Skip to main content

Complications of ADT for Prostate Cancer: Osteoporosis and the Risk of Fracture

  • Chapter
  • First Online:
  • 590 Accesses

Abstract

Patients with advanced disease usually receive hormonal therapy, such as androgen deprivation therapy (ADT). Although ADT is initially very effective for prostate cancer, long-term ADT is known to be associated with various side effects. Among them ADT is associated with the deterioration of bone health, including an increased risk of fracture from osteoporosis and the development of bone metastasis. For patients with conditions associated with fragility, such as osteoporosis in patients treated with ADT, it is important to estimate the risk of fracture. In order to identify the patients who require bone-supportive treatment for osteoporosis, the bone mineral density is assessed by dual-energy X-ray absorptiometry. The Fracture Risk Assessment Tool (FRAX) has been developed to evaluate the risk of fracture, and likely improves the assessment of the risk of fracture through the inclusion of patient characteristics. The maintenance of bone health is very important for achieving long survival because skeletal fractures are associated with shortened survival. Clinicians must pay attention to bone health and provide specific management for osteoporosis in prostate cancer patients.

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

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover 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

Learn about institutional subscriptions

References

  1. Bolam KA, Galvao DA, Spry N, Newton RU, Taaffe DR. AST-induced bone loss in men with prostate cancer: exercise as a potential countermeasure. Prostate Cancer Prostatic Dis. 2012;15(4):329–38.

    Article  CAS  PubMed  Google Scholar 

  2. Center JR, Nguyen TV, Schneider D, Sambrook PN, Eisman JA. Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet. 1999;353(9156):878–82.

    Article  CAS  PubMed  Google Scholar 

  3. Oefelein MG, Ricchiuti VS, Conrad PW, Goldman H, Bodner D, Resnick MI, Seftel A. Clinical predictors of androgen-independent prostate cancer and survival in the prostate-specific antigen era. Urology. 2002;60(1):120–4.

    Article  PubMed  Google Scholar 

  4. Egerdie B, Saad F. Bone health in the prostate cancer patient receiving androgen deprivation therapy: a review of present and future management options. Can Urol Assoc J. 2010;4(2):129–35.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. 2003;423(6937):337–42.

    Article  CAS  PubMed  Google Scholar 

  6. Hofbauer LC, Schoppet M. Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular diseases. JAMA. 2004;292(4):490–5.

    Article  CAS  PubMed  Google Scholar 

  7. Higano CS. Androgen-deprivation-therapy-induced fractures in men with nonmetastatic prostate cancer: what do we really know? Nat Clin Pract Urol. 2008;5(1):24–34.

    Article  PubMed  Google Scholar 

  8. Perez EA, Weilbaecher K. Aromatase inhibitors and bone loss. Oncology (Williston Park). 2006;20(9):1029–39; discussion 1039–40, 1042, 1048

    Google Scholar 

  9. Alibhai SM, Duong-Hua M, Cheung AM, Sutradhar R, Warde P, Fleshner NE, Paszat L. Fracture types and risk factors in men with prostate cancer on androgen deprivation therapy: a matched cohort study of 19,079 men. J Urol. 2010;184(3):918–23.

    Article  PubMed  Google Scholar 

  10. Morote J, Morin JP, Orsola A, Abascal JM, Salvador C, Trilla E, Raventos CX, Cecchini L, Encabo G, Reventos J. Prevalence of osteoporosis during long-term androgen deprivation therapy in patients with prostate cancer. Urology. 2007;69(3):500–4.

    Article  PubMed  Google Scholar 

  11. Kiratli BJ, Srinivas S, Perkash I, Terris MK. Progressive decrease in bone density over 10 years of androgen deprivation therapy in patients with prostate cancer. Urology. 2001;57(1):127–32.

    Article  CAS  PubMed  Google Scholar 

  12. Izumi K, Mizokami A, Sugimoto K, Narimoto K, Miwa S, Maeda Y, Kadono Y, Takashima M, Koh E, Namiki M. Risedronate recovers bone loss in patients with prostate cancer undergoing androgen-deprivation therapy. Urology. 2009;73(6):1342–6.

    Article  PubMed  Google Scholar 

  13. Shahinian VB, Kuo YF, Freeman JL, Goodwin JS. Risk of fracture after androgen deprivation for prostate cancer. N Engl J Med. 2005;352(2):154–64.

    Article  CAS  PubMed  Google Scholar 

  14. Seeman E, Bianchi G, Khosla S, Kanis JA, Orwoll E. Bone fragility in men—where are we? Osteoporos Int. 2006;17(11):1577–83.

    Article  CAS  PubMed  Google Scholar 

  15. Kanis JA, Johnell O, Oden A, Johansson H, McCloskey E. FRAX and the assessment of fracture probability in men and women from the UK. Osteoporos Int. 2008;19(4):385–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Dhanapal V, Reeves DJ. Bone health management in prostate cancer patients receiving androgen deprivation therapy. J Oncol Pharm Pract. 2012;18(1):84–90.

    Article  PubMed  Google Scholar 

  17. Adler RA, Hastings FW, Petkov VI. Treatment thresholds for osteoporosis in men on androgen deprivation therapy: T-score versus FRAX. Osteoporos Int. 2010;21(4):647–53.

    Article  CAS  PubMed  Google Scholar 

  18. James H 3rd, Aleksic I, Bienz MN, Pieczonka C, Iannotta P, Albala D, Mariados N, Mouraviev V, Saad F. Comparison of fracture risk assessment tool score to bone mineral density for estimating fracture risk in patients with advanced prostate cancer on androgen deprivation therapy. Urology. 2014;84(1):164–8.

    Article  PubMed  Google Scholar 

  19. Kawahara T, Fusayasu S, Izumi K, Yokomizo Y, Ito H, Ito Y, Kurita K, Furuya K, Hasumi H, Hayashi N, et al. Bone management in Japanese patients with prostate cancer: hormonal therapy leads to an increase in the FRAX score. BMC Urol. 2016;16(1):32.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Ellis GK, Bone HG, Chlebowski R, Paul D, Spadafora S, Smith J, Fan M, Jun S. Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. J Clin Oncol. 2008;26(30):4875–82.

    Article  CAS  PubMed  Google Scholar 

  21. McClung MR, Lewiecki EM, Cohen SB, Bolognese MA, Woodson GC, Moffett AH, Peacock M, Miller PD, Lederman SN, Chesnut CH, et al. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med. 2006;354(8):821–31.

    Article  CAS  PubMed  Google Scholar 

  22. Miller PD, Bolognese MA, Lewiecki EM, McClung MR, Ding B, Austin M, Liu Y, San Martin J, AMG Bone Loss Study Group. 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(2):222–9.

    Article  CAS  PubMed  Google Scholar 

  23. Smith MR, Egerdie B, Hernandez Toriz N, Feldman R, Tammela TL, Saad F, Heracek J, Szwedowski M, Ke C, Kupic A, et al. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med. 2009;361(8):745–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Boonen S, Reginster JY, Kaufman JM, Lippuner K, Zanchetta J, Langdahl B, Rizzoli R, Lipschitz S, Dimai HP, Witvrouw R, et al. Fracture risk and zoledronic acid therapy in men with osteoporosis. N Engl J Med. 2012;367(18):1714–23.

    Article  CAS  PubMed  Google Scholar 

  25. Reid DM, Devogelaer JP, Saag K, Roux C, Lau CS, Reginster JY, Papanastasiou P, Ferreira A, Hartl F, Fashola T, et al. Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomised controlled trial. Lancet. 2009;373(9671):1253–63.

    Article  CAS  PubMed  Google Scholar 

  26. Suzuki Y, Nawata H, Soen S, Fujiwara S, Nakayama H, Tanaka I, Ozono K, Sagawa A, Takayanagi R, Tanaka H, et al. Guidelines on the management and treatment of glucocorticoid-induced osteoporosis of the Japanese Society for Bone and Mineral Research: 2014 update. J Bone Miner Metab. 2014;32(4):337–50.

    Article  PubMed  Google Scholar 

  27. Smith MR, Kabbinavar F, Saad F, Hussain A, Gittelman MC, Bilhartz DL, Wynne C, Murray R, Zinner NR, Schulman C, et al. Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer. J Clin Oncol. 2005;23(13):2918–25.

    Article  PubMed  Google Scholar 

  28. Smith MR, Saad F, Coleman R, Shore N, Fizazi K, Tombal B, Miller K, Sieber P, Karsh L, Damiao R, et al. Denosumab and bone-metastasis-free survival in men with castration-resistant prostate cancer: results of a phase 3, randomised, placebo-controlled trial. Lancet. 2012;379(9810):39–46.

    Article  CAS  PubMed  Google Scholar 

  29. Smith MR, Saad F, Oudard S, Shore N, Fizazi K, Sieber P, Tombal B, Damiao R, Marx G, Miller K, et al. Denosumab and bone metastasis-free survival in men with nonmetastatic castration-resistant prostate cancer: exploratory analyses by baseline prostate-specific antigen doubling time. J Clin Oncol. 2013;31(30):3800–6.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Parker C, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, Fossa SD, Chodacki A, Wiechno P, Logue J, Seke M, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013;369(3):213–23.

    Article  CAS  PubMed  Google Scholar 

  31. Saad F, Carles J, Gillessen S, Heidenreich A, Heinrich D, Gratt J, Levy J, Miller K, Nilsson S, Petrenciuc O, et al. Radium-223 and concomitant therapies in patients with metastatic castration-resistant prostate cancer: an international, early access, open-label, single-arm phase 3b trial. Lancet Oncol. 2016;17(9):1306–16.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hiroji Uemura M.D., Ph.D .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Uemura, H. (2018). Complications of ADT for Prostate Cancer: Osteoporosis and the Risk of Fracture. In: Arai, Y., Ogawa, O. (eds) Hormone Therapy and Castration Resistance of Prostate Cancer. Springer, Singapore. https://doi.org/10.1007/978-981-10-7013-6_16

Download citation

  • DOI: https://doi.org/10.1007/978-981-10-7013-6_16

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-10-7012-9

  • Online ISBN: 978-981-10-7013-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics