OBJECTIVES: Denosumab is recomended for preventing skeletal-related events (SREs) in adults with bone metastases from breast cancer (BC). Since recently generic zoledronic acid (ZA) became available, the aim of present study was to access the cost-effectiveness of denosumab vs. brand or generic ZA in the prevention of SREs in Kazakhstani patients with BC.  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 BC 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 for all costs. 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 1044 tenge lower costs than brand ZA, 568558 tenge higher costs than generic ZA, 1.28 fewer SREs per BC patient. The estimated incremental total direct costs per SRE avoided with the use of denosumab were -816 tenge (instead of brand ZA) and 444186 tenge (instead of generic ZA). Results were robust to one-way sensitivity analyses. CONCLUSIONS: With assumption that brand and generic ZAs are equally effective in the prevention of SREs in BC patients, denosumab seems to be cost-effective alternative for brand ZA, and costly alternative for generic ZA from a perspective of Ministry of Health of Republic of Kazakhstan.