Loop diuretics have mixed effects on fracture risk

In an analysis of fracture risk associated with loop diuretic use among postmenopausal women in the Women’s Health Initiative (WHI) study, investigators demonstrated no significant association between loop diuretic use and fractures or changes in bone mineral density (BMD). With prolonged use of loop diuretics, however, the risk of fracture was modestly increased. These study results were published in the Archives of Internal Medicine.

In this prospective study, women aged 50 to 79 years who were enrolled in the WHI from October 1993 through December 1998 were subsequently observed for a mean of 7.7 years. Eligible patients included those in the WHI observational study and clinical trials who were not part of the active hormone or calcium plus vitamin D arms (3,411 loop diuretic users and 130,444 nonusers). In this study population, 3,820 women had congestive heart failure (CHF) (842 loop diuretic users and 2,978 nonusers). Among all loop diuretic users, 88.9% were treated with furosemide, 7.8% were treated with bumetanide, 2.9% were treated with torsemide, and 0.4% were treated with ethacrynic acid. Medication use was recorded at baseline and at the 3-year visit. Fractures were self-reported and adjudicated; hip fractures were verified by review of medical records or radiologic reports. In a subset of patients, bone mineral density (BMD) of the total hip, anterior-posterior lumbar spine, and total body was measured at baseline and at the 3-year visit.

After adjustments for multiple covariates, no statistically significant difference was observed between loop diuretic use and total fractures (HR=1.09; 95% CI, 1.00–1.19), hip fractures (HR=1.21; 95% CI, 0.91–1.60), clinical vertebral fractures (HR=1.17; 95% CI, 0.92–1.48), and falls (HR=1.02; 95% CI, 0.96–1.08). An increased risk for other clinical fractures (HR=1.16; 95% CI, 1.01–1.33) and total fractures (HR=1.16; 95% CI, 1.03–1.31) was observed among patients who had been treated with loop diuretics for >3 years.

Among women with CHF, loop diuretic use was associated with a reduced risk of hip fractures (HR=0.44; 95% CI, 0.21–0.94) and clinical vertebral fractures (HR=0.46; 95% CI, 0.21–0.97) after adjustments for multiple covariates.

In the subset of patients who underwent BMD measurement, no significant differences were observed between loop diuretic users and nonusers in total hip, lumbar spine, or total body BMD at baseline and at Year 3 after adjustments for covariates.

This study was limited by several factors, including the absence of information on loop diuretic doses, a minimal exposure to loop diuretics other than furosemide, and a lack of data on the prefracture health of the study participants, which was assessed only at baseline.

Because the risk of fracture appeared to increase with prolonged exposure to loop diuretics, the authors suggested that “it may be important to consider fracture prevention measures in women who receive loop diuretic therapy.”

Source
Carbone LD, Johnson KC, Bush AJ, et al. Loop diuretic use and fracture in postmenopausal women: Findings from the Women’s Health Initiative. Arch Intern Med. 2009;169:132–140.