The use of thiazide diuretics is associated with a significantly decreased risk for fracture, according to the results of a meta-analysis of prospective cohort studies published in Osteoporosis International.
Investigators from the University of Nevada in Las Vegas identified studies from the MEDLINE, EBASE, SCOPUS, and the Cochrane Database of Systematic Reviews databases. In the analysis, the authors included 11 eligible cohort studies involving 2,193,160 participants.
Overall, those taking thiazide diuretic medications had a significant 14% reduction in the risk for all fractures (relative risk [RR], 0.86; 95% CI, 0.80-0.93; P =.009) and an 18% reduction in the risk for hip fracture (RR, 0.82; 95% CI, 0.80-0.93; P =.009) compared with participants not taking these medications. However, when the analysis was limited to only high-quality original studies, the effect size with thiazide became slightly weaker (RR, 0.89; 95% CI, 95% CI, 0.80-0.99; P =.005). Effect sizes were also diminished when only studies with a larger sample size (>10,000 participants; RR, 0.90; 95% CI, 0.80-1.00; P =.002) or only studies published after 2007 (RR, 0.92; 95% CI, 0.82-1.02; P =.001) were included in the analysis.
Results from subgroup analyses demonstrated some variations. Pooled effects generated from studies that controlled for certain bone mass density-related factors revealed weaker protective effects of thiazides on fracture risk. Controlling for hormone replacement therapy somewhat reduced the association between thiazide use and the risk for fracture. Similar results were also observed in subgroup analyses when body mass index was adjusted.
The authors concluded that although the analyses suggest significant reduction in the risk for fracture with thiazide diuretics, the variations observed in the subgroup analyses warrant further investigation. They further argue that thiazide diuretic use as antihypertensive treatment and osteoporotic fracture prevention should be prescribed with caution.
Xiao X, Xu Y, Wu Q. Thiazide diuretic usage and risk of fracture: a meta-analysis of cohort studies [published online March 25, 2018]. Osteoporosis Int. doi:10.1007/s00198-018-4486-9