Genetically Proxied Bone Mineral Density and Osteoporosis and the Risk of Sudden Sensorineural Hearing Loss: A Two-Sample Mendelian Randomization Study

We performed a two-sample Mendelian randomization study to evaluate the causal relationships between genetically proxied bone mineral density (BMD), osteoporosis liability, and sudden sen-sorineural hearing loss (SSNHL) using publicly available genome-wide association study summary statistics from UK Biobank and FinnGen. The primary analysis was the inverse-variance weighted multiplicative random-effects (IVW-MRE) model, supplemented by prespecified sensitivity analyses. For BMD (203 SNPs), no significant association with SSNHL risk was found (OR = 1.02, 95% CI: 0.87–1.20, p = 0.81), and leave-one-out analysis revealed that the estimate was unstable with significant horizontal pleiotropy. For osteoporosis liability (2 SNPs), despite a statistically significant IVW-MRE estimate (OR = 0.87, 95% CI: 0.82–0.92), the direction was opposite to our prespecified hypothesis, and prespecified sensitivity analyses were not estimable. In conclusion, this study did not find robust causal evidence linking BMD or osteoporosis to SSNHL. The significant but reverse-directional estimate for osteoporosis should not be interpreted as a protective causal effect due to the extremely low number of instruments and potential sample overlap.