Prolonged Loop Diuretic Use Linked to Higher Fracture Risk in Postmenopausal Women

Laurie Barclay, MD

January 28, 2009

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January 28, 2009 — Prolonged use, but not ever-use, of loop diuretics is linked to a higher fracture risk in postmenopausal women, according to the results of a study reported in the January 26 issue of the Archives of Internal Medicine.

"The relationship of loop diuretics to bone mineral density (BMD), falls, and fractures in postmenopausal women has not been established," write Laura D. Carbone, MD, MS, from the Department of Veterans Affairs Medical Center, University of Tennessee Health Science Center in Memphis, and colleagues. "The purpose of this article is to examine the association between loop diuretic use and changes in BMD, falls, and fractures in patients enrolled in the Women's Health Initiative, including women with and without CHF [congestive heart failure]."

Of 133,855 women enrolled in the Women's Health Initiative from October 29, 1993, to December 31, 1998, there were 3411 users and 130,444 nonusers of loop diuretics. Of these, 300 users and 9124 nonusers of loop diuretics had BMD measurements at baseline and at year 3. Incident falls and fractures were determined for a mean of 7.7 years.

No significant association was identified between ever-use of loop diuretics and total fractures (hazard ratio [HR], 1.09; 95% confidence interval [CI], 1.00 - 1.19), hip (HR, 1.21; 95% CI, 0.91 - 1.60), and clinical vertebral fractures (HR, 1.17; 95% CI, 0.92 - 1.48) and falls (HR, 1.02; 95% CI, 0.96 - 1.08), after adjustment for covariates.

With more than 3 years' use of loop diuretics, there was an increased risk for other clinical fractures (HR, 1.16; 95% CI, 1.01 - 133) and total fractures (HR, 1.16; 95% CI, 1.03 - 1.31). Changes in BMD were not associated with use of loop diuretics.

Limitations of this study include inability to adjust for prefracture health, except at baseline, or for low levels of 25-hydroxyvitamin D; lack of information on doses of loop diuretics used or on the exact date that use of these drugs was discontinued; few users of loop diuretics other than furosemide; fall history based on self-report; few hip and vertebral fractures in those with congestive heart failure; lack of generalizability to populations with lower calcium intakes, to those primarily being treated with loop diuretics, or to men; and findings not applicable to thiazide-type diuretics.

"After adjustment for confounding variables, no significant association was found between ever use of loop diuretics and changes in BMD, falls, and fractures," the study authors write. "Loop diuretics were used by women in poor health who were already at risk for fractures. However, prolonged use of loop diuretics was associated with higher fracture risk in postmenopausal women."

The National Heart, Lung, and Blood Institute of Health funds the Women's Health Initiative Program. Dr. Carbone has received grant support from Procter & Gamble and honoraria from Merck, Novartis, Procter & Gamble, and Aventis.

Arch Intern Med. 2009;169:132-140.

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