Skip to main content

Advertisement

SpringerLink
Log in

The role of bisphosphonates in the management of metastatic prostate cancer

  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

Most men with advanced prostate cancer have primarily skeletal metastases, which are responsible for most of the morbidity and mortality of prostate cancer. Although bone lesions are osteoblastic in radiographic appearance, recent evidence has demonstrated that anti-osteoclast therapy with bisphosphonates reduces skeletal-related complications in hormone-refractory prostate cancer. This observation may be explained by the demonstration that osteoclast activity is greatly upregulated even in osteoblastic metastases. Furthermore, androgen deprivation therapy, the mainstay of treatment for advanced prostate cancer, leads to increased bone resorption and reduces bone mineral density. These effects can be ameliorated, and potentially completely prevented, by coadministration of bisphosphonates. These findings may point to a role for bisphosphonates in men with prostate cancer even prior to the development of skeletal metastases. Determination of whether such early therapy ultimately results in delayed time to skeletal progression or in improved survival will require large randomized studies.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Rogers MJ, Watts DJ, Russell RG: Overview of bisphosphonates. Cancer 1997, 80(Suppl):1652–1660.

    Article  PubMed  CAS  Google Scholar 

  2. WattsNB. Treatment of osteoporosis with bisphosphonates. Rheum Dis Clin North Am 2001, 27:197–214.

    Article  PubMed  CAS  Google Scholar 

  3. Berenson JR, Lichtenstein A, Porter L, et al.: Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. Myeloma Aredia Study Group. N Engl J Med 1996, 334:488–493. This randomized, controlled study was the first convincing demonstration that bone-targeted therapy could prevent skeletal complications caused by malignancy.

    Article  PubMed  CAS  Google Scholar 

  4. Hortobagyi GN, Theriault RL, Porter L, et al.: Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone metastases. Protocol 19 Aredia Breast Cancer Study Group. N Engl J Med 1996, 335:1785–1791. This large randomized, placebo-controlled study in 382 women receiving chemotherapy for metastatic breast cancer showed that the addition of pamidronate leads to significant reduction in skeletal complications.

    Article  PubMed  CAS  Google Scholar 

  5. PatersonAH: Adjuvant bisphosphonate therapy: the future. Semin Oncol 2001, 28(Suppl 11):81–85.

    Article  PubMed  CAS  Google Scholar 

  6. Diel IJ, Solomayer EF, Bastert G: Bisphosphonates and the prevention of metastasis: first evidences from preclinical and clinical studies. Cancer 2000, 88(Suppl):3080–3088.

    Article  PubMed  CAS  Google Scholar 

  7. Clarke NW, McClure J, George NJ: Morphometric evidence for bone resorption and replacement in prostate cancer. Br J Urol 1991, 68:74–80.

    PubMed  CAS  Google Scholar 

  8. Clarke NW, McClure J, George NJ: Osteoblast function and osteomalacia in metastatic prostate cancer. Eur Urol 1993, 24:286–290.

    PubMed  CAS  Google Scholar 

  9. Percival RC, Urwin GH, Harris S, et al.: Biochemical and histological evidence that carcinoma of the prostate is associated with increased bone resorption. Eur J Surg Oncol 1987, 13:41–49.

    PubMed  CAS  Google Scholar 

  10. Garnero P, Buchs N, Zekri J, et al.: Markers of bone turnover for the management of patients with bone metastases from prostate cancer. Br J Cancer 2000, 82:858–864.

    Article  PubMed  CAS  Google Scholar 

  11. Berruti A, Dogliotti L, Bitossi R, et al.: Incidence of skeletal complications in patients with bone metastatic prostate cancer and hormone refractory disease: predictive role of bone resorption and formation markers evaluated at baseline. J Urol 2000, 164:1248–1253.

    Article  PubMed  CAS  Google Scholar 

  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 2001, 345:948–955. This small randomized phase III study proved that ADT causes significant bone resorption and loss of BMD in men with prostate cancer, and that pamidronate significantly reduces bone loss in this population.

    Article  PubMed  CAS  Google Scholar 

  13. Adami S, Salvagno G, Guarrera G, et al.: Dichloromethylene-diphosphonate in patients with prostatic carcinoma metastatic to the skeleton. J Urol 1985, 134:1152–1154.

    PubMed  CAS  Google Scholar 

  14. Carey PO, Lippert MC: Treatment of painful prostatic bone metastases with oral etidronate disodium. Urology 1988, 32:403–407.

    Article  PubMed  CAS  Google Scholar 

  15. Clarke NW, McClure J, George NJ: Disodium pamidronate identifies differential osteoclastic bone resorption in metastatic prostate cancer. Br J Urol 1992, 69:64–70.

    Article  PubMed  CAS  Google Scholar 

  16. Kylmala T, Tammela TL, Lindholm TS, Seppanen J: The effect of combined intravenous and oral clodronate treatment on bone pain in patients with metastatic prostate cancer. Ann Chir Gynaecol 1994, 83:316–319.

    PubMed  CAS  Google Scholar 

  17. Clarke NW, Holbrook IB, McClure J, George NJ: Osteoclast inhibition by pamidronate in metastatic prostate cancer: a preliminary study. Br J Cancer 1991, 63:420–423.

    PubMed  CAS  Google Scholar 

  18. SmithJA Jr: Palliation of painful bone metastases from prostate cancer using sodium etidronate: results of a randomized, prospective, double-blind, placebo-controlled study. J Urol 1989, 141:85–87.

    PubMed  Google Scholar 

  19. Adami S, Mian M: Clodronate therapy of metastatic bone disease in patients with prostatic carcinoma. Recent Results Cancer Res 1989, 116:67–72.

    PubMed  CAS  Google Scholar 

  20. Elomaa I, Kylmala T, Tammela T, et al.: Effect of oral clodronate on bone pain: a controlled study in patients with metastic prostatic cancer. Int Urol Nephrol 1992, 24:159–166.

    Article  PubMed  CAS  Google Scholar 

  21. Dearnaley D, Sydes M: Preliminary evidence that oral clodronate delays symptomatic progression of bone metastases from prostate cancer: first results of the MRC PR05 trial [abstract]. Proc ASCO 2001, 20:174a.

    Google Scholar 

  22. Ernst D, Tannock I, Venner P, et al.: Randomized placebo controlled trial of mitoxantrone/prednisone and clodronate versus mitoxantrone/prednisone alone in patients with hormone refractory prostate cancer and pain: National Cancer Institute of Canada Clinical Trials Group Study [abstract]. Proc ASCO 2002, 21:705a.

    Google Scholar 

  23. Saad F, Gleason DM, Murray R, et al.: A randomized, placebocontrolled trial of zoledronic acid in patients with hormonerefractory metastatic prostate carcinoma. J Natl Cancer Inst 2002, 94:1458–1468. This important phase III randomized study proved that anti-osteoclast therapy can be beneficial even in radiographically osteoblastic disease, with significant reduction in skeletal-related events for men treated with zoledronic acid compared with placebo. This study was the basis for the approval of zoledronic acid to treat men with skeletal metastases from hormone-refractory prostate cancer.

    PubMed  CAS  Google Scholar 

  24. Canil CM, Tannock IF: Should bisphosphonates be used routinely in patients with prostate cancer metastatic to bone? J Natl Cancer Inst 2002, 94:1422–1423.

    PubMed  CAS  Google Scholar 

  25. Berenson JR, Rosen LS, Howell A, et al.: Zoledronic acid reduces skeletal-related events in patients with osteolytic metastases. Cancer 2001, 91:1191–1200. A phase III double-blind study in patients with skeletal lesions caused by metastatic breast cancer or multiple myeloma. Infusion of 2.0 or 4.0 mg, but not of 0.4 mg, of zoledronic acid was at least as effective and well-tolerated as pamidronate infusion in treatment of osteolytic metastases.

    Article  PubMed  CAS  Google Scholar 

  26. Rosen L, Gordon D, Tchekmedyian S, et al.: Zoledronic acid significantly reduces skeletal-related events in patients with bone metastases from solid tumors [abstract]. Proc ASCO 2002, 21:1179a.

    Google Scholar 

  27. Stoch SA, Parker RA, Chen L, et al.: Bone loss in men with prostate cancer treated with gonadotropin-releasing hormone agonists. J Clin Endocrinol Metab 2001, 86:2787–2791.

    Article  PubMed  CAS  Google Scholar 

  28. 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, 57:127–132.

    Article  PubMed  CAS  Google Scholar 

  29. Ross RW, Small EJ: Osteoporosis in men treated with androgen deprivation therapy for prostate cancer. J Urol 2002, 167:1952–1956.

    Article  PubMed  CAS  Google Scholar 

  30. Reid IR, Brown JP, Burckhardt P, et al.: Intravenous zoledronic acid in postmenopausal women with low bone mineral density. N Engl J Med 2002, 346:653–661. Intriguing demonstration in a randomized, blinded study that treatment of postmenopausal women with zoledronic acid every 3, 6, or 12 months significantly increases BMD. Annual treatment with this potent bisphosphonate was just as effective as more frequent administration in increasing BMD and decreasing biochemical markers of bone resorption.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Hematology/Oncology, Massachusetts General Hospital, 100 Blossom Street, Cox 640, 02114, Boston, MA, USA

    M. Dror Michaelson MD, PhD

Authors
  1. M. Dror Michaelson MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthew R. Smith MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Michaelson, M.D., Smith, M.R. The role of bisphosphonates in the management of metastatic prostate cancer. Curr Oncol Rep 5, 245–249 (2003). https://doi.org/10.1007/s11912-003-0117-4

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11912-003-0117-4

Keywords

Search

Navigation