A causal association between osteoporosis and postural instability: a Mendelian randomization study

Many observational studies have found an association between osteoporosis and postural instability. However, it is unclear whether there is a genetic causal relationship between osteoporosis and postural instability. In this study, we conducted a two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between osteoporosis and postural instability, with osteoporosis represented by bone mineral density (BMD). We used random effects Inverse Variance Weighted (IVW), weighted median, and MR-Egger methods after Steiger filtering, followed by FDR correction, to assess the causal relationship. We also used the Cochran Q statistic and MR-PRESSO to detect and exclude heterogeneity, the MR-Egger intercept to detect horizontal pleiotropy, and the leave-one-out method for sensitivity analyses. After excluding the heterogeneity in causal estimates across different SNPs and after Steiger filtering, the inverse variance weighted analysis showed a significant negative correlation between femoral neck BMD (FN-BMD) and the occurrence of postural instability, with an OR of 0.9171 (95% CI: 0.8745-0.9617; FDR P.value = 0.0009). Similar results were obtained in the weighted median analysis, with an OR of 0.923 (95% CI: 0.8717-0.9733; FDR P = 0.0180), and in the analysis of lumbar spine BMD (LS-BMD) in IVW, with an OR of 0.9491 (95% CI: 0.9156-0.9838; FDR P.value = 0.0129). However, there was no significant correlation between forearm BMD (FA-BMD) and postural instability. Further analysis showed no horizontal pleiotropy or heterogeneity in FN-BMD and LS-BMD after excluding heterogeneous SNPs. This study demonstrates a causal association between BMD and postural instability, suggesting that individuals with osteoporosis may be at higher risk of experiencing postural instability.