Skip to main content

Advertisement

Log in

Osteonecrosis of the jaw in patients with multiple myeloma treated with zoledronic acid

  • Original Article
  • Published:
Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

Intravenous bisphosphonates—the potent inhibitors of osteoclast-mediated bone resorption are among the most commonly prescribed drugs in the management of multiple myeloma (MM). Zoledronic acid (ZA) is a new generation potent intravenous bisphosphonate that has been approved for the treatment and prevention of bone lesions, and/or hypercalcemia associated with MM. Osteonecrosis of the jaw (ONJ) is an emerging serious side effect of the new generation bisphosphonates with a growing number of reports related to this pathological entity. ONJ usually appears following oral surgical and dental procedures but sometimes occur spontaneously. These cases are mostly seen and treated by dentists and oral surgeons. The aim of this study was to discuss the frequency, characteristics, risk factors, management and histopathological features of ZA induced ONJ based on the literature and illustrated with five own cases. Thirty-two patients with MM who received ZA for a median period of 26.5 ± 18.7 months (min: 5 months, max: 76 months) were evaluated. ONJ was detected in five patients and mean drug duration time was 34 months. The frequency was 15% and the patients were usually symptomatic. There was no significant difference in terms of the duration of ZA in patients with and without ONJ. Management of these established cases were performed with medical treatment, minor debridement, sequestrectomy, and combining bone resection with autologous platelet rich plasma. Our data indicate that ZA therapy has a major role in the development of ONJ a fact that should be considered by physicians treating MM patients.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Dunstan CR, Felsenberg D, Seibel MJ (2007) Therapy insight: the risks and benefits of bisphosphonates for the treatment of tumor-induced bone disease. Nat Clin Pract Oncol 4:42–55

    Article  PubMed  CAS  Google Scholar 

  2. Melo MD, Obeid G (2005) Osteonecrosis of the maxilla in a patient with a history of bisphosphonate therapy. J Can Dent Assoc 71:111–113

    PubMed  Google Scholar 

  3. Robinson NA, Yeo JF (2004) Bisphosphonates—a word of caution. Ann Acad Med Singap 33:48–49

    PubMed  CAS  Google Scholar 

  4. Diego R, D’Orto O, Pagani D, Agazzi A, Marzano U, Derada Troletti G, Fontanella W, Pignataro L (2007) Bisphosphonate-associated osteonecrosis of the jaws—a therapeutic dilemma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 103:e1–e5

    Article  PubMed  Google Scholar 

  5. Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL (2004) Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg 62:527–534

    Article  PubMed  Google Scholar 

  6. Hughes DE, MacDonald BR, Russell RG, Gowen M (1989) Inhibition of osteoclast-like cell formation by bisphosphonates in long-term cultures of human bone marrow. J Clin Invest 83:1930–1935

    Article  PubMed  CAS  Google Scholar 

  7. Rogers MJ, Gordon S, Benford HL, Coxon FP, Luckman SP, Monkkonen J, Frith JC (2000) Cellular and molecular mechanisms of action of bisphosphonates. Cancer 15(88):2961–2978

    Article  Google Scholar 

  8. Hughes DE, Wright KR, Uy HL, Sasaki A, Yoneda T, Roodman GD, Mundy GR, Boyce BF (1995) Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. J Bone Miner Res 10:1478–1487

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  10. Zervas K, Verrou E, Teleioudis Z, Vahysevanos K, Banti A, Mihou D, Krikelis D, Terpos E (2006) Incidence, risk factors and management of osteonecrosis of the jaw in patients with multiple myeloma: a single-centre experience in 303 patients. Br J Haematol 134:620–623

    Article  PubMed  CAS  Google Scholar 

  11. Prophet EB, Mills B, Arrington JB, Sobin LH (1992) Laboratory methods in histotechnology. Armed Forces Institute of Pathology. AM Registry of Pathology Washington DC

  12. Bagan JV, Murillo J, Jimenez Y, Poveda R, Milian MA, Sanchis JM, Silvestre FJ, Scully C (2005) Avascular jaw osteonecrosis in association with cancer chemotherapy: series of 10 cases. J Oral Pathol Med 34:120–123

    Article  PubMed  CAS  Google Scholar 

  13. Melo MD, Obeid G (2005) Osteonecrosis of the jaws in patients with a history of receiving bisphosphonate therapy: strategies for prevention and early recognition. J Am Dent Assoc 136:1675–1681

    PubMed  CAS  Google Scholar 

  14. Pogrel MA, Miller CE (2003) A case of maxillary necrosis. J Oral Maxillofac Surg 61:489–493

    Article  PubMed  CAS  Google Scholar 

  15. Reuther T, Schuster T, Mende U, Kubler A (2003) Osteoradionecrosis of the jaws as a side effect of radiotherapy of head and neck tumour patients—a report of a thirty year retrospective review. Int J Oral Maxillofac Surg 32:289–295

    Article  PubMed  CAS  Google Scholar 

  16. Ruggiero SL, Fantasia J, Carlson E (2006) Bisphosphonate-related osteonecrosis of the jaw: background and guidelines for diagnosis, staging and management. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 102:433–441

    Article  PubMed  Google Scholar 

  17. Vannucchi AM, Ficarra G, Antonioli E, Bosi A (2005) Osteonecrosis of the jaw associated with zoledronate therapy in a patient with multiple myeloma. Br J Haematol 128:738

    Article  PubMed  Google Scholar 

  18. Hansen T, Kunkel M, Weber A, Kirkpatrick CJ (2006) Osteonecrosis of the jaws in patients treated with bisphosphonates-histomorphologic analysis in comparison with infected osteoradionecrosis. J Oral Pathol Med 35:155–160

    Article  PubMed  Google Scholar 

  19. Hansen T, Kunkel M, Springer E, Walter C, Weber A, Siegel E, Kirkpatrick CJ (2007) Actinomycosis of the jaws-histopathological study of 45 patients shows significant involvement in bisphosphonate-associated osteonecrosis and infected osteoradionecrosis. Virchows Arch 451:1009–1017

    Article  PubMed  Google Scholar 

  20. Font Gomez R, Garcia MLM, Martinez JMO (2008) Osteochemonecrosis of the jaws due to bisphosphonate treatments. Update. Med Oral Patol Oral Cir Bucal 13:318–324

    Google Scholar 

  21. Sarin J, DeRossi SS, Akintoye SO (2008) Updates on bisphosphonates and potential pathobiology of bisphosphonate-induced jaw osteonecrosis. Oral Dis 14:277–285

    Article  PubMed  CAS  Google Scholar 

  22. Woo SB, Hellstein JW, Kalmar JR (2006) Narrative review: bisphosphonates and osteonecrosis of the jaws. Ann Intern Med 144:753–761

    PubMed  CAS  Google Scholar 

  23. Ardine M, Generali D, Donadio M et al (2006) Could the long-term persistence of low serum calcium levels and high serum parathyroid hormone levels during bisphosphonate treatment predispose metastatic breast cancer patients to undergo osteonecrosis of the jaw? Ann Oncol 17:1336–1337

    Article  PubMed  CAS  Google Scholar 

  24. Suda K, Udugawa N, Sato N (2004) Suppression of osteoprotegrin expression by prostaglandin E2 crucially involved in lipopolysaccharide-induced osteoclast formation. J Immunol 172:2504–2508

    PubMed  CAS  Google Scholar 

  25. Li EC, Davis LE (2003) Zoledronic acid: a new parenteral bisphosphonate. Clin Ther 25:2669–2708

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  27. Hoff AO, Toth BB, Altundag K, Johnson MM, Warneke CL, Hu M, Nooka A, Sayegh G, Guarneri V, Desrouleaux K, Cui J, Adamus A, Gagel RF, Hortobagyi GN (2008) Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates. J Bone Miner Res 23:826–836

    Article  PubMed  CAS  Google Scholar 

  28. Van Poznak C, Estilo C (2006) Osteonecrosis of the jaw in cancer patients receiving IV bisphosphonates. Oncology (Williston Park) 20:1053–1065

    Google Scholar 

  29. Bamias A, Kastritis E, Bamia C, Moulopoulos LA, Melakopoulos I, Bozas G, Koutsoukou V, Gika D, Anagnostopoulos A, Papadimitriou C, Terpos E, Dimopoulos MA (2005) Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors. J Clin Oncol 23:8580–8587

    Article  PubMed  Google Scholar 

  30. Moehler TM, Hillengass J, Glasmacher A, Goldschmidt H (2006) Thalidomide in multiple myeloma. Curr Pharm Biotechnol 7:431–440

    Article  PubMed  CAS  Google Scholar 

  31. Tosi P, Zamagni E, Cangini D, Tacchetti P, Di Raimondo F, Catalano L, D’Arco A, Ronconi S, Cellini C, Offidani M, Perrone G, Ceccolini M, Brioli A, Tura S, Baccarani M, Cavo M (2006) Osteonecrosis of the jaws in newly diagnosed multiple myeloma patients treated with zoledronic acid and thalidomide-dexamethasone. Blood 108:3951–3952

    Article  PubMed  CAS  Google Scholar 

  32. Marx RE, Sawatari Y, Fortin M, Broumand V (2005) Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention and treatment. J Oral Maxillofac Surg 63:1567–1575

    Article  PubMed  Google Scholar 

  33. Woeller A, Gering A, Brix M, Bettega G, Lebeau J (2006) Bone necrosis of the jaws in five patients taking bisphosphonates. Rev Stomatol Chir Maxillofac 107:417–422

    Article  PubMed  CAS  Google Scholar 

  34. Farrugia MC, Summerlin DJ, Krowiak E, Huntley T, Freeman S, Borrowdale R, Tomich C (2006) Osteonecrosis of the mandible or maxilla associated with the use of new generation bisphosphonates. Laryngoscope 116:115–120

    Article  PubMed  Google Scholar 

  35. American Dental Association Council on Scientific Affairs (2006) Dental management of patients receiving oral bisphosphonate therapy: expert panel recommendations. J Am Dent Assoc 137:1144–1150

    Google Scholar 

  36. Katz H (2005) Endodontic implications of bisphosphonate-associated osteonecrosis of the jaws: a report of three cases. J Endod 31:831–834

    Article  PubMed  Google Scholar 

  37. Curi MM, Cossolin GS, Koga DH, Araujo SR, Feher O, Dos Santos MO, Zardetto C (2007) Treatment of avascular osteonecrosis of the mandible in cancer patients with a history of bisphosphonate therapy by combining bone resection and autologous platelet-rich plasma: report of 3 cases. J Oral Maxillofac Surg 65:349–355

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sevil Altundag Kahraman.

About this article

Cite this article

Cetiner, S., Sucak, G.T., Kahraman, S.A. et al. Osteonecrosis of the jaw in patients with multiple myeloma treated with zoledronic acid. J Bone Miner Metab 27, 435–443 (2009). https://doi.org/10.1007/s00774-009-0047-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-009-0047-9

Keywords

Navigation