Skip to main content
SpringerLink
Log in

Romosozumab: A Review in Postmenopausal Osteoporosis

  • Adis Drug Evaluation
  • Published:
Drugs & Aging Aims and scope Submit manuscript

A Correction to this article was published on 21 October 2020

This article has been updated

Abstract

Romosozumab (Evenity®), a humanized monoclonal antibody, promotes bone formation and inhibits bone resorption by inhibiting sclerostin, a protein involved in the regulation of bone formation. Subcutaneous romosozumab is approved in several countries, including those of the EU for treating severe osteoporosis as well as in the USA for osteoporosis in postmenopausal women at high risk of fracture. In pivotal phase III trials (FRAME and ARCH), 12 months’ once-monthly romosozumab 210 mg significantly reduced vertebral and clinical fracture risk versus placebo and oral alendronate in postmenopausal women with osteoporosis. After patients transitioned from romosozumab to 12–24 months of subcutaneous denosumab or oral alendronate, fracture risks were significantly improved versus placebo-to-denosumab and alendronate-only treatment. In these trials and a phase IIIb trial, romosozumab significantly increased bone mineral density (BMD) relative to placebo, alendronate and subcutaneous teriparatide at 12 months, with these benefits maintained 12–24 months after patients transitioned from romosozumab to alendronate or denosumab in pivotal trials. Romosozumab had a generally manageable tolerability profile. While further clinical experience is needed to more definitively establish its efficacy and safety, including its CV safety, romosozumab extends the treatment options in postmenopausal women with osteoporosis who have a high risk of fracture and in those who have failed or are intolerant to other available osteoporosis therapy.

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

Similar content being viewed by others

Change history

  • 21 October 2020

    Unfortunately the sections were published incorrectly in the original article.

References

  1. Eastell R, O'Neill TW, Hofbauer LC, et al. Postmenopausal osteoporosis. Nat Rev Dis Prim. 2016;2:16069.

    Article  Google Scholar 

  2. Manolagas SC, O'Brien CA, Almeida M. The role of estrogen and androgen receptors in bone health and disease. Nat Rev Endocrinol. 2013;9(12):699–712.

    Article  CAS  Google Scholar 

  3. Alswat KA. Gender disparities in osteoporosis. J Clin Med Res. 2017;9(5):382–7.

    Article  Google Scholar 

  4. Baron R, Kneissel M. WNT signaling in bone homeostasis and disease: from human mutations to treatments. Nat Med. 2013;19(2):179–92.

    Article  CAS  Google Scholar 

  5. Appelman-Dijkstra NM, Papapoulos SE. Sclerostin inhibition in the management of osteoporosis. Calcif Tissue Int. 2016;98(4):370–80.

    Article  CAS  Google Scholar 

  6. Solling ASK, Harslof T, Langdahl B. The clinical potential of romosozumab for the prevention of fractures in postmenopausal women with osteoporosis. Ther Adv Musculoskelet Dis. 2018;10(5–6):105–15.

    Article  Google Scholar 

  7. Geusens P. New insights into treatment of osteoporosis in postmenopausal women. RMD Open. 2015;1(Suppl 1):e000051.

    Article  Google Scholar 

  8. Cosman F. Anabolic therapy and optimal treatment sequences for patients with osteoporosis at high risk for fracture. Endocr Pract. 2020. https://doi.org/10.4158/EP-2019-0596.

    Article  Google Scholar 

  9. European Medicines Agency. Romosozumab (Evenity™): EU summary of product characteristics. 2019. https://www.ema.europa.eu/. Accessed 7 Aug 2020.

  10. AMGEN. Romosozumab (Evenity™): US prescribing information. 2019. https://www.pi.amgen.com/~/media/amgen/repositorysites/pi-amgen-com/evenity/evenity_pi.ashx. Accessed 7 Aug 2020.

  11. Cosman F, Crittenden DB, Adachi JD, et al. Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med. 2016;375(16):1532–43.

    Article  CAS  Google Scholar 

  12. Saag KG, Petersen J, Brandi ML, et al. Romosozumab or alendronate for fracture prevention in women with osteoporosis. N Engl J Med. 2017;377(15):1417–27.

    Article  CAS  Google Scholar 

  13. Langdahl BL, Libanati C, Crittenden DB, et al. Romosozumab (sclerostin monoclonal antibody) versus teriparatide in postmenopausal women with osteoporosis transitioning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial. Lancet. 2017;390(10102):1585–94.

    Article  CAS  Google Scholar 

  14. Chavassieux P, Chapurlat R, Portero-Muzy N, et al. Bone-forming and antiresorptive effects of romosozumab in postmenopausal women with osteoporosis: bone histomorphometry and microcomputed tomography analysis after 2 and 12 months of treatment. J Bone Miner Res. 2019;34(9):1597–608.

    Article  CAS  Google Scholar 

  15. US Center for Drug Evaluation and Research. Romosozumab (EVENITY™): multi-discipline review. 2019. https://www.accessdata.fda.gov/. Accessed 7 Aug 2020.

  16. McClung MR, Grauer A, Boonen S, et al. Romosozumab in postmenopausal women with low bone mineral density. N Engl J Med. 2014;370(5):412–20.

    Article  CAS  Google Scholar 

  17. Padhi D, Allison M, Kivitz AJ, et al. Multiple doses of sclerostin antibody romosozumab in healthy men and postmenopausal women with low bone mass: a randomized, double-blind, placebo-controlled study. J Clin Pharmacol. 2014;54(2):168–78.

    Article  CAS  Google Scholar 

  18. Lewiecki EM, Dinavahi RV, Lazaretti-Castro M, et al. One year of romosozumab followed by two years of denosumab maintains fracture risk reductions: results of the FRAME extension study. J Bone Miner Res. 2019;34(3):419–28.

    Article  CAS  Google Scholar 

  19. Geusens P, Oates M, Miyauchi A, et al. The effect of 1 year of romosozumab on the incidence of clinical vertebral fractures in postmenopausal women with osteoporosis: results from the FRAME study. JBMR Plus. 2019;3(10):e10211.

    Article  Google Scholar 

  20. Cosman F, Crittenden DB, Ferrari S, et al. Romosozumab FRAME study: a post hoc analysis of the role of regional background fracture risk on nonvertebral fracture outcome. J Bone Miner Res. 2018;33(8):1407–16.

    Article  CAS  Google Scholar 

  21. Lau EMC, Dinavahi R, Woo YC, et al. Romosozumab or alendronate for fracture prevention in East Asian patients: a subanalysis of the phase III, randomized ARCH study [abstract no. P659]. Osteoporosis Int. 2019;30(Suppl 2):S524.

    Google Scholar 

  22. Miyauchi A, Dinavahi RV, Crittenden DB, et al. Increased bone mineral density for 1 year of romosozumab, vs placebo, followed by 2 years of denosumab in the Japanese subgroup of the pivotal FRAME trial and extension. Arch Osteoporos. 2019;14:59.

    Article  Google Scholar 

  23. Cosman F, Lewiecki EM, Ebeling PR, et al. Levels of improvements in bone mineral density in postmenopausal women with osteoporosis treated with romosozumab: a post hoc analysis of the ARCH phase 3 trial [abstract no. P1089]. Osteoporosis Int. 2019;30(Suppl 2):S732–S733733.

    Google Scholar 

  24. Krishna SM, Seto SW, Jose RJ, et al. Wnt signaling pathway inhibitor sclerostin inhibits angiotensin II-induced aortic aneurysm and atherosclerosis. Arterioscler Thromb Vasc Biol. 2017;37(3):553–66.

    Article  CAS  Google Scholar 

  25. Turk JR, Deaton AM, Yin J, et al. Nonclinical cardiovascular safety evaluation of romosozumab, an inhibitor of sclerostin for the treatment of osteoporosis in postmenopausal women at high risk of fracture. Regul Toxicol Pharmacol. 2020;115:104697.

    Article  CAS  Google Scholar 

  26. European Medicines Agency. Romosozumab (Evenity™): EU public assessment report. 2019. https://www.ema.europa.eu/. Accessed 7 Aug 2020.

  27. Amgen Canada. Health Canada approves EVENITY® for the treatment of osteoporosis in postmenopausal women at high risk for fracture [media release]. 2019. https://www.amgen.ca.

  28. Astellas Pharma Inc. Evenity® subcutaneous injection 105 mg syringe launched in Japan for the treatment of osteoporosis with high risk of fracture [media release]. 2019. https://www.astellas.com.

  29. Oleksik AM, Ewing S, Shen W, et al. Impact of incident vertebral fractures on health related quality of life (HRQOL) in postmenopausal women with prevalent vertebral fractures. Osteoporos Int. 2005;16(8):861–70.

    Article  Google Scholar 

  30. National Osteoporosis Guideline Group. Clinical guideline for the prevention and treatment of osteoporosis. 2017. https://www.sheffield.ac.uk/NOGG/. Accessed 7 Aug 2020.

  31. Camacho PM, Petak SM, Binkley N, et al. American Association of Clinical Endocrinologists and American College of Endocrinology Clinical Practice Guidelines for the diagnosis and treatment of postmenopausal osteoporosis: 2020 update. Endocr Pract. 2020;26(Suppl 1):1–46.

    Article  Google Scholar 

  32. STADA Arzneimittel AG. Teriparatide (Movymia®): EU summary of product characteristics. 2020. https://www.ema.europa.eu/. Accessed 7 Aug 2020.

  33. Amgen Europe B. V. Denosumab (Prolia®): EU summary of product characteristics. 2020. https://www.ema.europa.eu/. Accessed 7 Aug 2020.

  34. Nishiyama KK, Cohen A, Young P, et al. Teriparatide increases strength of the peripheral skeleton in premenopausal women with idiopathic osteoporosis: a pilot HR-pQCT study. J Clin Endocrinol Metab. 2014;99(7):2418–25.

    Article  CAS  Google Scholar 

  35. Boonen S, Marin F, Obermayer-Pietsch B, et al. Effects of previous antiresorptive therapy on the bone mineral density response to two years of teriparatide treatment in postmenopausal women with osteoporosis. J Clin Endocrinol Metab. 2008;93(3):852–60.

    Article  CAS  Google Scholar 

  36. Miller PD, Delmas PD, Lindsay R, et al. Early responsiveness of women with osteoporosis to teriparatide after therapy with alendronate or risedronate. J Clin Endocrinol Metab. 2008;93(10):3785–93.

    Article  CAS  Google Scholar 

  37. Obermayer-Pietsch BM, Marin F, McCloskey EV, et al. Effects of two years of daily teriparatide treatment on BMD in postmenopausal women with severe osteoporosis with and without prior antiresorptive treatment. J Bone Miner Res. 2008;23(10):1591–600.

    Article  CAS  Google Scholar 

  38. Cummings SR, McCulloch C. Explanations for the difference in rates of cardiovascular events in a trial of alendronate and romosozumab. Osteoporos Int. 2020;31(6):1019–21.

    Article  CAS  Google Scholar 

  39. Kranenburg G, Bartstra JW, Weijmans M, et al. Bisphosphonates for cardiovascular risk reduction: a systematic review and meta-analysis. Atherosclerosis. 2016;252:106–15.

    Article  CAS  Google Scholar 

  40. Sing CW, Wong AY, Kiel DP, et al. Association of alendronate and risk of cardiovascular events in patients with hip fracture. J Bone Miner Res. 2018;33(8):1422–34.

    Article  CAS  Google Scholar 

  41. Kang JH, Keller JJ, Lin HC. Bisphosphonates reduced the risk of acute myocardial infarction: a 2-year follow-up study. Osteoporos Int. 2013;24(1):271–7.

    Article  CAS  Google Scholar 

  42. Wolfe F, Bolster MB, O'Connor CM, et al. Bisphosphonate use is associated with reduced risk of myocardial infarction in patients with rheumatoid arthritis. J Bone Miner Res. 2012;28:984–91.

    Article  Google Scholar 

  43. Reid IR, Horne AM, Mihov B, et al. Fracture prevention with zoledronate in older women with osteopenia. N Engl J Med. 2018;379(25):2407–16.

    Article  CAS  Google Scholar 

  44. 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(8):756–65.

    Article  CAS  Google Scholar 

  45. Cosman F, Crittenden DB, Ferrari S, et al. FRAME study: the foundation effect of building bone with 1 year of romosozumab leads to continued lower fracture risk after transition to denosumab. J Bone Miner Res. 2018;33(7):1219–26.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

During the peer review process, the manufacturer of romosozumab was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Author information

Authors and Affiliations

  1. Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand

    Julia Paik & Lesley J. Scott

Authors
  1. Julia Paik
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lesley J. Scott
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Julia Paik.

Ethics declarations

Funding

The preparation of this review was not supported by any external funding.

Authorship and Conflict of interest

J. Paik and L. Scott are salaried employees of Adis International Ltd/Springer Nature, and declare no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content.

Ethics approval, Consent to participate, Consent to publish, Availability of data and material, Code availability

Not applicable.

Additional information

The original version of this article was revised: “Unfortunately the sections were published incorrectly.”

Enhanced material for this Adis Drug Evaluation can be found at https://doi.org/10.6084/m9.figshare.12805619.

The manuscript was reviewed by: J. P. Devogelaer, Department of Rheumatology, Université Catholique de Louvain, Saint-Luc University Hospital, Brussels, Belgium; P. Geusens, Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, Netherlands; I. Reid, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Paik, J., Scott, L.J. Romosozumab: A Review in Postmenopausal Osteoporosis. Drugs Aging 37, 845–855 (2020). https://doi.org/10.1007/s40266-020-00793-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40266-020-00793-8

Search

Navigation