UC San Diego

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.