Context:​ Fragility fractures cause significant morbidity and mortality. Effective osteoporosis treatment can reduce fracture incidence, but it is not known whether it reduces mortality.

Objective:​ The aim of the study was to determine whether effective osteoporosis treatment reduces mortality.

Data Sources:​ We searched Medline and the Cochrane Central Register of Trials prior to September 2008, as well as 2000–2008 American Society for Bone and Mineral Research conference abstracts.

Study Selection:​ Eligible studies were randomized placebo-controlled trials of approved doses of medications with proven efficacy in preventing both vertebral and nonvertebral fractures, in which the study duration was longer than 12 months and there were more than 10 deaths. Trials of estrogen and selective estrogen receptor modulators were specifically excluded.

Data Extraction:​ Data were extracted from the text of the retrieved articles, published meta-analyses, or the Food and Drug Administration web site.

Data Synthesis:​ Eight eligible studies of four agents (risedronate, strontium ranelate, zoledronic acid, and denosumab) were included in the primary analysis. During two alendronate studies, the treatment dose changed, and those studies were only included in secondary analyses. In the primary analysis, treatment was associated with an 11% reduction in mortality (relative risk, 0.89;​ 95% confidence interval, 0.80–0.99;​ P = 0.036). In the secondary analysis, the results were similar (relative risk, 0.90;​ 95% confidence interval, 0.81–1.0;​ P = 0.044). Mortality reduction was not related to age or incidence of hip or nonvertebral fracture, but was greatest in trials conducted in populations with higher mortality rates.

Conclusions:​ Treatments for osteoporosis with established vertebral and nonvertebral fracture efficacy reduce mortality in older, frailer individuals with osteoporosis who are at high risk of fracture.