Effect of Osteoporosis Treatment on Mortality: A Meta-Analysis

Abstract

Substantial morbidity and mortality is associated with fragility fractures. Between 10% and 20% of individuals who suffer hip fractures die within 1 year, and there is also significant mortality following vertebral and other nonvertebral fractures. Systematic reviews and meta-analyses have provided clear evidence that effective osteoporosis treatment can reduce the incidence of both vertebral and nonvertebral fractures, but it is unclear whether it can reduce mortality. Only one large randomized controlled trial of osteoporosis treatment investigating the effectiveness of zoledronic acid reported a statistically significant survival benefit in patients with vertebral and other nonvertebral fractures. This retrospective literature review examined placebo-controlled randomized trials of osteoporosis treatment to determine whether effective osteoporosis treatment reduced mortality. Data from randomized placebo-controlled trials of osteoporosis treatments were obtained from MEDLINE, the Cochrane Central Register of Trials and the annual conference abstracts (2000–2008) of the American Society for Bone and Mineral Research. Other sources of data were company web sites, published meta-analyses, and the Food and Drug Administration web site. All included trials used approved doses of medications with proven efficacy in preventing both vertebral and nonvertebral fractures, had trial durations longer than 1 year, and a number of study deaths greater than 10. Specific exclusion criteria included trials of estrogen and/or selective estrogen receptor modulators. The 8 studies meeting inclusion and exclusion criteria and included in the primary analysis investigated 4 agents (risedronate, strontium ranelate, zoledronic acid, and denosumab). In 2 other trials meeting eligibility criteria (both using alendronate), the treatment dose was changed during the study; therefore, data from these studies were only included in secondary analyses. Osteoporosis treatment in the primary analysis was associated with an 11% reduction in mortality; the relative risk (RR) was 0.89, with a 95% confidence interval (CI) of 0.80 to 0.99 (P = 0.036). Similar results were found in the secondary analysis including the 2 alendronate studies (RR, 0.90; 95% CI, 0.81–1.0; P = 0.044). Meta-regression analyses showed that reduced mortality was not associated with mean age, incidence of hip or nonvertebral fracture in the placebo group, or vertebral or nonvertebral fracture risk reduction, but was related to the mortality rate in the placebo group (P = 0.030). The mortality benefit appeared to be similar among the different drug classes in the analysis. These findings show that the use of agents with proven efficacy for vertebral and nonvertebral fracture to treat older, frailer individuals with osteoporosis who are at high risk of fractures reduces mortality by approximately 10%.