Zhu Kun, An ZiJie, Li YaWei, Zhang Qiaoyu, Zhang Feng, Zhao Rui, Yu Haiyang, Yao Qingqiang
Department of Orthopaedics, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Department of Orthopaedics, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China.
Sci Rep. 2025 Mar 25;15(1):10234. doi: 10.1038/s41598-025-93793-w.
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.
许多观察性研究发现骨质疏松症与姿势不稳之间存在关联。然而，骨质疏松症与姿势不稳之间是否存在遗传因果关系尚不清楚。在本研究中，我们进行了一项两样本孟德尔随机化（MR）分析，以研究骨质疏松症与姿势不稳之间的因果关系，用骨矿物质密度（BMD）代表骨质疏松症。我们在Steiger过滤后使用随机效应逆方差加权（IVW）、加权中位数和MR-Egger方法，随后进行FDR校正，以评估因果关系。我们还使用Cochran Q统计量和MR-PRESSO来检测和排除异质性，用MR-Egger截距检测水平多效性，并采用留一法进行敏感性分析。在排除不同单核苷酸多态性（SNP）因果估计中的异质性并经过Steiger过滤后，逆方差加权分析显示股骨颈骨密度（FN-BMD）与姿势不稳的发生之间存在显著负相关，比值比（OR）为0.9171（95%置信区间：0.8745 - 0.9617；FDR P值 = 0.0009）。加权中位数分析也得到了类似结果，OR为0.923（95%置信区间：0.8717 - 0.9733；FDR P = 0.0180），IVW分析腰椎骨密度（LS-BMD）时，OR为0.9491（95%置信区间：0.9156 - 0.9838；FDR P值 = 0.0129）。然而，前臂骨密度（FA-BMD）与姿势不稳之间没有显著相关性。进一步分析表明，在排除异质性SNP后，FN-BMD和LS-BMD不存在水平多效性或异质性。本研究证明了BMD与姿势不稳之间存在因果关联，表明骨质疏松症患者可能有更高的姿势不稳风险。
