Journal of Oral and Maxillofacial Surgery
Volume 68, Issue 2 , Pages 243-253 , February 2010

Prevalence of Osteonecrosis of the Jaw in Patients With Oral Bisphosphonate Exposure

These data were presented in part at the 90th Annual Meeting of the Endocrine Society, San Francisco, CA, June 15-18, 2008.

  • Joan C. Lo, MD

      Affiliations

    • Research Scientist, Division of Research, Kaiser Permanente Northern California, Oakland, and Associate Clinical Professor, Department of Medicine, University of California, San Francisco, School of Medicine, San Francisco, CA
    • Corresponding Author InformationAddress correspondence and reprint requests to Dr Lo: Division of Research, Kaiser Permanente Northern California, 2000 Broadway, Oakland, CA 94612
    • ,
  • Felice S. O'Ryan, DDS

      Affiliations

    • Director, Division of Maxillofacial Surgery, Kaiser Permanente Oakland Medical Center, Oakland, CA
    • ,
  • Nancy P. Gordon, ScD

      Affiliations

    • Research Scientist, Division of Research, Kaiser Permanente Northern California, Oakland, CA
    • ,
  • Jingrong Yang, MA

      Affiliations

    • Data Consultant, Division of Research, Kaiser Permanente Northern California, Oakland, CA
    • ,
  • Rita L. Hui, PharmD, MS

      Affiliations

    • Outcomes Research Scientist, Pharmacy Outcomes Research Group, Drug Information Services, Kaiser Permanente California, Oakland, CA
    • ,
  • Daniel Martin, DDS

      Affiliations

    • Resident, Division of Maxillofacial Surgery, Kaiser Permanente Oakland Medical Center, and Department of Oral and Maxillofacial Surgery, Highland General Hospital, Oakland, CA
    • ,
  • Matthew Hutchinson, DDS

      Affiliations

    • Resident, Division of Maxillofacial Surgery, Kaiser Permanente Oakland Medical Center, and Department of Oral and Maxillofacial Surgery, Highland General Hospital, Oakland, CA
    • ,
  • Phenius V. Lathon

      Affiliations

    • Project Manager, Division of Research, Kaiser Permanente Northern California, Oakland, CA
    • ,
  • Gabriela Sanchez

      Affiliations

    • Project Manager, Division of Research, Kaiser Permanente Northern California, Oakland, CA
    • ,
  • Paula Silver

      Affiliations

    • Project Manager, Division of Research, Kaiser Permanente Northern California, Oakland, CA
    • ,
  • Malini Chandra

      Affiliations

    • Senior Consulting Data Analyst, Division of Research, Kaiser Permanente Northern California, Oakland, CA
    • ,
  • Carolyn A. McCloskey, MD

      Affiliations

    • Epidemiologist, US Food and Drug Administration, Center for Drug Evaluation and Research, Office of Surveillance and Epidemiology, Silver Spring, MD
    • ,
  • Judy A. Staffa, PhD

      Affiliations

    • Associate Director for Regulatory Research, US Food and Drug Administration, Center for Drug Evaluation and Research, Office of Surveillance and Epidemiology, Silver Spring, MD
    • ,
  • Mary Willy, PhD

      Affiliations

    • Senior Risk Analyst, US Food and Drug Administration, Center for Drug Evaluation and Research, Office of Surveillance and Epidemiology, Silver Spring, MD
    • ,
  • Joe V. Selby, MD, MPH

      Affiliations

    • Director, Division of Research, Kaiser Permanente Northern California, Oakland, CA
    • ,
  • Alan S. Go, MD

      Affiliations

    • Research Scientist, Division of Research, Kaiser Permanente Northern California, Oakland, and Associate Professor, Departments of Medicine and Epidemiology and Biostatistics, University of California, San Francisco, School of Medicine, San Francisco, CA
    • ,
  • Predicting Risk of Osteonecrosis of the Jaw with Oral Bisphosphonate Exposure (PROBE) Investigators

References 

  1. American Association of Oral and Maxillofacial Surgeons. Position paper on bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg. 2007;65:369
  2. Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: A growing epidemic. J Oral Maxillofac Surg. 2003;61:1115
  3. Migliorati CA. Bisphosphanates and oral cavity avascular bone necrosis. J Clin Oncol. 2003;21:4253
  4. Marx RE, Sawatari Y, Fortin M, et al. Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: Risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg. 2005;63:1567
  5. Ruggiero SL, Mehrotra B, Rosenberg TJ, et al. Osteonecrosis of the jaws associated with the use of bisphosphonates: A review of 63 cases. J Oral Maxillofac Surg. 2004;62:527
  6. Woo SB, Hellstein JW, Kalmar JR. Narrative [corrected] review: Bisphosphonates and osteonecrosis of the jaws. Ann Intern Med. 2006;144:753
  7. Badros A, Weikel D, Salama A, et al. Osteonecrosis of the jaw in multiple myeloma patients: Clinical features and risk factors. J Clin Oncol. 2006;24:945
  8. Mavrokokki T, Cheng A, Stein B, et al. Nature and frequency of bisphosphonate-associated osteonecrosis of the jaws in Australia. J Oral Maxillofac Surg. 2007;65:415
  9. Wang EP, Kaban LB, Strewler GJ, et al. Incidence of osteonecrosis of the jaw in patients with multiple myeloma and breast or prostate cancer on intravenous bisphosphonate therapy. J Oral Maxillofac Surg. 2007;65:1328
  10. Pozzi S, Marcheselli R, Sacchi S, et al. Bisphosphonate-associated osteonecrosis of the jaw: A review of 35 cases and an evaluation of its frequency in multiple myeloma patients. Leuk Lymph. 2007;48:56
  11. Jadu F, Lee L, Pharoah M, et al. A retrospective study assessing the incidence, risk factors and comorbidities of pamidronate-related necrosis of the jaws in multiple myeloma patients. Ann Oncol. 2007;18:2015
  12. Reid IR. Osteonecrosis of the jaw: Who gets it, and why?. Bone. 2009;44:4
  13. Ruggiero SL, Mehrotra B: Bisphosphonate-related osteonecrosis of the jaw: Diagnosis, prevention, and treatment. Annu Rev Med Epub 2008 Oct 17
  14. Hoff AO, Toth BB, Altundag K, et al. Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates. J Bone Miner Res. 2008;23:826
  15. Brooks JK, Gilson AJ, Sindler AJ, et al. Osteonecrosis of the jaws associated with use of risedronate: Report of 2 new cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;103:780
  16. Marx RE, Cillo JE, Ulloa JJ. Oral bisphosphonate-induced osteonecrosis: Risk factors, prediction of risk using serum CTX testing, prevention, and treatment. J Oral Maxillofac Surg. 2007;65:2397
  17. Dental management of patients receiving oral bisphosphonate therapy (Expert panel recommendations). J Am Dent Assoc. 2006;137:1144
  18. Yarom N, Yahalom R, Shoshani Y, et al. Osteonecrosis of the jaw induced by orally administered bisphosphonates: Incidence, clinical features, predisposing factors and treatment outcome. Osteoporos Int. 2007;18:1363
  19. Kumar SK, Meru M, Sedghizadeh PP, et al. Osteonecrosis of the jaws secondary to bisphosphonate therapy: A case series. J Contemp Dent Pract. 2008;9:63
  20. Felsenberg D, Hoffmeister B, Amling M, et al. Kiefernekrosen nach hoch dosierter bisphosphonattherapie. Deutsches Arzteblatt. 2006;103:A3078
  21. Khosla S, Burr D, Cauley J, et al. Bisphosphonate-associated osteonecrosis of the jaw: Report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2007;22:1479
  22. Sambrook P, Olver I, Goss A. Bisphosphonates and osteonecrosis of the jaw. Aust Fam Physician. 2006;35:801
  23. SDI Total Patient Tracker, Years 2002-2007. Data extracted May 27, 2008, and May 28, 2008
  24. Oehrli MD, Quesenberry CP, Leyden W. Northern California Cancer Registry: 2007 Annual Report on Trends, Incidence, and Outcomes: Kaiser Permanente, Northern California Cancer Registry. November 2007;
  25. Fireman BH, Quesenberry CP, Somkin CP, et al. Cost of care for cancer in a health maintenance organization. Health Care Financ Rev. 1997;18:51
  26. Lo JC, Pressman AR, Omar MA, et al. Persistence with weekly alendronate therapy among postmenopausal women. Osteoporos Int. 2006;17:922
  27. Statement by Merck & Company (Incorporated: Regarding Fosamax (alendronate sodium) and rare cases of osteonecrosis of the jaw. Product News). www.merck.com/newsroom/press_releases/product/fosamax_statement.htmlAccessed July 30, 2008
  28. Fontanarosa PB, Rennie D, DeAngelis CD. Postmarketing surveillance—Lack of vigilance, lack of trust. JAMA. 2004;292:2647
  29. Tarassoff P, Csermak K. Avascular necrosis of the jaws: Risk factors in metastatic cancer patients. J Oral Maxillofac Surg. 2003;61:1238
  30. Jung TI, von der Gablentz J, Hoffmeister B, et al. Osteonecrosis of jaw under bisphosphonate therapy: Patient profile and risk assessment. J Bone Miner Res. 2007;2007:S298
  31. Chiandussi S, Biasotto M, Dore F, et al. Clinical and diagnostic imaging of bisphosphonate-associated osteonecrosis of the jaws. Dentomaxillofac Radiol. 2006;35:236
  32. Phal PM, Myall RW, Assael LA, et al. Imaging findings of bisphosphonate-associated osteonecrosis of the jaws. AJNR Am J Neuroradiol. 2007;28:1139
  33. Raje N, Woo SB, Hande K, et al. Clinical, radiographic, and biochemical characterization of multiple myeloma patients with osteonecrosis of the jaw. Clin Cancer Res. 2008;14:2387
  34. Dodson TB, Raje NS, Caruso PA, et al. Case records of the Massachusetts General Hospital: Case 9-2008: A 65-year-old woman with a nonhealing ulcer of the jaw. N Engl J Med. 2008;358:1283
  35. Chang J. ODS postmarketing safety review (Department of Health and Human Services, Public Health Office, Food and Drug Administration, 2004). www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4095B2_03_04-FDA-TAB3.pdfAccessed July 30, 2008
  36. Junquera L, Gallego L. Nonexposed bisphosphonate-related osteonecrosis of the jaws: Another clinical variant?. J Oral Maxillofac Surg. 2008;66:1516
  37. McMahon RE, Bouquot JE, Glueck CJ, et al. Staging bisphosphonate-related osteonecrosis of the jaw should include early stages of disease. J Oral Maxillofac Surg. 2007;65:1899
  38. Vieillard MH, Maes JM, Penel G, et al. Thirteen cases of jaw osteonecrosis in patients on bisphosphonate therapy. Joint Bone Spine. 2008;75:34
  39. Bagan JV, Jimenez Y, Diaz JM, et al: Osteonecrosis of the jaws in intravenous bisphosphonate use: Proposal for a modification of the clinical classification. Oral Oncol Epub 2008 Aug 18
  40. Woo SB, Mawardi H, Treister N: Comments on “Osteonecrosis of the jaws in intravenous bisphosphonate use: Proposal for a modification of the clinical classification.” Oral Oncol Epub 2008 Nov 25
  41. Walter C, Grotz KA, Kunkel M, et al. Prevalence of bisphosphonate associated osteonecrosis of the jaw within the field of osteonecrosis. Support Care Cancer. 2007;15:197
  42. Bilezikian JP. Osteonecrosis of the jaw—Do bisphosphonates pose a risk?. N Engl J Med. 2006;355:2278
  43. Hellstein JW, Marek CL. Bisphosphonate osteochemonecrosis (bis-phossy jaw): Is this phossy jaw of the 21st century?. J Oral Maxillofac Surg. 2005;63:682

 This study was funded by the US Food and Drug Administration (HHSF223200510008C), the National Institute of Child Health and Human Development at the National Institutes of Health (K12 HD052163), and the Kaiser Permanente Community Benefit Program; a portion of this study was also supported by the National Center for Research Resources at the National Institutes of Health (UCSF-CTSI UL1 RR024131).

 J. Lo previously received research funding from Novartis; D. Martin previously owned stock in Merck & Company, Incorporated; a household family member of N. Gordon previously owned stock in Novartis Pharmaceuticals; a nonhousehold family member of F. O'Ryan is employed by Roche Laboratories; A. Go previously received research funding from Amgen and currently receives research funding from GlaxoSmithKline.

 The contents of this publication are solely the responsibility of the authors and do not represent the official views of the Food and Drug Administration or the National Institutes of Health.

PII: S0278-2391(09)00441-8

doi: 10.1016/j.joms.2009.03.050

Journal of Oral and Maxillofacial Surgery
Volume 68, Issue 2 , Pages 243-253 , February 2010

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