Osteoporosis International

, Volume 16, Issue 6, pp 707–711 | Cite as

Fracture risk in patients with prostate cancer on androgen deprivation therapy

  • Ana M. López
  • María A. Pena
  • Rafael Hernández
  • Fernando Val
  • Bernardo Martín
  • José A. Riancho
Original Article

Abstract

Although a decrease in bone mass is a well-known side effect of hormone therapy for prostate carcinoma, its clinical significance is unclear, as there is only scanty information about the incidence of fractures. Therefore, the aim of this study was to determine the risk of non-metastatic fractures in patients with prostate cancer undergoing androgen deprivation therapy. We performed a retrospective cohort study that comprised 288 patients with cancer who were subjected to androgen deprivation therapy (ADT). All were given LHRH agonists, and most of them also received peripheral androgen receptor blockers. The results were compared with a control group of 300 men that were not receiving ADT. The incidence rates of peripheral and vertebral fractures in the group of men on ADT were 1.9 and 0.8 per 100 patient-years, respectively. Incidence rates in the control group were 0.5 and 0.2, respectively. In the whole study group, 35 patients had at least one fracture during follow-up (25 on ADT, ten controls). Thus, the number of patients with at least one fracture was significantly higher in the group on ADT (P=0.001 by the log-rank test). The unadjusted risk ratio was 4.2 (CI 2.0–8.9). A similar value (risk ratio 3.6; CI 1.6–7.7, P=0.001) was found after it was adjusted for other factors, such as age or prior fractures. Therefore, ADT is associated with a fourfold increase in the incidence rate of both peripheral and vertebral fractures. Although the absolute incidence remains relatively small, preventive measures should be considered for high-risk patients.

Keywords

Androgens Anti-androgens Fractures LHRH agonists Osteoporosis Prostate cancer 

References

  1. 1.
    Bono AV (2004) Overview of current treatment strategies in prostate cancer. Eur Urol Suppl 3:2–7Google Scholar
  2. 2.
    Melton LJ III, Alothman KI, Khosla S, Achenbach SJ, Oberg AL, Zincke H (2003) Fracture risk following bilateral orchiectomy. J Urol 169:1747–1750PubMedGoogle Scholar
  3. 3.
    Ross RW, Small EJ (2002) Osteoporosis in men treated with androgen deprivation therapy for prostate cancer. J Urol 167:1952–1956PubMedGoogle Scholar
  4. 4.
    Goldray D, Weisman Y, Jaccard N, Merdler C, Chen J, Matzkin H (1993) Decreased bone density in elderly men treated with the gonadotropin-releasing hormone agonist decapeptyl (d-Trp-GnRH). J Clin Endocrinol Metab 76:288–290Google Scholar
  5. 5.
    Berruti A, Dogliotti L, Terrone C, Cerutti S, Isaia G, Tarabuzzi R, Reimondo G, Mari M, Ardissone P, De Luca S, Fasolis G, Fontana D, Rossetti SR, Angeli A (2002) Changes in bone mineral density, lean body mass and fat content as measured by dual energy X-ray absorptiometry in patients with prostate cancer without apparent bone metastases given androgen deprivation therapy. J Urol 167:2361–2367PubMedGoogle Scholar
  6. 6.
    Mittan D, Lee S, Miller E, Perez RC, Basler JW, Bruder JM (2002) Bone loss following hypogonadism in men with prostate cancer treated with GnRH analogs. J Clin Endocrinol Metab 87:3656–3661Google Scholar
  7. 7.
    Diamond T, Campbell J, Bryant C, Lynch WB (1998) 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 83:1561–1566PubMedGoogle Scholar
  8. 8.
    Oefelein MG, Ricchuiti V, Conrad W, Seftel A, Bodner D, Goldman H, Resnick M (2001) Skeletal fracture associated with androgen suppression induced osteoporosis: the clinical incidence and risk factors for patients with prostate cancer. J Urol 166:1724–1728PubMedGoogle Scholar
  9. 9.
    Vandevyver C, Vandenput L, Boonen S, Lindberg MK, Bouillon R, Ohlsson C (2004) Androgens and bone. Endocr Rev 25:389–425CrossRefPubMedGoogle Scholar
  10. 10.
    Falahati-Nini A, Riggs BL, Atkinson EJ, O’Fallon M, Estell R, Khosla S (2000) Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men. J Clin Invest 106:1533–1560Google Scholar
  11. 11.
    Slemenda CW, Longcope C, Zhou L, Hui SH, Peacock M, Johnston CC (1997) Sex steroids and bone mass in older men. Positive associations with serum estrogens and negative associations with androgens. J Clin Invest 100:1755–1759PubMedGoogle Scholar
  12. 12.
    Gennari L, Merlotti D, Martini G, Gonnelli S, Franci B, Campagna S, Lucani B, Dal Canto N, Valenti R, Gennari C, Nuti R (2003) Longitudinal association between sex hormone levels, bone loss, and bone turnover in elderly men. J Clin Endocrinol Metab 88:5333.Google Scholar
  13. 13.
    Zarrabeitia A, Zarrabeitia MT, Valero C, González-Macías J, Riancho JA (2004) Age-related influence of common aromatase gene polymorphisms on bone mass of healthy men. Bone 35:243–248PubMedGoogle Scholar
  14. 14.
    McGrath SA, Diamond T (1995) Osteoporosis as a complication of orchiectomy in 2 elderly men with prostatic cancer. J Urol 154:535–536PubMedGoogle Scholar
  15. 15.
    Collinson MP, Tyrrel CJ, Hutton C (1994) Osteoporosis occurring in two patients receiving LHRH analogs for carcinoma of the prostate. Calcif Tissue Int 54:327–328PubMedGoogle Scholar
  16. 16.
    Dhillon T, Waxman J (2003) Osteoporosis and prostate cancer. Br J Cancer 89:779–780PubMedGoogle Scholar
  17. 17.
    Diamond TH, Higano CS, Smith MR, Guise TA, Singer FR (2004) Osteoporosis in men with prostate carcinoma receiving androgen-deprivation therapy: recommendations for diagnosis and therapies. Cancer 100:892–899PubMedGoogle Scholar
  18. 18.
    Kiratli BJ, Srinivas S, Perkash I, Terris MK (2001) Progressive decrease in bone density over 10 years of androgen deprivation therapy in patients with prostate cancer. Urology 57:127–132PubMedGoogle Scholar
  19. 19.
    Stoch SA, Parker RA, Chen L, Bubley G, Ko YJ, Vincelette A, Greenspan SL (2001) Bone loss in men with prostate cancer treated with gonadotropin-releasing hormone agonists. J Clin Endocrinol Metab 86:2787–2791Google Scholar
  20. 20.
    Townsend MF, Sanders WH, Northway RO, Graham SD Jr (1997) Bone fractures associated with luteinizing hormone-releasing hormone agonists used in the treatment of prostate carcinoma. Cancer 79:545–550PubMedGoogle Scholar
  21. 21.
    Hatano T, Oishi Y, Furuta A, Iwamuro S, Tashiro K (2000) Incidence of bone fracture in patients receiving luteinizing hormone-releasing hormone agonists for prostate cancer. BJU Int 86:449–452PubMedGoogle Scholar
  22. 22.
    Ismail AA, Pye SR, Cockerill WC, Lunt M, Silman AJ, Reeve J, et al (2002) Incidence of limb fracture across Europe: results from the European prospective osteoporosis study (EPOS). Osteoporos Int 13:565–571CrossRefPubMedGoogle Scholar
  23. 23.
    Orwoll ES (1998) Osteoporosis in men. Endocr Metab Clin N Am 27:349–367Google Scholar
  24. 24.
    Sanders KM, Seeman E, Ugoni AM, Pasco JA, Martin TJ, Skoric B, Nicholson GC, Kotowicz MA (1999) Age- and gender-specific rate of fractures in Australia: a population-based study. Osteoporos Int 10:240–247CrossRefPubMedGoogle Scholar
  25. 25.
    Smith MR, McGovern FJ, Fallon MA, Schoenfeld D, Kantoff PW, Finkelstein JS (2001) Low bone mineral density in hormone-naive men with prostate carcinoma. Cancer 91:2238–2245PubMedGoogle Scholar
  26. 26.
    Wei JT, Gross M, Jaffe CA, Gravlin K, Lahaie M, Faerber GJ, Cooney KA (1999) Androgen deprivation therapy for prostate cancer results in significant loss of bone density. Urology 54:607–611PubMedGoogle Scholar
  27. 27.
    Smith MR, Eastham J, Gleason DM, Shasha D, Tchekmedyian S, Zinner N (2003) Randomized controlled trial of zoledronic acid to prevent bone loss in men receiving androgen deprivation therapy for nonmetastatic prostate cancer. J Urol 169:2008–2012PubMedGoogle Scholar
  28. 28.
    Smith MR, McGovern FJ, Zietman AL, Fallon MA, Hayden DL, Schoenfeld DA, Kantoff PW, Finkelstein JS (2001) Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer. N Engl J Med 345:948–955CrossRefPubMedGoogle Scholar
  29. 29.
    Diamond TH, Winters J, Smith A, De Souza P, Kersley JH, Lynch WJ, Bryant C (2001) The antiosteoporotic efficacy of intravenous pamidronate in men with prostate carcinoma receiving combined androgen blockade: a double blind, randomized, placebo-controlled crossover study. Cancer 92:1444–1450PubMedGoogle Scholar
  30. 30.
    Leder BZ, Smith MR, Fallon MA, Lee ML, Finkelstein JS (2001) Effects of gonadal steroid suppression on skeletal sensitivity to parathyroid hormone in men. J Clin Endocrinol Metab 86:511–516CrossRefPubMedGoogle Scholar
  31. 31.
    Smith MR, Fallon MA, Lee H, Finkelstein JS (2004) Raloxifene to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer: a randomized controlled trial. J Clin Endocrinol Metab 89:3841–3846Google Scholar
  32. 32.
    Taxel P, Kennedy DG, Fall PM, Willard AK, Clive JM, Raisz LG (2001) The effect of aromatase inhibition on sex steroids, gonadotropins, and markers of bone turnover in older men. J Clin Endocrinol Metab 86:2869–2874CrossRefPubMedGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2005

Authors and Affiliations

  • Ana M. López
    • 1
  • María A. Pena
    • 2
  • Rafael Hernández
    • 3
  • Fernando Val
    • 4
  • Bernardo Martín
    • 3
  • José A. Riancho
    • 2
  1. 1.Department of Oncology, Hospital U.M. ValdecillaSantanderSpain
  2. 2.Department of Internal Medicine, Hospital U.M. ValdecillaUniversity of CantabriaSantanderSpain
  3. 3.Department of Urology, Hospital U.M. ValdecillaUniversity of CantabriaSantanderSpain
  4. 4.Department of Pathology, Hospital U.M. ValdecillaUniversity of CantabriaSantanderSpain

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