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Definition, Clinical Features and Staging of Medication-Related Osteonecrosis of the Jaw

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Medication-Related Osteonecrosis of the Jaws

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Abstract

Medication-related osteonecrosis of jaw (MRONJ) has become a well-known side effect of bisphosphonate therapy which predominantly occurs in patients suffering from malignant diseases who receive intravenous administrations of nitrogen-containing bisphosphonates. More recently, similar problems have been described after treatment with denosumab.

The majority of ONJ cases under bisphosphonate treatment occurred in the mandible (around 2/3 of the cases) with a predilection for the molar and premolar regions in both jaws. Besides exposed necrotic bone, pain and swelling of the surrounding soft tissues as well as intra- or extra-oral sinus tracts are typical signs of MRONJ. Furthermore, complications like abscess formation, pathological fractures, sinusitis and impairment of inferior alveolar nerve function might occur. Staging of MRONJ is usually performed according to the recommendations of the American Association of Oral and Maxillofacial Surgeons.

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References

  1. Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic [Letter]. J Oral Maxillofac Surg. 2003;61:1115.

    Article  PubMed  Google Scholar 

  2. Wang J, Goodger NM, Pogrel MA. Osteonecrosis of the jaw associated with cancer chemotherapy. J Oral Maxillofac Surg. 2003;61:1104–7.

    Article  CAS  PubMed  Google Scholar 

  3. Migliorati CA. Bisphosphonates and oral cavity avascular bone necrosis. J Clin Oncol. 2003;21(22):4253–4.

    Article  PubMed  Google Scholar 

  4. Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL. Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg. 2004;62(5):527–34.

    Article  PubMed  Google Scholar 

  5. Aghaloo TL, Felsenfeld AL, Tetradis S. Osteonecrosis of the jaw in a patient on denosumab. J Oral Maxillofac Surg. 2010;68(5):959–63.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Stopeck AT, Lipton A, Body JJ, Steger GG, Tonkin K, de Boer RH, et al. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J Clin Oncol. 2010;28(35):5132–9.

    Article  CAS  PubMed  Google Scholar 

  7. Henry DH, Costa L, Goldwasser F, Hirsh V, Hungria V, Prausova J, et al. Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol. 2011;29(9):1125–32.

    Article  CAS  PubMed  Google Scholar 

  8. Saad F, Brown JE, Van Poznak C, Ibrahim T, Stemmer SM, Stopeck AT, et al. Incidence, risk factors, and outcomes of osteonecrosis of the jaw: integrated analysis from three blinded active-controlled phase III trials in cancer patients with bone metastases. Ann Oncol. 2012;23(5):1341–7.

    Article  CAS  PubMed  Google Scholar 

  9. Lipton A, Fizazi K, Stopeck AT, Henry DH, Brown JE, Yardley DA, et al. Superiority of denosumab to zoledronic acid for prevention of skeletal-related events: a combined analysis of 3 pivotal, randomised, phase 3 trials. Eur J Cancer. 2012;48(16):3082–92.

    Article  CAS  PubMed  Google Scholar 

  10. Van den Wyngaert T, Wouters K, Huizing MT, Vermorken JB. RANK ligand inhibition in bone metastatic cancer and risk of osteonecrosis of the jaw (ONJ): non bis in idem? Support Care Cancer. 2011;19(12):2035–40.

    Article  PubMed  Google Scholar 

  11. Ruggiero SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B, et al. American Association of Oral and Maxillofacial Surgeons Special Committee Position Paper on Medication-Related Osteonecrosis of the Jaw. J Oral and Maxillofac Surg 2014;72(10):1938–56.

    Google Scholar 

  12. Advisory Task Force on Bisphosphonate-Related Osteonecrosis of the Jaws. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg. 2007;65:369–76.

    Article  Google Scholar 

  13. Otto S, Schuler K, Ihrler S, Ehrenfeld M, Mast G. Osteonecrosis or metastases of the jaw or both? Case report and review of the literature. J Oral Maxillofac Surg. 2010;68(5):1185–8.

    Article  PubMed  Google Scholar 

  14. Bedogni A, Saia G, Ragazzo M, Bettini G, Capelli P, D'Alessandro E, et al. Bisphosphonate-associated osteonecrosis can hide jaw metastases. Bone. 2007;41(6):942–5.

    Article  CAS  PubMed  Google Scholar 

  15. Bamias A, Kastritis E, Bamia C, Moulopoulos LA, Melakopoulos I, Bozas G, et al. Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors. J Clin Oncol. 2005;23(34):8580–7.

    Article  PubMed  Google Scholar 

  16. Otto S, Schreyer C, Hafner S, Mast G, Ehrenfeld M, Stürzenbaum S, et al. Bisphosphonate-related osteonecrosis of the jaws - characteristics, risk factors, clinical features, localization and impact on oncological treatment. J Craniomaxillofac Surg. 2012;40(4):303–9.

    Article  PubMed  Google Scholar 

  17. Abu-Id MH, Warnke PH, Gottschalk J, Springer I, Wiltfang J, Acil Y, et al. “Bis-phossy jaws” – high and low risk factors for bisphosphonate-induced osteonecrosis of the jaw. J Craniomaxillofac Surg. 2008;36(2):95–103.

    Article  PubMed  Google Scholar 

  18. Otto S, Abu-Id MH, Fedele S, Warnke PH, Becker ST, Kolk A, et al. Osteoporosis and bisphosphonates-related osteonecrosis of the jaw: not just a sporadic coincidence–a multi-centre study. J Craniomaxillofac Surg. 2011;39(4):272–7.

    Article  PubMed  Google Scholar 

  19. Rugani P, Luschin G, Jakse N, Kirnbauer B, Lang U, Acham S. Prevalence of bisphosphonate-associated osteonecrosis of the jaw after intravenous zoledronate infusions in patients with early breast cancer. Clin Oral Investig. 2013;18(2):401–7.

    Article  PubMed  Google Scholar 

  20. Hoff AO, Toth BB, Altundag K, Johnson MM, Warneke CL, Hu M, et al. Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates. J Bone Miner Res. 2008;23:826–36.

    Article  CAS  PubMed  Google Scholar 

  21. Walter C, Al-Nawas B, Frickhofen N, Gamm H, Beck J, Reinsch L, et al. Prevalence of bisphosphonate associate osteonecrosis of the jaws in multiple myeloma patients. Head Face Med. 2010;6:11. doi:10.1186/1746-160X-6-11.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Yarom N, Yahalom R, Shoshani Y, Hamed W, Regev E, Elad S. Osteonecrosis of the jaw induced by orally administered bisphosphonates: incidence, clinical features, predisposing factors and treatment outcome. Osteoporos Int. 2007;18(10):1363–70.

    Article  CAS  PubMed  Google Scholar 

  23. Assaf AT, Zrnc TA, Riecke B, Wikner J, Zustin J, Friedrich RE, et al. Intraoperative efficiency of fluorescence imaging by Visually Enhanced Lesion Scope (VELscope®) in patients with bisphosphonate related osteonecrosis of the jaw (MRONJ). J Craniomaxillofac Surg. 2013;42(5):e157–64. doi:10.1016/j.jcms.2013.07.014. pii: S1010-5182(13)00212-6.

    Google Scholar 

  24. Assaf AT, Smeets R, Riecke B, Weise E, Gröbe A, Blessmann M, et al. Incidence of bisphosphonate-related osteonecrosis of the jaw in consideration of primary diseases and concomitant therapies. Anticancer Res. 2013;33(9):3917–24.

    CAS  PubMed  Google Scholar 

  25. Mehanna P, Goddard R. Bisphosphonate associated osteonecrosis: an unusual case. Aust Dent J. 2010;55(3):311–3.

    Article  CAS  PubMed  Google Scholar 

  26. Soda T, Fukumoto R, Hayashi T, Oka D, Fujimoto N, Koide T. A case of prostate cancer associated with bisphosphonate-related osteonecrosis of the jaw followed by retropharyngeal abscess. Hinyokika Kiyo. 2013;59(9):587–91.

    PubMed  Google Scholar 

  27. Matsushita A, Kamigaki S, Nakamura Y. A case of brain abscess secondary to bisphosphonate-related osteonecrosis of the jaws in metastatic bone lesions from breast carcinoma. Gan To Kagaku Ryoho. 2013;40(5):631–3.

    PubMed  Google Scholar 

  28. Otto S, Hafner S, Grötz KA. The role of inferior alveolar nerve involvement in bisphosphonate-related osteonecrosis of the jaw. J Oral Maxillofac Surg. 2009;67(3):589–92. doi:10.1016/j.joms.2008.09.028.

    Article  PubMed  Google Scholar 

  29. Assaf AT, Jürgens TP, Benecke AW, Riecke B, Blessmann M, Zrnc TA, et al. Numb chin syndrome. A rare and often overlooked symptom. J Orofac Pain. 2014;28(1):80–90. 01/2014 Date accepted: 2013-07-19.

    Google Scholar 

  30. Sierra-Hidalgo F, de Pablo-Fernández E, Correas-Callero E, Villarejo-Galende A. Numb chin syndrome caused by bisphosphonates-induced osteonecrosis of the jaw. Rev Neurol. 2009;49(4):190–2.

    CAS  PubMed  Google Scholar 

  31. Otto S, Pautke C, Hafner S, Hesse R, Reichardt LF, Mast G, et al. Pathologic fractures in bisphosphonate-related osteonecrosis of the jaw—review of the literature and review of our own cases. Craniomaxillofac Trauma Reconstr. 2013;6(3):147–54.

    Article  PubMed Central  PubMed  Google Scholar 

  32. Mast G, Otto S, Mücke T, Schreyer C, Bissinger O, Kolk A, et al. Incidence of maxillary sinusitis and oro-antral fistulae in bisphosphonate-related osteonecrosis of the jaw. J Craniomaxillofac Surg. 2012;40(7):568–71.

    Article  PubMed  Google Scholar 

  33. Piesold JU, Al-Nawas B, Grötz KA. Osteonecrosis of the jaws by long term therapy with bisphosphonates. Mund Kiefer Gesichtschir. 2006;10(5):287–300.

    Article  PubMed  Google Scholar 

  34. Saldanha S, Shenoy VK, Eachampati P, Uppal N. Dental implications of bisphosphonate-related osteonecrosis. Gerodontology. 2012;29(3):177–87.

    Article  PubMed  Google Scholar 

  35. Di Fede O, Fusco V, Matranga D, Solazzo L, Gabriele M, Gaeta GM, et al. Osteonecrosis of the jaws in patients assuming oral bisphosphonates for osteoporosis: a retrospective multi-hospital-based study of 87 Italian cases. Eur J Intern Med. 2013;24(8):784–90. pii: S0953-6205(13)00139-8.

    Article  PubMed  Google Scholar 

  36. Grötz KA, Piesold JU, Al-Nawas B. Bisphosphonat-assoziierte Kiefernekrose (BPONJ) und andere Medikamenten-assoziierte Kiefernekrosen1e18. http://www.awmf.org. 2012, (007/091).

  37. Jadu F, Lee L, Pharoah M, Reece D, Wang L. 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(12):2015–9.

    Article  CAS  PubMed  Google Scholar 

  38. Marx RE, Sawatari Y, Fortin M, Broumand V. Bisphosphonate-induced exposed bone (osteonecrosis/osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment. J Oral Maxillofac Surg. 2005;63(11):1567–75.

    Article  PubMed  Google Scholar 

  39. Saussez S, Javadian R, Hupin C, Magremanne M, Chantrain G, Loeb I, et al. Bisphosphonate-related osteonecrosis of the jaw and its associated risk factors: a Belgian case series. Laryngoscope. 2009;119(2):323–9.

    Article  CAS  PubMed  Google Scholar 

  40. Thumbigere-Math V, Michalowicz BS, Hodges JS, Tsai ML, Swenson KK, Rockwell L, et al. Periodontal disease as a risk factor for bisphosphonate-related osteonecrosis of the jaw. J Periodontol. 2013;85(2):226–33.

    Article  PubMed Central  PubMed  Google Scholar 

  41. Tsao C, Darby I, Ebeling PR, Walsh K, O’Brien-Simpson N, Reynolds E, et al. Oral health risk factors for bisphosphonate-associated jaw osteonecrosis. J Oral Maxillofac Surg. 2013;71(8):1360–6.

    Article  PubMed  Google Scholar 

  42. Ficarra G, Beninati F, Rubino I, Vannucchi A, Longo G, Tonelli P, et al. Osteonecrosis of the jaws in periodontal patients with a history of bisphosphonates treatment. J Clin Periodontol. 2005;32(11):1123–8.

    Article  CAS  PubMed  Google Scholar 

  43. Merigo E, Manfredi M, Meleti M, Corradi D, Vescovi P. Jaw bone necrosis without previous dental extractions associated with the use of bisphosphonates (pamidronate and zoledronate): a four-case report. J Oral Pathol Med. 2005;34(10):613–7.

    Article  CAS  PubMed  Google Scholar 

  44. Mignogna MD, Fedele S, Lo Russo L, Ciccarelli R, Lo Muzio L. Case 2. Osteonecrosis of the jaws associated with bisphosphonate therapy. J Clin Oncol. 2006;24(9):1475–7.

    Article  PubMed  Google Scholar 

  45. Vannucchi AM, Ficarra G, Antonioli E, Bosi A. Osteonecrosis of the jaw associated with zoledronate therapy in a patient with multiple myeloma. Br J Haematol. 2005;128(6):738.

    Article  PubMed  Google Scholar 

  46. Gutta R, Louis PJ. Bisphosphonates and osteonecrosis of the jaws: science and rationale. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;104(2):186–93.

    Article  PubMed  Google Scholar 

  47. Hewitt C, Farah CS. Bisphosphonate-related osteonecrosis of the jaws: a comprehensive review. J Oral Pathol Med. 2007;36(6):319–28.

    Article  CAS  PubMed  Google Scholar 

  48. Lam DK, Sandor GK, Holmes HI, Evans AW, Clokie CM. A review of bisphosphonate-associated osteonecrosis of the jaws and its management. J Can Dent Assoc. 2007;73(5):417–22.

    PubMed  Google Scholar 

  49. Mariotti A. Bisphosphonates and osteonecrosis of the jaws. J Dent Educ. 2008;72(8):919–29.

    PubMed  Google Scholar 

  50. Migliorati CA, Siegel MA, Elting LS. Bisphosphonate-associated osteonecrosis: a long-term complication of bisphosphonate treatment. Lancet Oncol. 2006;7(6):508–14.

    Article  CAS  PubMed  Google Scholar 

  51. Miksad RA, Lai KC, Dodson TB, Woo SB, Treister NS, Akinyemi O, et al. Quality of life implications of bisphosphonate-associated osteonecrosis of the jaw. Oncologist. 2011;16(1):121–32.

    Article  PubMed Central  PubMed  Google Scholar 

  52. Patel S, Choyee S, Uyanne J, Nguyen AL, Lee P, Sedghizadeh PP, et al. Non-exposed bisphosphonate-related osteonecrosis of the jaw: a critical assessment of current definition, staging, and treatment guidelines. Oral Dis. 2012;18(7):625–32.

    Article  CAS  PubMed  Google Scholar 

  53. Junquera L, Gallego L. Nonexposed bisphosphonate-related osteonecrosis of the jaws: another clinical variant? J Oral Maxillofac Surg. 2008;66(7):1516–7.

    Article  PubMed  Google Scholar 

  54. Fedele S, Porter SR, D’Aiuto F, Aljohani S, Vescovi P, Manfredi M, et al. Nonexposed variant of bisphosphonate-associated osteonecrosis of the jaw: a case series. Am J Med. 2010;123(11):1060–4.

    Article  CAS  PubMed  Google Scholar 

  55. Vescovi P, Nammour S. Bisphosphonate-related osteonecrosis of the jaw (MRONJ) therapy. A critical review. Minerva Stomatol. 2010;59(4):181–203. 204–13.

    Google Scholar 

  56. Hutchinson M, O’Ryan F, Chavez V, Lathon PV, Sanchez G, Hatcher DC, et al. Radiographic findings in bisphosphonate-treated patients with stage 0 disease in the absence of bone exposure. J Oral Maxillofac Surg. 2010;68(9):2232–40.

    Article  PubMed  Google Scholar 

  57. Mawardi H, Treister N, Richardson P, Anderson K, Munshi N, Faiella RA, et al. Sinus tracts–an early sign of bisphosphonate-associated osteonecrosis of the jaws? J Oral Maxillofac Surg. 2009;67(3):593–601.

    Article  PubMed  Google Scholar 

  58. Polizzotto MN, Cousins V, Schwarer AP. Bisphosphonate-associated osteonecrosis of the auditory canal. Br J Haematol. 2006;132(1):114.

    Article  PubMed  Google Scholar 

  59. Salzman R, Hoza J, Perina V, Stárek I. Osteonecrosis of the external auditory canal associated with oral bisphosphonate therapy: case report and literature review. Otol Neurotol. 2013;34(2):209–13.

    Article  PubMed  Google Scholar 

  60. Fizazi K, Carducci M, Smith M, Damião R, Brown J, Karsh L, et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet. 2011;377(9768):813–22.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Henry D, Vadhan-Raj S, Hirsh V, von Moos R, Hungria V, Costa L, et al. Delaying skeletal-related events in a randomized phase 3 study of denosumab versus zoledronic acid in patients with advanced cancer: an analysis of data from patients with solid tumors. Support Care Cancer. 2013;22(3):679–87.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Oral and Maxillofacial Surgery, Ludwig-Maximilians-University of Munich, Munich, Germany

    Sven Otto MD, DMD, FEBOMFS

  2. Department of Oral and Maxillofacial Surgery, Kyungpook National University, Daegu, Korea

    Tae-Geon Kwon DDS, PhD

  3. Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg Eppendorf, Hamburg, Germany

    Alexandre Th. Assaf MD, DMD, FEBOMFS

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  1. Sven Otto MD, DMD, FEBOMFS
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  2. Tae-Geon Kwon DDS, PhD
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  3. Alexandre Th. Assaf MD, DMD, FEBOMFS
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Correspondence to Sven Otto MD, DMD, FEBOMFS .

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  1. Department of Oral and Maxillofacial Sur, Ludwig-Maximilians-University of Munich, Munich, Germany

    Sven Otto

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Otto, S., Kwon, TG., Assaf, A.T. (2015). Definition, Clinical Features and Staging of Medication-Related Osteonecrosis of the Jaw. In: Otto, S. (eds) Medication-Related Osteonecrosis of the Jaws. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-43733-9_4

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  • DOI: https://doi.org/10.1007/978-3-662-43733-9_4

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