0

The full content of Annals is available to subscribers

Subscribe/Learn More  >
Articles |

Low-Dose Hydrochlorothiazide and Preservation of Bone Mineral Density in Older Adults: A Randomized, Double-Blind, Placebo-Controlled Trial

Andrea Z. LaCroix, PhD; Susan M. Ott, MD; Laura Ichikawa, MS; Delia Scholes, PhD; and William E. Barlow, PhD
[+] Article and Author Information

Copyright ©2004 by the American College of Physicians


Ann Intern Med. 2000;133(7):516-526. doi:10.7326/0003-4819-133-7-200010030-00010
Text Size: A A A

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.

Figures

Grahic Jump Location
Figure 1.
Trial design and participant flow.nnnnnnn

* Reasons for ineligibility included concomitant medications ( = 15), medical history ( = 113), abnormal blood pressure ( = 83), abnormal electrocardiogram ( = 93), physical examination findings ( = 18), abnormal results on laboratory tests ( = 103), or other ( = 29).

Grahic Jump Location
Grahic Jump Location
Figure 2.
Mean change from baseline in bone mineral density (BMD) at the total hip during 3 years of follow-up in 205 women (top) and 115 men (bottom) who were 60 to 79 years of age, according to study group.

Solid lines represent the 25-mg hydrochlorothiazide group, dotted lines represent the 12.5-mg hydrochlorothiazide group, and dashed lines represent the placebo group. Error bars represent 95% CIs.

Grahic Jump Location
Grahic Jump Location
Figure 3.
Mean change from baseline in bone mineral density (BMD) at the posterior–anterior spine during 3 years of follow-up in 205 women (top) and 115 men (bottom) who were 60 to 79 years of age, according to study group.

Solid lines represent the 25-mg hydrochlorothiazide group, dotted lines represent the 12.5-mg hydrochlorothiazide group, and dashed lines represent the placebo group. Error bars represent 95% CIs.

Grahic Jump Location
Grahic Jump Location
Figure 4.
Mean change from baseline in total-body bone mineral density (BMD) during 3 years of follow-up in 205 women (top) and 115 men (bottom) who were 60 to 79 years of age, according to study group.

Solid lines represent the 25-mg hydrochlorothiazide group, dotted lines represent the 12.5-mg hydrochlorothiazide group, and dashed lines represent the placebo group. Error bars represent 95% CIs.

Grahic Jump Location

Tables

References

Letters

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Comments

Submit a Comment
Submit a Comment

Summary for Patients

Low-Dose Diuretic To Preserve Bone Density in Older Adults

Copyright ©2004 by the American College of Physicians

Read More...

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.

Toolkit

Buy Now

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Advertisement
Related Articles
Related Point of Care
Topic Collections
PubMed Articles
Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.
(Required)
(Required)