Archives of Osteoporosis

, 13:94 | Cite as

Cost-effectiveness analysis of drugs for osteoporosis treatment in elderly Japanese women at high risk of fragility fractures: comparison of denosumab and weekly alendronate

  • Tomohiro YoshizawaEmail author
  • Tomofumi Nishino
  • Ichiro Okubo
  • Masashi Yamazaki
Original Article



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.


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.


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.


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.


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.


Osteoporosis Cost-utility analysis Denosumab Alendronate Willingness-to-pay 



We would like to express our greatest appreciation to Dr. Shu-Ling Hoshi, from the Department of Health Care Policy and Health Economics, Faculty of Medicine, University of Tsukuba, for her useful discussion and idea regarding this work and to Rebecca Tollefson, DVM, from Edanz Group ( for editing a draft of this manuscript.

Compliance with ethical standards

Conflicts of interest


Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

11657_2018_509_MOESM1_ESM.doc (88 kb)
ESM 1 (DOC 87 kb)


  1. 1.
    Orimo H, Yaegashi Y, Hosoi T, Fukushima Y, Onoda T, Hashimoto T, Sakata K (2016) Hip fracture incidence in Japan: estimates of new patients in 2012 and 25-year trends. Osteoporos Int 27:1777–1784CrossRefGoogle Scholar
  2. 2.
    Imai N, Endo N, Shobugawa Y, Ibuchi S, Suzuki H, Miyasaka D, Sakuma M (2017) A decrease in the number and incidence of osteoporotic hip fractures among elderly individuals in Niigata, Japan, from 2010 to 2015. J Bone Miner Metab.
  3. 3.
    Hagino H, Nakamura T, Fujiwara S, Oeki M, Okano T, Teshima R (2009) Sequential change in quality of life for patients with incident clinical fractures: a prospective study. Osteoporos Int 20:695–702CrossRefGoogle Scholar
  4. 4.
    Tsuboi M, Hasegawa Y, Suzuki S, Wingstrand H, Thorngren KG (2007) Mortality and mobility after hip fracture in Japan: a ten-year follow-up. J Bone Joint Surg Br 89:461–466CrossRefGoogle Scholar
  5. 5.
    Harada A, Matsui Y, Takemura M, Wakao N, Ota T (2005) Cost-utility analysis of osteoporosis. Nihon Ronen Igakkai Zasshi 42:596–608 In JapaneseCrossRefGoogle Scholar
  6. 6.
    Committee of Japanese Guidelines for the Prevention and Treatment of Osteoporosis (2015) The Japanese guidelines for the prevention and treatment of osteoporosis (2015 edn). Life Science Publishing, Tokyo. In JapaneseGoogle Scholar
  7. 7.
    Shiroiwa T, Fukuda T, Ikeda S, Takura T, Moriwaki K (2017) Development of an official guideline for the economic evaluation of drugs/medical devices in Japan. Value Health 20:372–378CrossRefGoogle Scholar
  8. 8.
    Nagase T (2016) Market of osteoporosis treatment drugs. Kokusai Iyakuhin Jouhou 1072:6–14 In JapaneseGoogle Scholar
  9. 9.
    Murad MH, Drake MT, Mullan RJ, Mauck KF, Stuart LM, Lane MA, Abu Elnour NO, Erwin PJ, Hazem A, Puhan MA, Li T, Montori VM (2012) Clinical review. Comparative effectiveness of drug treatments to prevent fragility fractures: a systematic review and network meta-analysis. J Clin Endocrinol Metab 97:1871–−1880CrossRefGoogle Scholar
  10. 10.
    Looler AC, Wahner HW, Dunn WL, Calvo MS, Harris TB, Heyse SP, Johnston CC Jr, Lindsay R (1998) Updated data on proximal femur bone mineral levels of US adults. Osteoporos Int 8:468–489CrossRefGoogle Scholar
  11. 11.
    Orimo H, Yaegashi Y, Onoda T, Fukushima Y, Hosoi T, Sakata K (2009) Hip fracture incidence in Japan: estimates of new patients in 2007 and 20-year trends. Arch Osteoporos 4:71–77CrossRefGoogle Scholar
  12. 12.
    Jonsson B, Strom O, Eisman JA, Papaioannou A, Siris ES, Tosteson A, Kanis JA (2011) Cost-effectiveness of denosumab for the treatment of postmenopausal osteoporosis. Osteoporos Int 22:967–982CrossRefGoogle Scholar
  13. 13.
    Strom O, Borgstrom F, Kanis JA, Jonsson B (2009) Incorporating adherence into health economic modelling of osteoporosis. Osteoporos Int 20:23–34CrossRefGoogle Scholar
  14. 14.
    Moriwaki K, Komaba H, Noto S, Yanagisawa S, Takiguchi T, Inoue H, Toujo T, Fukagawa M, Takahashi HE (2013) Cost-effectiveness of alendronate for the treatment of osteopenic postmenopausal women in Japan. J Bone Miner Res 28:395–403CrossRefGoogle Scholar
  15. 15.
    Kanis JA, Johnell O, De Laet C et al (2004) A meta-analysis of previous fracture and subsequent fracture risk. Bone 35:375–382CrossRefGoogle Scholar
  16. 16.
    Hagino H, Sawaguchi T, Endo N, Ito Y, Nakano T, Watanabe Y (2012) The risk of a second hip fracture in patients after their first hip fracture. Calcif Tissue Int 90:14–21CrossRefGoogle Scholar
  17. 17.
    Japan Ministry of Health, Labour and Welfare (2018) Life table for Japanese. Accessed 31 Mar 2018
  18. 18.
    Hayashi Y (2007) Economical viewpoint of treatment of osteoporosis. Nihon Rinsho 65:609–614 In JapanesePubMedGoogle Scholar
  19. 19.
    Black DM, Cummings SR, Karpf DB et al (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet 348:1535–1541CrossRefGoogle Scholar
  20. 20.
    Boonen S, Adachi JD, Man Z, Cummings SR, Lippuner K, Törring O, Gallagher JC, Farrerons J, Wang A, Franchimont N, San Martin J, Grauer A, McClung M (2011) Treatment with denosumab reduces the incidence of new vertebral and hip fractures in postmenopausal women at high risk. J Clin Endocrinol Metab 96:1727–1736CrossRefGoogle Scholar
  21. 21.
    McClung MR, Boonen S, Torring O et al (2012) Effect of denosumab treatment on the risk of fractures in subgroups of women with postmenopausal osteoporosis. J Bone Miner Res 27:211–−218CrossRefGoogle Scholar
  22. 22.
    Kishimoto H, Maehara M (2015) Compliance and persistence with daily, weekly, and monthly bisphosphonates for osteoporosis in Japan: analysis of data from the CISA. Arch Osteoporos 10:231CrossRefGoogle Scholar
  23. 23.
    Bone HG, Bolognese MA, Yuen CK, Kendler DL, Miller PD, Yang YC, Grazette L, San Martin J, Gallagher JC (2011) Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass. J Clin Endocrinol Metab 96:972–980CrossRefGoogle Scholar
  24. 24.
    Karlsson L, Lundkvist J, Psachoulia E, Intorcia M, Strom O (2015) Persistence with denosumab and persistence with oral bisphosphonates for the treatment of postmenopausal osteoporosis: a retrospective, observational study, and a meta-analysis. Osteoporos Int 26:2401–2411CrossRefGoogle Scholar
  25. 25.
    Hadji P, Papaioannou N, Gielen E, Feudjo Tepie M, Zhang E, Frieling I, Geusens P, Makras P, Resch H, Möller G, Kalouche-Khalil L, Fahrleitner-Pammer A (2015) Persistence, adherence, and medication-taking behavior in women with postmenopausal osteoporosis receiving denosumab in routine practice in Germany, Austria, Greece, and Belgium: 12-month results from a European non-interventional study. Osteoporos Int 26:2479–2−89CrossRefGoogle Scholar
  26. 26.
    National Health Insurance Drug List (2018) Jihou Press, Tokyo. In JapaneseGoogle Scholar
  27. 27.
    Kondo A, Zierler BK, Isokawa Y, Hagino H, Ito Y (2009) Comparison of outcomes and costs after hip fracture surgery in three hospitals that have different care systems in Japan. Health Policy 91:204–210CrossRefGoogle Scholar
  28. 28.
    Konno S, Togawa D, Kamae I, Inoue Y, Kikuchi S (2009) Burden of illness of conservative medical management to vertebral compression fracture in Japanese osteoporosis patients. Orthop Surg 60:1022–1039 In JapaneseGoogle Scholar
  29. 29.
    Reward for Nursing Care (2015) Igaku-tsushin-sha, Tokyo, Japan. In JapaneseGoogle Scholar
  30. 30.
    Nawata S, Yamada Y, Ikeda S, Ikegami N (2000) EuroQol study of the elderly general population: relationship with IADL and other attributes. Iryo to shakai 10:76–86 In JapaneseCrossRefGoogle Scholar
  31. 31.
    Imai H, Fujii Y, Fukuda Y, Nakao H, Yahata Y (2008) Health-related quality of life and beneficiaries of long-term care insurance in Japan. Health Policy 85:349–355CrossRefGoogle Scholar
  32. 32.
    Mori T, Crandall CJ, Ganz DA (2017) Cost-effectiveness of denosumab versus oral alendronate for elderly osteoporotic women in Japan. Osteoporos Int 28:1733–1744CrossRefGoogle Scholar
  33. 33.
    Medical Fee Schedule (2016) Igaku-tsushin-sha, Tokyo, Japan. In JapaneseGoogle Scholar
  34. 34.
    University of Sheffield (2018) FRAX WHO Fracture Risk Assessment Tool. Japan. Accessed 6 Aug 2018. In Japanese
  35. 35.
    Japan Ministry of Health, Labour and Welfare (2018) Average value of height / weight. Accessed 6 Aug 2018. In Japanese
  36. 36.
    Shiroiwa T, Sung YK, Fukuda T, Lang HC, Bae SC, Tsutani K (2010) International survey on willingness-to-pay (WTP) for one additional QALY gained: what is the threshold of cost effectiveness? Health Econ 19:422–437CrossRefGoogle Scholar
  37. 37.
    Parthan A, Kruse M, Yurgin N, Huang J, Viswanathan HN, Taylor D (2013) Cost effectiveness of denosumab versus oral bisphosphonates for postmenopausal osteoporosis in the US. Appl Health Econ Health Policy 11:485–497CrossRefGoogle Scholar
  38. 38.
    Karnon J, Shafie AS, Orji N, Usman SK (2016) 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 14(11)Google Scholar
  39. 39.
    Tsourdi E, Langdahl B, Cohen-Solal M, Aubry-Rozier B, Eriksen EF, Guanabens N, Obermayer-Pietsch B, Ralston SH, Eastell R, Zillikens MC (2017) Discontinuation of denosumab therapy for osteoporosis: a systematic review and position statement by ECTS. Bone 105:11–17CrossRefGoogle Scholar
  40. 40.
    Hiligsmann M, Reginster JY (2011) Cost effectiveness of denosumab compared with oral bisphosphonates in the treatment of post-menopausal osteoporotic women in Belgium. PharmacoEconomics 29:895–911CrossRefGoogle Scholar
  41. 41.
    Kothawala P, Badamgarav E, Ryu S, Miller RM, Halbert RJ (2007) Systematic review and meta-analysis of real-world adherence to drug therapy for osteoporosis. Mayo Clin Proc 82:1493–1501CrossRefGoogle Scholar
  42. 42.
    Freemantle N, Satram-Hoang S, Tang ET, Kaur P, Macarios D, Siddhanti S, Borenstein J, Kendler DL (2012) Final results of the DAPS (Denosumab Adherence Preference Satisfaction) study: a 24-month, randomized, crossover comparison with alendronate in postmenopausal women. Osteoporos Int 23:317–326CrossRefGoogle Scholar
  43. 43.
    Adler RA, El-Hajj Fuleihan G, Bauer DC et al (2016) Managing osteoporosis in patients on long-term bisphosphonate treatment: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 31:16–−35CrossRefGoogle Scholar
  44. 44.
    Teo BJ, Koh JS, Goh SK, Png MA, Chua DT, Howe TS (2014) Post-operative outcomes of atypical femoral subtrochanteric fracture in patients on bisphosphonate therapy. Bone Joint J 96-b:658–−664CrossRefGoogle Scholar
  45. 45.
    Japan Ministry of Health, Labour and Welfare (2018) the Central Social Insurance Medical Council, cost effectiveness assessment expert group meeting. Accessed 31 Mar 2018. In Japanese

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2018

Authors and Affiliations

  • Tomohiro Yoshizawa
    • 1
    Email author
  • Tomofumi Nishino
    • 1
  • Ichiro Okubo
    • 2
  • Masashi Yamazaki
    • 1
  1. 1.Department of Orthopaedic Surgery, Faculty of MedicineUniversity of TsukubaTsukubaJapan
  2. 2.Yokohama City Institute of Public HealthYokohamaJapan

Personalised recommendations