Cholecystectomy and the risk of osteoporosis and fractures: a systematic review and meta-analysis.

Background: Cholecystectomy is a common surgical procedure for gallbladder diseases. Removal of the gallbladder alters bile flow and may affect the absorption of fat-soluble vitamins, especially vitamin D, which could influence bone metabolism. However, epidemiological studies have yielded inconsistent findings regarding its association with osteoporosis and fractures. Objectives: To systematically evaluate the association between cholecystectomy and the risks of osteoporosis and fractures, and to examine potential effect modification by age. Design: Systematic review and meta-analysis of cohort studies. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, cohort studies published up to June 1, 2025, were identified through comprehensive searches of PubMed, Embase, and Web of Science. Eligible studies compared individuals who underwent cholecystectomy with non-surgical controls and reported outcomes of osteoporosis or fractures. Study quality was assessed using the Newcastle-Ottawa Scale. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using a random-effects model. Subgroup analyses were conducted according to age and adjustment for confounders. Results: Four high-quality cohort studies, including more than 1.5 million participants, were eligible. Meta-analysis demonstrated a modest but statistically significant increase in fracture risk after cholecystectomy (pooled HR = 1.07; 95% CI, 1.05-1.10; I² = 50%). The association was stronger among individuals younger than 50 years (pooled HR = 1.14; 95% CI, 1.12-1.16), while no significant association was found among those aged ⩾50 years. For osteoporosis, the pooled estimate was inconclusive due to substantial heterogeneity (I² = 97%) and limited data (HR = 1.09; 95% CI, 0.88-1.37). Conclusion: Cholecystectomy may be associated with a small increase in fracture risk, particularly among younger adults, although the absolute risk remains low. Evidence for osteoporosis is inconclusive due to high heterogeneity and limited studies. Further large-scale prospective studies are needed to clarify these associations and mechanisms. Trial registration: PROSPERO (CRD420251071872).