We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Review |

Hormone Replacement Therapy and Prevention of Nonvertebral Fractures A Meta-analysis of Randomized Trials

David J. Torgerson, PhD; Sally E. M. Bell-Syer, MSc
JAMA. 2001;285(22):2891-2897. doi:10.1001/jama.285.22.2891.
Text Size: A A A
Published online

Context Hormone replacement therapy (HRT) is widely considered to reduce fractures, but this belief is based on observational data; evidence from randomized trials is lacking.

Objective To conduct a systematic review of all randomized trials of HRT that have reported or collected nonvertebral fracture data but that may not have focused on fracture prevention.

Data Sources The MEDLINE, EMBASE, Science Citation Index, and Cochrane Controlled Trials Register databases were searched from 1997 through 2000 and a search was conducted of all recent systematic reviews to identify older studies. Authors were contacted to establish whether fracture data had been collected but not reported. Researchers in the field and pharmaceutical companies also were contacted to try to identify unpublished studies.

Study Selection Trials were included in which participants had been randomized to at least 12 months of therapy and data on nonvertebral fractures at any other site and due to any cause were available. Of 70 initially identified studies, 22 were included in the analysis.

Data Extraction Both investigators extracted data independently and appraised trial quality according to the Jadad scale, which assesses the methods of randomization, concealment allocation, and reporting of withdrawals and dropouts. Disagreements were resolved by discussion.

Data Synthesis There was an overall 27% reduction in nonvertebral fractures in a pooled analysis (reduction favoring HRT in relative risk [RR], 0.73; 95% confidence interval [CI], 0.56-0.94; P = .02). This effect was greater among women randomized to HRT who had a mean age younger than 60 years (RR, 0.67; 95% CI, 0.46-0.98; P = .03). Among women with a mean age of 60 years or older, there was a reduced effect (RR, 0.88; 95% CI, 0.71-1.08; P = .22). For hip and wrist fractures alone, the effectiveness of HRT appeared more marked (RR, 0.60; 95% CI, 0.40-0.91; P = .02), particularly for women younger than 60 years (RR, 0.45; 95% CI, 0.26-0.79; P = .005).

Conclusions Our meta-analysis of randomized controlled trials of HRT noted a statistically significant reduction in nonvertebral fractures. However, this effect may be attenuated in older women.

Figures in this Article

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?


Figure 1. Relative Risk Plot of Trials Pooled by Random Effects Model
Graphic Jump Location
Size of data markers reflects size of sample. Asterisk indicates test for heterogeneity, χ221 = 26.42; P = .19. Test for overall effect, z = 2.39; P = .02.
Figure 2. Funnel Plot of Published and Unpublished Studies
Graphic Jump Location
Meta-analysis weight represents the importance of the study and is derived from Figure 1. The dotted line represents the point of no effect.



Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.


Some tools below are only available to our subscribers or users with an online account.

280 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

See Also...
Articles Related By Topic
Related Collections
PubMed Articles

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis
Evidence to Support the Update

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis
Evidence to Support the Update