jbm > Volume 29(2); 2022 > Article
Kang, Choi, Johnson, and Yang: Cost-Effectiveness of Denosumab for the Treatment of Postmenopausal Osteoporosis in South Korea

Abstract

Background

Osteoporosis is a progressive skeletal disease associated with an increased risk of bone fracture. This study aimed to estimate the cost-effectiveness of denosumab for osteoporotic fracture prevention compared to bisphosphonates (alendronate, ibandronate, risedronate, and zoledronate) and selective estrogen receptor modulators (raloxifene) in a cohort of postmenopausal women with osteoporosis.

Methods

A Markov model was used to evaluate the cost and effectiveness of denosumab versus comparators. The model had a cycle length of 6 months and was run from the age of 68 years to individual patients’ lifetime or the age of 100 years. The health states considered in the model were well, hip fracture, vertebral fracture, wrist fracture, other osteoporotic fracture, post-hip fracture, post-vertebral fracture, and death. Recent local data were used as inputs for the model parameters. A discount rate of 4.5% was applied to both costs and outcomes.

Results

From the perspective of the healthcare system, denosumab was cost-effective or cost-saving compared to all comparators, considering one unit of Korea’s gross domestic product per capita, USA dollar (USD) 34,870. Denosumab was cost-saving compared to ibandronate (oral) and raloxifene. Compared to alendronate, denosumab was cost-effective with an incremental cost-effectiveness ratio (ICER) of USD 767.10 per quality-adjusted life year (QALY). The ICER of denosumab vs. ibandronate IV, risedronate, and zoledronate was USD 685.63, USD 1,469.71, USD 4,668.53 per QALY, respectively.

Conclusions

The findings of this analysis suggest that denosumab is a cost-effective therapeutic option for preventing fractures in postmenopausal women with osteoporosis in South Korea.

INTRODUCTION

Osteoporosis is a systemic and progressive skeletal disease, which leads to a reduction in bone mass and quality.[1] Epidemiological data from 2020 Health Insurance Review & Assessment Service (HIRA) suggest approximately 22% of adults in Korea suffer from osteoporosis.[2] Low bone mineral density (BMD) reduces bone strength which makes bones more susceptible to fracture. The clinical sequelae of osteoporotic fractures are serious. Osteoporosis is associated with significant fracture-related morbidity [3] since the majority of fractures occur at the hip, spine, and distal radius, which leads to loss of body function and acute pain.[4,5] Patients who experienced a fracture were more likely to have a re-fracture, and patients who experienced a re-fracture within 3 years of the first fracture have a 20% higher mortality rate than those who did not.[6] According to the 2020 report of the Korean Society for Bone and Mineral Research osteoporotic fractures are associated with functional limitations and excess mortality of 17%, meaning preventing fractures has important implications for public health.[7]
In addition to negative clinical effects of osteoporosis-induced fracture, including increased mortality, reduced quality of life, and increased subsequent fracture rate, osteoporosis is accompanied by a considerable burden on healthcare resources. As the elderly population, the major age group with osteoporosis in Korea, continues to expand, and the social costs associated with osteoporotic fractures are also expected to increase. A recent study predicted that if the treatment and diagnosis rates of osteoporosis increase by 50% and 44%, respectively, from 2020 to 2040, 4.3 million osteoporotic fractures would be avoided, which will save the healthcare system up to 13.5 billion USA dollar (USD).[8] Thus, improving the treatment effectiveness of osteoporosis and preventing fractures is an important treatment goal that not only provides clinical benefits to patients but also reduces the economic burden on the healthcare system.
Denosumab is an antiresorptive agent targeting the receptor activator of nuclear factor-κB ligand. In the Future REvascularization Evaluation in patients with Diabetes mellitus: optimal management of Multivessel disease (FREEDOM) clinical trial and its extension trials, long-term use of denosumab for (up to 10 years) has been reported to be effective in preventing fractures.[9,10] Unlike most oral osteoporotic drugs that should be taken daily/weekly/monthly, denosumab is subcutaneously injected every 6 months. Due to its convenience, adherence to medication is superior in denosumab compared to other oral drugs. In Korea denosumab has been reimbursed as the first-line treatment for osteoporosis since 2019.[11] In addition, the list price of denosumab decreased by 17.6% in December 2020 compared to the initial list price in 2017.[12] Nevertheless, there is a lack of research comparing the cost-effectiveness of denosumab at the new list price with alternative treatments in Korea. The purpose of this study was to estimate the cost-effectiveness of denosumab for osteoporotic fracture prevention compared with bisphosphonates (alendronate, ibandronate, risedronate, zoledronate) and selective estrogen receptor modulator (SERM; raloxifene) in a cohort of postmenopausal women in Korea.

METHODS

For this cost-effectiveness analysis, the previously published Markov model for cost-effectiveness analysis,[13] was utilized. The Markov model is useful when a decision problem involves continuous risk over time, when the timing of events is important, and when important events may happen more than once.[14]

1. Analysis

The current Markov model presented the cost per quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER). ICER is expressed as the ratio of the difference in total cost between denosumab and each comparator to the difference in health outcomes. The difference in health outcomes was measured in QALYs between denosumab and each comparator. If the ICER of denosumab compared to other anti-osteoporosis drugs was lower than the willingness to pay threshold of 1 gross domestic product (GDP), denosumab will be suggested to be a cost-effective option. Also, suppose the cost of denosumab group was lower than the other drug group, since denosumab decreased the number of fractures, ICER will be negative. In that case, denosumab will be suggested as a cost-saving option. One unit of Korea’s GDP per capita was applied for willingness to pay threshold in accordance with the World Health Organization (WHO) recommendations.[15]

2. Sensitivity analysis

We conducted a one-way deterministic sensitivity analysis for each comparison. Sensitivity analyses were performed by changing the key model inputs and assumptions. Also, the weighted average drug costs of each comparator were applied for sensitivity analysis. The results are presented as the costs per QALY gained.

3. Model structure

The current model was used to evaluate the costs and effectiveness of denosumab and other comparators (alendronate, risedronate, ibandronate, zoledronate, raloxifene) for the treatment of osteoporosis in postmenopausal women. The comparator drugs have been selected considering their reimbursement criteria and line of therapy in the recent Korean market situation. The model has a cycle length of 6 months and was run from age 68 years, the average age of postmenopausal women with osteoporosis in South Korea, to individual patients’ lifetime or the age of 100 years. The model utilized a healthcare system perspective to include direct medical costs. The model is a cohort-based model designed in Microsoft Excel (Microsoft Corp., Redmond, WA, USA).
The model was comprised of eight health states: (1) well; (2) hip fracture; (3) vertebral fracture; (4) wrist fracture; (5) other osteoporotic fracture (non-hip/non-vertebral/non-wrist osteoporotic fracture); (6) post-hip fracture; (7) post vertebral fracture; and (8) dead (Fig. 1).
The target population in the model is defined as average postmenopausal women with osteoporosis in Korea. Based on 2014 HIRA-National Patients Sample data, the average age of postmenopausal women with osteoporosis patients was 68 years.[16] All people entered the model in the ‘well’ state. From there, probabilities of sustaining a fracture, remaining healthy, or dying determined transitions to other health states in each cycle. After one cycle in a given fracture state, patients had a risk of sustaining a subsequent fracture, moving to the post-fracture state (either post-hip or post-vertebral fracture) or dying, depending on the previous healthy state.
We assumed that patients with wrist fractures or other osteoporotic fractures could transition to the ‘well’ state and do not move to the ‘dead’ state, while patients in the hip fracture and vertebral fracture state cannot move to the ‘well’ state but can move to the ‘dead’ state. A patient who has already experienced a hip fracture was only at risk of dying or sustaining subsequent hip fractures (not other fracture types). The model also assumed patients who had sustained a vertebral fracture are at risk of sustaining subsequent vertebral fractures, hip fractures, or dying. Since the model assumed that the patient who sustains a hip fracture or vertebral fracture may not incur future wrist or other osteoporotic fractures ever again, the model slightly underestimated less severe fractures (wrist fracture, other fractures). Therefore, this limitation was addressed by estimating and adding the number of these missed downstream fractures based on the method previously used.[13,17]
It was assumed that health statuses did not affect drug administration, and an adverse event (e.g., gastrointestinal [GI] disorder) was not considered in the model.

4. Model input

1) Incidence of fracture and mortality

General population mortality was estimated using the Korean statistical information service (KOSTAT) complete life table from 2019 for 50 years and older women. The baseline fracture prevalence of osteoporosis patients was calculated from the 2020 National Health Insurance Service (NHIS) Ilsan hospital report.[18] The incidence of each fracture type according to the age group was extracted from the HIRA report about healthcare utilization of osteoporosis and prescription status (Supplementary Table 1).[19] The mortality rate after vertebral fracture was calculated at 5-year intervals based on Lee et al. [20]. The mortality rate after hip fracture was based on 10-year intervals of standardized mortality ratio from data presented in Yoon et al. [21]. The mortality rate of fractures at other sites was calculated by combining the results of studies by Barret et al. [22] and Kanis et al. [23] (Supplementary Table 1). We assumed that 30% of the excess mortality (compared to normal mortality) after hip, vertebral, and other fractures were associated with the fracture event, which is a widely accepted assumption in previous studies.[13,24] However, wrist fracture was assumed to not be associated with excess mortality, and the excess mortality of hip and vertebral fractures lasts for 8 years.

2) Cost

According to HIRA pharmacoeconomics guideline, only direct medical costs and transportation cost were considered in the model. Direct medical costs included in this study were cost of: drug therapy, osteoporotic fracture treatment, nursing home costs, BMD measurement, physician visits, subcutaneous (SC) infusion, intravenous (IV) infusion, and pharmacy visits. The regimen of each drug therapy was extracted from the Korean Ministry of Food and Drug Safety, and the cost was extracted from HIRA drug ceiling price list. It was assumed that BMD is measured once a year in patients receiving treatment. Denosumab was associated with 2 physician visits and 2 SC infusions yearly in the model. Drugs delivered intravenously (zoledronate, ibandronate IV) were assumed to be associated with IV infusion and physician visits (once a year for zoledronate, four times yearly for ibandronate). Oral drugs (alendronate, ibandronate [oral], risedronate, raloxifene) were assumed to be associated with physician visits and pharmacy visits four times yearly. Indirect costs were not included in the model. All costs were presented in Korean won (KRW) and converted to USD using the average exchange rate during the first half of 2021 (1 USD=1,117.73 KRW).[25] A discount rate of 4.5% per annum was applied to both costs and outcomes according to the most recent Korean guidelines for economic evaluation from 2021.[26] The cost of treatment of direct clinical events, fractures, and medical resource utilization in the first year after fracture for each fracture type were extracted from HIRA big data of 2021.[27] The cost of physician visits, IV and SC injections, and BMD measurement were informed by HIRA fee-for-service prices for 2020 (Supplementary Table 2).[28] The out-of-pocket copayment rate was based on the average rate of orthopedics departments in tertiary hospitals derived from the NHIS report in 2019.[29] Drug cost was based on the ceiling price of the original drug of each comparator,[30] and the original drug prices were applied in the base-case analysis (Supplementary Table 2). The weighted average drug costs of each comparator based on HIRA weighted average drug cost table 2021 [27,28,31] were applied for sensitivity analysis (Supplementary Table 2). Transportation cost was derived from the KOSTAT 2020 transportation price index.[32]

3) Treatment efficacy

Barrionuevo et al. [33], a recently published network meta-analysis, was used to inform treatment-specific fracture reduction efficacy because of its robustness as a systematic review of osteoporosis treatment efficacy of denosumab and comparators. Freemantle et al. [34], another network meta-analysis including denosumab and comparators’ efficacy, was applied in the sensitivity analysis, although it does not report efficacy values for ibandronate and raloxifene to hip fracture (Supplementary Table 3). Maximum treatment duration for a fully persistent patient was assumed to be 5 years. Persistence data were based on Li et al. [35] using their long-term estimates through 5 years. When patients discontinue drug administration, the model assumed the treatment effect does not stop immediately but continues through the “offset time” after treatment is stopped. In the model, offset time was assumed to be as long as the time on treatment, up to a maximum of 2 years. Even though differential effects for treatments should be based on solid evidence, very few studies have evaluated offset time, and the findings were inconsistent. Thus, since there is not robust evidence to support differential offsets, we assumed the same period for all treatments. This is a limitation of this analysis and should be taken into account.

4) Utility

Utility values for the general population of 50 years or older was sourced from the 2014 Korea National Health and Nutrition Examination Survey result.[16] Reduction in quality of life within one year after hip, vertebral, and wrist fracture and within the second or following years after hip or vertebral fracture was based on a meta-analysis and clinician experience.[16] Wrist fractures and “other fractures” were estimated to have no quality-of-life reduction in the second and subsequent years (Supplementary Table 2). The gained life years (quantity) and quality of life were combined into a single measure of health, which is the QALYs.

RESULTS

1. Base-case analysis

In the base-case scenario applying efficacy input based on Barrionuevo et al. [33], we examined the cost-effectiveness of denosumab compared to other comparators. Denosumab was found to be cost-effective compared to alendronate, ibandronate IV, risedronate, and zoledronate or cost-saving compared to ibandronate (oral) and raloxifene considering the willingness-to-pay threshold of one GDP per capita, USD 34,870 (International Monetary Fund, 2021) (Table 1).

2. Sensitivity analysis

One-way sensitivity analysis showed that the model results were most sensitive to a variation of utility values within 10% and a variation of efficacy values within the confidence interval (CI) (Table 2). A range of 10% was determined in consultation with investigators of this study. If the utility values were increased by 10%, or if the upper boundary of CI in efficacy input were applied, the cost per QALY gained increased substantially. If medical costs were high as 10%, the costs per QALY gained would increase. Assuming decreased discount rate for cost and effect, the cost per QALY gained would decrease. Applying lower fracture prevalence decreased the costs per QALY relative to the base case level.
The sensitivity analysis using efficacy input based on Freemantle et al. [34] also showed the cost-effectiveness of denosumab compared to comparators. Denosumab was cost-saving compared to ibandronate IV, ibandronate (oral), and raloxifene. Denosumab was cost-effective compared to alendronate, risedronate, and zoledronate. In the sensitivity analysis where drug cost is based on a weighted average cost, and efficacy is based on Barrionuevo et al. [33], denosumab was also cost-effective (alendronate, ibandronate IV, risedronate, zoledronate) or cost-saving (ibandronate [oral], raloxifene) compared to all comparators considering willingness to pay threshold. This result aligns with the result of the base-case scenario. In the sensitivity analysis where drug cost is based on weighted average price and efficacy is based on Freemantle et al. [34], denosumab was found to be cost-effective (alendronate, risedronate, zoledronate) or cost-saving (ibandronate IV, ibandronate [oral], raloxifene). The sensitivity analysis ICER from each comparison is presented in Table 2. Overall, there was no result that exceeded the willingness-to-pay threshold (USD 34,870), which is in line with the base-analysis, showing the robustness of the cost-effectiveness analysis result.

DISCUSSION

This study estimated the cost-effectiveness of denosumab compared with alendronate, risedronate, ibandronate, zoledronate, and raloxifene from the South Korean healthcare system’s perspective. The base-case population was post-menopausal women with osteoporosis. The model structure is well validated and similar chosen to represent the average patient treated for postmenopausal osteoporosis in Korea. In this analysis, the model structure is consistent with previously published model.[16] However, in this model, model has been updated with all currently reimbursable drug options in Korea as comparators. The results of this analysis demonstrated that denosumab is a cost-effective treatment option to reduce the risk of fracture in postmenopausal Korean women with osteoporosis compared to other osteoporosis agents. Specifically, denosumab is cost-effective compared with alendronate, ibandronate IV, risedronate, zoledronate and cost-saving compared with ibandronate (oral) and raloxifene. The ICER of denosumab compared to other antiosteoporosis drugs was below the willingness to pay threshold of 1 GDP, as recommended by WHO. Therefore, considering the threshold, denosumab is suggested to be a cost-effective option for treating postmenopausal osteoporotic women.
The findings from this study provide insights into the cost-effectiveness of denosumab versus alendronate, ibandronate IV, ibandronate (oral), risedronate, raloxifene and zoledronate, all the reimbursed drugs for treating osteoporosis in Korea. The results from our models are consistent with previous economic evaluations in Japan that have found denosumab to be cost-effective in the treatment of postmenopausal osteoporosis with a willingness to pay of USD 50,000.[36] Likewise, denosumab has been shown to be cost-effective in different settings such as the USA, Canada, several countries in the European Union, and Australia.[13,17,36-40]
There are unmet therapeutic needs for treating osteoporotic postmenopausal women since some patients are forced to discontinue bisphosphonates and SERM agents due to their complexity of administration or side effects. Individuals with limited public health literacy, for example, were shown to have poor oral bisphosphonates persistence [41] and the poor persistence rate of bisphosphonates for osteoporosis treatment is associated with increased fracture risk.[42] Bisphosphonates also have a contraindication for use in patients with renal impairment.[43] However, the pharmacokinetics and pharmacodynamics of denosumab at the standard dose are not affected by renal impairment.[44] The findings from Mosca et al. [45], showed that raloxifene, a SERM agent used as one of the comparators in our analysis, is associated with an increased risk for fatal stroke and venous thromboembolism while another study showed denosumab could be used without the risk of stroke and venous thromboembolism.[44] Although discontinuation of denosumab can lead to reversal of bone turnover suppression and rapid loss of BMD gained during treatment, denosumab has confirmed long-term efficacy and safety in 10 years extension to the FREEDOM study. According to the FREEDOM study, denosumab treated patients not only showed increases in BMD without plateau, but also showed low rates of adverse events. Furthermore, previous studies reported that denosumab treated patients improved BMD significantly more than bisphosphonates.[46,47] In our analysis, although denosumab had relatively high cost among compared drugs, it showed considerably lower cost per QALY estimates, which can be explained due to the superior efficacy of denosumab compared to other treatments. Thus, denosumab could be a cost-effective therapeutic alternative to bisphosphonates and raloxifene for postmenopausal women with osteoporosis.
There are several limitations to the generalizability of our findings. GI disorder, the common adverse reaction to bisphosphonates, was not considered in the model. The model excluded GI disorder as a conservative approach for denosumab. However, this limitation should have a minimum impact on the ICER, according to a cost-effectiveness analysis in a Swedish setting, in which GI disorder of alendronate was included in a sensitivity analysis.[13]
Secondly, even though this analysis applied recent data from the Korean clinical settings and market changes such as post-evaluation on drug cost or market share, utility value [16] and the mortality rate of other fractures (non-hip/non-vertebral/non-wrist osteoporotic fracture) [22,23] were calculated using data from other countries due to the lack of local data. Thus, sensitivity analysis was conducted to assess these limitations. The results from varying the utility values by 10% suggested a similar conclusion, which in turn demonstrated the model’s robustness.
Despite limitations, this study is the first study to demonstrate the cost-effectiveness of denosumab compared with all the other drugs reimbursed as first-line therapy in osteoporotic postmenopausal women in Korea. Specifically, this analysis considered up-to-date Korean reimbursement circumstances and drug costs. The model showed the cost-effective feature of denosumab which is in alignment with studies from other countries.[13,38-40] Also, the efficacy data included in the model was from a network meta-analysis.[35] According to the HIRA economic evaluation guideline,[26] network meta-analysis is recommended for indirect treatment comparison if head-to-head randomized controlled trial results are not available.
The findings of this study offer important evidence for public health policymakers and healthcare providers to ensure adequate access to appropriate therapies to deal with Korea’s increasing burden of osteoporosis and fracture risk.

Acknowledgments

Professor Yong-Chan Ha from Department of Orthopaedic Surgery, Chung-Ang University, College of Medicine, Seoul, Korea also contributed to the study as scientific advisor.

DECLARATIONS

Authors’ contributions

Conceptualization: JYK and HY; Data curation: JYK and LC; Formal analysis: LC; Methodology: BJ; Writing - original draft: JYK and HY; Writing - review & editing: JYK, LC, BJ, and HY; All authors read and approved the final manuscript.

Ethics approval and consent to participate

Not applicable.

Conflict of interest

JYK and HY are employees of Amgen Inc. Except for that, no potential conflict of interest relevant to this article was reported.

Funding

Funding for this study was provided by Amgen Korea.

Fig. 1
Structure of the denosumab Markov cohort model. Arrows to the health state “dead” were excluded for simplification, cycle length was 6 months.
jbm-2022-29-2-83f1.jpg
Table 1
Base-case analysis result
Denosumab vs. Alendronate Denosumab vs. Ibandronate (IV) Denosumab vs. Ibandronate (oral) Denosumab vs. Risedronate Denosumab vs. Raloxifene Denosumab vs. Zoledronate
Cost difference (KRW) 43,230 41,260 −16,787 97,809 −128,888 161,674
QALY 0.050 0.054 0.053 0.060 0.055 0.031
Life years 0.010 0.010 0.010 0.012 0.012 0.007
ICER (KRW) 856,407 766,354 Cost-saving 1,642,742 Cost-saving 5,218,159
ICER (USD) 767.10 685.63 Cost-saving 1,469.71 Cost-saving 4,668.53

QALY, quality-adjusted life year; ICER, incremental cost-effectiveness ratio.

Table 2
Sensitivity analysis result (cost [KRW] per quality-adjusted life year gained)
One-way sensitivity analyses Alendronate Ibandronate (IV) Ibandronate (oral) Risedronate Raloxifene Zoledronate
Base case 856,407 766,354 Cost-saving 1,642,742 Cost-saving 5,218,159
Cost+10% 283,739 110,548 Cost-saving 1,081,777 Cost-saving 4,628,109
Cost−10% 1,429,076 1,422,160 333,827 2,203,707 Cost-saving 5,808,208
Utility+10% 2,115,287 1,955,354 Cost-saving 3,855,952 Cost-saving 11,360,991
Utility−10% 540,470 479,673 Cost-saving 1,051,157 Cost-saving 3,413,807
Efficacy+10% 720,936 698,040 Cost-saving 1,604,863 Cost-saving 6,023,533
Efficacy−10% 120,601 838,676 Cost-saving 1,011,613 Cost-saving 4,468,643
Efficacy lower CI Cost-saving 1,952,804 451,894 Cost-saving Cost-saving 2,253,057
Efficacy upper CI 4,038,533 Cost-saving Cost-saving 5,548,484 Cost-saving 11,529,533
Discount rate 0% 86,644 120,158 Cost-saving 528,758 Cost-saving 2,726,020
Discount rate 3% 569,902 525,130 Cost-saving 1,240,317 Cost-saving 4,326,451
Discount rate 5% 957,462 851,544 Cost-saving 1,782,320 Cost-saving 5,526,808
Fracture prevalence 5.54% 1,578,635 1,495,353 314,746 2,427,148 Cost-saving 6,291,162
Fracture prevalence 7.10% 1,351,179 1,265,753 116,137 2,180,178 Cost-saving 5,952,464
GP visit 5 times/year 419,613 766,354 Cost-saving 1,306,973 Cost-saving 5,218,159
Efficacy input (Freemantle) 1,638,252 Cost-saving Cost-saving 2,519,481 Cost-saving 11,732,008
Drug cost: weighted average cost (Barrionuevo) 813,679 489,572 Cost-saving 1,937,564 Cost-saving 5,218,159
Drug cost: weighted average cost (Freemantle) 1,593,003 Cost-saving Cost-saving 2,826,111 Cost-saving 11,732,008

REFERENCES

1. McNamara LM. Perspective on post-menopausal osteoporosis: establishing an interdisciplinary understanding of the sequence of events from the molecular level to whole bone fractures. J R Soc Interface 2010 7:353-72. https://doi.org/10.1098/rsif.2009.0282 .
crossref pmid pmc pdf
2. Health Insurance Review & Assessment Service. Healthcare bigdata hub: Disease subdivision statistics 2019-2021 2022 [cited by 2022 Feb 1]. Available from: https://opendata.hira.or.kr/op/opc/olap3thDsInfo.do#none .

3. Lips P, Cooper C, Agnusdei D, et al. Quality of life as outcome in the treatment of osteoporosis: the development of a questionnaire for quality of life by the European Foundation for Osteoporosis. Osteoporos Int 1997 7:36-8. https://doi.org/10.1007/bf01623457 .
crossref pmid pdf
4. Lips P, van Schoor NM. Quality of life in patients with osteoporosis. Osteoporos Int 2005 16:447-55. https://doi.org/10.1007/s00198-004-1762-7 .
crossref pmid pdf
5. Ahn SH, Park SM, Park SY, et al. Osteoporosis and osteoporotic fracture fact sheet in Korea. J Bone Metab 2020 27:281-90. https://doi.org/10.11005/jbm.2020.27.4.281 .
crossref pmid pmc pdf
6. Yoo JI, Ha YC, Park KS, et al. Incidence and mortality of osteoporotic refractures in Korea according to nationwide claims data. Yonsei Med J 2019 60:969-75. https://doi.org/10.3349/ymj.2019.60.10.969 .
crossref pmid pmc pdf
7. Korean Society for Bone Mineral Research. Policy brief for osteoporosis management in super-aged society. Seoul, KR: Korean Society for Bone Mineral Research; 2020.

8. Jackson M, Yang KH, Gitlin M, et al. Estimating the future clinical and economic benefits of improving osteoporosis diagnosis and treatment among women in South Korea: a simulation projection model from 2020 to 2040. Arch Osteoporos 2021 16:115. https://doi.org/10.1007/s11657-021-00952-3 .
crossref pmid pdf
9. Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009 361:756-65. https://doi.org/10.1056/NEJMoa0809493 .
crossref pmid
10. Bone HG, Wagman RB, Brandi ML, et al. 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension. Lancet Diabetes Endocrinol 2017 5:513-23. https://doi.org/10.1016/s2213-8587(17)30138-9 .
crossref pmid
11. Health Chosun. Amgen ‘Prolia®’, Expanding health insurance coverage as first-line therapy for osteoporosis 2019 [cited by 2022 Feb 1]. Available from: https://health.chosun.com/site/data/html_dir/2019/03/29/2019032901997.html .

12. Dailypharm. Prolia dominates the osteoporosis drug market 2021 [cited by 2021 Feb 24]. Available from: https://www.dailypharm.com/Users/News/NewsView.html?ID=273716 .

13. Jönsson B, Ström O, Eisman JA, et al. Cost-effectiveness of Denosumab for the treatment of postmenopausal osteoporosis. Osteoporos Int 2011 22:967-82. https://doi.org/10.1007/s00198-010-1424-x .
crossref pmid pmc pdf
14. Sonnenberg FA, Beck JR. Markov models in medical decision making: a practical guide. Med Decis Making 1993 13:322-38. https://doi.org/10.1177/0272989x9301300409 .
crossref pmid pdf
15. Edejer TT, Baltussen R, Adam T, et al. Making choices in health: WHO guide to cost-effectiveness analysis. Geneva, CH: World Health Organization; 2003.

16. Bae G, Kwon HY. Cost-effectiveness of denosumab for post-menopausal osteoporosis in South Korea. Korean J Clin Pharm 2018 28:131-7. https://doi.org/10.24304/kjcp.2018.28.2.131 .
crossref
17. Chau D, Becker DL, Coombes ME, et al. Cost-effectiveness of denosumab in the treatment of postmenopausal osteoporosis in Canada. J Med Econ 2012 15:Suppl 1. 3-14. https://doi.org/10.3111/13696998.2012.737393 .
crossref pmid
18. Noh SH, Lee SH, Zhang HY, et al. Trends in osteoporosis treatment and incidence of osteoporotic fracture in Korea. Goyang, KR: National Health Insurance Service Ilsan Hospital; 2021.

19. Jang S, Park C, Jang S, et al. Medical service utilization with osteoporosis. Endocrinol Metab 2010 25:326-39. https://doi.org/10.3803/EnM.2010.25.4.326 .
crossref
20. Lee YK, Jang S, Jang S, et al. Mortality after vertebral fracture in Korea: analysis of the National Claim Registry. Osteoporos Int 2012 23:1859-65. https://doi.org/10.1007/s00198-011-1833-5 .
crossref pmid pdf
21. Yoon HK, Park C, Jang S, et al. Incidence and mortality following hip fracture in Korea. J Korean Med Sci 2011 26:1087-92. https://doi.org/10.3346/jkms.2011.26.8.1087 .
crossref pmid pmc pdf
22. Barrett JA, Baron JA, Beach ML. Mortality and pulmonary embolism after fracture in the elderly. Osteoporos Int 2003 14:889-94. https://doi.org/10.1007/s00198-003-1494-0 .
crossref pmid pdf
23. Kanis JA, Oden A, Johnell O, et al. The burden of osteoporotic fractures: a method for setting intervention thresholds. Osteoporos Int 2001 12:417-27. https://doi.org/10.1007/s001980170112 .
crossref pmid pdf
24. Kanis JA, Adams J, Borgström F, et al. The cost-effectiveness of alendronate in the management of osteoporosis. Bone 2008 42:4-15. https://doi.org/10.1016/j.bone.2007.10.019 .
crossref pmid
25. Seoul Money Brokerage. Foreign exchange rate 2022 [cited by 2022 Feb 1]. Available from: https://www.smbs.biz/ExRate/StdExRate.jsp .

26. Health Insurance Review & Assessment Service. Pharmaceutical economic evaluation guidelines. Wonju, KR: Health Insurance Review & Assessment Service; 2021.

27. Health Insurance Review & Assessment Service. Healthcare bigdata hub: Disease classification (stage 3) statistics 2021 [cited by 2022 Feb 1]. Available from: https://opendata.hira.or.kr/op/opc/olap3thDsInfo.do#none .

28. Health Insurance Review & Assessment Service. Fee-for-service price 2020. Wonju, KR: Health Insurance Review & Assessment Service; 2020.

29. National Health Insurance Service. Status report of healthcare coverage. Wonju, KR: National Health Insurance Service; 2019.

30. Korean National Health Insurance Service. Drug reimbursement price ceiling table. Wonju, KR: Korean National Health Insurance Service; 2021.

31. Korean National Health Insurance Service. Weighted-average drug price table. Wonju, KR: Korean National Health Insurance Service; 2021.

32. Statistics Korea. Consumer price index 2020 [cited by 2022 Feb 1]. Available from: https://kostat.go.kr/incomeNcpi/cpi/index.action .

33. Barrionuevo P, Kapoor E, Asi N, et al. Efficacy of pharmacological therapies for the prevention of fractures in postmenopausal women: A network meta-analysis. J Clin Endocrinol Metab 2019 104:1623-30. https://doi.org/10.1210/jc.2019-00192 .
crossref pmid pdf
34. Freemantle N, Cooper C, Diez-Perez A, et al. Results of indirect and mixed treatment comparison of fracture efficacy for osteoporosis treatments: a meta-analysis. Osteoporos Int 2013 24:209-17. https://doi.org/10.1007/s00198-012-2068-9 .
crossref pmid pmc pdf
35. Li L, Roddam A, Gitlin M, et al. Persistence with osteoporosis medications among postmenopausal women in the UK General Practice Research Database. Menopause 2012 19:33-40. https://doi.org/10.1097/gme.0b013e318221bacd .
crossref pmid
36. Mori T, Crandall CJ, Ganz DA. Cost-effectiveness of denosumab versus oral alendronate for elderly osteoporotic women in Japan. Osteoporos Int 2017 28:1733-44. https://doi.org/10.1007/s00198-017-3940-4 .
crossref pmid pdf
37. Hiligsmann M, Reginster JY. Cost effectiveness of denosumab compared with oral bisphosphonates in the treatment of post-menopausal osteoporotic women in Belgium. Pharmacoeconomics 2011 29:895-911. https://doi.org/10.2165/11539980-000000000-00000 .
crossref pmid
38. Karnon J, Shafie AS, Orji N, et al. What are we paying for? A cost-effectiveness analysis of patented denosumab and generic alendronate for postmenopausal osteoporotic women in Australia. Cost Eff Resour Alloc 2016 14:11. https://doi.org/10.1186/s12962-016-0060-5 .
crossref pmid pmc pdf
39. Parthan A, Kruse M, Yurgin N, et al. Cost effectiveness of denosumab versus oral bisphosphonates for postmenopausal osteoporosis in the US. Appl Health Econ Health Policy 2013 11:485-97. https://doi.org/10.1007/s40258-013-0047-8 .
crossref pmid pdf
40. Ström O, Jönsson B, Kanis JA. Intervention thresholds for denosumab in the UK using a FRAX®-based cost-effectiveness analysis. Osteoporos Int 2013 24:1491-502. https://doi.org/10.1007/s00198-012-2115-6 .
crossref pmid pdf
41. Park JH, Park EK, Koo DW, et al. Compliance and persistence with oral bisphosphonates for the treatment of osteoporosis in female patients with rheumatoid arthritis. BMC Musculoskelet Disord 2017 18:152. https://doi.org/10.1186/s12891-017-1514-4 .
crossref pmid pmc pdf
42. Imaz I, Zegarra P, González-Enríquez J, et al. Poor bisphosphonate adherence for treatment of osteoporosis increases fracture risk: systematic review and meta-analysis. Osteoporos Int 2010 21:1943-51. https://doi.org/10.1007/s00198-009-1134-4 .
crossref pmid pdf
43. Ministry of Food and Drug Safety. Fosamax tab (Alendronate sodium) 2008 [cited by 2021 Feb 8]. Available from: https://nedrug.mfds.go.kr/pbp/CCBBB01/getItemDetail?itemSeq=200811126 .

44. Ministry of Food and Drug Safety. Prolia® Pre-filled syringe (Denosumab) 2014 [cited by 2014 Sep 29]. Available from: https://nedrug.mfds.go.kr/pbp/CCBBB01/getItemDetail?itemSeq=201404452 .

45. Mosca L, Grady D, Barrett-Connor E, et al. Effect of raloxifene on stroke and venous thromboembolism according to subgroups in postmenopausal women at increased risk of coronary heart disease. Stroke 2009 40:147-55. https://doi.org/10.1161/strokeaha.108.518621 .
crossref pmid pmc
46. Benjamin B, Benjamin MA, Swe M, et al. Review on the comparison of effectiveness between denosumab and bisphosphonates in post-menopausal osteoporosis. Osteoporos Sarcopenia 2016 2:77-81. https://doi.org/10.1016/j.afos.2016.03.003 .
crossref pmid pmc
47. Lyu H, Jundi B, Xu C, et al. Comparison of denosumab and bisphosphonates in patients with osteoporosis: A meta-analysis of randomized controlled trials. J Clin Endocrinol Metab 2019 104:1753-65. https://doi.org/10.1210/jc.2018-02236 .
crossref pmid pmc


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