Meta-analysis of the efficacy of hormone replacement therapy in treating and preventing osteoporosis in postmenopausal women

Objective: To review the effect of hormone replacement therapy (HRT) on bone density and fractures in postmenopausal women. Data Source: We searched MEDLINE and EMBASE from 1966 to 1999, the Cochrane Controlled Register, citations of relevant articles, and proceedings of international meetings for eligible randomized controlled trials. We contacted osteoporosis investigators to identify additional studies, and primary authors for unpublished data. Study Selection: We included 57 studies that randomized postmenopausal women to HRT or a control (placebo or calcium/vitamin D) and were of at least 1 yr in duration. Seven of these studies reported fractures. Data Abstraction: For each study, three independent reviewers assessed the methodological quality and abstracted the data. Data Synthesis: HRT showed a trend toward reduced incidence of vertebral fractures [relative risk (RR) 0.66, 95% confidence interval (CI) 0.41-1.07; 5 trials] and nonvertebral fractures (RR 0.87, 95% CI 0.71-1.08; 6 trials). HRT had a consistent effect on bone mineral density (BMD) at all sites. The difference between HRT and control in the percent change in bone density at 2 yr was 6.76 (5.83, 7.89; 21 trials) at the lumbar spine and 4.53 (3.68, 5.36; 14 trials) and 4.12 (3.45, 4.80; 9 trials) at the forearm and femoral neck, respectively. Conclusions: HRT has a consistent, favorable and large effect on bone density at all sites. The data show a nonsignificant trend toward a reduced incidence in vertebral and nonvertebral fractures.