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Denosumab

A Review of its Use in the Treatment of Postmenopausal Osteoporosis

Drugs & Aging volume 28, pages 63–82 (2011)Cite this article

Abstract

Denosumab (Prolia®) is a human recombinant monoclonal antibody that is approved for the treatment of postmenopausal osteoporosis in women at high or increased risk of fracture in the US, the EU and several other countries. Denosumab has a novel mechanism of action; it binds to receptor activator of nuclear factor κB ligand and inhibits bone resorption by inhibiting osteoclast formation, function and survival.

In postmenopausal women with osteoporosis, denosumab reduced the risk of vertebral, nonvertebral and hip fractures compared with placebo over 3 years in the large, phase III FREEDOM study. In postmenopausal women with low bone mineral density (BMD) or osteoporosis, treatment with denosumab increased BMD and decreased markers of bone turnover more than alendronate in those who were essentially treatment-naive in the 1-year DECIDE study and also in the 1-year STAND study, in which women were switched from alendronate to denosumab or continued alendronate treatment. Denosumab was generally well tolerated in clinical trials, although long-term effects of very low bone turnover remain to be established.

Denosumab is administered once every 6 months via subcutaneous injection, which may be a preferred method of administration and may improve adherence to treatment compared with other osteoporosis treatments. Denosumab is a valuable new option for the treatment of postmenopausal osteoporosis in women at increased or high risk of fractures, and may be useful as a first-line treatment in women at increased risk of fractures who are unable to take other osteoporosis treatments.

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References

  1. Lewiecki EM. Treatment of osteoporosis with denosumab. Maturitas 2010 Jun; 66(2): 182–6

    PubMed  Article  CAS  Google Scholar 

  2. Kanis JA, Burlet N, Cooper C, et al. European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 2008 Apr; 19(4): 399–428

    PubMed  Article  CAS  Google Scholar 

  3. Burge R, Dawson-Hughes B, Solomon DH, et al. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005–2025. J Bone Miner Res 2007 Mar; 22(3): 465–75

    PubMed  Article  Google Scholar 

  4. Kanis JA, Johnell O. Requirements for DXA for the management of osteoporosis in Europe. Osteoporos Int 2005 Mar; 16(3): 229–38

    PubMed  Article  CAS  Google Scholar 

  5. National Osteoporosis Foundation. Clinician’s guide to prevention and treatment of osteoporosis. Washington, DC: National Osteoporosis Foundation, 2010

    Google Scholar 

  6. Prolia™ (denosumab) injection, for subcutaneous use: US prescribing information. Thousand Oaks (CA): Amgen Inc., 2010

  7. Prolia 60mg solution for injection in a pre-filled syringe: EU summary of product characteristics. Breda: Amgen Europe B.V., 2010 May 26

  8. Xgeva™ (denosumab) injection, for subcutaneous use: US prescribing information. Thousand Oaks (CA): Amgen Inc., 2010

  9. Bone HG, Bolognese MA, Yuen CK, et al. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women. J Clin Endocrinol Metab 2008 Jun; 93(6): 2149–57

    PubMed  Article  CAS  Google Scholar 

  10. Genant HK, Engelke K, Hanley DA, et al. Denosumab improves density and strength parameters as measured by QCT of the radius in postmenopausal women with low bone mineral density. Bone 2010 Jul; 47(1): 131–9

    PubMed  Article  CAS  Google Scholar 

  11. Kearns AE, Khosla S, Kostenuik PJ. Receptor activator of nuclear factor KB ligand and osteoprotegerin regulation of bone remodeling in health and disease. Endocr Rev 2008 Apr; 29(2): 155–92

    PubMed  Article  CAS  Google Scholar 

  12. Kostenuik PJ, Nguyen HQ, McCabe J, et al. Denosumab, a fully human monoclonal antibody to RANKL, inhibits bone resorption and increases BMD in knock-in mice that express chimeric (murine/human) RANKL. J Bone Miner Res 2009 Feb; 24(2): 182–95

    PubMed  Article  CAS  Google Scholar 

  13. Ominsky MS, Schroeder J, Jolette J, et al. Decreased bone turnover and porosity are associated with improved bone strength in ovariectomized (OVX) cynomolgus monkeys treated with denosumab, a fully human RANKL antibody [abstract no. S409]. J Bone Miner Res 2007 Sep 1; (22 Suppl. 1): 126

    Google Scholar 

  14. Ominsky MS, Schroeder J, Smith SY, et al. Denosumab (AMG 162), a fully human RANKL antibody, improves cortical and cancellous bone mass and bone strength in ovariectomized cynomolgus monkeys [abstract no. 1082]. J Bone Miner Res 2007 Sep 1; 22Suppl. 1: 23

    Google Scholar 

  15. Ominsky MS, Smith SY, Vlasseros F, et al. Transition from alendronate to denosumab in ovariectomized cynomolgus monkeys maintained or improved cortical and trabecular bone mass, without altering the linear relationship between bone mass and bone strength [abstract no. 1072]. 30th Annual Meeting of the American Society for Bone and Mineral Research; 2008 Sep 12–16; Montreal (QC)

  16. Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009 Aug 20; 361(8): 756–65

    PubMed  Article  CAS  Google Scholar 

  17. Kendler DL, Roux C, Benhamou CL, et al. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. J Bone Miner Res 2010 Jan; 25(1): 72–81

    PubMed  Article  CAS  Google Scholar 

  18. Reid IR, Miller PD, Brown JP, et al. Effects of denosumab on bone histomorphometry: the FREEDOM and STAND studies. J Bone Miner Res 2010 Oct; 25(10): 2256–65

    PubMed  Article  CAS  Google Scholar 

  19. Seeman E, Delmas PD, Hanley DA, et al. Microarchitectural deterioration of cortical and trabecular bone: differing effects of denosumab and alendronate. J Bone Miner Res 2010 Aug; 25(8): 1886–94

    PubMed  Article  Google Scholar 

  20. Bekker PJ, Holloway DL, Rasmussen AS, et al. A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res 2004 Jul; 19(7): 1059–66

    PubMed  Article  CAS  Google Scholar 

  21. Brown JP, Prince RL, Deal C, et al. 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 2009 Jan; 24(1): 153–61

    PubMed  Article  CAS  Google Scholar 

  22. Eastell R, Christiansen C, Grauer A, et al. Effects of denosumab on bone turnover markers in postmenopausal osteoporosis. J Bone Miner Res. Epub 2010 Sep 13

    Google Scholar 

  23. Eastell R, Bauer D, Christiansen C, et al. The relationship between baseline bone resorption and fracture risk reduction with denosumab [abstract no. A09001429]. 31st Annual Meeting of the American Society for Bone and Mineral Research; 2009 Sep 11–15; Denver (CO)

  24. Miller PD, Bolognese MA, Lewiecki EM, et al. Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial. Bone 2008 Aug; 43(2): 222–9

    PubMed  Article  CAS  Google Scholar 

  25. Gerstenfeld LC, Sacks DJ, Pelis M, et al. Comparison of effects of the bisphosphonate alendronate versus the RANKL inhibitor denosumab on murine fracture healing. J Bone Miner Res 2009; 24(2): 196–208

    PubMed  Article  CAS  Google Scholar 

  26. Ferrari-Lacraz S, Ferrari S. Do RANKL inhibitors (denosumab) affect inflammation and immunity? Osteoporos Int. Epub 2010 Jun 23

    Google Scholar 

  27. Rodriguez RD, Sutjandra L, Peterson MC, et al. Population pharmacokinetic meta-analysis of denosumab in healthy and cancer subjects and postmenopausal women with osteopenia or osteoporosis [abstract no. 278]. AAPS J 2009; 11Suppl. 1

    Google Scholar 

  28. McClung MR, Lewiecki EM, Cohen SB, et al. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 2006 Feb 23; 354(8): 821–31

    PubMed  Article  CAS  Google Scholar 

  29. Lewiecki EM, Miller PD, McClung MR, et al. Two-year treatment with denosumab (AMG 162) in a randomized phase 2 study of postmenopausal women with low BMD. J Bone Miner Res 2007 Dec; 22(12): 1832–41

    PubMed  Article  CAS  Google Scholar 

  30. Siris E, Silverman S, Viswanathan H, et al. Evaluation of health-related quality of life in postmenopausal women who participated in the FREEDOM trial [abstract no. A09001317]. 31st Annual Meeting of the American Society for Bone and Mineral Research; 2009 Sep 11–15; Denver (CO)

  31. Boonen S, McClung M, Minisola S, et al. Effect of denosumab on the incidence of hip, new vertebral, and non-vertebral fractures over 3 years among postmenopausal women with higher fracture risk: a subgroup analysis from the FREEDOM study [abstract no. A09001311]. 31st Annual Meeting of the American Society for Bone and Mineral Research; 2009 Sep 11–15; Denver (CO)

  32. Cummings S, McClung M, Bone H, et al. The effect of denosumab on risk of fractures in subgroups of women with osteoporosis [abstract no. A09003284]. 31st Annual Meeting of the American Society for Bone and Mineral Research; 2009 Sep 11–15; Denver (CO)

  33. Kendler DL, Bessette L, Hill CD, et al. Preference and satisfaction with a 6-month subcutaneous injection versus a weekly tablet for treatment of low bone mass. Osteoporos Int 2010; 21: 837–46

    PubMed  Article  CAS  Google Scholar 

  34. Adami S, Gilchrist N, Lyritis G, et al. Effect of denosumab on fracture healing in postmenopausal women with osteoporosis: results from the FREEDOM trial [abstract no. OP24]. 37th European Symposium on Calcified Tissues; 2010 Jun 26–30; Glasgow

  35. Hiligsmann M, Reginster JY. Potential cost-effectiveness of denosumab for the treatment of postmenopausal osteoporotic women. Bone 2010 Jul; 47(1): 34–40

    PubMed  Article  CAS  Google Scholar 

  36. Jönsson B, Ström O, Eisman JA, et al. Cost-effectiveness of denosumab for the treatment of postmenopausal osteoporosis. Osteoporos Int. Epub 2010 Oct 9

    Google Scholar 

  37. Strom O, Macarios D, Badamgarav E, et al. A UK denosumab cost-effectiveness model incorporating FRAX and adherence [abstract no. A09001963]. 31st Annual Meeting of the American Society for Bone and Mineral Research; 2009 Sep 11–15; Denver (CO)

  38. Lewiecki EM. Managing osteoporosis: challenges and strategies. Cleve Clin J Med 2009 Aug; 76(8): 457–66

    PubMed  Article  Google Scholar 

  39. Miller PD, Derman RJ. What is the best balance of benefits and risks among anti-resorptive therapies for postmenopausal osteoporosis? Osteoporos Int 2010 Nov; 21(11): 1793–802

    PubMed  Article  CAS  Google Scholar 

  40. Pazianas M, Cooper C, Ebetino FH, et al. Long-term treatment with bisphosphonates and their safety in postmenopausal osteoporosis. Ther Clin Risk Manag 2010; 6: 325–43

    PubMed  CAS  Google Scholar 

  41. Amgen. FDA approves Amgen’s Prolia™ (denosumab) for treatment of postmenopausal women with osteoporosis at high risk for fracture [media release]. 2010 Jun 1 [online]. Available from URL: http://www.amgen.com

  42. Kyrgidis A, Toulis KA. Denosumab-related osteonecrosis of the jaws. Osteoporos Int. Epub 2010 Mar 20

    Google Scholar 

  43. Warriner AH, Curtis JR. Adherence to osteoporosis treatments: room for improvement. Curr Opin Rheumatol 2009 Jul; 21(4): 356–62

    PubMed  Article  CAS  Google Scholar 

  44. Siris ES, Pasquale MK, Wang Y, et al. Estimating bisphosphonate use and fracture reduction among U.S. women age 45 and older, 2001–2008. J Bone Miner Res. Epub 2010 Jul 26

    Google Scholar 

  45. Kendler DL, McClung MR, Freemantle N, et al. Adherence, preference, and satisfaction of postmenopausal women taking denosumab or alendronate. Osteoporos Int. Epub 2010 Sep 9

    Google Scholar 

  46. Amgen. Extension study to evaluate the long term safety and efficacy of denosumab in the treatment of osteoporosis [ClinicalTrials.gov identifier NCT00523341]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://clinicaltrials.gov [Accessed 2010 Sep 2]

  47. Qaseem A, Snow V, Shekelle P, et al. Pharmacologic treatment of low bone density or osteoporosis to prevent fractures: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2008 Sep 16; 149(6): 404–15

    PubMed  Google Scholar 

  48. National Institute for Health and Clinical Excellence. Denosumab for the prevention of osteoporotic fractures in postmenopausal women: final appraisal determination [online]. Available from URL: http://www.nice.org.uk/nicemedia/live/12174/50755/50755.pdf [Accessed 2010 Sep 25]

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  1. Adis, a Wolters Kluwer Business, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, North Shore 0754, Auckland, New Zealand

    Marit D. Moen & Susan J. Keam

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  1. Marit D. Moen
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Correspondence to Marit D. Moen.

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Moen, M.D., Keam, S.J. Denosumab. Drugs Aging 28, 63–82 (2011). https://doi.org/10.2165/11203300-000000000-00000

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Keywords

  • Bone Mineral Density
  • Vertebral Fracture
  • Alendronate
  • Denosumab
  • Nonvertebral Fracture