P = 0.01162.), while no significant causal effects were observed for wet, early, or late AMD. Reverse MR analysis did not indicate any causal effect of AMD on OP. No significant horizontal pleiotropy or heterogeneity was detected in any of the analyses. CONCLUSION: Osteoporosis may increase the risk of AMD in women. The MR analysis provides some genetic evidence supporting a potential causal link between osteoporosis and dry AMD. In clinical practice, patients with osteoporosis-particularly elderly women-should be considered at potential high risk for dry AMD, and early fundus screening may facilitate the early detection and intervention of dry AMD.