BACKGROUND: Treatment guidelines recommend drug treatment to prevent fractures for some postmenopausal women who have low bone mass (osteopenia) but do not have osteoporosis or a history of clinical fractures. OBJECTIVE: To estimate the societal costs and health benefits of alendronate drug treatment to prevent fractures in postmenopausal women with osteopenia. DESIGN: Markov model with 8 health states: no fracture, post-distal forearm fracture, post-clinical vertebral fracture, post-radiographic (but clinically inapparent) vertebral fracture, post-hip fracture, post-hip and vertebral fractures, post-other fracture, and death. DATA SOURCES: Population-based studies of age-specific fracture rates and costs, prospectively measured estimates of disutility after fractures, and the Fracture Intervention Trial of alendronate versus placebo to prevent fracture. TARGET POPULATION: Postmenopausal women 55 to 75 years of age with femoral neck T-scores between -1.5 and -2.4. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTIONS: Five years of alendronate therapy or no drug treatment. OUTCOME MEASURES: Costs, quality-adjusted life-years, and incremental cost-effectiveness ratios. RESULTS OF BASE-CASE ANALYSIS: For women with no additional fracture risk factors, the cost per quality-adjusted life-year gained ranged from 70,000 dollars to 332,000 dollars, depending on age and femoral neck bone density. RESULTS OF SENSITIVITY ANALYSES: Results were sensitive to changes in fracture risk reduction attributable to alendronate and alendronate cost. LIMITATIONS: Results apply only to postmenopausal white women residing in the United States. CONCLUSION: Alendronate therapy for postmenopausal women with femoral neck T-scores better than -2.5 and no history of clinical fractures or other bone mineral density-independent risk factors for fracture is not cost-effective, assuming U.S. costs of alendronate and currently available estimates of alendronate efficacy in osteopenic women.