Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Myeloma

A different schedule of zoledronic acid can reduce the risk of the osteonecrosis of the jaw in patients with multiple myeloma

Abstract

Osteonecrosis of the jaw (ONJ) is a reported complication of bisphosphonate use. The incidence ranges between 6 and 13% and seems to be higher in people treated with zoledronic acid (ZA) than with pamidronate. We retrospectively evaluated the incidences of ONJ and skeletal-related events (SRE) in 106 patients with multiple myeloma divided in two groups according to the schedule of administration of bisphosphonates: 51 received monthly administrations until tolerated (group A, standard schedule), 55 were treated monthly during the first year and then every 3 months (group B, reduced schedule). The incidence of SRE was similar (15.1 per 100 person years in group A and 17.7 in group B). ONJ occurred in seven patients, six in group A and one in group B (P=0.049). The risk of ONJ was eight-fold lower with the reduced schedule than with the standard schedule. The only significant risk factor for ONJ was the type of bisphosphonate (P=0.006). The incidence of ONJ was significantly higher with ZA than with pamidronate + ZA (9.1 vs 1.6 per 100 person-years). No ONJ was observed in patients treated only with pamidronate. A reduced schedule of ZA may be safer than the standard schedule while maintaining anti-resorptive efficacy.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Kyle RA, Gertz MA, Witzig TE, Lust JA, Lacy MQ, Dispenzieri A et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc 2003; 78: 21–33.

    Article  PubMed  Google Scholar 

  2. Roodman GD . Pathogenesis of myeloma bone disease. Blood Cells Mol Dis 2004; 32: 290–292.

    Article  CAS  PubMed  Google Scholar 

  3. Coleman RE, Purohit OP . Osteoclast inhibition for the treatment of bone metastases. Cancer Treat Rev 1993; 19: 79–103.

    Article  CAS  PubMed  Google Scholar 

  4. Berenson JR, Lichtenstein A, Porter L, Dimopoulos MA, Bordoni R, George S et al. Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. N Engl J Med 1996; 334: 488–493.

    Article  CAS  PubMed  Google Scholar 

  5. Berenson JR, Lichtenstein A, Porter L, Dimopoulos MA, Bordoni R, George S et al. Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. Myeloma Aredia Study Group. J Clin Oncol 1998; 16: 593–602.

    Article  CAS  PubMed  Google Scholar 

  6. Green JR, Muller K, Jaeggi KA . preclinical pharmacology of CGP 42'446, a new, potent heterocyclic bisphosphonate compound. J Bone Miner Res 1994; 9: 745–751.

    Article  CAS  PubMed  Google Scholar 

  7. Major PP, Coleman RE . Zoledronic acid in the treatment of hypercalcemia of malignancy: results of the international clinical development program. Semin Oncol 2001; 28: 17–24.

    Article  CAS  PubMed  Google Scholar 

  8. Rosen LS, Gordon D, Kaminski M, Howell A, Belch A, Mackey J et al. Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma. Cancer 2003; 98: 1735–1744.

    Article  CAS  PubMed  Google Scholar 

  9. Marx RE . Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 2003; 61: 1115–1117.

    Article  PubMed  Google Scholar 

  10. Durie BG, Katz M, Crowley J . Osteonecrosis of the jaw and bisphosphonates. N Engl J Med 2005; 353: 99–102.

    Article  CAS  PubMed  Google Scholar 

  11. Bamias A, Kastritis E, Bamia C, Moulopoulos LA, Melakopoulos I, Bozas G et al. Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors. J Clin Oncol 2005; 23: 8580–8587.

    Article  PubMed  Google Scholar 

  12. Badros A, Weikel D, Salama A, Goloubeva O, Schneider A, Rapoport A et al. Osteonecrosis of the jaw in multiple myeloma patients: clinical features and risk factors. J Clin Oncol 2006; 24: 945–952.

    Article  CAS  PubMed  Google Scholar 

  13. Berenson JR, Hillner BE, Kyle RA, Anderson K, Lipton A, Yee GC et al. American Society of Clinical Oncology clinical practice guidelines: the role of bisphosphonates in multiple myeloma. J Clin Oncol 2002; 20: 3719–3736.

    Article  PubMed  Google Scholar 

  14. Lacy MQ, Dispensieri A, Gertz MA, Greipp PR, Gollbach KL, Hayman SR et al. Mayo Clinic Consensus Statement for the use of bisphosphonates in multiple myeloma. Mayo Clin Proc 2006; 81: 1047–1053.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A Corso.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Corso, A., Varettoni, M., Zappasodi, P. et al. A different schedule of zoledronic acid can reduce the risk of the osteonecrosis of the jaw in patients with multiple myeloma. Leukemia 21, 1545–1548 (2007). https://doi.org/10.1038/sj.leu.2404682

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2404682

Keywords

This article is cited by

Search

Quick links