Thiazide Use and Fracture Risk: An Updated Bayesian Meta-Analysis

The association between thiazide use and fracture risk is still controversial. We conducted an updated meta-analysis on the association between thiazide use and fracture risk. We systematically searched PubMed, Embase, and Cochrane library databases for all types of human studies, including observational and experimental studies that were published up until July 2019. We also manually searched the reference lists of relevant studies. The pooled relative risks (RRs) with 95% credible interval (CrI) were calculated using a Bayesian hierarchical random effect model. A total of 19 case-control (N = 496,568 subjects) and 21 cohort studies (N = 4,418,602 subjects) were included in this meta-analysis. The pooled RR for fractures associated with thiazide use was 0.87 (95% CrI: 0.70-0.99) in case-control and 0.95 (95% CrI: 0.85-1.08) in cohort studies. The probabilities that thiazide use reduces any fracture risk by more than 0% were 93% in case-control studies and 72% in cohort studies. Significant heterogeneity was found for both case-control (p < 0.001, I = 75%) and cohort studies (p < 0.001, I = 97.2%). Thiazide use was associated with reduced fracture risk in case-control studies, but not in cohort studies. The associations demonstrated in case-control studies might be driven by inherent biases, such as selection bias and recall bias. Thus, thiazide use may not be a protective factor for fractures.