OBJECTIVES: To evaluate the cost-effectiveness of bone densitometry screening for Belgian women aged 55 and older combined with 5 years Alendronate therapy in osteoporotic women (femoral neck t-score =-2,5) versus no screening and no treatment. METHODS: A microsimulation Markov model was developed. The model used a lifetime horizon, a Belgian societal perspective and recorded the full patient history by the use of tracker variables. Each prior fracture had an impact on transition probabilities, costs and QALY level. All the model parameters were selected from Belgian literature when available and from systematic literature review otherwise. Analyses were realized at the ages of 55, 60, 65, 70, 75, 80 and 85 years and for women with 0 to 4 clinical risk factors. Sensitivity analyses were run on persistence level. RESULTS: Costs per QALY gained for the screen and treat strategy versus no intervention with optimal persistence and no clinical risk factor were €49,711, €25,392 and €10,487 for the ages of 55, 65 and 75 years respectively. With realistic persistence, these values were respectively €61,373, €35,780 and €14,302. With one clinical risk factor and optimal persistence, these values were €31,320, €11,507 and cost-saving. And with two clinical risk factors, these values were €18,206, €2,588 and cost-saving. CONCLUSION: Universal bone densitometry followed by Alendronate treatment in the presence of osteoporosis seems highly cost-effective (cost per QALY gained = €30,000) for women aged 65 and older (with optimal persistence), for women aged 70 and older (with realistic persistence) and for women with at least one clinical risk factor aged 60 or older (even under realistic persistence assumption). We concluded that screening individuals with or more clinical risk factors is more cost-effective than universal screening and should be recommended.