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Evidence summaries

Thiazide Diuretics and Fractures

Thiazide users may have over 20% reduction of hip fracture risk. Level of evidence: "C"

A Cochrane review [Abstract]1 included 21 observational studies with nearly 400 000 subjects; 6 of them were cohort studies (n=121 965) and 15 were case-control studies (n=277 397). Two cohort studies appear to involve the same cohort so there were only 5 unique ones. No randomized control trials were found. Meta-analysis of cohort studies showed that thiazide use was associated with a reduction in risk of hip fracture by 24% (RR 0.76, 95% CI 0.64 to 0.89). A pooled summary statistics for case-control studies was not provided because of high heterogeneity ( I2 = 62%).

A review 2 on the effects of both osteoporotic and non-osteoporotic medications on fracture risk and bone mineral density (BMD) found that evidence for the association between the use of thiazide diuretics and fracture risk mainly derives from observational studies. Only one RCT has been published, and reported that chlorthalidone use resulted in a lower risk of hip and pelvic fractures when compared to amlodipine or lisinopril use. Most studies involving thiazides and BMD were conducted in patients with kidney stones or in postmenopausal women, all showing a positive effect of thiazide diuretics on BMD.

    References

    • Aung K, Htay T. Thiazide diuretics and the risk of hip fracture. Cochrane Database Syst Rev 2011;(10):CD005185. [PubMed]
    • van der Burgh AC, de Keyser CE, Zillikens MC et al. The Effects of Osteoporotic and Non-osteoporotic Medications on Fracture Risk and Bone Mineral Density. Drugs 2021;81(16):1831-1858. [PubMed]

Primary/Secondary Keywords