Current Osteoporosis Reports

, Volume 9, Issue 1, pp 20–24

Androgen Deprivation and Bone

  • Jean-Baptiste Lattouf
  • Hicham Fadlallah
  • Fred Saad
Article

Abstract

Bone health in men with prostate cancer on androgen deprivation therapy (ADT) has gained increased attention in recent years. Therapies that are becoming available to prevent bone loss and associated complications are changing practice for this patient population. In addition to basic vitamin D and calcium supplementation, bisphosphonates may be an option to treat these patients, and denosumab, a receptor activator of nuclear factor-κB ligand inhibitor, has been proven to be effective in preventing bone loss through a randomized clinical trial. This review examines the importance of bone health in patients on ADT, with an overview of available treatment modalities and guidelines for managing these patients.

Keywords

Androgen deprivation Prostate cancer Bisphosphonates Denosumab 

References

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

  1. 1.
    Saad F, Clarke N, Colombel M. Natural history and treatment of bone complications in prostate cancer. Eur Urol 2006;49:429–40.CrossRefPubMedGoogle Scholar
  2. 2.
    Higano CS. Bone loss and the evolving role of bisphosphonate therapy in prostate cancer. Urol Oncol 2003;21:392–8.PubMedGoogle Scholar
  3. 3.
    Oefelein MG, Ricchiuti VS, Conrad PW, et al. Clinical predictors of androgen-independent prostate cancer and survival in the prostate-specific antigen era. Urology 2002;60:120–4.CrossRefPubMedGoogle Scholar
  4. 4.
    Shahinian VB, Kuo YF, Freeman JL, Goodwin JS. Risk of fracture after androgen deprivation for prostate cancer. N Engl J Med 2005;352:154–6.CrossRefPubMedGoogle Scholar
  5. 5.
    Melton LJ 3 rd, Atkinson EJ, Cooper C, O’Fallon WM, Riggs BL. Vertebral fractures predict subsequent fractures. Osteoporos Int 1999;10:214–21.CrossRefPubMedGoogle Scholar
  6. 6.
    Lau E, Ong K, Kurtz S, Schmier J, Edidin A. Mortality following the diagnosis of a vertebral compression fracture in the Medicare population. J Bone Joint Surg Am 2008;90:1479–86.CrossRefPubMedGoogle Scholar
  7. 7.
    Oefelein MG, Ricchiuti V, Conrad W, Resnick MI. Skeletal fractures negatively correlate with overall survival in men with prostate cancer. J Urol 2002;168:1005–7.CrossRefPubMedGoogle Scholar
  8. 8.
    Hatano T, Oishi Y, Furuta A, Iwamuro S, Tashiro K. Incidence of bone fracture in patients receiving luteinizing hormone releasing hormone agonists for prostate cancer. BJU Int 2000;86:449–52.CrossRefPubMedGoogle Scholar
  9. 9.
    Galvao DA, Spry NA, Taaffe Dr, et al. Changes in muscle, fat and bone mass after 36 weeks of maximal androgen blockade for prostate cancer. BJU Int 2008;102:44–7.CrossRefPubMedGoogle Scholar
  10. 10.
    Smith MR. Osteoporosis during androgen deprivation therapy for prostate cancer. Urology 2002;60(suppl 1):79–85.CrossRefPubMedGoogle Scholar
  11. 11.
    Smith MR, Fallon MA, Goode MJ. Cross-sectional study of bone turnover during bicalutamide monotherapy for prostate cancer. Urology 2003;61:127–31.CrossRefPubMedGoogle Scholar
  12. 12.
    Smith MR, McGovern FJ, Zietman AL, et al. Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer. N Engl J Med 2000;345:948–55.CrossRefGoogle Scholar
  13. 13.
    Smith MR, Eastham J, Gleason DM, Shasha D, Tchekmedyian S, Zinner N. Randomized controlled trial of zoledronic acid to prevent bone loss in men receiving androgen deprivation therapy for nonmetastatic prostate cancer. J Urol 2003;169:2008–12.CrossRefPubMedGoogle Scholar
  14. 14.
    Saad F, Gleason DM, Murray R, et al. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst 2002;94:1458–68.PubMedGoogle Scholar
  15. 15.
    Orwoll E, Ettinger M, Weiss S, et al. Alendronate for the treatment of osteoporosis in men. N Eng J Med 2000;343:604–10.CrossRefGoogle Scholar
  16. 16.
    Ettinger B, Pressman A, Schein J. Clinic visits and hospital admissions for care of acid-related upper gastrointestinal disorders in women using alendronate for osteoporosis. Am J Manag Care 1998;4:1377–82.PubMedGoogle Scholar
  17. 17.
    Diamond T, Campbell J, Bryant C, Lynch W. The effect of combined androgen blockade on bone turnover and bone mineral densities in men treated for prostate carcinoma: longitudinal evaluation and response to intermittent cyclic etidronate therapy. Cancer 1998;83:1561–6.CrossRefPubMedGoogle Scholar
  18. 18.
    Smith MR, McGovern FJ, Zietman AL, et al. Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer. N Eng J Med 2001;354:948–55.CrossRefGoogle Scholar
  19. 19.
    Small EJ, Smith MR, Seaman JJ, Petrone S, Kowalski MO. Combined analysis of two multicenter, randomized, placebo-controlled studies of pamidronate disodium for the palliation of bone pain in men with metastatic prostate cancer. J Clin Oncol 2003;21:4277–84.CrossRefPubMedGoogle Scholar
  20. 20.
    Reid IR, Brown JP, Burckhardt P, et al. Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Eng J Med 2002;346:653–61.CrossRefGoogle Scholar
  21. 21.
    Diamond TH, Winters J, Smith A, et al. The antiosteoporotic efficacy of intravenous pamidronate in men with prostate carcinoma receiving combined androgen blockade: a double blind, randomized, placebo-controlled crossover study. Cancer 2001;92:1444–50.CrossRefPubMedGoogle Scholar
  22. 22.
    Smith MR, McGovern FJ, Zietman AL, et al. Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer. N Eng J Med 2001;345:948–55.CrossRefGoogle Scholar
  23. 23.
    Lipton A, Small E, Saad F, et al. The new bisphosphonate, Zometa (zoledronic acid), decreases skeletal complications in both osteolytic and osteoblastic lesions: a comparison to pamidronate. Cancer Invest 2002;20(suppl 2):45–54.CrossRefPubMedGoogle Scholar
  24. 24.
    Smith MR, Eastham J, Gleason DM, Shasha D, Tchekmedyian S, Zinner N. Randomized controlled trial of zoledronic acid to prevent bone loss in men receiving androgen deprivation therapy for nonmetastatic prostate cancer. J Urol 2003;169:2008–12.CrossRefPubMedGoogle Scholar
  25. 25.
    Saad F, Gleason DM, Murray R, et al. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst 2004;96:879–82.CrossRefPubMedGoogle Scholar
  26. 26.
    Green JR, Müller K, Jaeggi KA. Preclinical pharmacology of CGP 42xx’446, a new, potent, heterocyclic bisphosphonate compound. J Bone Miner Res 1994;9:745–51.CrossRefPubMedGoogle Scholar
  27. 27.
    Saad F, Gleason DM, Murray R, et al. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst 2002;94:1458–68.PubMedGoogle Scholar
  28. 28.
    Ross RW, Small EJ. Osteoporosis in men treated with androgen deprivation therapy for prostate cancer. J Urol 2002;167:1952–6.CrossRefPubMedGoogle Scholar
  29. 29.
    Saad F, Schulman CC. Role of bisphosphonates in prostate cancer. Eur Urol 2004;45:26–34.CrossRefPubMedGoogle Scholar
  30. 30.
    Wong R, Wiffen PJ. Bisphosphonates for the relief of pain secondary to bone metastases. Cochrane Database Syst Rev 2002;:CD002068.Google Scholar
  31. 31.
    Khosla S, Burr D, Cauley J, et al. Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 2007;22:1479–91.CrossRefPubMedGoogle Scholar
  32. 32.
    Kyrgidis A, Toulis KA. Denosumab-related osteonecrosis of the jaws. Osteoporos Int 2010;:. [Epub ahead of print]Google Scholar
  33. 33.
    Conte P, Guarneri V. Safety of intravenous and oral bisphosphonates and compliance with dosing regimens. Oncologist 2004;9(suppl 4):28–37.CrossRefPubMedGoogle Scholar
  34. 34.
    Aapro M, Abrahamsson PA, Body JJ, et al. Guidance on the use of bisphosphonates in solid tumours: recommendations of an international expert panel. Ann Oncol 2008;19:420–32.CrossRefPubMedGoogle Scholar
  35. 35.
    Polascik TJ. Bone health in prostate cancer patients receiving androgen-deprivation therapy: the role of bisphosphonates. Prostate Cancer Prostatic Dis 2008;11:13–19.CrossRefPubMedGoogle Scholar
  36. 36.
    Boyle WJ, Simone WS, Lacey DL. Osteoclast differentiation and activation. Nature 2003;423:337–42.CrossRefPubMedGoogle Scholar
  37. 37.
    Schwarz EM, Ritchlin CT. Clinical development of anti-RANKL therapy. Arthritis Res Ther 2007;9(suppl 1):S7.CrossRefPubMedGoogle Scholar
  38. 38.
    McClung MR, Lewiecki EM, Cohen SB, et al. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 2006;354:821–31.CrossRefPubMedGoogle Scholar
  39. 39.
    Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009;361:756–65.CrossRefPubMedGoogle Scholar
  40. 40.
    Ellis GK, Bone HG, Chlebowski R, et al. Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. J Clin Oncol 2008;26:4875–82.CrossRefPubMedGoogle Scholar
  41. 41.
    •• Smith MR, Egerdie B, Hernàndez Toriz N, et al. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med 2009;361:745–55. This is a pivotal trial reporting for the first time an active agent that prevents BMD loss and reduction in vertebral fractures in patients with nonmetastatic prostate cancer on ADT.CrossRefPubMedGoogle Scholar
  42. 42.
    Saad F, Higano CS, Sartor O, et al. The role of bisphosphonates in the treatment of prostate cancer: recommendations from an expert panel. Clinical Genitourin Cancer 2006;4:257–62.CrossRefGoogle Scholar
  43. 43.
    Oncken C, Prestwood K, Kleppinger A, Wang Y, Cooney J, Raisz L. Impact of smoking cessation on bone mineral density in postmenopausal women. J Womens Health (Larchmt) 2006;15:1141–50.CrossRefGoogle Scholar
  44. 44.
    Tucker KL, Morita K, Qiao N, Hannan MT, Cupples LA, Kiel DP. Colas, but not other carbonated beverages, are associated with low bone mineral density in older women: the Framingham Osteoporosis Study. Am J Clin Nutr 2006;84:936–42.PubMedGoogle Scholar
  45. 45.
    Prentice A. Diet, nutrition, and the prevention of osteoporosis. Public Health Nutr 2004;7:227–43.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Jean-Baptiste Lattouf
    • 1
  • Hicham Fadlallah
    • 1
  • Fred Saad
    • 1
  1. 1.Departments of Surgery and UrologyCentre Hospitalier de l’Université de MontréalMontrealCanada

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