A patient-level Markov decision model was used to simulate a virtual cohort of 500,000 women 40 years old and over, in relation to osteoporosis-related hip, clinical vertebral, and wrist bone fractures events. Sixteen different screening options of three main scenario groups were compared: (1) the status quo (no specific national prevention program); (2) a universal primary prevention program; and (3) a universal screening and treatment program based on the 10-year absolute risk of fracture. The outcomes measured were total directs costs from the perspective of the public health care system, number of fractures, and quality-adjusted life-years (QALYs). Results show that an option consisting of a program promoting physical activity and treatment if a fracture occurs is the most cost-effective (CE) (cost/fracture averted) alternative and also the only cost saving one, especially for women 40 to 64 years old. In women who are 65 years and over, bone mineral density (BMD)-based screening and treatment based on the 10-year absolute fracture risk calculated using a Canadian Association of Radiologists and Osteoporosis Canada (CAROC) tool is the best next alternative. In terms of cost-utility (CU), results were similar. For women less than 65 years old, a program promoting physical activity emerged as cost-saving but BMD-based screening with pharmacological treatment also emerged as an interesting alternative. In conclusion, a program promoting physical activity is the most CE and CU option for women 40 to 64 years old. BMD screening and pharmacological treatment might be considered a reasonable alternative for women 65 years old and over because at a healthcare capacity of $50,000 Canadian dollars ($CAD) for each additional fracture averted or for one QALY gained its probabilities of cost-effectiveness compared to the program promoting physical activity are 63% and 75%, respectively, which could be considered socially acceptable. Consideration of the indirect costs could change these findings. © 2013 American Society for Bone and Mineral Research