Causal association between cholecystectomy and fracture: A Mendelian randomization study

Area of Science:

• Epidemiology
• Genetics
• Surgical Outcomes

Background:

• Observational studies suggest a link between cholecystectomy and increased fracture risk.
• The causal nature of this association remains uncertain, necessitating further investigation.

Purpose of the Study:

• To investigate the potential causal relationship between cholecystectomy and various fracture types.
• To differentiate between cholecystectomy as a cause or consequence of fractures.

Main Methods:

• Employed a two-sample Mendelian randomization (MR) approach, primarily using inverse variable weighting (IVW).
• Utilized Bayesian weighted MR, MR-Egger, weighted mode, simple mode, and weighted median for robust analysis.
• Conducted sensitivity analyses, including MR-Egger's intercept method, to assess pleiotropy and data stability.

Main Results:

• No significant causal effect of cholecystectomy on any of the investigated fracture types was found (all P > 0.05).
• Reverse analysis indicated that femur fractures (P=0.01) and shoulder/upper arm fractures (P=0.01) were associated with an increased risk of cholecystectomy.
• Sensitivity analyses confirmed the absence of horizontal pleiotropy, supporting the validity of the findings.

Conclusions:

• The study does not support a causal link between cholecystectomy and an increased risk of fracture.
• Findings suggest that certain fractures might precede and potentially influence the decision for cholecystectomy.
• Results contrast with previous observational studies, highlighting the importance of causal inference methods.