Low-Dose Hydrochlorothiazide and Preservation of Bone Mineral Density in Older Adults

A Randomized, Double-Blind, Placebo-Controlled Trial

  1. Andrea Z. LaCroix, PhD;
  2. Susan M. Ott, MD;
  3. Laura Ichikawa, MS;
  4. Delia Scholes, PhD; and
  5. William E. Barlow, PhD
  1. From Group Health Cooperative of Puget Sound, Fred Hutchinson Cancer Research Center, and University of Washington, Seattle, Washington.

    Abstract

    Background: 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.

    Objective: To determine the effect of hydrochlorothiazide on rates of bone loss in older adults.

    Design: Randomized, double-blind, placebo-controlled trial with 3-year follow-up.

    Setting: A large health maintenance organization in western Washington State.

    Participants: 320 healthy, normotensive adults (205 women, 115 men) 60 to 79 years of age.

    Intervention: Random assignment to one of three study groups: 12.5 mg of hydrochlorothiazide per day, 25 mg of hydrochlorothiazide per day, or placebo.

    Measurements: 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.

    Results: 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.

    Conclusions: 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.

    Article and Author Information

    • Acknowledgments: The authors thank Ciba-Geigy for providing the study medication for this trial, Sherry Falls and Donna Edgerton, RN, for their many contributions to this study, and the dedicated women and men who faithfully participated over the past 5 years.

    • Grant Support: By the National Institutes of Health (AG09825). Selected laboratory tests were performed by the University of Washington Clinical Nutrition Research Unit, which is sponsored by the National Institutes of Health (P30 DK35816).

    • Requests for Single Reprints: Andrea Z. LaCroix, PhD, Center for Health Studies, Group Health Cooperative of Puget Sound, 1730 Minor Avenue, Suite 1600, Seattle, WA 98101-1448.

    • Current Author Addresses: Drs. LaCroix, Barlow, and Scholes and Ms. Ichikawa: Center for Health Studies, Group Health Cooperative of Puget Sound, 1730 Minor Avenue, Suite 1600, Seattle, WA 98101-1448.

    • Dr. Ott: Department of Medicine, Division of Metabolism, BB-545 Health Sciences Building, University of Washington, Box 356426, Seattle, WA 98112.

    • Author Contributions: Conception and design: A.Z. LaCroix, S.M. Ott, D. Scholes, W.E. Barlow.

    • Analysis and interpretation of the data: A.Z. LaCroix, S.M. Ott, L. Ichikawa, D. Scholes, W.E. Barlow.

    • Drafting of the article: A.Z. LaCroix, S.M. Ott, W.E. Barlow.

    • Critical revision of the article for important intellectual content: A.Z. LaCroix, S.M. Ott, D. Scholes, W.E. Barlow.

    • Final approval of the article: A.Z. LaCroix, S.M. Ott, D. Scholes, W.E. Barlow.

    • Provision of study materials or patients: A.Z. LaCroix, S.M. Ott.

    • Statistical expertise: A.Z. LaCroix, L. Ichikawa, W.E. Barlow.

    • Obtaining of funding: A.Z. LaCroix, S.M. Ott.

    • Administrative, technical, or logistic support: A.Z. LaCroix, S.M. Ott.

    • Collection and assembly of data: A.Z. LaCroix, S.M. Ott, L. Ichikawa, D. Scholes.

    Summary for Patients

    • Summaries for Patients:Low-Dose Diuretic To Preserve Bone Density in Older Adults Ann Intern Med October 3, 2000 133:I-30
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    1. Ann Intern Med October 3, 2000 vol. 133 no. 7 516-526
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