Skip to main content

Advertisement

SpringerLink
Log in

Cost-effectiveness of 3 versus 6 years of zoledronic acid treatment before bisphosphonate holiday for women with osteoporosis

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Summary

We evaluated the cost-effectiveness of recurrent periods of 3 versus 6 years of zoledronic acid treatment prior to 3-year bisphosphonate holidays for US postmenopausal women with osteoporosis and femoral neck BMD T-scores between − 2.5 and − 3.5. We found that cycles of 3 years of treatment followed by holidays is likely to be the more cost-effective option.

Introduction

We compared the effectiveness and cost-effectiveness of cycles of 3 years versus 6 years of zoledronic acid treatment prior to 3-year bisphosphonate holidays for US postmenopausal women with osteoporosis.

Methods

We developed an individual-level state-transition microsimulation cost-effectiveness model to compare treatment strategies over the lifetime of recurrent periods of 3 years of zoledronic acid followed by 3-year holidays (zoledronic acid 3/3), recurrent periods of 6 years of zoledronic acid followed by 3-year holidays (zoledronic acid 6/3), and no zoledronic acid treatment for women with osteoporosis and femoral neck BMD T-scores between − 2.5 and − 3.5.

Results

Base-case analysis and all key parameter sensitivity analysis findings for every treatment initiation age evaluated (50, 60, 70, and 80) revealed that zoledronic acid 3/3 was consistently the most cost-effective strategy, assuming a willingness-to-pay of $100,000 per quality-adjusted life-year (QALY). In general, the zoledronic acid 3/3 and 6/3 strategies were relatively close in effectiveness (QALYs) over the lifetime; however, lifetime direct health care costs were on average approximately $2000 lower for the 3/3 strategy. Probabilistic sensitivity analysis results revealed that the zoledronic acid 3/3 strategy was favored in greater than 70% of the iterations for a willingness-to-pay threshold of $100,000/QALY for all treatment initiation ages evaluated.

Conclusions

After 3 years of zoledronic acid treatment for postmenopausal women with osteoporosis and femoral neck BMD T-scores between − 2.5 and − 3.5, taking 3-year holidays before restarting another treatment cycle is likely to be more cost-effective over the lifetime than cycles of 6 years of treatment prior to 3-year holidays.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Wright NC, Looker AC, Saag KG, Curtis JR, Delzell ES, Randall S, Dawson-Hughes B (2014) The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res 29:2520–2526

    Article  Google Scholar 

  2. U.S. Department of Health and Human Services. Bone health and osteoporosis: a report of the Surgeon General. Rockville, MD: U.S. Department of Health and Human Services, Office of the Surgeon General, 2004

  3. Osteoporosis prevention, diagnosis, and therapy. NIH Consens Statement. 2000;17(1):1–45

  4. Lin JT, Lane JM (2004) Osteoporosis: a review. Clin Orthop Relat Res 126–134

  5. Nguyen ND, Ahlborg HG, Center JR, Eisman JA, Nguyen TV (2007) Residual lifetime risk of fractures in women and men. J Bone Miner Res 22:781–788

    Article  Google Scholar 

  6. Blume SW, Curtis JR (2011) Medical costs of osteoporosis in the elderly Medicare population. Osteoporos Int 22:1835–1844

    Article  CAS  Google Scholar 

  7. Adami G, Jaleel A, Curtis JR, Delzell E, Chen R, Yun H, Daigle S, Arora T, Danila MI, Wright NC, Cadarette SM, Mudano A, Foster J, Saag KG (2020) Temporal trends and factors associated with bisphosphonate discontinuation and restart. J Bone Miner Res 35:478–487

    Article  CAS  Google Scholar 

  8. Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S, Lindsay R, National Osteoporosis F (2014) Clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int 25:2359–2381

    Article  CAS  Google Scholar 

  9. Black DM, Bauer DC, Schwartz AV, Cummings SR, Rosen CJ (2012) Continuing bisphosphonate treatment for osteoporosis–for whom and for how long? N Engl J Med 366:2051–2053

    Article  CAS  Google Scholar 

  10. Adler RA, El-Hajj Fuleihan G, Bauer DC, Camacho PM, Clarke BL, Clines GA, Compston JE, Drake MT, Edwards BJ, Favus MJ, Greenspan SL, McKinney R Jr, Pignolo RJ, Sellmeyer DE (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 31:16–35

    Article  CAS  Google Scholar 

  11. Camacho PM, Petak SM, Binkley N, Diab DL, Eldeiry LS, Farooki A, Harris ST, Hurley DL, Kelly J, Lewiecki EM, Pessah-Pollack R, McClung M, Wimalawansa J, Watts NB (2020) American Association of Clinical Endocrinologists/American College of Endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis-2020 update. Endocr Pract 26:1–46

    Article  Google Scholar 

  12. Black DM, Reid IR, Boonen S, Bucci-Rechtweg C, Cauley JA, Cosman F, Cummings SR, Hue TF, Lippuner K, Lakatos P, Leung PC, Man Z, Martinez RL, Tan M, Ruzycky ME, Su G, Eastell R (2012) The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res 27:243–254

    Article  CAS  Google Scholar 

  13. Cosman F, Cauley JA, Eastell R, Boonen S, Palermo L, Reid IR, Cummings SR, Black DM (2014) Reassessment of fracture risk in women after 3 years of treatment with zoledronic acid: when is it reasonable to discontinue treatment? J Clin Endocrinol Metab 99:4546–4554

    Article  CAS  Google Scholar 

  14. Looker AC, Borrud LG, Hughes JP, Fan B, Shepherd JA, Melton LJ 3rd (2012) Lumbar spine and proximal femur bone mineral density, bone mineral content, and bone area: United States, 2005–2008. Vital Health Stat 11(251):1–132

    Google Scholar 

  15. Jackson SA, Tenenhouse A, Robertson L (2000) Vertebral fracture definition from population-based data: preliminary results from the Canadian Multicenter Osteoporosis Study (CaMos). Osteoporos Int 11:680–687

    Article  CAS  Google Scholar 

  16. Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakotos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR, HORIZON Pivotal Fracture Trial (2007) Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 356:1809–1822

    Article  CAS  Google Scholar 

  17. Tosteson AN, Jonsson B, Grima DT, O’Brien BJ, Black DM, Adachi JD (2001) Challenges for model-based economic evaluations of postmenopausal osteoporosis interventions. Osteoporos Int 12:849–857

    Article  CAS  Google Scholar 

  18. Ettinger B, Black DM, Dawson-Hughes B, Pressman AR, Melton LJ 3rd (2010) Updated fracture incidence rates for the US version of FRAX. Osteoporos Int 21:25–33

    Article  CAS  Google Scholar 

  19. Krege JH, Wan X, Lentle BC, Berger C, Langsetmo L, Adachi JD, Prior JC, Tenenhouse A, Brown JP, Kreiger N, Olszynski WP, Josse RG, Goltzman D, CaMos Research Group (2013) Fracture risk prediction: importance of age, BMD and spine fracture status. Bonekey Rep 2:404

    Article  Google Scholar 

  20. Fink HA, Milavetz DL, Palermo L, Nevitt MC, Cauley JA, Genant HK, Black DM, Ensrud KE (2005) What proportion of incident radiographic vertebral deformities is clinically diagnosed and vice versa? J Bone Miner Res 20:1216–1222

    Article  Google Scholar 

  21. Federal Supply Schedule. Available at: https://www.herc.research.va.gov/include/page.asp?id=pharmaceutical-costs

  22. Kilgore ML, Curtis JR, Delzell E, Becker DJ, Arora T, Saag KG, Morrisey MA (2013) A close examination of healthcare expenditures related to fractures. J Bone Miner Res 28:816–820

    Article  Google Scholar 

  23. Genworth 2018 Cost of Care Survey. Available at: https://www.genworth.com/aging-and-you/finances/cost-of-care.html

  24. Sanders GD, Neumann PJ, Basu A, Brock DW, Feeny D, Krahn M, Kuntz KM, Meltzer DO, Owens DK, Prosser LA, Salomon JA, Sculpher MJ, Trikalinos TA, Russell LB, Siegel JE, Ganiats TG (2016) Recommendations for conduct, methodological practices, and reporting of cost-effectiveness analyses: Second Panel on Cost-Effectiveness in Health and Medicine. JAMA 316:1093–1103

    Article  Google Scholar 

  25. Fryback DG, Dunham NC, Palta M, Hanmer J, Buechner J, Cherepanov D, Herrington SA, Hays RD, Kaplan RM, Ganiats TG, Feeny D, Kind P (2007) US norms for six generic health-related quality-of-life indexes from the National Health Measurement study. Med Care 45:1162–1170

    Article  Google Scholar 

  26. Hiligsmann M, Ethgen O, Richy F, Reginster JY (2008) Utility values associated with osteoporotic fracture: a systematic review of the literature. Calcif Tissue Int 82:288–292

    Article  CAS  Google Scholar 

  27. Brazier JE, Green C, Kanis JA (2002) A systematic review of health state utility values for osteoporosis-related conditions. Osteoporos Int 13:768–776

    Article  CAS  Google Scholar 

  28. Solomon DH, Patrick AR, Schousboe J, Losina E (2014) The potential economic benefits of improved postfracture care: a cost-effectiveness analysis of a fracture liaison service in the US health-care system. J Bone Miner Res 29:1667–1674

    Article  Google Scholar 

  29. Arias E (2019) United States life tables, 2017. Natl Vital Stat Rep 68:1–66

    PubMed  Google Scholar 

  30. Social Security Administration Actuarial Life Table. Available at: https://www.ssa.gov/oact/STATS/table4c6.html

  31. Orces CH (2013) In-hospital hip fracture mortality trends in older adults: the National Hospital Discharge Survey, 1988–2007. J Am Geriatr Soc 61:2248–2249

    Article  Google Scholar 

  32. LeBlanc ES, Hillier TA, Pedula KL, Rizzo JH, Cawthon PM, Fink HA, Cauley JA, Bauer DC, Black DM, Cummings SR, Browner WS (2011) Hip fracture and increased short-term but not long-term mortality in healthy older women. Arch Intern Med 171:1831–1837

    Article  Google Scholar 

  33. Society of Actuaries Long-Term Care Experience Committee Intercompany Study Report 6 1984–2007. Available at: https://www.soa.org/globalassets/assets/files/research/exp-study/research-ltc-study-1984-report.pdf

  34. Tajeu GS, Delzell E, Smith W, Arora T, Curtis JR, Saag KG, Morrisey MA, Yun H, Kilgore ML (2014) Death, debility, and destitution following hip fracture. J Gerontol A Biol Sci Med Sci 69:346–353

    Article  Google Scholar 

  35. Brown JP, Morin S, Leslie W, Papaioannou A, Cheung AM, Davison KS, Goltzman D, Hanley DA, Hodsman A, Josse R, Jovaisas A, Juby A, Kaiser S, Karaplis A, Kendler D, Khan A, Ngui D, Olszynski W, Ste-Marie LG, Adachi J (2014) Bisphosphonates for treatment of osteoporosis: expected benefits, potential harms, and drug holidays. Can Fam Physician 60:324–333

    PubMed  PubMed Central  Google Scholar 

  36. Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, Bauer DC, Genant HK, Haskell WL, Marcus R, Ott SM, Torner JC, Quandt SA, Reiss TF, Ensrud KE (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet 348:1535–1541

    Article  CAS  Google Scholar 

  37. 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 19:422–437

    Article  Google Scholar 

  38. Black DM, Cauley JA, Wagman R, Ensrud K, Fink HA, Hillier TA, Lui LY, Cummings SR, Schousboe JT, Napoli N (2018) The ability of a single BMD and fracture history assessment to predict fracture over 25 years in postmenopausal women: the Study of Osteoporotic Fractures. J Bone Miner Res 33:389–395

    Article  Google Scholar 

  39. Nayak S, Greenspan SL (2020) Cost-effectiveness of five versus ten years of alendronate treatment prior to drug holiday for women with osteoporosis. Osteoporos Int 31:1273–1282

    Article  CAS  Google Scholar 

  40. Reid IR, Black DM, Eastell R, Bucci-Rechtweg C, Su G, Hue TF, Mesenbrink P, Lyles KW, Boonen S (2020) Reduction in the risk of clinical fractures after a single dose of zoledronic acid 5 milligrams. J Clin Endocrinol Metab 98:557–563

    Article  Google Scholar 

Download references

Funding

Drs. Nayak and Greenspan were supported by NIH grant R21AR072930 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Greenspan was also supported by NIH grants P30AG024827, K07AG052668, R01AG050302, and R01AG052123 from the National Institute on Aging.

Author information

Authors and Affiliations

  1. Berkeley Madonna, Inc., 1025 Peralta Ave, CA, 94706, Albany, USA

    S. Nayak

  2. University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    S. L. Greenspan

Authors
  1. S. Nayak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. L. Greenspan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. Nayak.

Ethics declarations

Conflicts of interest

Smita Nayak declares no conflict of interest. Susan L. Greenspan receives research funding from Amgen.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 40 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nayak, S., Greenspan, S.L. Cost-effectiveness of 3 versus 6 years of zoledronic acid treatment before bisphosphonate holiday for women with osteoporosis. Osteoporos Int 33, 229–238 (2022). https://doi.org/10.1007/s00198-021-06010-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-021-06010-5

Keywords

Search

Navigation