Journal of Cancer Research and Clinical Oncology

, Volume 136, Issue 8, pp 1117–1124 | Cite as

Bisphosphonate-induced osteonecrosis of the jaw: a review of 2,400 patient cases




Bisphosphonates (BPs) are bone-remodeling inhibitors that are used to manage bone metastases and osteoporosis. Osteonecrosis of the jaw, however, can occur during treatment. This complication is poorly understood and is called “bisphosphonate-induced osteonecrosis of the jaw” (BIOJ).


We performed a PubMed-based review of all of the described cases of BIOJ from January 2003 (the year of the first description) to September 2009. Issues of clinical relevance, such as the primary diagnosis and type of treatment, were evaluated for each patient case.


We retrieved 2,408 cases, 88% of which were associated with intravenous therapy, primarily with zoledronate. Of the total number of cases, 89% were associated with the treatment of a malignant condition, particularly multiple myeloma (43% of the cases). Of all the BIOJ cases, 67% were preceded by tooth extraction and only 35% of patients were cured.


Prevention is better than treatment, and the establishment of meticulous oral hygiene and surgical procedures prior to commencing BP treatment is important for preventing BIOJ. Our review summarizes the current knowledge about this severe complication. Future studies, especially basic research studies, are needed to better understand this devastating disease.


Bisphosphonates Osteonecrosis of the jaws Epidemiology Retrospective 


Conflict of interest statement

All authors disclose no financial and personal relationships with other people or organizations that could inappropriately influence (bias) the work. Olivier Filleul, Emerence Crompot, Sven Saussez.


  1. Allen MR, Burr DB (2008) Mandible matrix necrosis in beagle dogs after 3 years of daily bisphosphonate treatment. J Oral Maxillofac Surg 66:987–994CrossRefPubMedGoogle Scholar
  2. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws (2007) J Oral Maxillofac Surg 65:369–376Google Scholar
  3. Bedogni A, Blandamura S, Lokmic Z, Palumbo C, Ragazzo M, Ferrari F et al (2008) Bisphosphonate-associated jawbone osteonecrosis : a correlation between imaging techniques and histopathology. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 105:358–364CrossRefPubMedGoogle Scholar
  4. Carlson ER, Basile JD (2009) The role of surgical resection in the management of bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg 67:85–95CrossRefPubMedGoogle Scholar
  5. Cheng A, Mavrokokki A, Carter G, Stein B, Fazzalari NL, Wilson DF et al (2005) The dental implications of bisphosphonates and bone disease. Aust Dent J 50:4–13CrossRefGoogle Scholar
  6. Curi MM, Cossolin GSI, Koga DH, Araùjo SR, Feher O, dos Santos MO et al (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 65:349–355CrossRefPubMedGoogle Scholar
  7. Dannemann C, Grätz KW, Zwahlen R (2006) Clinical experience with bisphosphonate-induced osteochemonecrosis of the jaw. Swiss Med Wkly 136:504–509PubMedGoogle Scholar
  8. Durie BGM (2007) Use of bisphosphonates in multiple myeloma: IMWG response to Mayo Clinic consensus statement. Mayo Clin Proc 82:516–517CrossRefPubMedGoogle Scholar
  9. Durie BGM, Katz M, Crowley J (2005) Osteonecrosis of the jaw and bisphosphonates. N Engl J Med 353:99–102CrossRefPubMedGoogle Scholar
  10. Hellstein JW, Marek CL (2005) Bisphosphonate osteochemonecrosis (bis-phossy jaw): is this phossy jaw of the 21st century? J Oral Maxillofac Surg 63:682–689CrossRefPubMedGoogle Scholar
  11. Kyle RA, Yee GC, Somerfield MR, Flynn PJ, Halabi S, Jagannath S et al (2007) American society of clinical oncology 2007 clinical practice guideline update on the role of bisphosphonates in multiple myeloma. J Clin Oncol 25:2464–2472CrossRefPubMedGoogle Scholar
  12. Leite AF, Figueiredo PT, Melo NS, Acevedo AC, Cavalcanti MG, Paula M et al (2006) Bisphosphonate-associated osteonecrosis of the jaws. Report of a case and literature review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 102:14–21CrossRefPubMedGoogle Scholar
  13. Marx RE (2003) Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofacial Surg 61:115–117CrossRefGoogle Scholar
  14. Mavrokokki T, Cheng A, Stein B, Goss A (2007) Nature and frequency of bisphosphonate-associated osteonecrosis of the jaws in Australia. J Oral Maxillofac Surg 65:415–423CrossRefPubMedGoogle Scholar
  15. Ortega C, Montemurro F, Faggiulo R et al (2007) Osteonecrosis of the jaw in prostate cancer patients with bone metastases treated with zoledronate: a retrospective analysis. Acta Oncol (Madr) 46:664–668CrossRefGoogle Scholar
  16. Pozzi S, Marcheselli R, Sacchi S, Baldini L, Angrilli F, Pennese E et al (2007) Bisphosphonate-associated osteonecrosis of the jaw: a review of 35 cases and an evaluation of its frequency in multiple myeloma patients. Leuk Lymphoma 48:56–64CrossRefPubMedGoogle Scholar
  17. 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 102:433–441CrossRefPubMedGoogle Scholar
  18. Saussez S, Javadian R, Hupin C, Magremanne M, Chantrain G, Loeb I et al (2009) Bisphosphonate-related osteonecrosis of the jaws and its associated risk factors: a Belgian case series. Laryngoscope 119:323–329CrossRefPubMedGoogle Scholar
  19. Vescovi P, Merigo E, Manfredi M, Meleti M, Fornaini C, Bonanini M et al (2008) Nd:YAG laser biostimulation in the treatment of bisphosphonate-associated osteonecrosis of the jaws: clinical experience in 28 cases. Photomed Laser Surg 26:37–46CrossRefPubMedGoogle Scholar
  20. Walter C, Grötz KA, Kunkel M, Al-Nawas B (2007) Prevalence of bisphosphonate associated osteonecrosis of the jaw within the field of osteonecrosis. Support Care Cancer 15:197–202CrossRefPubMedGoogle Scholar
  21. Wang EP, Kaban LB, Strewler GJ, Raje N, Troulis MJ (2007) Incidence of osteonecrosis of the jaw in patients with multiple myeloma and breast or prostate cancer on intravenous bisphosphonate therapy. J Oral Maxillofac Surg 65:1328–1331CrossRefPubMedGoogle Scholar
  22. Woo SB, Hellstein JW, Kalmar JR (2006) Systematic review: bisphosphonates and osteonecrosis of the jaws. Ann Intern Med 144:753–761PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Faculty of Medicine and Pharmacy, Department of Anatomy and Cellular BiologyUniversity of Mons (UMons)MonsBelgium
  2. 2.Department of Oto-Rhino-LaryngologyCHU St-PierreBrusselsBelgium

Personalised recommendations