Andrea Z. LaCroix, PhD; Susan M. Ott, MD; Laura Ichikawa, MS; Delia Scholes, PhD; William E. Barlow, PhD
Thiazide may have beneficial effects on bone mineral density and may reduce risk for hip fracture. However, the existence of a causal role remains uncertain because experimental evidence is limited.
To determine the effect of hydrochlorothiazide on rates of bone loss in older adults.
Randomized, double-blind, placebo-controlled trial with 3-year follow-up.
A large health maintenance organization in western Washington State.
320 healthy, normotensive adults (205 women, 115 men) 60 to 79 years of age.
Random assignment to one of three study groups: 12.5 mg of hydrochlorothiazide per day, 25 mg of hydrochlorothiazide per day, or placebo.
Bone mineral density using dual-energy x-ray absorptiometry at the total hip, posterior–anterior spine, and total body; blood and urine markers of bone metabolism; incident falls, clinical fractures, and radiographic vertebral fractures.
309 of 320 participants completed the 36-month visit (97%). Adherence to study medication throughout follow-up was high in all participants (81.6% to 89.7%) except men in the high-dose hydrochlorothiazide group (60.5%). According to intention-to-treat analysis, the 36-month differences in percentage change in total hip bone mineral density were 0.79 percentage point (95% CI, −0.12 to 1.71) for the 12.5-mg hydrochlorothiazide group and 0.92 percentage point (CI, −0.001 to 1.85) for the 25-mg group compared with placebo (P = 0.03). Percentage change at the posterior–anterior spine was significantly greater for the 25-mg hydrochlorothiazide group at 6 months (intergroup difference, 1.04 percentage points [CI, 0.22 to 1.86]) compared with placebo (P = 0.005); at 36 months, this difference was 0.82 percentage point (CI, −0.36 to 2.01; P = 0.12). No significant differences were seen in total-body bone mineral density between the treatment groups. Treatment effects were stronger in women than in men.
In healthy older adults, low-dose hydrochlorothiazide preserves bone mineral density at the hip and spine. The modest effects observed over 3 years, if accumulated over 10 to 20 years, may explain the one-third reduction in risk for hip fracture associated with thiazide in many epidemiologic studies.
LaCroix AZ, Ott SM, Ichikawa L, et al. Low-Dose Hydrochlorothiazide and Preservation of Bone Mineral Density in Older Adults: A Randomized, Double-Blind, Placebo-Controlled Trial. Ann Intern Med. 2000;133:516–526. doi: https://doi.org/10.7326/0003-4819-133-7-200010030-00010
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Published: Ann Intern Med. 2000;133(7):516-526.
Endocrine and Metabolism, Geriatric Medicine, Metabolic Bone Disorders.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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