Osteoporosis is a common chronic condition which poses a substantial clinical, economic, and health-related quality-of-life (HRQOL) burden to the individual, the U.S. health care system, and society in general. The overall objective of this study was to evaluate the economic, clinical and humanistic outcomes of current osteoporosis interventions employed in the prevention of osteoporotic fractures in the Department of Defense (DoD) population. The overall objective encompassed four primary objectives: to assess the epidemiology of osteoporotic fracture in women ≥ age 50; to determine the effectiveness of current osteoporosis interventions; to identify significant risk factors and other covariates in the prediction of osteoporotic fracture; and to determine the cost-effectiveness of current osteoporosis interventions. A three-year sample-based retrospective cohort study was conducted using DoD health care and prescription claims from fiscal years 2000 to 2003. Using an intent-to-treat study design, a total of 49,851 women ≥ age 50 were followed for osteoporotic fracture. The effectiveness of the vinterventions was determined by performing a series of both logistic and direct Cox proportional hazard regressions. The net-benefit regression method of cost-effectiveness was employed to determine the cost-effectiveness of the treatment interventions and to determine the importance of covariates on the marginal cost-effectiveness of an intervention, while statistically controlling for the presence of risk factors and other covariates. The epidemiologic study results showed that the three-year cumulative incidence of an osteoporotic fracture was 2.5 % for the cohort (0.4% in patients without a diagnosis of osteoporosis; 6.1% in patients with a diagnosis of osteoporosis). The intervention effectiveness results obtained from the logistic regression model and the direct Cox proportional-hazards model were consistent and suggested that women treated with the combination of alendronate and HRT are at a lower risk for any fracture, hip fracture, and vertebral fracture when compared to no treatment. In contrast, treatment with alendronate or HRT alone was not found to provide a statistically significant decreased risk of any fracture, hip fracture, vertebral fracture, or wrist fracture when compared to no treatment. The results of this study revealed that the risk of osteoporotic fracture increased: 4-fold with a prior fracture, 4% with each year over 50, and between 38 and 55% with oral corticosteroid use > 1-year (in a three-year period). The findings also suggest that statin use was associated with a decreased risk of osteoporotic fracture. The results from the net-benefit regression method of CEA showed that the current use of DoD’s osteoporosis treatment interventions is not cost-effective in the short-term when compared to no treatment. However, this study provided evidence that the current treatment interventions become more cost-effective when targeted at high risk populations, such as patients with a prior osteoporotic fracture or patients ≥ age 65. The results of this study were potentially influenced by the presence of selection bias.