Association between loop diuretic use and fracture risk

Loop diuretic use has been shown to be associated with an increased fracture risk, but the findings have been inconsistent. The present meta-analysis suggests that loop diuretics show a significant positive association with the overall risk of total fractures and, specifically, hip fractures.

Despite being widely used, there is limited, prospective randomized trial evidence regarding the skeletal effects of loop diuretics. Previous observational studies have reported conflicting findings regarding the association between loop diuretic use and the risk of fractures.

This meta-analysis of observational studies assessed the association between loop diuretic use and the risk of fractures. The PubMed, EMBASE, and OVID databases were searched for prospective cohort and case-control studies. Relative risks (RR) with 95% confidence intervals (CI) were derived using random-effects models throughout the analysis.

Thirteen studies (4 cohort studies and 9 case-control studies) were included, involving 842,644 participants and 108,247 fracture cases. Compared with non-users, people who had taken loop diuretics had an approximately 15% higher risk of total fractures (95% CI, 1.04-1.26; p<0.01), with high heterogeneity between studies (I2=80.5%; p<0.01). The RR was 1.14 (95% CI, 1.08-1.19) for hip fractures and 0.99 (95% CI, 0.93-1.05) for lower arm or wrist fractures. The RR was 1.05 (95% CI, 1.00-1.11) in prospective cohort studies and 1.22 (95% CI, 1.00-1.44) in case-control studies. There was no evidence of publication bias.

The results suggest that loop diuretics show a significant positive association with the overall risk of total fractures and hip fractures.