Causal association between cholecystectomy and fracture: A Mendelian randomization study

Previous observational studies have reported that cholecystectomy is associated with an increased risk of fracture. However, the causality of this association remains unclear. This study aimed to explore the causal relationship between cholecystectomy and fracture using a Mendelian randomization (MR) approach. Our primary analytical method was the comprehensive two-sample MR analysis, with inverse variable weighting (IVW) serving as the main analysis technique. In addition, we use Bayesian weighted MR analysis to further confirm the results of IVW method. To enhance the robustness of our findings, we employed multiple analytical approaches including MR-Egger, weighted mode, simple mode, and weighted median. We further conducted sensitivity analyses to validate the stability and feasibility of our dataset. The results of IVW methods showed that there had no significant causal effect of cholecystectomy on fracture (forward P value: .82, .63, .96, .60, .19, .40, .58, .38, .37, .97, and .50 for fracture of wrist and hand, fracture of femur, fracture of foot, fracture of forearm, fracture of lower leg, fracture of lumbar spine and pelvis, fracture of neck, fracture of ribs, fracture of shoulder and upper arm, fracture of skull and facial bones, and fracture of spine), the results of Bayesian weighted MR showed similar results (P > .05). In the reverse, fracture of femur (P = .01) and fracture of shoulder and upper arm (P = .01) showed increased risks of cholecystectomy. The sensitivity analysis showed that none of our analyses were horizontally pleiotropic (P > .05 for MR-Egger's intercept method). Our results do not support the causal effect of cholecystectomy on fracture, which was opposite to most previous observational studies.