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Romosozumab: a Review of Efficacy, Safety, and Cardiovascular Risk

  • Therapeutics and Medical Management (S Jan De Beur and B Clarke, Section Editors)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Authors review the safety and efficacy of romosozumab for the treatment of osteoporosis as demonstrated in three phase III clinical trials and offer insights into the potential cardiovascular risk associated with its use.

Recent Findings

Incidence of new vertebral fracture is dramatically reduced with 12 months of romosozumab use in comparison to both placebo and active bisphosphonate control groups in patients with postmenopausal osteoporosis. Significant non-vertebral anti-fracture benefit was also demonstrated in patients with more severe osteoporosis. Numerical increases in cardiovascular events call into question the safety of romosozumab use, particularly in patients with cardiovascular history or at high cardiovascular risk.

Summary

Romosozumab has impressive anti-fracture effects in postmenopausal women with high risk for fragility fracture. Despite no significant differences in baseline cardiovascular risk factors between groups, a numerical increase in serious cardiovascular adverse events was demonstrated with romosozumab in randomized trials with no discernable etiology. Until more real-world evidence is available, romosozumab should not be used in patients with a recent cardiovascular event and should be used cautiously in patients with high cardiovascular risk. Romosozumab’s place in therapy is likely patients with severe postmenopausal osteoporosis and low cardiovascular risk.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Teriparatide [package insert]. Indianapolis, IN: Eli Lilly and Company; 2002.

  2. Abaloparatide [package insert]. Waltham, MA: Radius Health, Inc; 2017.

  3. Romosozumab [package insert]. Thousand Oaks, CA: Amgen, Inc; 2019.

  4. Weivoda MM, Youssef SJ, Oursler MJ. Sclerostin expression and functions beyond the osteocyte. Bone. 2017;96:45–50. https://doi.org/10.1016/j.bone.2016.11.024.

    Article  CAS  PubMed  Google Scholar 

  5. Balemans W, Ebeling M, Patel N, van Hul E, Olson P, Dioszegi M, et al. Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet. 2001;10(5):537–43. https://doi.org/10.1093/hmg/10.5.537.

    Article  CAS  PubMed  Google Scholar 

  6. Brunkow ME, Gardner JC, Van Ness J, et al. Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet. 2001;68(3):577–89. https://doi.org/10.1086/318811.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. •• Cosman F, Crittenden DB, Adachi JD, et al. Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med. 2016;375(16):1532–43. https://doi.org/10.1056/NEJMoa1607948.

    Article  CAS  PubMed  Google Scholar 

  8. •• 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. https://doi.org/10.1056/NEJMoa1708322.

    Article  CAS  PubMed  Google Scholar 

  9. •• Lewiecki EM, Blicharski T, Goemaere S, et al. A phase III randomized placebo-controlled trial to evaluate efficacy and safety of romosozumab in men with osteoporosis. J Clin Endocrinol Metab. 2018;103(9):3183–93. https://doi.org/10.1210/jc.2017-02163.

    Article  PubMed  Google Scholar 

  10. Cosman F, Crittenden DB, Ferrari S, Lewiecki EM, Jaller-Raad J, Zerbini C, 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. https://doi.org/10.1002/jbmr.3439.

    Article  CAS  PubMed  Google Scholar 

  11. • Amgen, Inc. BLA 761062 Romosozumab: U. S. Food and Drug Administration/Center for Drug Evaluation and Research; Division of Bone, Reproductive, and Urologic Products: FDA Briefing document. Amgen, Inc. Jan 16, 2019. https://www.fda.gov/media/121257/download (accessed 2020 May 04).

  12. • Amgen, Inc. BLA 761062 Romosozumab: U. S. Food and Drug Administration/Center for Drug Evaluation and Research; Division of Bone, Reproductive, and Urologic Products Office of Drug Evaluation III Multidisciplinary Review and Evaluation document. Amgen, Inc. July 9, 2018. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/761062Orig1s000MultidisciplineR.pdf (accessed 2020 May 01).

  13. Miller PD, Hattersley G, Riis BJ, Williams GC, Lau E, Russo LA, et al. Effect of Abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial [published correction appears in JAMA. 2017 Jan 24;317(4):442]. JAMA. 2016;316(7):722–33. https://doi.org/10.1001/jama.2016.11136.

    Article  CAS  PubMed  Google Scholar 

  14. Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med. 2007;356(18):1809–22. https://doi.org/10.1056/NEJMoa067312.

    Article  CAS  PubMed  Google Scholar 

  15. Zhu D, Mackenzie NC, Millán JL, Farquharson C, MacRae VE. The appearance and modulation of osteocyte marker expression during calcification of vascular smooth muscle cells. PLoS One. 2011;6(5):e19595. https://doi.org/10.1371/journal.pone.0019595.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. van Lierop AH, Appelman-Dijkstra NM, Papapoulos SE. Sclerostin deficiency in humans. Bone. 2017;96:51–62. https://doi.org/10.1016/j.bone.2016.10.010.

    Article  CAS  PubMed  Google Scholar 

  17. 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. https://doi.org/10.1007/s00198-012-2213-5.

    Article  CAS  PubMed  Google Scholar 

  18. 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. https://doi.org/10.1002/jbmr.3448.

    Article  CAS  PubMed  Google Scholar 

  19. Kim DH, Rogers JR, Fulchino LA, Kim CA, Solomon DH, Kim SC. Bisphosphonates and risk of cardiovascular events: a meta-analysis. PLoS One. 2015;10(4):e0122646. Published 2015 Apr 17. https://doi.org/10.1371/journal.pone.0122646.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kranenburg G, Bartstra JW, Weijmans M, de Jong PA, Mali WP, Verhaar HJ, et al. Bisphosphonates for cardiovascular risk reduction: a systematic review and meta-analysis. Atherosclerosis. 2016;252:106–15. https://doi.org/10.1016/j.atherosclerosis.2016.06.039.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA

    Cy Fixen

  2. PGY2 Ambulatory Care Pharmacy Resident, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA

    Jennifer Tunoa

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  1. Cy Fixen
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Correspondence to Cy Fixen.

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Fixen, C., Tunoa, J. Romosozumab: a Review of Efficacy, Safety, and Cardiovascular Risk. Curr Osteoporos Rep 19, 15–22 (2021). https://doi.org/10.1007/s11914-020-00652-w

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  • DOI: https://doi.org/10.1007/s11914-020-00652-w

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