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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.

Aims: This study assessed the cost-effectiveness of denosumab for treating postmenopausal women with osteoporosis (PMO) at high risk of fracture in Thailand. Materials and methods: A published Markov cohort cost-effectiveness model was populated with country-specific data as available and other published data as needed. The model used a societal perspective, lifetime horizon, efficacy data from network meta-analysis of trials, and included costs for direct medical and non-medical care, informal care, and osteoporosis treatments to compare denosumab to no pharmacologic treatment (calcium and vitamin D supplements only) and to oral weekly alendronate. The base case (high-risk population) included postmenopausal women with femoral neck T-score ≤-2.5, mean age 65 years at entry, and history of vertebral fracture. Results: High-risk women with osteoporosis using denosumab had the greatest number of life years and quality-adjusted life-years (QALYs) with higher reductions in hip and vertebral fracture incidence compared with patients with no pharmacologic treatment. The incremental cost-effectiveness ratio (ICER) was 119,575 Thai Baht (THB) per QALY for denosumab versus no pharmacologic treatment and 199,186 THB per QALY for denosumab versus alendronate. Among Thai postmenopausal women with high-risk of fractures, denosumab was cost-effective compared with no pharmacologic treatment at a willingness-to-pay threshold of 160,000 THB per QALY. One-way sensitivity analysis showed models were most sensitive to changes in denosumab pricing. Limitations: Data from other countries used when country-specific data were unavailable may not accurately reflect the true experience in Thailand. The model focused explicitly on hip, vertebral, and wrist fractures, and therefore provides a conservative estimate of the overall potential impact of osteoporosis-related fracture. The fracture risk was not adjusted to reflect potential changes in risk after denosumab treatment discontinuation. Conclusions: In Thailand, denosumab offers a cost-effective osteoporosis treatment option versus no pharmacologic treatment in postmenopausal women at high risk of fracture.

Aims: Bone complications (also known as skeletal-related events [SREs]) pose significant health and financial burdens on patients with bone metastases. Denosumab demonstrated superiority over zoledronic acid in delaying the time to first SRE. This study examined the lifetime cost-effectiveness of denosumab vs zoledronic acid from both US payer and societal perspectives. Methods: This analysis used a lifetime Markov model and included patients with breast cancer, prostate cancer, and other solid tumors and bone metastases. The societal perspective included direct medical, direct non-medical, and indirect costs associated with denosumab and zoledronic acid; the payer perspective included direct medical costs only. Bone complication rates for each tumor type were estimated from three pivotal phase 3 studies and modified to reflect real-world incidence. Results: From a societal perspective, compared with zoledronic acid, denosumab use resulted in an incremental cost of $9,043, an incremental benefit of 0.128 quality-adjusted life-years (QALYs), a lifetime cost per QALY of $70,730, and a net monetary benefit (NMB) of $10,135 in favor of denosumab. Direct drug costs for denosumab ($28,352) were higher than zoledronic acid/untreated ($578), but were offset by reduced costs associated with bone complications. From a payer perspective, denosumab use was associated with an incremental cost of $13,396, and an incremental benefit of 0.128 QALYs, for a cost of $104,778 per QALY and an NMB of $5,782 in favor of denosumab. Limitations: Some model inputs had limited information and, given that the results may be sensitive to changes in these inputs, our findings should be interpreted within the context of the data inputs and modeling assumptions used in the analysis. Conclusions: Denosumab is a cost-effective option to prevent bone complications in patients with solid tumors when considering both payer and broader societal perspectives.

Aim: The approved indication for denosumab (120 mg) was expanded in 2018 to include skeletal-related event (SRE) prevention in patients with multiple myeloma (MM). Therefore, a cost-effectiveness analysis was conducted comparing denosumab with zoledronic acid (ZA) for SRE prevention in patients with MM from the national healthcare system perspective in a representative sample of European countries: Austria, Belgium, Greece, and Italy. Methods: The XGEVA global economic model for patients with MM was used to calculate incremental cost-effectiveness ratios (ICERs) for denosumab vs ZA over a lifetime horizon. Clinical inputs were derived from the denosumab vs ZA randomized, phase 3 study ("20090482") in patients newly-diagnosed with MM, and comprised real-world adjusted SRE rates, serious adverse event (SAE) rates, treatment duration, dose intensity, progression-free survival (PFS), and overall survival (OS). Economic inputs comprised country-specific denosumab and ZA acquisition and administration costs, SRE and SAE management costs, and discount rates. Health utility decrements associated with MM disease progression, SRE and SAE occurrence, and route of administration were included. Results: Estimated ICERs (cost per quality-adjusted life-year [QALY] gained) for denosumab vs ZA in Austria, Belgium, Greece, and Italy were €26,294, €17,737, €6,982, and €27,228, respectively. Using 1-3 times gross domestic product (GDP) per capita per QALY as willingness to pay thresholds, denosumab was 69-94%, 84-96%, 79-96%, and 50-92% likely to be cost-effective vs ZA, respectively. Limitations: Economic inputs were derived from various sources, and time to event inputs were extrapolated from 20090482 study data. Conclusions: Denosumab is cost-effective vs ZA for SRE prevention in patients with MM in Austria, Belgium, Greece, and Italy, based on often-adopted World Health Organization thresholds. This conclusion is robust to changes in model parameters and assumptions. Cost-effectiveness estimates varied across the four countries, reflecting differences in healthcare costs and national economic evaluation guidelines.

Background: Bone metastases are highly prevalent in breast, prostate, lung and colon cancers. Their symptoms negatively affect quality of life and functionality and optimal management can mitigate these problems. There are two different targeted agents to treat them: bisphosphonates (pamidronate and zoledronic acid) and the monoclonal antibody denosumab. Estimates of cost-effectiveness are still mixed., Objective: To conduct a systematic review of economic studies that compares these two options., Method: Literature search comprised eight databases and keywords for bone metastases, bisphosphonates, denosumab, and economic studies were used. Data were extracted regarding their methodologic characteristics and cost-effectiveness analyses. All studies were evaluated regarding to its methodological quality., Results: A total of 263 unique studies were retrieved and six met inclusion criteria. All studies were based on clinical trials and other existing literature data, and they had high methodological quality. Most found unfavorable cost-effectiveness for denosumab compared with zoledronic acid, with adjusted ICERS that ranged from $4638-87,354 per SRE avoided and from US$57,274-4.81 M. per QALY gained, which varied widely according to type of tumor, time horizon, among others. Results were sensitive to drug costs, time to first skeletal-related event (SRE), time horizon, and utility., Conclusions: Denosumab had unfavorable cost-effectiveness compared with zoledronic acid in most of the included studies. New economic studies based on real-world data and longer time horizons comparing these therapeutic options are needed.

Objective: To assess the cost-effectiveness as well as adherence and patient preference for denosumab compared with oral bisphosphonates for the treatment of osteoporosis., Data Sources: Two comprehensive PubMed literature searches (from data inception to December 2017) were performed. The first search included the terms osteoporosis, denosumab, bisphosphonate, and adherence or persistence or compliance or preference. The search terms osteoporosis, denosumab, cost, and effectiveness were used in the second literature search. Additional references were included from reviewing literature citations., Study Selection and Data Extraction: All English-language clinical trials on adherence (as compliance and persistence) or patient preference for denosumab compared with oral bisphosphonates were evaluated. In addition, articles analyzing the cost-effectiveness of denosumab compared with generic alendronate were evaluated., Data Synthesis: Four studies that assessed patient preference showed positive outcomes for preference and satisfaction for subcutaneous use of denosumab every 6 months versus oral alendronate weekly, oral ibandronate monthly, or oral risedronate monthly. Three studies evaluated persistence and compliance and/or adherence and showed improved persistence and compliance rates with denosumab compared with bisphosphonate therapy. Twelve articles and 3 abstracts assessed cost-effectiveness of denosumab compared with generic alendronate. The majority of articles showed that denosumab was cost-effective, and even cost-saving in patients older than 75 years of age and those who have a history of previous fractures, lower bone mineral density T-scores, and more risk factors., Conclusions: Denosumab compared with oral bisphosphonates may improve patient preference and adherence as well as provide a cost-effective treatment strategy, especially among higher-risk and older adults with osteoporosis.

This study's purpose was to clarify the cost-effectiveness of osteoporosis treatment. Denosumab treatment was cost-effective compared with alendronate treatment for elderly Japanese women at high risk of fragility fractures. Denosumab treatment might be cost-effective for patients with lower bone mineral density., Purpose: In Japan's super-aged society, the prevention and treatment of osteoporosis are a critical issue with implications for the medical economy. This study's purpose was to clarify the cost-effectiveness of osteoporosis treatment with denosumab versus weekly alendronate for elderly Japanese women at high risk of fragility fractures., Methods: A Markov model was used for simulation analysis. The modeled population was 75-year-old Japanese women with a bone mineral density (BMD) of 65% of the young adult mean (YAM) (T-score, - 2.87) and a history of previous vertebral body fracture. The simulation model was repeated until patient age reached 100 years or death. Analysis was performed from the societal perspective. Costs and epidemiological data were derived from previous studies. The incremental cost-effectiveness ratio (ICER) was calculated from the simulation. We compared the ICER with willingness-to-pay. Additional analyses were performed with different combinations of age and BMD. Sensitivity analysis verified the robustness of the analysis., Results: For the modeled population, the ICER of denosumab versus alendronate treatment was estimated at US$40,241/quality-adjusted life year (QALY). The ICER of denosumab for 80-year-old women whose BMD was 60% of YAM was estimated at US$22,469/QALY., Conclusions: Assuming willingness-to-pay as US$50,000/QALY, denosumab treatment for 75-year-old Japanese women with a BMD of 65% of YAM and a history of previous vertebral body fracture was cost-effective compared with alendronate treatment. Among over 75 years of age, denosumab treatment might be more cost-effective than alendronate for patients with a BMD of 65% of YAM or lower.

Objective: A large, pivotal, phase 3 trial in patients with newly diagnosed multiple myeloma (MM) demonstrated that denosumab, compared with zoledronic acid, was non-inferior for the prevention of skeletal-related events (SREs), extended the observed median progression-free survival (PFS) by 10.7 months, and showed significantly less renal toxicity. The cost-effectiveness of denosumab vs zoledronic acid in MM in the US was assessed from societal and payer perspectives., Methods: The XGEVA Global Economic Model was developed by integrating data from the phase 3 trial comparing the efficacy of denosumab with zoledronic acid for the prevention of SREs in MM. SRE rates were adjusted to reflect the real-world incidence. The model included utility decrements for SREs, administration, serious adverse events (SAEs), and disease progression. Drug, administration, SRE management, SAEs, and anti-MM treatment costs were based on data from published studies. For the societal perspective, the model additionally included SRE-related direct non-medical costs and indirect costs. The net monetary benefit (NMB) was calculated using a willingness-to-pay threshold of US$150,000. One-way deterministic and probabilistic sensitivity analyses were conducted., Results: From a societal perspective, compared with zoledronic acid, the use of denosumab resulted in an incremental cost of US$26,329 and an incremental quality-adjusted life-year (QALY) of 0.2439, translating into a cost per QALY gained of US$107,939 and a NMB of US$10,259 in favor of denosumab. Results were sensitive to SRE rates and PFS parameters., Limitations: Costs were estimated from multiple sources, which varied by tumor type, patient population, country, and other parameters. PFS and overall survival were extrapolated beyond the follow-up of the primary analysis using fitted parametric curves., Conclusion: Denosumab's efficacy in delaying or preventing SREs, potential to improve PFS, and lack of renal toxicity make it a cost-effective option for the prevention of SREs in MM compared with zoledronic acid.

Purpose Skeletal-related events (SREs) such as pathologic fracture, spinal cord compression, or the necessity for radiation or surgery to bone metastasis cause considerable morbidity, decrements in quality of life, and costs to the health care system. The results of a recent large randomized trial (Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology [CALGB/Alliance 70604]) showed that zoledronic acid (ZA) every 3 months was noninferior to monthly ZA in reducing the risks of SREs. We sought to determine the cost-effectiveness (CE) of monthly ZA, ZA every 3 months, and monthly denosumab in women with breast cancer and skeletal metastases. Methods Using a Markov model, costs per SRE avoided were calculated for the three treatments. Sensitivity analyses were performed where denosumab SRE probabilities were assumed to be 50%, 75%, and 90% lower than the ZA SRE probabilities. Quality-adjusted life-years were also calculated. The analysis was from the US payer perspective. Results The mean costs of the denosumab treatment strategy are nine-fold higher than generic ZA every 3 months. Quality-adjusted life-years were virtually identical in all the three treatment arms; hence, the optimal treatment would be ZA every 3 months because it was the least costly treatment. The sensitivity analyses showed that relative to ZA every 3 months, the incremental costs per mean SRE avoided for denosumab ranged from $162,918 to $347,655. Conclusion ZA every 3 months was more CE in reducing the risks of SRE than monthly denosumab. This analysis was one of the first to incorporate the costs of generic ZA and one of the first independent CE analyses not sponsored by either Novartis or Amgen, the makers of ZA and denosumab, respectively. ZA every 3 months is the more CE option and more reasonable alternative to monthly denosumab.

Aims: This study assessed the cost-effectiveness of the subcutaneous RANKL inhibitor, denosumab, vs the intravenous bisphosphonate, zoledronic acid, for the prevention of skeletal-related events (SREs) in patients with prostate cancer, breast cancer, and other solid tumors (OST) in the Czech Republic., Materials and Methods: A lifetime Markov model was developed to compare the effects of denosumab and zoledronic acid on costs (including drug costs and administration, patient management, SREs, and adverse events), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios from a national payer perspective. Different discount rates, time horizons, SRE rates, distributions, and nature (asymptomatic vs all SREs), and the inclusion of treatment discontinuation were considered in scenario analyses. The robustness of the model was tested using deterministic and probabilistic sensitivity analyses., Results: Across tumor types, denosumab was associated with fewer SREs, improved QALYs, and higher total costs over a lifetime. The incremental cost per QALY gained for denosumab vs zoledronic acid was 382,673 CZK for prostate cancer, 408,450 CZK for breast cancer, and 608,133 CZK for OST. Incremental costs per SRE avoided for the same tumor type were 54,007 CZK, 51,765 CZK, and 94,426 CZK, respectively. In scenario analyses, the results remained similar to baseline, when different discount rates and time horizons were considered. At a non-official willingness-to-pay threshold of 1.2 million CZK, the probabilities of denosumab being cost-effective vs zoledronic acid were 0.64, 0.67, and 0.49 for prostate cancer, breast cancer, and OST, respectively., Limitations: The SRE rates used were obtained from clinical trials; studies suggest rates may be higher in clinical practice. Additional evidence on real-world SRE rates could further improve the accuracy of the modeling., Conclusions: Compared with zoledronic acid, denosumab provides a cost-effective treatment option for the prevention of SREs in patients with prostate cancer, breast cancer, and OST in the Czech Republic.

Purpose: The goal of this study was to assess and compare the potential clinical and economic value of emerging bone-forming agents using the only currently available agent, teriparatide, as a reference case in patients at high, near-term (imminent, 1- to 2-year) risk of osteoporotic fractures, extending to a lifetime horizon with sequenced antiresorptive agents for maintenance treatment., Methods: Analyses were performed by using a Markov cohort model accounting for time-specific fracture protection effects of bone-forming agents followed by antiresorptive treatment with denosumab. The alternative bone-forming agent profiles were defined by using assumptions regarding the onset and total magnitude of protection against fractures with teriparatide. The model cohort comprised 70-year-old female patients with T scores below -2.5 and a previous vertebral fracture. Outcomes included clinical fractures, direct costs, and quality-adjusted life years. The simulated treatment strategies were compared by calculating their incremental "value" (net monetary benefit)., Findings: Improvements in the onset and magnitude of fracture protection (vs the teriparatide reference case) produced a net monetary benefit of $17,000,000 per 10,000 treated patients during the (1.5-year) bone-forming agent treatment period and $80,000,000 over a lifetime horizon that included 3.5 years of maintenance treatment with denosumab., Implications: Incorporating time-specific fracture effects in the Markov cohort model allowed for estimation of a range of cost savings, quality-adjusted life years gained, and clinical fractures avoided at different levels of fracture protection onset and magnitude. Results provide a first estimate of the potential "value" new bone-forming agents (romosozumab and abaloparatide) may confer relative to teriparatide., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the cost efficacy of available regimens for therapy of osteoporosis as defined as the cost time's number need to treat to prevent one fracture., Methods: Existing meta-analyses were supplemented through electronic databases SCOPUS and PubMed between 2013 (a date overlapping the latest meta-analyses) and March 2016. Primary references included all randomized controlled trials of anti-osteoporotic drugs versus comparators using search terms "osteoporosis," "random," and "trial.", Results: There were 43 evaluable randomized, double-blind, placebo-controlled trials in 71,809 postmenopausal women comparing fracture frequency. Trials were similar in recruitment age (mean ± SD, 67.3 ± 8.1 years) and follow-up duration (25.5 ± 12.6 months). Cost comparisons were evaluated for a treatment strategy assuming generic alendronate as first-line therapy. Denosumab and teriparatide showed benefits in vertebral fracture reduction over alendronate at incremental costs respectively of $46,000 and $455,000 per fracture prevented. Zoledronate, recently released as a generic, would be either less expensive or comparable in cost. None of the alternate medicines were statistically better in preventing hip fractures. Teriparatide was more effective in preventing nonvertebral fractures at an incremental cost of $1,555,000., Conclusion: The most cost-effective initial therapy of postmenopausal osteoporosis is generic oral alendronate or generic parenteral zoledronate. There is no statistically significant difference in efficacy of available drugs to prevent hip fractures. There are limited data to suggest switching drugs after sustaining an osteoporotic fracture while on oral alendronate therapy, although generic zoledronate may be considered on the basis of side effects or questions of medication adherence., Abbreviations: ALN = alendronate; DEN = denosumab; IBN = ibandronate; NNT = number needed to treat; OR = odds ratio; RCT = randomized controlled trial; RIS = risedronate; RLN = raloxifene; TER = teriparatide; ZOL = zoledronate.

We constructed a Markov microsimulation model among hypothetical cohorts of community-dwelling elderly osteoporotic Japanese women without prior hip or vertebral fractures over a lifetime horizon. Compared with weekly oral alendronate for 5 years, denosumab every 6 months for 5 years is cost-saving or cost-effective at a conventionally accepted threshold., Introduction: The objective of the study was to examine the cost-effectiveness of subcutaneous denosumab every 6 months for 5 years compared with weekly oral alendronate for 5 years in Japan., Methods: We calculated incremental cost-effectiveness ratios [ICERs] (2016 US dollars [$] per quality-adjusted life year [QALY]), using a Markov microsimulation model among hypothetical cohorts of community-dwelling osteoporotic Japanese women without prior hip or vertebral fractures at various ages of therapy initiation (65, 70, 75, and 80 years) over a lifetime horizon from three perspectives: societal, healthcare sector, and government., Results: Denosumab was cost-saving compared with alendronate at ages 75 and 80 years from any of the three perspectives. The ICERs of denosumab compared with alendronate were $25,700 and $5000 per QALY at ages 65 and 70 years from a societal perspective and did not exceed a willingness-to-pay of $50,000 per QALY from the other two perspectives. In deterministic sensitivity analyses, results were sensitive to changes in the effectiveness of denosumab for reducing hip fracture and clinical vertebral fracture and the rate ratio of non-persistence with denosumab compared to alendronate. In probabilistic sensitivity analyses, the probabilities of denosumab being cost-effective compared with alendronate were 89-100% at a willingness-to-pay of $50,000 per QALY., Conclusions: Among community-dwelling elderly osteoporotic women in Japan, denosumab every 6 months for 5 years is cost-saving or cost-effective at a conventionally accepted threshold of willingness-to-pay at all ages examined, compared with weekly alendronate for 5 years. This study provides insight to clinicians and policymakers regarding the relative economic value of osteoporosis treatments in elderly women.

Fortunately, novel agents are nowadays available for the management of patients with castration-resistant prostate cancer (CRPC). Denosumab is a new bone-protective agent, approved for the prevention and management of skeletal-related events. Studies have demonstrated that denosumab has better efficacy and similar rate of adverse effects in comparison with zoledronic acid, which was the standard bone-protective agent. In the present review we study the cost-effectiveness of denosumab in patients with CRPC.

Denosumab is a new drug developed for the treatment of osteoporosis. Moreover, increasing evidences link denosumab with benefits in cancer, an area of interest for those in charge of the postmenopausal health. Denosumab has shown efficacy in the control of bone loss associated with hypogonadic states created by chemotherapy in breast and other cancers. Moreover, some studies reveal efficacy in reducing the progression of metastases. A panel of experts from the Spanish Menopause Society has met to develop usage recommendations based on the best available evidence., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)