Prevalent vertebral deformities are predictive of future clinical fractures independent of bone density. We used a Markov model with eight health states to estimate from the societal perspective the cost-effectiveness of using spine radiographs to identify postmenopausal women age 60 or older with one or more vertebral deformities and then treat them with anti-resorptive drug therapy to prevent fractures. We compared three strategies: 5 years of amino-bisphosphonate (alendronate) therapy for all, 5 years of alendronate therapy for only those with prevalent a radiographic vertebral deformity or no initial alendronate treatment. Lifetime direct medical and indirect costs, quality adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were tracked. For women with one or more prevalent vertebral deformities, the costs per QALY gained ranged from $5,084 (for an 80 year old with a T-score of –2.4) to $5,084 (for an 80 year old with a T-score of –2.4) to 61,192 (for a 60 year old with a T-score of –1.0). For women without prevalent vertebral deformity, the costs per QALY gained ranged from $41,897 (for a 60 year old with a T-score of –2.4) to $41,897 (for a 60 year old with a T-score of –2.4) to 166,219 (for an 80 year old with a T-score of –1.0). These results were modestly sensitive to reasonable changes in fracture rates, disutility, discount rates and assumptions about the accuracy of spinal radiographs for detecting vertebral deformity. Assuming a societal willingness to pay per QALY gained of $50,000, the strategy of performing spine radiographs in post-menopausal osteopenic women with T-scores at or below –1.5 and treating those with 1 or more prevalent vertebral deformities is likely to be cost-effective. However, further research on the accuracy of vertebral deformity ascertainment from routine clinical radiographs and on the efficacy of amino-bisphosphonate drugs for reducing the risk of non-vertebral fractures in osteopenic women is needed to define more precisely the subset of osteopenic post-menopausal women in whom use of spinal radiographs is most cost-effective.