Thiazide diuretic usage and risk of fracture: a meta-analysis of cohort studies

Inconsistent findings in regard to association between thiazide diuretic use and the risk of fracture have been reported during the past decade. This updated meta-analysis, which pooled data from 11 qualified prospective designed studies, found that thiazides have a significant protective effect on fracture risk. An updated comprehensive meta-analysis examine the association between thiazide diuretic use and therisk of fracture is needed. Cohort studies regarding thiazide diuretic exposure and the risk of fracture, published from inception to May 1 2017, were identified through MEDLINE, EMBASE, SCOPUS, and the Cochrane Database of Systematic Reviews. The literature search, study selection, study appraisal, and data extraction were pre-defined in the protocol and were independently conducted by two investigators. Due to the heterogeneity of the original studies, a random effects model was used to pool the confounder-adjusted relative risk (RR). Eleven eligible cohort studies involving 2,193,160 participants were included for analysis. Overall, thiazide diuretic users, as compared with non-users, had a significant 14% reduction in the risk of all fractures (relative risk [RR], 0.86; 95% confidence interval [CI], 0.80-0.93; p = 0.009) and an 18% reduction in the risk of hip fracture (RR, 0.82; 95%CI, 0.80-0.93; p = 0.009). However, the effect size associated with thiazide use became slightly weaker when the analysis was limited to only high-quality original studies (quality score > 8) (RR, 0.89; 95%CI, 0.80-0.99; p = 0.005), studies with a larger sample size (> 10,000) (RR, 0.90; 95%CI, 0.80-1.00; p = 0.002), and studies published after 2007 (RR, 0.92; 95%CI, 0.82-1.02; p = 0.001). Our findings indicate that thiazide diuretic use may convey a decreased risk of fracture and as such, the protective effect of this class of medicine should be considered when prescribing thiazide diuretics in clinical practice.