Skip to main content
SpringerLink
Log in

Bisphosphonate Treatment of Lytic Bone Metastases

  • Leading Article
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Abstract

Tumour-induced osteolysis or lytic bone disease is mediated by osteoclast activation. Osteoclasts can be activated directly by tumour products or indirectly through an influence on other cells. By reducing osteoclastic activity, bisphosphonates inhibit bone resorption. Pamidronate is a second-generation amino-bisphosphonate that is a potent inhibitor of osteoclastic activity. In multiple myeloma, a phase III study has shown that the proportion of patients at the end of 21 months who had any skeletal event was significantly lower in the pamidronate group (38%) than in the placebo group (58%). The therapeutic benefit was independent of the type of antimyeloma chemotherapy. Patients who received pamidronate had significant decrease in bone pain and delayed deterioration in performance status and quality of life. Overall there was no survival advantage in patients who received pamidronate. In similar fashion, in 2 phase III breast cancer trials, patients who received pamidronate had fewer skeletal events, decrease in bone pain and analgesic use, and slower deterioration of performance status that in those patients receiving placebo. Again, there was no survival advantage in these patients. Recent studies suggest that the bisphosphonates clodronate can prevent the development of bone metastases in patients with breast cancer.

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

  1. Stashenko P, Dewhirst FE, Peros WJ, et al. Synergistic interactions between interleukin 1, tumor necrosis factor, and lymphotoxin in bone resorption. J Immunol 1987; 138: 1464–8

    PubMed  CAS  Google Scholar 

  2. Mundy GR. Mechanisms of osteolytic bone destruction. Bone 1991; 12Suppl 1: 1–6

    Article  Google Scholar 

  3. Lahtinen R, Laakso M, Palva I, et al. Randomized, placebo-controlled multicentre trial of clodronic acid in multiple myeloma. Lancet 1992; 340: 1049–52

    Article  PubMed  CAS  Google Scholar 

  4. Man Z, Otero AB, Rendo P, et al. Use of pamidronate for multiple myeloma osteolytic lesions. Lancet 1990; 335: 663

    Article  PubMed  CAS  Google Scholar 

  5. Theibaud D, Leyuraz S, Von Fliedner V, et al. Treatment of bone metastases from breast cancer and myeloma with pamidronate. Eur J Cancer 1991; 27: 37–41

    Article  Google Scholar 

  6. Belch AR, Bergsagel DE, Wilson K, et al. Effect of daily etidronate acid on the osteolysis of multiple myeloma. J Clin Oncol 1991; 9: 1397–402

    PubMed  CAS  Google Scholar 

  7. Heim ME, Clemens MR, Queisser W, et al. Prospective randomized trial of dichloromethylene bisphosphonate (clodronate) in patients with multiple myeloma requiring treatment: a multicenter study. Onkologie 1995; 18: 439–48

    Article  Google Scholar 

  8. Berenson JR, Lichtenstein A, Porter L, et al. Efficacy of pamidronate in reducing the skeletal events in patients with advanced multiple myeloma. N Engl J Med 1996; 334: 488–93

    Article  PubMed  CAS  Google Scholar 

  9. Coleman RE, Rubens RD. The clinical course of bone metastases from breast cancer. Br J Cancer 1987, 55: 61–6

    Article  PubMed  CAS  Google Scholar 

  10. Siris ES, Hyman GA, Canfield RE. Effects of dichloromethylene diphosphonate in women with breast carcinoma metastatic to the skeleton. Am J Med 1983; 74: 401–6

    Article  PubMed  CAS  Google Scholar 

  11. Elomaa I, Blomqvist C, Grohn P, et al. Long-term controlled trial of bisphosphonate in patients with osteolytic bone metastases. Lancet 1983; I: 146–9

    Article  Google Scholar 

  12. Paterson AHG, Powles TJ, Kanis TA, et al. Double-blind controlled trial of oral clodronic acid in patients with bone metastases from breast cancer. J Clin Oncol 1993; 11: 59–65

    PubMed  CAS  Google Scholar 

  13. van Breukern FJM, Bijroet OLM, VanOosterom AT. Inhibition of osteolytic bone lesions by (3-amino-1-hydroxypropylidene)-1, 1-bisphosphonate (APD). Lancet 1979; I: 805–6

    Google Scholar 

  14. Coleman RE, Woll PJ, Miles M, et al. Treatment of bone metastases from breast cancer with (3-amino-l-hydroxypropylidene)-1, 1-bisphosphonate (APD). Br J Cancer 1988; 48: 621–5

    Article  Google Scholar 

  15. Morton AR, Cantrill JA, Pillai GV, et al. Sclerosis of lytic bone metastases after disodium aminohydroxypropylidene bisphosphonate (APD) in patients with breast carcinoma. BMJ 1988; 297: 772–3

    Article  PubMed  CAS  Google Scholar 

  16. Burckhardt P, Thiebaud D, Percy L, et al. Treatment of tumor-induced osteolysis by APD. Recent Results Cancer Res 1989; 116: 54–66

    Article  PubMed  CAS  Google Scholar 

  17. van Holten-Verzantvoort ATM, Zwinderman AH, Aaronson NK, et al. The effect of supportive pamidronate treatment on aspects of quality of life of patients with advanced breast cancer. Eur J Cancer 1991; 27: 544–9

    Article  PubMed  Google Scholar 

  18. van Holten-Verzantvoort ATM, Kroon HM, Bijvoet OLM, et al. Palliative pamidronate treatment in patients with bone metastases from breast cancer. J Clin Oncol 1993; 11: 491–8

    PubMed  Google Scholar 

  19. Glover D, Lipton A, Keller A, et al. Intravenous pamidronate disodium treatment of bone metastases in patients with breast cancer: a dose-seeking study. Cancer 1994; 74: 2949–55

    Article  PubMed  CAS  Google Scholar 

  20. Hortobagyi GN, Theriault RL, Porter L, et al. Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone metastases. N Engl J Med 1996; 335: 1785–91

    Article  PubMed  CAS  Google Scholar 

  21. Lipton A, Theriault R, Leff R, et al. Long-term reduction of skeletal complications in breast cancer patients with osteolytic bone metastases receiving hormone therapy by monthly 90 mg pamidronate (Aredia) infusions [abstract no. 531]. Proceedings of the American Society of Clinical Oncology (ASCO): 1997 May 17–20; Denver, 16

  22. Conte PF, Latreille J, Maurik L, et al. Delay in progression of bone metastases in breast cancer patients treated with intravenous pamidronate: results from a multinational randomized controlled trial. J Clin Oncol 1996; 14: 2552–9

    PubMed  CAS  Google Scholar 

  23. Lipton A, Hortobagyi G, Simeone J, et al. Progression of bone metastases in breast cancer patients receiving pamidronate [abstract no. 469]. Proceedings of the American Society of Clinical Oncology (ASCO): 1998 May 16–19; Los Angeles

  24. Kanis JA, Powles T, Paterson AHG, et al. Clodronate decreases the frequency of skeletal metastases in women with breast cancer. Bone 1996; 19: 663–7

    Article  PubMed  CAS  Google Scholar 

  25. van Holten-Verzantvoort ATM, Hermans J, Beex LVAM, et al. Does supportive pamidronate treatment prevent or delay the first manifestation of bone metastases in breast cancer patients? Eur J Cancer 1996; 32A: 450–4

    Article  PubMed  Google Scholar 

  26. Diel IJ, Solomayer EF, Costa SD, et al. Reduction in new metastases in breast cancer with adjuvant clodronate treatment. N Engle J Med 1998; 339: 357–63

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Haematology/Oncology, The Milton S. Hershey Medical Center, Hershey, Pennsylvania, 17033, USA

    Allan Lipton

  2. West Los Angeles Veterans Affairs Medical Center and UCLA School of Medicine, Los Angeles, California, USA

    James R. Berenson

Authors
  1. Allan Lipton
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. James R. Berenson
    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

Lipton, A., Berenson, J.R. Bisphosphonate Treatment of Lytic Bone Metastases. Drugs & Aging 14, 241–246 (1999). https://doi.org/10.2165/00002512-199914040-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002512-199914040-00001

Keywords

Search

Navigation