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Link: prolonged use of loop diuretics, fracture risk in postmenopausal women
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There was no link found between ever use of loop diuretics and changes in bone mineral density, falls and fractures; however, prolonged use was associated with higher fracture risk in postmenopausal women, according to results published in the Archives of Internal Medicine.
“No significant differences were found between loop diuretic users and nonusers in baseline bone mineral density of the total hip, lumbar spine, total body, year three bone mineral density of the total hip, lumbar spine, total body or change in bone mineral density measurements from baseline to year three,” the researchers wrote.
They examined a possible relationship of loop diuretics with changes in BMD, falls and fractures in postmenopausal women. They included users (n=3,411) and nonusers (n=130,444) of loop diuretics enrolled in the Women’s Health Initiative from Oct. 29, 1993 to Dec. 31, 1998. Incident falls and fractures for a mean of 7.7 years were determined. The researchers also examined users (n=300) and nonusers (n=9,124) who had BMD measurements at baseline and at three years.
When adjusting for age, ethnicity and BMI, there was a link found between loop diuretic use and total fractures (HR=1.31; 95% CI, 1.20-1.42), hip fractures (HR=1.75; 95% CI, 1.34-2.28), clinical vertebral fractures (HR=1.68; 95% CI, 1.35-2.10), other fractures (HR=1.27; 95% CI, 1.15-1.41) and at least two falls (HR=1.37; 95% CI, 1.30-1.45), according to the study. No association was found between loop diuretic use and lower arm or wrist fractures (HR=1.17; 95% CI, 0.97-1.41).
The association between ever use of loop diuretics 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=1.01; 95% CI, 0.96-1.08) did not reach statistical significance. There was a slight 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) with use of loop diuretics for more than three years.
In minimally adjusted models for women with incident congestive heart failure, loop diuretic use was inversely associated with vertebral fractures, but not hip fractures (HR=0.69; 95% CI, 0.35-1.37). Use was inversely associated with hip fractures (HR=0.44; 95% CI, 0.21-0.94) and clinical vertebral fractures (HR=0.46; 95% CI, 0.21-0.97). There were 16 hip fractures and 23 clinical vertebral fractures.
In a subset of women with adjudicated incident congestive HF who had imaging procedures documenting impaired systolic or diastolic function, the HR was 0.27 (95% CI, 0.06-1.23) for hip fractures and 0.39 (95% CI, 0.10-1.50) for clinical vertebral fractures, although findings did not reach statistical significance. No differences were found between loop diuretic users and nonusers in baseline BMD of the total hip (P=.45), lumbar spine (P=.31), total body (P=.29), year three BMD of the total hip (P=.34), lumbar spine (P=.05), total body (P=.05) or change in BMD measurements from baseline to year three.
Based on these findings, the researchers suggest that “it may be important to consider fracture prevention measures in women who receive loop diuretic therapy.” – by Christen Haigh
Arch Intern Med. 2009;169:132-140.
Loop diuretics may contribute to fracture risk by increasing calcium diuresis leading to calcium deficiency, secondary hyperparathyroidism, increased bone turnover and decreased bone quality and strength. Loop diuretics may also make individuals more likely to fall. The final sentence of this paper states the real problem with the study. It states that, 'Loop diuretics are most commonly used by women in poor health who are already at risk for falls, fractures and loss of BMD.' Because the data in this paper was captured from the WHI and was not empowered to answer the questions about loop diuretic use and fracture risk, the data only documented that long-time loop diuretic users were at increased risk for 'other clinical fractures' and 'total fractures' (but not specifically hip fractures, vertebral fractures and lower arm or wrist fractures.) As the authors point out in their own comments, the data did not measure the effect of loop diuretics on calcium excretion or measure vitamin D levels (important in falls), identify patient frailty (a risk factor for fractures) or identify when some of the patients may have stopped taking the loop diuretics. So the answer to the question, are loop diuretics an independent risk factor, remains unanswered, although there is a suggestion that prolonged use may in fact increase that risk in postmenopausal women.
– Donald A. Bergman, MD
Endocrine Today Editorial Board member