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Introduction: This study aims to assess the cost effectiveness of romosozumab versus teriparatide, both sequenced to denosumab, for the treatment of severe postmenopausal osteoporosis at very high risk of fractures in Mexican women., Methods: A Markov model was used to assess the relative cost effectiveness of 1 year of romosozumab versus 2 years of teriparatide, both sequenced to denosumab for a total treatment duration of 5 years. Outcomes for a cohort of women with a mean age of 74 years, a T-score ≤-2.5 and a previous fragility fracture were simulated over a lifetime horizon. The analysis was conducted from the perspective of the Mexican healthcare system and used a discount rate of 5% per annum. To inform relative fracture incidence, the bone mineral density (BMD) advantage of romosozumab over teriparatide was translated into relative risks of fracture, using relationships provided by a meta-regression of osteoporosis therapy trials. Outcomes were assessed in terms of lifetime costs (2023 Mexican pesos), quality-adjusted life years (QALYs) and life-years gained (LYs)., Results: Base case results showed that, compared with teriparatide/ denosumab, romosozumab/ denosumab reduced costs by $51,363 MXN per patient and yielded 0.03 additional QALYs and 0.01 LYs. Scenario analyses and probabilistic sensitivity analyses confirmed that results are robust to uncertainty in model assumptions and inputs., Conclusions: Results show that romosozumab/ denosumab produces greater health benefits at a lower total cost than teriparatide/ denosumab., Competing Interests: TAM, LG, EY and LMC are employed by Amgen. JPDM has served as a consultant for Amgen and has received research grants from them. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2025 Diaz Martinez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: International guidelines state that bone-targeted agents such as denosumab or zoledronic acid at doses used for bone metastasis are not indicated for patients with metastatic castration-sensitive prostate cancer (mCSPC) with bone metastases. Whereas denosumab has never been studied in this patient population, zoledronic acid has been shown to be ineffective in decreasing the risk for skeletal-related events. This study estimates the prevalence and economic consequences of real-world use of bone-targeted agents for mCSPC patients in Switzerland., Methods: To estimate the frequency of bone-targeted agent administration and skeletal-related events, data from a non-interventional, cross-sectional survey involving oncologists across Switzerland (SAKK 95/16) was combined with data from the Swiss National Institute for Cancer Epidemiology and Registration (NICER). Economic parameters were calculated from the perspective of the healthcare system over the median time to prostate-specific antigen (PSA) progression for the extrapolated patient group, using data from NICER. The cost calculation covered costs for bone-targeted agents, their administration and skeletal-related events. The time to PSA progression (33.2 months), as well as the probability and cost of skeletal-related events were derived from the literature., Results: The survey was answered by 86 physicians treating 417 patients, of whom 106 (25.4%) had prostate cancer, with 36 (34.0%) of these mCSPC. The majority of mCSPC patients (52.8%, n = 19) received bone-targeted agents monthly. Denosumab was the treatment of choice in 84.2% of patients (n = 16). Extrapolation using data from NICER indicated that 568 mCSPC patients may be treated with bone-targeted agents at doses used for bone metastasis  every year in Switzerland, leading to estimated total costs of more than CHF 8.3 million over 33.2 months. Because of its more frequent prescription and higher price, it appears that almost 93% of the total costs can be attributed to denosumab. For both denosumab and zoledronic acid, the most expensive components were the cost of administration and the drug cost, making up more than 90% of the total costs, with the rest being costs of skeletal-related events., Conclusions: This study found that the administration of bone-targeted agents in doses used for bone-metastatic diseases to prevent skeletal-related events is frequent in the setting of mCSPC and results in significant costs for the healthcare system.