Journal of Oral and Maxillofacial Surgery
Volume 68, Issue 5 , Pages 959-963 , May 2010

Osteonecrosis of the Jaw in a Patient on Denosumab

  • Tara L. Aghaloo, DDS, MD, PhD

      Affiliations

    • Associate Professor, Section of Oral and Maxillofacial Surgery, School of Dentistry, University of California, Los Angeles, Los Angeles, CA
    • Corresponding Author InformationAddress correspondence and reprint requests to Dr Aghaloo: University of California, Los Angeles, 10833 Le Conte Avenue, CHS 53–076, Los Angeles, CA 90095
    • ,
  • Alan L. Felsenfeld, DDS, MA

      Affiliations

    • Professor of Clinical Dentistry, Section of Oral and Maxillofacial Surgery, School of Dentistry, University of California, Los Angeles, Los Angeles, CA
    • ,
  • Sotirios Tetradis, DDS, PhD

      Affiliations

    • Professor, Section of Oral and Maxillofacial Radiology, School of Dentistry, University of California, Los Angeles, Los Angeles, CA

References 

  1. Woo SB, Hellstein JW, Kalmar JR. Narrative [corrected] review: Bisphosphonates and osteonecrosis of the jaws. Ann Intern Med. 2006;144:753
  2. Shane E, Goldring S, Christakos S, et al. Osteonecrosis of the jaw: More research needed. J Bone Miner Res. 2006;21:1503
  3. Weitzman R, Sauter N, Eriksen EF, et al. Critical review: Updated recommendations for the prevention, diagnosis, and treatment of osteonecrosis of the jaw in cancer patients—May 2006. Crit Rev Oncol/Hematol. 2007;62:148
  4. Woodmansey KF, White RK, He J. Osteonecrosis related to intraosseous anesthesia: Report of a case. J Endod. 2009;35:288
  5. Meer S, Coleman H, Altini M, et al. Mandibular osteomyelitis and tooth exfoliation following zoster-CMV co-infection. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;101:70
  6. Pogrel MA, Miller CE. A case of maxillary necrosis. J Oral Maxillofac Surg. 2003;61:489
  7. Farah CS, Savage NW. Oral ulceration with bone sequestration. Aust Dent J. 2003;48:61
  8. Glueck CJ, McMahon RE, Bouquot JE, et al. A preliminary pilot study of treatment of thrombophilia and hypofibrinolysis and amelioration of the pain of osteonecrosis of the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1998;85:64
  9. Schwartz HC. Osteonecrosis of the jaws: A complication of cancer chemotherapy. Head Neck Surg. 1982;4:251
  10. Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: A growing epidemic. J Oral Maxillofac Surg. 2003;61:1115
  11. Tarassoff P, Csermak K. Avascular necrosis of the jaws: Risk factors in metastatic cancer patients. J Oral Maxillofac Surg. 2003;61:1238
  12. Bone HG, Hosking D, Devogelaer JP, et al. Ten years' experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med. 2004;350:1189
  13. Odac M. Package insert revisions re: Osteonecrosis of the jaws: Zometa injection and Aredia injection. Package insert. 2005;
  14. Bamias A, Kastritis E, Bamia C, et al. Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: Incidence and risk factors. J Clin Oncol. 2005;23:8580
  15. 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
  16. 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
  17. Migliorati CA. Bisphosphanates and oral cavity avascular bone necrosis. J Clin Oncol. 2003;21:4253
  18. Mortensen M, Lawson W, Montazem A. Osteonecrosis of the jaw associated with bisphosphonate use: Presentation of seven cases and literature review. Laryngoscope. 2007;117:30
  19. Zervas K, Verrou E, Teleioudis Z, et al. 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. 2006;134:620
  20. Bagan JV, Murillo J, Jimenez Y, et al. Avascular jaw osteonecrosis in association with cancer chemotherapy: Series of 10 cases. J Oral Pathol Med. 2005;34:120
  21. Clarke BM, Boyette J, Vural E, et al. Bisphosphonates and jaw osteonecrosis: The UAMS experience. Otolaryngol Head Neck Surg. 2007;136:396
  22. Durie BG, Katz M, Crowley J. Osteonecrosis of the jaw and bisphosphonates. N Engl J Med. 2005;353:99
  23. Khamaisi M, Regev E, Yarom N, et al. Possible association between diabetes and bisphosphonate-related jaw osteonecrosis. J Clin Endocrinol Metab. 2007;92:1172
  24. 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 Lymphoma. 2007;48:56
  25. Reid IR, Bolland MJ, Grey AB. Is bisphosphonate-associated osteonecrosis of the jaw caused by soft tissue toxicity?. Bone. 2007;41:318
  26. Allen MR, Burr DB. The pathogenesis of bisphosphonate-related osteonecrosis of the jaw: So many hypotheses, so few data. J Oral Maxillofac Surg. 2009;67:61
  27. Wood J, Bonjean K, Ruetz S, et al. Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. J Pharmacol Exp Ther. 2002;302:1055
  28. Mehrotra B, Ruggiero S. Bisphosphonate complications including osteonecrosis of the jaw. Hematol Am Soc Hematol Educ Program. 2006;356:
  29. Ruggiero SL, Fantasia J, Carlson E. Bisphosphonate-related osteonecrosis of the jaw: Background and guidelines for diagnosis, staging and management. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;102:433
  30. Geusens P. Emerging treatments for postmenopausal osteoporosis—Focus on Denosumab. Clin Interv Aging. 2009;4:241
  31. Lewiecki EM. Denosumab update. Curr Opin Rheumatol. 2009;21:369
  32. Thomas DM, Skubitz KM. Giant cell tumour of bone. Curr Opin Oncol. 2009;21:338
  33. Fizazi K, Lipton A, Mariette X, et al. Randomized phase II trial of Denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates. J Clin Oncol. 2009;27:1564
  34. Ruggiero SL, Dodson TB, Assael LA, et al. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws—2009 Update. J Oral Maxillofac Surg. 2009;67:2
  35. Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature. 2003;423:337
  36. Teitelbaum SL. Osteoclasts: What do they do and how do they do it?. Am J Pathol. 2007;170:427
  37. Baud'Huin M, Lamoureux F, Duplomb L, et al. RANKL, RANK, osteoprotegerin: Key partners of osteoimmunology and vascular diseases. Cell Mol Life Sci. 2007;64:2334
  38. Tat SK, Padrines M, Theoleyre S, et al. OPG/membranous—RANKL complex is internalized via the clathrin pathway before a lysosomal and a proteasomal degradation. Bone. 2006;39:706
  39. Hofbauer LC, Heufelder AE. Role of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin in bone cell biology. J Mol Med. 2001;79:243
  40. WHO. Pathology and Genetics of Tumours of Soft Tissue and Bone. Lyon: IARC Publishing; 2002;
  41. Morgan T, Atkins GJ, Trivett MK, et al. Molecular profiling of giant cell tumor of bone and the osteoclastic localization of ligand for receptor activator of nuclear factor kappaB. Am J Pathol. 2005;167:117
  42. Fujimoto N, Nakagawa K, Seichi A, et al. A new bisphosphonate treatment option for giant cell tumors. Oncol Rep. 2001;8:643
  43. Tse LF, Wong KC, Kumta SM, et al. Bisphosphonates reduce local recurrence in extremity giant cell tumor of bone: A case-control study. Bone. 2008;42:68
  44. Thomas D, Chawla S, Skubitz K, et al. Denosumab treatment of giant cell tumor of bone: Interim analysis of an open-label phase II study. J Clin Oncol. 2008;26:10500
  45. Shipman CM, Rogers MJ, Apperley JF, et al. Bisphosphonates induce apoptosis in human myeloma cell lines: A novel anti-tumour activity. Br J Haematol. 1997;98:665
  46. Murakami H, Takahashi N, Sasaki T, et al. A possible mechanism of the specific action of bisphosphonates on osteoclasts: Tiludronate preferentially affects polarized osteoclasts having ruffled borders. Bone. 1995;17:137
  47. Hughes DE, Wright KR, Uy HL, et al. Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. J Bone Miner Res. 1995;10:1478
  48. Sato M, Grasser W. Effects of bisphosphonates on isolated rat osteoclasts as examined by reflected light microscopy. J Bone Miner Res. 1990;5:31
  49. Rogers MJ, Gordon S, Benford HL, et al. Cellular and molecular mechanisms of action of bisphosphonates. Cancer. 2000;88:2961
  50. Rogers MJ. From molds and macrophages to mevalonate: A decade of progress in understanding the molecular mode of action of bisphosphonates. Calcif Tissue Int. 2004;75:451
  51. Luckman SP, Hughes DE, Coxon FP, et al. Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. J Bone Miner Res. 1998;13:581
  52. Coxon FP, Helfrich MH, Van't Hof R, et al. Protein geranylgeranylation is required for osteoclast formation, function, and survival: Inhibition by bisphosphonates and GGTI-298. J Bone Miner Res. 2000;15:1467
  53. Zerial M, Stenmark H. Rab GTPases in vesicular transport. Curr Opin Cell Biol. 1993;5:613
  54. Sato M, Grasser W, Endo N, et al. Bisphosphonate action (Alendronate localization in rat bone and effects on osteoclast ultrastructure). J Clin Invest. 1991;88:2095
  55. Jung A, Bisaz S, Fleisch H. The binding of pyrophosphate and two diphosphonates by hydroxyapatite crystals. Calcif Tissue Res. 1973;11:269
  56. Reddy GK, Mughal TI, Roodman GD. Novel approaches in the management of myeloma-related skeletal complications. Support Cancer Ther. 2006;4:15
  57. Romas E. Clinical applications of RANK-ligand inhibition. Int Med J. 2009;39:110
  58. Bekker PJ, Holloway DL, Rasmussen AS, et al. A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J Bone Miner Res. 2004;19:1059
  59. McClung MR, Lewiecki EM, Cohen SB, et al. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med. 2006;354:821
  60. Body JJ, Facon T, Coleman RE, et al. A study of the biological receptor activator of nuclear factor-kappaB ligand inhibitor, Denosumab, in patients with multiple myeloma or bone metastases from breast cancer. Clin Cancer Res. 2006;12:1221
  61. Brown JP, Prince RL, Deal C, et al. Comparison of the effect of Denosumab and alendronate on BMD and biochemical markers of bone turnover in postmenopausal women with low bone mass: A randomized, blinded, phase 3 trial. J Bone Miner Res. 2009;24:153
  62. Lipton A, Steger GG, Figueroa J, et al. Randomized active-controlled phase II study of Denosumab efficacy and safety in patients with breast cancer-related bone metastases. J Clin Oncol. 2007;25:4431
  63. Lipton A, Steger GG, Figueroa J, et al. Extended efficacy and safety of Denosumab in breast cancer patients with bone metastases not receiving prior bisphosphonate therapy. Clin Cancer Res. 2008;14:6690
  64. 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
  65. Amgen. http://www.amgen.com/media/media_pr_detail.jsp?releaseID=1316081Accessed September 22, 2009

 This work was supported by NIH/NIDCR DE019465 grant.

PII: S0278-2391(09)01940-5

doi: 10.1016/j.joms.2009.10.010

Journal of Oral and Maxillofacial Surgery
Volume 68, Issue 5 , Pages 959-963 , May 2010

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