Skip to main content

Epidemiology of Osteonecrosis of the Jaws from Antiresorptive Treatment

  • Chapter
  • 935 Accesses

Abstract

Osteonecrosis of the jaws (ONJ), also called “dead jawbone,” is a complication of bisphosphonate (BP) and denosumab treatment of osteoporosis. The first cases associated with bisphosphonate were reported in 2003, and in recent years a significant knowledge has evolved. The incidence is low, but those affected may suffer from pain, loss of gums and teeth, and thus significant loss of masticatory function. This chapter gives an overview of classification as it relates to epidemiology and of the epidemiology of this important condition.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Notes

  1. 1.

    *Important References

    **Very Important References

References

*Important References

**Very Important References

  1. *Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg. 2003;61(9):1115–7. *This is the first paper describing start of the new epidemic of ONJ related to the use of bisphosphonate. This paper is important and the foundation for many subsequent papers.

    Article  PubMed  Google Scholar 

  2. 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 

  3. 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 

  4. Brunello A, Saia G, Bedogni A, Scaglione D, Basso U. Worsening of osteonecrosis of the jaw during treatment with sunitinib in a patient with metastatic renal cell carcinoma. Bone. 2009;44:173–5.

    Article  PubMed  CAS  Google Scholar 

  5. Hopp RN, Pucci J, Santos-Silva AR, Jorge J. Osteonecrosis after administration of intravitreous bevacizumab. J Oral Maxillofac Surg. 2012;70(3):632–5.

    Article  PubMed  Google Scholar 

  6. Jacobsen C, Zemann W, Obwegeser JA, Grätz KW, Metzler P. The phosphorous necrosis of the jaws and what can we learn from the past: a comparison of “phossy” and “bisphossy” jaw. Oral Maxillofac Surg. doi:10.1007/s10006-012-0376-z. Published online 28 Dec 2012.

    Google Scholar 

  7. Migliorati CA, Casiglia J, Epstein J, Jacobsen PL, Siegel MA, Woo SB. Managing the care of patients with bisphosphonate-associated osteonecrosis: an American academy of oral medicine position paper. J Am Dent Assoc. 2005;136(12):1658–68.

    Article  PubMed  CAS  Google Scholar 

  8. *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(4):433–41. *This paper is the consensus paper of the American Association of Oral & Maxillofacial Surgery. It was the first to establish an overview, which was adopted as a global standard of current knowledge in 2006.

    Article  PubMed  Google Scholar 

  9. AAOMS. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg. 2007;65(3):369–76.

    Article  Google Scholar 

  10. **Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B. American association of oral and maxillofacial surgeons position paper on bisphosphonate-related osteonecrosis of the jaw – 2009 update. Aust Endod J. 2009;35(3):119–30. **This paper is an update of the consensus paper from 2006. It introduced stage 0 ONJ and updated the literature.

    Article  PubMed  Google Scholar 

  11. Hellstein JW, Adler RA, Edwards B, et al. Managing the care of patients receiving antiresorptive therapy for prevention and treatment of osteoporosis: executive summary of recommendations from the American dental association council on scientific affairs. J Am Dent Assoc. 2011;142(11):1243–51.

    Article  PubMed  CAS  Google Scholar 

  12. Ruggerio SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B, et al. Medication-related osteonecrosis of the jaw – 2014 update. In: American Association of Oral and Maxillofacial Surgeons Position Paper (AAOMS).

    Google Scholar 

  13. Pautke C, Kreutzer P, Weitz J, Knödler K, et al. Bisphosphonate related osteonecrosis of the jaw: a minipig large animal model. Bone. 2012;51:592–9.

    Article  PubMed  CAS  Google Scholar 

  14. Abtahi J, Agholme F, Aspenberg P. Prevention of osteonecrosis of the jaw by mucoperiosteal coverage in a rat model. Int J Oral Maxillofac Surg. 2013;42:632–6.

    Article  PubMed  CAS  Google Scholar 

  15. *Otto S, Pautke C, Opelz C, Westphal I, et al. Osteonecrosis of the jaw: effect of bisphosphonate type, local concentration, and acidic milieu on the pathomechanism. J Oral Maxillofac Surg. 2010;68:2837–45. *This paper emphasized the importance of concentration and dose of bisphosphonate for ONJ and introduce the potential importance of infection for ONJ.

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  18. *Schiodt M, Reibel J, Oturai P, Kofod T. Comparison of nonexposed and exposed bisphosphonate-induced osteonecrosis of the jaws: a retrospective analysis from the Copenhagen cohort and a proposal for an updated classification system. Oral Surg Oral Med Oral Pathol Oral Radiol. 2014;117:204–13. *This paper demonstrated that non-exposed ONJ is biologically not different from exposed ONJ, and should be included into the definition of ONJ. The paper also suggested new criteria for classification of non-exposed ONJ.

    Article  PubMed  Google Scholar 

  19. *Fedele S, Bedogni G, Scoletta M, Favia G, Colella G, Agrillo A, et al. Up to a quarter of patients with osteonecrosis of the jaw associated with antiresorptive agents remain undiagnosed. Br J Oral Maxillofac Surg. 2014, 10; E-version before print. *This paper demonstrated that a high proportion of ONJ may remain undiagnosed because they are non-exposed, and therefore do not qualify for the current (2009) AAOMS definition of ONJ (ref. [8]).

    Google Scholar 

  20. Walter C, Al-Nawas B, Grötz KA, Thomas C, et al. Prevalence and risk factors of bisphosphonate-associated osteonecrosis of the jaw in prostate cancer patients with advanced disease treated with zoledronate. Eur Urol. 2008;54:1066–72.

    Article  PubMed  Google Scholar 

  21. Bamias A, Kastritis E, Bamia C, Moulopoulos LA, et al. Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors. Clin Oncol. 2005;23:8580–7.

    Article  Google Scholar 

  22. Yamazaki T, Yamori M, Yamanoto K, Saito K, et al. Risk of osteomyelitis of the jaw induced by oral bisphosphonates in patients taking medication for osteoporosis: a hospital-based cohort study in Japan. Bone. 2012;51:882–7.

    Article  PubMed  CAS  Google Scholar 

  23. Vahtsevanos K, Kyrgidis A, Verrou E, et al. Longitudinal cohort study of risk factors in cancer patients of bisphosphonate-related osteonecrosis of the jaw. J Clin Oncol. 2009;27(32):5356–62.

    Article  PubMed  CAS  Google Scholar 

  24. Boonyapakorn T, Schirmer I, Reichart PA, Sturm I, Massenkeil G. Bisphosphonate-induced osteonecrosis of the jaws: prospective study of 80 patients with multiple myeloma and other malignancies. Oral Oncol. 2008;44:857–69.

    Article  PubMed  CAS  Google Scholar 

  25. Lo JC, O’Ryan FS, Gordon NP, et al. Prevalence of osteonecrosis of the jaw in patients with oral bisphosphonate exposure. J Oral Maxillofac Surg. 2010;68(2):243–53.

    Article  PubMed  Google Scholar 

  26. Borrromeo GL, Brand C, Clement JG, McCullough M, Crighton L, Hepworth G, Wark JD. A large Case-control study reveals a positive association between bisphosphonate use and delayed dental healing and osteonecrosis of the jaw. J Bone Miner Res. 2014;Epub. doi:10.1002/JMR.2179

    Google Scholar 

  27. Solomon DH, Mercer E, Woo SB, Avorn J, Schneeweiss S, Treister N. Defining the epidemiology of bisphosphonate-associated osteonecrosis of the jaw: prior work and current challenges. Osteoporos Int. 2013;24(1):237–44.

    Article  PubMed  CAS  Google Scholar 

  28. Lee S-H. Chang S-S, Lee M, Chan R-C, Lee C-C. Risk of osteonecrosis in patients taking bisphosphonates for prevention of osteoporosis: a systematic review and meta-analysis. Osteoporos Int Online. Published 17 Dec 2013. doi:10.1007/s00198-013-2575-3

    Google Scholar 

  29. **Barasch A, Cunha-Cruz J, Curro FA, Hujoel P, Sung AH, Vena D, Voinea-Griffin AE, CONDOR Collaborative Group. Risk factors for osteonecrosis of the jaws: a case-control study from the CONDOR dental PBRN. J Dent Res. 2011;90(4):439–44. **This paper demonstrated a number of risk factors for ONJ including providing odds ratio of risk, which are reported in Table 13.3. Notably, oral suppuration, tooth extraction, and bisphosphonate treatment of long duration are important risk factors.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Otto S, Abu-Id MH, Fedele S, 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 

  31. Jacobsen C, Metzler P, Obwegeser JA, Zemann W, Graetz KW. Osteopathology of the jaw associated with bone resorption inhibitors: what have we learned in the last 8 years? A single-centre experience with 110 patients. Swiss Med Wkly. 2012;142:w13605.

    PubMed  Google Scholar 

  32. Otto S, Baumann S, Ehrenfeld M, Pautke C. Successful surgical management of osteonecrosis of the jaw due to RANK-ligand inhibitor treatment using fluorescence guided bone resection. J Cranio Maxiallofac Surg. 2013;41:694–8.

    Article  Google Scholar 

  33. Yarom N, Yahalom R, Shoshani Y, Hamed W, Regev E, Elad S. 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  Google Scholar 

  34. Mavrokokki T, Cheng A, Stein B, Goss A. Nature and frequency of bisphosphonate-associated osteonecrosis of the jaws in Australia. J Oral Maxillofac Surg. 2007;65(3):415–23.

    Article  PubMed  Google Scholar 

  35. Wessel JH, Dodson TB, Zavras AI. Zoledronate, smoking, and obesity are strong risk factors for osteonecrosis of the jaw: a case-control study. J Oral Maxillofac Surg. 2008;66(4):625–31.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Sarasquete ME, et al. Bisphosphonate-related osteonecrosis of the jaw is associated with polymorphisms of the cytochrome P450 CYP2C8 in multiple myeloma: a genome-wide single nucleotide polymorphism analysis. Blood. 2008;112(7):2709–12.

    Article  PubMed  CAS  Google Scholar 

  37. Raje N, et al. Clinical, radiographic, and biochemical characterization of multiple myeloma patients with osteonecrosis of the jaw. Clin Cancer Res. 2008;14(8):2387–95.

    Article  PubMed  CAS  Google Scholar 

  38. Otto S, Schreyer C, Hafner 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 

  39. Fede D, 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 Int Med. 2013;24:784–90.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Morten Schiødt DDS, Dr.Odont .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Schiødt, M. (2016). Epidemiology of Osteonecrosis of the Jaws from Antiresorptive Treatment. In: Silverman, S., Abrahamsen, B. (eds) The Duration and Safety of Osteoporosis Treatment. Springer, Cham. https://doi.org/10.1007/978-3-319-23639-1_13

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-23639-1_13

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-23638-4

  • Online ISBN: 978-3-319-23639-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics