Skip to main content
SpringerLink
Log in

Denosumab: Clinical Applications, Outcomes, and Perspectives in Osteoporosis

  • Chapter
  • First Online:
Pharmacological Interventions for Osteoporosis

Part of the book series: Tissue Repair and Reconstruction ((TRR))

  • 91 Accesses

Abstract

Increased understanding of the pathways involved in bone metabolism has led to the development of highly specific biologic medications that can be used in the treatment of osteoporosis. In this chapter, we will review the clinical uses of denosumab, a fully human IgG2 monoclonal antibody which regulates the bone remodeling pathway. We will provide the reader a basic understanding of the properties, safety, and efficacy of this monoclonal antibody and its clinical applications in the prevention and treatment of osteoporosis and other skeletal related events.

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

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 16.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Hanley DA, Adachi JD, Bell A et al (2012) Denosumab: mechanism of action and clinical outcomes. Int J Clin Pract 66:1139–1146

    Article  Google Scholar 

  2. Boyce BF, Xing L (2007) The RANKL/RANK/OPG pathway. Curr Osteoporos Rep 5:98–104

    Article  Google Scholar 

  3. Lacey DL, Boyle WJ, Simonet WS et al (2012) Bench to bedside: elucidation of the OPG-RANK-RANKL pathway and the development of denosumab. Nat Rev Drug Discov 11:401–419

    Article  Google Scholar 

  4. Cummings SR, San Martin J, McClung MR et al (2009) Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 361:756–765

    Article  Google Scholar 

  5. Bone HG, Wagman RB, Brandi ML et al (2017) 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 5:513–523

    Article  Google Scholar 

  6. Ominsky MS, Libanati C, Niu QT et al (2015) Sustained modeling-based bone formation during adulthood in cynomolgus monkeys may contribute to continuous BMD gains with denosumab. J Bone Miner Res 30:1280–1289

    Article  Google Scholar 

  7. Brown JP, Prince RL, Deal C al (2009) Comparison of the effect of denosumab and alendronate on BMD and biochemical markers of bone turnover in postmenopausal women with low bone mass: a randomized, blinded, phase 3 trial. J Bone Miner Res 24:153–161

    Google Scholar 

  8. Kendler DL, Roux C, Benhamou CL et al (2010) Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. J Bone Miner Res 25:72–81

    Article  Google Scholar 

  9. Management of Osteoporosis in Postmenopausal Women: The 2021 Position Statement of The North American Menopause Society’’ Editorial Panel (2021) Management of osteoporosis in postmenopausal women: the 2021 position statement of The North American Menopause Society. Menopause 28:973–997

    Google Scholar 

  10. Shoback D, Rosen CJ, Black DM et al (2020) Pharmacological management of osteoporosis in postmenopausal women: an endocrine society guideline update. J Clin Endocrinol Metab 105:dgaa048. https://doi.org/10.1210/clinem/dgaa048

  11. Cummings SR, Ferrari S, Eastell R et al (2018) Vertebral fractures after discontinuation of denosumab: a post hoc analysis of the randomized placebo-controlled FREEDOM trial and its extension. J Bone Miner Res 33:190–198

    Article  Google Scholar 

  12. Miyazaki T, Tokimura F, Tanaka S (2014) A review of denosumab for the treatment of osteoporosis. Patient Prefer Adherence 8:463–471

    Article  Google Scholar 

  13. Nitta K, Yajima A, Tsuchiya K (2017) Management of osteoporosis in chronic kidney disease. Intern Med 56:3271–3276

    Article  Google Scholar 

  14. Thongprayoon C, Acharya P, Acharya C et al (2018) Hypocalcemia and bone mineral density changes following denosumab treatment in end-stage renal disease patients: a meta-analysis of observational studies. Osteoporos Int 29:1737–1745

    Article  Google Scholar 

  15. Dave V, Chiang CY, Booth J et al (2015) Hypocalcemia post denosumab in patients with chronic kidney disease stage 4–5. Am J Nephrol 41:129–137

    Article  Google Scholar 

  16. Gnant M, Pfeiler G, Dubsky PC et al (2015) Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet 386:433–443

    Article  Google Scholar 

  17. Rachner TD, Göbel A, Jaschke NP et al (2020) Challenges in preventing bone loss induced by aromatase inhibitors. J Clin Endocrinol Metab 105:dgaa463. https://doi.org/10.1210/clinem/dgaa463

  18. Lipton A (2009) Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. Breast Dis 2:195–196

    Google Scholar 

  19. The Lancet Diabetes Endocrinology (2021) Osteoporosis: overlooked in men for too long. Lancet Diabetes Endocrinol 9:1. https://doi.org/10.1016/S2213-8587(20)30408-3

    Article  Google Scholar 

  20. Langdahl BL, Teglbjærg CS, Ho PR et al (2015) A 24-month study evaluating the efficacy and safety of denosumab for the treatment of men with low bone mineral density: results from the ADAMO trial. J Clin Endocrinol Metab 100:1335–1342

    Article  Google Scholar 

  21. Nakamura T, Matsumoto T, Sugimoto T et al (2014) Clinical Trials Express: fracture risk reduction with denosumab in Japanese postmenopausal women and men with osteoporosis: denosumab fracture intervention randomized placebo controlled trial (DIRECT). J Clin Endocrinol Metab 99:2599–2607

    Article  Google Scholar 

  22. Brown JE, Handforth C, Compston JE et al (2020) Guidance for the assessment and management of prostate cancer treatment-induced bone loss. A consensus position statement from an expert group. J Bone Oncol 25:100311. https://doi.org/10.1016/j.jbo.2020.100311

  23. Kanis JA, Harvey NC, Cooper C et al (2016) A systematic review of intervention thresholds based on FRAX: a report prepared for the National Osteoporosis Guideline Group and the International Osteoporosis Foundation. Arch Osteoporos 11:25. https://doi.org/10.1007/s11657-016-0278-z

    Article  Google Scholar 

  24. Serpa Neto A, Tobias-Machado M, Esteves MA et al (2012) Bisphosphonate therapy in patients under androgen deprivation therapy for prostate cancer: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis 15:36–44

    Article  Google Scholar 

  25. Smith MR, Egerdie B, Hernández Toriz N et al (2009) Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med 361:745–755

    Article  Google Scholar 

  26. Doria C, Leali PT, Solla F et al (2016) Denosumab is really effective in the treatment of osteoporosis secondary to hypogonadism in prostate carcinoma patients? A prospective randomized multicenter international study. Clin Cases Miner Bone Metab 13:195–199

    Google Scholar 

  27. Fizazi K, Carducci M, Smith M et al (2011) Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet 377:813–822

    Article  Google Scholar 

  28. Smith MR, Saad F, Coleman R et al (2012) Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial. Lancet 379:39–46

    Article  Google Scholar 

  29. Fardet L, Petersen I, Nazareth I (2015) Monitoring of patients on long-term glucocorticoid therapy: a population-based cohort study. Medicine 94:e647. https://doi.org/10.1097/MD.0000000000000647

    Article  Google Scholar 

  30. Buckley L, Guyatt G, Fink HA et al (2017) 2017 American College of Rheumatology guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Rheumatol 69:1521–1537

    Article  Google Scholar 

  31. Compston J, Cooper A, Cooper C et al (2017) UK clinical guideline for the prevention and treatment of osteoporosis. Arch Osteoporos 12:43. https://doi.org/10.1007/s11657-017-0324-5

    Article  Google Scholar 

  32. Saag KG, Emkey R, Schnitzer TJ et al (1998) Alendronate for the prevention and treatment of glucocorticoid-induced osteoporosis. Glucocorticoid-induced osteoporosis intervention study group. N Engl J Med 339:292–299

    Article  Google Scholar 

  33. Reid DM, Hughes RA, Laan RF et al (2000) Efficacy and safety of daily risedronate in the treatment of corticosteroid-induced osteoporosis in men and women: a randomized trial. European corticosteroid-induced osteoporosis treatment study. J Bone Miner Res 15:1006–1013

    Article  Google Scholar 

  34. Reid DM, Devogelaer JP, Saag K et al (2009) Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomised controlled trial. Lancet 373:1253–1263

    Article  Google Scholar 

  35. Recker RR, Gallagher R, MacCosbe PE (2005) Effect of dosing frequency on bisphosphonate medication adherence in a large longitudinal cohort of women. Mayo Clin Proc 80:856–861

    Article  Google Scholar 

  36. Saag KG, Shane E, Boonen S et al (2007) Teriparatide or alendronate in glucocorticoid-induced osteoporosis. N Engl J Med 357:2028–2039

    Article  Google Scholar 

  37. Saag KG, Pannacciulli N, Geusens P et al (2019) Denosumab versus risedronate in glucocorticoid-induced osteoporosis: final results of a twenty-four-month randomized, double-blind, double-dummy trial. Arthritis Rheumatol 71:1174–1184

    Article  Google Scholar 

  38. Buckley L, Guyatt G, Fink HA et al (2017) American College of Rheumatology Guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res 69:1095–1110

    Article  Google Scholar 

  39. American College of Rheumatology (2022) American College of Rheumatology guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. https://www.rheumatology.org/Practice-Quality/Clinical-Support/Clinical-Practice-Guidelines/Glucocorticoid-Induced-Osteoporosis. Accessed 02 Apr 2023

  40. Mok CC, Ho LY, Ma KM (2015) Switching of oral bisphosphonates to denosumab in chronic glucocorticoid users: a 12-month randomized controlled trial. Bone 75:222–228

    Article  Google Scholar 

  41. Iseri K, Iyoda M, Watanabe M et al (2018) The effects of denosumab and alendronate on glucocorticoid-induced osteoporosis in patients with glomerular disease: a randomized, controlled trial. PLoS ONE 13:e0193846. https://doi.org/10.1371/journal.pone.0193846

    Article  Google Scholar 

  42. Saag KG, Wagman RB, Geusens P et al (2018) Denosumab versus risedronate in glucocorticoid-induced osteoporosis: a multicentre, randomised, double-blind, active-controlled, double-dummy, non-inferiority study. Lancet Diabetes Endocrinol 6:445–454

    Article  Google Scholar 

  43. Geusens P, Bevers MS, van Rietbergen B et al (2022) Effect of denosumab compared with risedronate on bone strength in patients initiating or continuing glucocorticoid treatment. J Bone Miner Res 37:1136–1146

    Article  Google Scholar 

  44. Matsuno H (2016) Assessment of distal radius bone mineral density in osteoporosis patients receiving denosumab, including those with rheumatoid arthritis and those receiving oral glucocorticoids. Drugs R D 16:347–353

    Article  Google Scholar 

  45. Hu MI, Glezerman IG, Leboulleux S et al (2014) Denosumab for treatment of hypercalcemia of malignancy. J Clin Endocrinol Metab 99:3144–3152

    Article  Google Scholar 

  46. Thosani S, Hu MI (2015) Denosumab: a new agent in the management of hypercalcemia of malignancy. Future Oncol 11:2865–2871

    Article  Google Scholar 

  47. Stewart AF (2005) Clinical practice. Hypercalcemia associated with cancer. N Engl J Med 352:373–379

    Article  Google Scholar 

  48. Major P, Lortholary A, Hon J et al (2001) Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. J Clin Oncol 19:558–567

    Article  Google Scholar 

  49. Major PP, Coleman RE (2001) Zoledronic acid in the treatment of hypercalcemia of malignancy: results of the international clinical development program. Semin Oncol 28:17–24

    Article  Google Scholar 

  50. Henry DH, Costa L, Goldwasser F et al (2011) Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol 29:1125–1132

    Article  Google Scholar 

  51. Raje N, Terpos E, Willenbacher W et al (2018) Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study. Lancet Oncol 19:370–381

    Article  Google Scholar 

  52. Diel IJ, Body JJ, Stopeck AT et al (2015) The role of denosumab in the prevention of hypercalcaemia of malignancy in cancer patients with metastatic bone disease. Eur J Cancer 51:1467–1475

    Article  Google Scholar 

  53. Raje N, Roodman GD, Willenbacher W et al (2018) A cost-effectiveness analysis of denosumab for the prevention of skeletal-related events in patients with multiple myeloma in the United States of America. J Med Econ 21:525–536

    Article  Google Scholar 

  54. Huang SY, Yoon SS, Shimizu K et al (2020) Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, randomized controlled phase 3 study-Asian subgroup analysis. Adv Ther 37:3404–3416

    Article  Google Scholar 

  55. Rosen LS, Gordon D, Tchekmedyian NS et al (2004) Long-term efficacy and safety of zoledronic acid in the treatment of skeletal metastases in patients with nonsmall cell lung carcinoma and other solid tumors: a randomized, Phase III, double-blind, placebo-controlled trial. Cancer 100:2613–2621

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Rheumatology Department, Mayo Clinic Arizona, Scottsdale, Az, USA

    Nouran Eshak

  2. Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA

    Afrina Rimu & Alexandra Hoffman

Authors
  1. Nouran Eshak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Afrina Rimu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alexandra Hoffman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nouran Eshak .

Editor information

Editors and Affiliations

  1. School of Life Sciences Translational Biomaterials and Medicine Group, University of Technology, Sydney, NSW, Australia

    Andy H. Choi

  2. Hawaii Pacific Health, Straub Clinic, Honolulu, HI, USA

    Sian Yik Lim

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Eshak, N., Rimu, A., Hoffman, A. (2023). Denosumab: Clinical Applications, Outcomes, and Perspectives in Osteoporosis. In: Choi, A.H., Yik Lim, S. (eds) Pharmacological Interventions for Osteoporosis. Tissue Repair and Reconstruction. Springer, Singapore. https://doi.org/10.1007/978-981-99-5826-9_2

Download citation

  • DOI: https://doi.org/10.1007/978-981-99-5826-9_2

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-99-5825-2

  • Online ISBN: 978-981-99-5826-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation