Journal of Oral and Maxillofacial Surgery
Volume 63, Issue 11 , Pages 1567-1575 , November 2005

Bisphosphonate-Induced Exposed Bone (Osteonecrosis/Osteopetrosis) of the Jaws: Risk Factors, Recognition, Prevention, and Treatment

  • Robert E. Marx, DDS

      Affiliations

    • Professor of Surgery and Chief, University of Miami Miller School of Medicine, Division of Oral and Maxillofacial Surgery, Miami, FL.
    • Corresponding Author InformationAddress correspondence and reprint requests to Dr Marx: Miller School of Medicine, Division of Oral and Maxillofacial Surgery, University of Miami, 9380 SW 150th St, Suite 190, Miami, FL 33157
    • ,
  • Yoh Sawatari, DDS

      Affiliations

    • Private Practice, Oral Surgery, Miami, FL; Former Resident, University of Miami Miller School of Medicine, Division of Oral and Maxillofacial Surgery, Miami, FL.
    • ,
  • Michel Fortin, DMD, PhD

      Affiliations

    • Oral and Maxillofacial Surgery Department, l’Enfant-Jésus Hospital Faculty of Dentistry, Laval University, Quebec City, Quebec, Canada; Former Fellow in Tumor and Reconstructive Surgery, University of Miami Miller School of Medicine, Division of Oral and Maxillofacial Surgery, Miami, FL.
    • ,
  • Vishtasb Broumand, DMD, MD

      Affiliations

    • Fellow in Tumor and Reconstructive Surgery, University of Miami School of Medicine, Division of Oral and Maxillofacial Surgery, Miami, FL.

References 

  1. Marx RE . Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws (A growing epidemic) . J Oral Maxillofac Surg . 2003;61:1115
  2. Migliorati CA . Bisphosphonates and oral cavity avascular bone necrosis (J Clin Oncol) . 2003;21:4253
  3. Ruggerio SI , Mekrotra B , Engroff SL . Osteonecrosis of the jaws associated with the use of bisphosphonates. A review of 63 cases . J Oral Maxillofac Surg . 2004;62:527
  4. Carter GD , Gross AN . Bisphosphonates and avascular necrosis of the jaw . Aust Dent J . 2003;48:268
  5. Estilo CL , Van Poznak CH , Williams T . Osteonecrosis of the maxilla and mandible in patients treated with bisphosphonates (A retrospective study) . Proc Am Soc Clin Oncol . 2004;22:750; (abstr)
  6. Martin TJ , Gill V . Bisphosphonates–Mechanism of action. Experimental and clinical pharmacology . Auctr Preser . 2000;23:130
  7. Marx RE . Osteoradionecrosis–A new concept of its pathophysiology . J Oral Maxillofac Surg . 1983;41:351
  8. Marx RE , Johnson RP . Studies in the radiobiology of osteoradionecrosis and their clinical significance . Oral Surg Oral Med Oral Pathol . 1987;64:379
  9. Zigic TM , Marcous C , Hungerford DS , et al.   Corticosteroid therapy associated with ischemic necrosis of bone in systemic lupus erythematosis . Am J Med . 1985;79:596
  10. Miller KD , Masur H , Jones EC , et al.   High prevalence of osteonecrosis of the femoral head in HIV-infected adults . Ann Intern Med . 2002;137:17
  11. Abu-Shakra M , Buskila D , Shoenfeld Y . Osteonecrosis in patients with SLE . Clin Reo Allergy Immunol . 2003;25:13
  12. Ghreck CJ , Freilberg R , Gruppo R , et al.   Thrombophillis and hypofibrinolysis . In:  Urbaniak RJ ,  Jones JP editor. Reversible Pathogenetic Etiologies of Osteonecrosis in Osteonecrosis (Etiology, Diagnosis and Treatment) . Rosemont, IL: American Academy of Orthopedic Surgeons; 2001;p. 105–110
  13. Beek ER , Lowick CWGM , Papapulos SE . Bisphosphonates suppress bone resorption by a direct effect on early osteoclast precursors without affecting the osteoclastogenic capacity of osteogenic cells (The role of protein geranylgeranylation in the action of nitrogen-containing bisphosphonates or osteoclast precursors) . Bone . 2002;30:64
  14. Rogers MJ , Gordon S , Benfored HL , et al.   Cellular and molecular mechanisms of action of bisphosphonates (Skeletal complications of malignancy) . Cancer Suppl . 2000;88:2961
  15. 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
  16. Beresen JR , Lichtenstein A , Porter L , et al.   Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma . N Engl J Med . 1996;334:488
  17. Fournier P , Boissier S , Filleur S , et al.   Bisphosphonates inhibit angiogenesis in vitro and testosterone-stimulated vascular regrowth in the ventral prostate in castrated rats . Cancer Res . 2002;62:6538
  18. Wood J , Bongean K , Ruetz S , et al.   Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid . J Pharm Exp Thesopuctus . 2002;302:1055
  19. D’Amato RJ , Loughman MS , Flynn E , et al.   Thalidomide is an inhibitor of angiogenesis . Natl Acad Sci U S A . 1994;91:4082
  20. Brem S , Zagzag D , Tsanaclis AM , et al.   Inhibition of angiogenesis and tumor growth in the brain. Suppression of endothelial cell turnovers by penicillamine and the depletion of capper, an angiogenic cofactor . Am J Pathol . 1990;134:1121
  21. Kaban LB , Mullchen JB , Ezekowitz RA , et al.   Antiangiogenic therapy of a recurrent giant cell tumor of the mandible with interferon alfa-2a . Pediatrics . 1999;103:1145
  22. O’Reilly MS , Boehn T , Skmy J , et al.   Endostatin, an endogenous inhibitor of angiogenesis and tumor growth . Cell . 1997;88:277
  23. Stinchcombe TE , Mitchell BS , Depcets-Smith N , et al.   PS-341 (Bortazomib) is active in multiple myeloma. Preliminary report of a phase I trial of the proteasome inhibitor PS-341 in patients with hematologic malignancies . Blood . 2000;96:516a; (abstr)
  24. Sim BK , O’Reilly MS , Liang H , et al.   A recombinant human angiostatin protein inhibits experimental primary and metastatic cancer . Cancer Res . 1997;57:1329
  25. Whyte M , Venhert D , Clements KL , et al.   Bisphosphonate-induced osteopetrosis . N Engl J Med . 2003;349:457
  26. Wang J , Goodgen NM , Pogrel MA . Osteonecrosis of the jaw associated with cancer chemotherapy . J Oral Maxillofac Surg . 2004;62:91

PII: S0278-2391(05)01187-0

doi: 10.1016/j.joms.2005.07.010

Journal of Oral and Maxillofacial Surgery
Volume 63, Issue 11 , Pages 1567-1575 , November 2005

Article Tools

* Image Usage & Resolution