子宫切除术与骨质疏松及相关骨折的孟德尔 随机化研究

Mendelian Randomization Study of Hysterectomy on Osteoporosis and Related Fractures

摘要: 目的：为研究子宫切除术与骨质疏松症及相关骨折(包括髋部、腕部和脊柱骨折)风险之间的关联性和因果关系。方法：使用全国健康与营养检查调查数据，通过多变量调查加权逻辑回归分析，研究子宫切除术与四个结果的关系：骨质疏松症、髋部骨折、腕部骨折和脊柱骨折。进行双样本孟德尔随机化(MR)分析，探讨遗传预测的子宫切除术对骨质疏松症和骨折的潜在因果效应。结果：在观察性分析中，子宫切除术与髋部骨折风险显著相关(OR = 1.688, 95% CI: 1.114~2.558, P = 0.015)，但与腕部骨折、脊柱骨折或总体骨质疏松症无关联。然而，在未使用激素替代的女性中，子宫切除术与骨质疏松症的风险有一定关联(OR = 1.269, 95% CI: 1.007~1.601, P = 0.046)。孟德尔随机化分析未支持子宫切除术与骨质疏松症或髋部骨折之间的因果关系，提示观察到的关联可能受到其他因素的干扰。结论：在观察性分析中，子宫切除术与髋部骨折及未使用MHT者的骨质疏松症有一定关联，但MR分析未能证实直接的因果关系。这些发现表明，子宫切除术可能是骨骼健康风险增加的高危因素——而非直接原因。

Abstract: Objective: To investigate the association and causal relationship between hysterectomy and the risk of osteoporosis and related fractures (including hip, wrist and spinal fractures). Methods: Using data from the National Health and Nutrition Examination Survey, this study investigated the relationship between hysterectomy and four outcomes: osteoporosis, hip fracture, wrist fracture, and spinal fracture, through multivariate weighted logistic regression analysis. A two-sample Mendelian randomization (MR) analysis was conducted to explore the potential causal effects of genetically predicted hysterectomy on osteoporosis and fractures. Result: In the observational analysis, hysterectomy was significantly associated with the risk of hip fracture (OR = 1.688, 95% CI: 1.114~2.558, P = 0.015), but not with wrist fracture, spinal fracture, or overall osteoporosis. However, in women not using hormone replacement therapy, hysterectomy was associated with the risk of osteoporosis (OR = 1.269, 95% CI: 1.007~1.601, P = 0.046). Mendelian randomization analysis did not support a causal relationship between hysterectomy and osteoporosis or hip fracture, suggesting that the observed association may be confounded by other factors. Conclusion: In observational analysis, hysterectomy was associated with hip fractures and osteoporosis in non-MHT patients, but MR analysis failed to confirm a direct causal relationship. These findings suggest that hysterectomy may be a high-risk factor—rather than a direct cause—for increased bone health risks.