PURPOSE: To estimate how much the improvement in bone mass accounts for the reduction in risk of vertebral fracture that has been observed in randomized trials of antiresorptive treatments for osteoporosis. METHODS: After a systematic search, we conducted a meta-analysis of 12 trials to describe the relation between improvement in spine bone mineral density and reduction in risk of vertebral fracture in postmenopausal women. We also used logistic models to estimate the proportion of the reduction in risk of vertebral fracture observed with alendronate in the Fracture Intervention Trial that was due to improvement in bone mineral density. RESULTS: Across the 12 trials, a 1% improvement in spine bone mineral density was associated with a 0.03 decrease (95% confidence interval [CI]: 0.02 to 0.05) in the relative risk (RR) of vertebral fracture. The reductions in risk were greater than predicted from improvement in bone mineral density; for example, the model estimated that treatments predicted to reduce fracture risk by 20% (RR = 0.80), based on improvement in bone mineral density, actually reduce the risk of fracture by about 45% (RR = 0.55). In the Fracture Intervention Trial, improvement in spine bone mineral density explained 16% (95% CI: 11% to 27%) of the reduction in the risk of vertebral fracture with alendronate. CONCLUSION: Improvement in spine bone mineral density during treatment with antiresorptive drugs accounts for a predictable but small part of the observed reduction in the risk of vertebral fracture.