OBJECTIVES: To assess, in the Belgian setting, the costs, efficacy, and cost-effectiveness of zoledronic acid 5mg (Aclasta) versus conventional therapies (tiludronate (Skelid), pamidronate (Aredia), and risedronate (Actonel)) in the management of patients with Paget's disease of bone (PDB). METHODS: Based on efficacy data from pivotal zoledronic acid 5mg clinical trials and the literature, a decision tree model was developed to reflect the treatment path with the different drugs compared. This model takes into account four health states and links efficacy data to Belgian resource use data. It covers a 2-year time horizon. The outcome measure chosen is time in response, defined as time in which serum alkaline phosphatase is controlled. Direct medical costs, from the perspective of the health care payer (INAMI/RIZIV) were considered and discounting was applied in the second year. The consumption of medical resources (drug treatments including administration costs, laboratory tests, and physician consultations) was assessed via expert opinion. RESULTS: Over two years, the expected average numbers of months in response for patients treated with zoledronic acid 5mg and conventional treatments (tiludronate, pamidronate, and risedronate) are: 20.9 months; 11.1 months; 9.3 months; and 16.2 months, respectively. Over this period, the expected average costs for patients treated with zoledronic acid 5mg and conventional treatments (tiludronate, pamidronate, and risedronate) are: 686€; 1525€; 1245€; and 793€, respectively. Hence, zoledronic acid 5mg dominates all the other bisphosphonates compared, i.e. zoledronic acid 5mg is less costly and more effective. This is mainly due to the lower average number of treatment cycles needed with zoledronic acid 5mg, also considering the improved compliance with the IV infusion. The probabilistic sensitivity analyses performed show that the results are robust. CONCLUSION: Based on our evaluation, in PDB, zoledronic acid 5mg is both more effective and less costly than the other bisphosphonates currently reimbursed in Belgium.