Current Rheumatology Reports

, Volume 11, Issue 3, pp 196–201 | Cite as

Denosumab for joints and bones

Article

Abstract

Denosumab is an investigational, fully human monoclonal antibody with a high affinity and specificity for receptor activator of nuclear factor κ B ligand (RANKL), a cytokine member of the tumor necrosis factor family. RANKL, an essential mediator of osteoclast formation, function, and survival, plays a major role in the pathogenesis of postmenopausal osteoporosis, structural damage in rheumatoid arthritis, and bone loss associated with other skeletal disorders. Denosumab suppresses bone turnover by inhibiting the action of RANKL on osteoclasts. Denosumab reduces bone turnover and increases bone mineral density in postmenopausal women with low bone mineral density, reduces fracture risk in women with postmenopausal osteoporosis, and inhibits structural damage in patients with rheumatoid arthritis when added to ongoing methotrexate treatment. It is generally well tolerated, with a good safety profile. Adverse and serious adverse events, including infections and malignancy, are similar in patients treated with denosumab or placebo.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Klibanski A, Adams-Campbell L, Bassford T, et al.: Osteoporosis prevention, diagnosis, and therapy. JAMA 2001, 285:785–795.CrossRefGoogle Scholar
  2. 2.
    US Department of Health and Human Services: Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: US Department of Health and Human Services, Office of the Surgeon General; 2004.Google Scholar
  3. 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, 22:465–475.PubMedCrossRefGoogle Scholar
  4. 4.
    International Osteoporosis Foundation: IOF Osteoporosis Teaching Slide Kit. Available at http://www.osteofound.org/health_professionals/teaching_resources/slide_kit.html. Accessed March 2006.
  5. 5.
    Dennison E, Cooper C: Epidemiology of osteoporotic fractures. Horm Res 2000, 54(Suppl 1):58–63.PubMedGoogle Scholar
  6. 6.
    Cooper C: The crippling consequences of fractures and their impact on quality of life. Am J Med 1997, 103(2A):12S–19S.PubMedCrossRefGoogle Scholar
  7. 7.
    Walsh NC, Crotti TN, Goldring SR, Gravallese EM: Rheumatic diseases: the effects of inflammation on bone. Immunol Rev 2005, 208:228–251.PubMedCrossRefGoogle Scholar
  8. 8.
    Kavanaugh A: Economic consequences of established rheumatoid arthritis and its treatment. Best Pract Res Clin Rheumatol 2007, 21:929–942.PubMedCrossRefGoogle Scholar
  9. 9.
    Bekker PJ, Holloway DL, Rasmussen AS, et al.: A singledose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res 2004, 19:1059–1066.PubMedCrossRefGoogle Scholar
  10. 10.
    Collin-Osdoby P: Regulation of vascular calcification by osteoclast regulatory factors RANKL and osteoprotegerin. Circ Res 2004, 95:1046–1057.PubMedCrossRefGoogle Scholar
  11. 11.
    Simonet WS, Lacey DL, Dunstan CR, et al.: Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 1997, 89:309–319.PubMedCrossRefGoogle Scholar
  12. 12.
    Hofbauer LC, Schoppet M: Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular diseases. JAMA 2004, 292:490–495.PubMedCrossRefGoogle Scholar
  13. 13.
    Bekker PJ, Holloway D, Nakanishi A, et al.: The effect of a single dose of osteoprotegerin in postmenopausal women. J Bone Miner Res 2001, 16:348–360.PubMedCrossRefGoogle Scholar
  14. 14.
    Lobo ED, Hansen RJ, Balthasar JP: Antibody pharmacokinetics and pharmacodynamics. J Pharm Sci 2004, 93:2645–2668.PubMedCrossRefGoogle Scholar
  15. 15.
    Tang L, Persky AM, Hochhaus G, Meibohm B: Pharmacokinetic aspects of biotechnology products. J Pharm Sci 2004, 93:2184–2204.PubMedCrossRefGoogle Scholar
  16. 16.
    Peterson MC, Stouch BJ, Martin SW, et al.: The pharmacokinetics of denosumab (AMG 162) following various multiple subcutaneous dosing regimens in postmenopausal women with low bone mass. J Bone Miner Res 2005, 20(Suppl 1):S293.Google Scholar
  17. 17.
    McClung MR, Lewiecki EM, Cohen SB, et al.: Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 2006, 354:821–831.PubMedCrossRefGoogle Scholar
  18. 18.
    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 bone mineral density. J Bone Miner Res 2007, 22:1832–1841.PubMedCrossRefGoogle Scholar
  19. 19.
    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, 43:222–229.PubMedCrossRefGoogle Scholar
  20. 20.
    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, 93:2149–2157.PubMedCrossRefGoogle Scholar
  21. 21.
    Brown JP, Prince RL, Deal C, et al.: Comparison of the effect of denosumab and alendronate on bone mineral density and biochemical markers of bone turnover in postmenopausal women with low bone mass: a randomized, blinded, phase 3 trial. J Bone Miner Res 2009, 24:153–161.PubMedCrossRefGoogle Scholar
  22. 22.
    Kendler DL, Benhamou CL, Brown JP, et al.: Effects of denosumab vs alendronate on bone mineral density (BMD), bone turnover markers (BTM), and safety in women previously treated with alendronate. J Bone Miner Res 2008, S473.Google Scholar
  23. 23.
    Cummings SR, McClung MR, Christiansen C, et al.: A phase III study of the effects of denosumab on vertebral, nonvertebral, and hip fracture in women with osteoporosis: results from the FREEDOM trial. J Bone Miner Res 2008, 23(Suppl 1):S80.Google Scholar
  24. 24.
    Amgen Inc: Form 8-K. Available at http://investors.amgen.com/phoenix.zhtml?c=61656&p=irol-sec. Accessed September 2008.
  25. 25.
    Cohen SB, Dore RK, Lane NE, et al.: Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. Arthritis Rheum 2008, 58:1299–1309.PubMedCrossRefGoogle Scholar
  26. 26.
    Arnett FC, Edworthy SM, Bloch DA, et al.: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988, 31:315–324.PubMedCrossRefGoogle Scholar
  27. 27.
    McQueen F, Lassere M, Edmonds J, et al.: OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Studies. Summary of OMERACT 6 MR Imaging Module. J Rheumatol 2003, 30:1387–1392.PubMedGoogle Scholar
  28. 28.
    van der Heijde D: How to read radiographs according to the Sharp/van der Heijde method. J Rheumatol 2000, 27:261–263.PubMedGoogle Scholar
  29. 29.
    Cohen SB, Lewiecki EM, Liu Y, et al.: Phase 2 study of denosumab (AMG 162) in postmenopausal women: subanalyses and supplemental safety. J Bone Miner Res 2005, 20(Suppl 1):S295.Google Scholar

Copyright information

© Current Medicine Group, LLC 2009

Authors and Affiliations

  1. 1.New Mexico Clinical Research & Osteoporosis CenterAlbuquerqueUSA

Personalised recommendations