Low-dose hydrochlorothiazide and preservation of bone mineral density in older adults - A randomized, double-blind, placebo-controlled trial

Background: Thiazide may have beneficial effects on bone mineral density an d 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 foll ow-up. Setting: A large health maintenance organization in western Washington Stat e. Participants: 320 healthy, normotensive adults (205 women, 115 men) 60 to 7 9 years of age. Intervention: Random assignment to one of three study groups: 12.5 mg of hy drochlorothiazide per day, 25 mg of hydrochlorothiazide per day, or placebo . Measurements: Bone mineral density using dual-energy x-ray absorptiometry a t the total hip, posterior-anterior spine, and total body; blood and urine markers of bone metabolism; incident falls, clinical fractures, and radiogr aphic vertebral fractures. Results: 309 of 320 participants completed the 36-month visit (97%). Adhere nce 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 p ercentage change in total hip bone mineral density were 0.79 percentage poi nt (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 s ignificantly greater for the 25-mg hydrochlorothiazide group at 6 months (i ntergroup difference, 1.04 percentage points [CI, 0.22 to 1.86]) compared w ith 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 i n total-body bone mineral density between the treatment groups. Treatment e ffects were stronger in women than in men. Conclusions: In healthy older adults, low-dose hydrochlorothiazide preserve s bone mineral density at the hip and spine. The modest effects observed ov er 3 years, if accumulated over 10 to 20 years, may explain the one-third r eduction in risk for hip fracture associated with thiazide in many epidemio logic studies.