OBJECTIVES: A phase III clinical trial demonstrated the advantage of denosumab over zoledronic acid(ZA) in delaying the first on-study and subsequent skeletal-related events(SREs) in patients with prostate cancer(PC). Recently, generic ZA became available. The purpose of this study was to examine the cost-effectiveness of denosumab vs. brand or generic ZA in the prevention of SREs in Kazakhstani patients with PC. METHODS: An excel-based Markov model was constructed with 4-week model cycles to analyse the cost-effectiveness of the treatments from the perspective of Ministry of Health with a 10-year time horison for PC cohort. Direct costs(in 2014 tenge) included costs of drug, adverse event and SRE(pathologic fracture, surgery to bone, radiation to bone, spinal cord compression) treatment. A discount rate of 3% per year was applied. Effectiveness was appraised based on the number of SREs. The health states were defined according to SRE occurance,SRE history and death. The model assumed that a maximum of 1 SRE could occur in each cycle. Transition probabilities were derived from the relevant phase III trials. Results were present in the incremental total cost per SRE avoided. One-way sensitivity analyses were performed to examine the robustness of the model. RESULTS: Over 10-year period, denosumab incurred 103091 tenge higher costs than brand ZA, 677133 tenge higher costs than generic ZA, 0.58 fewer SREs per PC patient; The estimated incremental total direct costs per SRE avoided with the use of denosumab were 177743 tenge (instead of brand ZA) and 1167470 tenge (instead of generic ZA). Results were robust to one-way sensitivity analyses. CONCLUSIONS: With assumption that brand and generic ZAs are equally effective, denosumab seems to be superior alternative for brand ZA (insignificant difference in costs), and costly alternative for generic ZA from a perspective of Ministry of Health of Republic of Kazakhstan.