Skip to main content

Advertisement

SpringerLink
Log in

Prevalence of bisphosphonate associated osteonecrosis of the jaw within the field of osteonecrosis

  • Original article
  • Published:
Supportive Care in Cancer Aims and scope Submit manuscript

Abstract

Objectives

Prevalence of bisphosphonate-associated osteonecrosis of the jaws within the catchment area of a university hospital maxillofacial unit and to review the outcome of treatment.

Methods

In a retrospective study, all patients with osteonecrosis, osteomyelitis and osteoradionecrosis treated in the period from January 2000 to March 2005 in the department for Maxillo Facial Surgery at the University of Mainz, Germany were analysed.

Results

Forty percent of the patients are grouped to odontogenic or surgically induced osteomyelitis. The second largest group (28%) were patients with osteoradionecrosis (ORN). Ten percent of all patients developed an osteonecrosis after treatment with bisphosphonates (BOJ). Eight percent showed osteomyelitis or sequester due to a trauma while 14% of all patients had osteomyelitis of unknown origin. All BOJ patients took bisphosphonates because of metastatic diseases of the bone (plasmocytoma, mamma carcinoma and prostate cancer) for up to 5 years. All had been administered a nitrogen-containing bisphosphonate (either pamidronat or zoledronat). Thirteen out of the 17 patients with BOJ and 14 of the 45 with ORN reported a possible trigger like previous tooth extraction, pressure denture sore or periodontal diseases.

Conclusion

These findings support the association of bisphosphonate therapy and osteonecrosis of the jaw. The importance of this new disease is characterised by the growing number of patients. The role of dental trigger factors and the poor surgical outcome both seem to justify a prophylactic dental care concept in high-risk patients.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Rogers MJ, Gordon S, Benford HL, Coxon FP, Luckman SP, Monkkonen J, Frith JC (2000) Cellular and molecular mechanisms of action of bisphosphonates. Cancer 88:2961–2978

    Article  PubMed  CAS  Google Scholar 

  2. Fleisch H (2002) Development of bisphosphonates. Breast Cancer Res 4:30–34

    Article  PubMed  CAS  Google Scholar 

  3. van der Pluijm G, Vloedgraven H, van Beek E, van der Wee-Pals L, Lowik C, Papapoulos S (1996) Bisphosphonates inhibit the adhesion of breast cancer cells to bone matrices in vitro. J Clin Invest 98:698–705

    PubMed  Google Scholar 

  4. Boissier S, Magnetto S, Frappart L, Cuzin B, Ebetino FH, Delmas PD, Clezardin P (1997) Bisphosphonates inhibit prostate and breast carcinoma cell adhesion to unmineralized and mineralized bone extracellular matrices. Cancer Res 57:3890–3894

    PubMed  CAS  Google Scholar 

  5. Clezardin P, Fournier P, Boissier S, Peyruchaud O (2003) In vitro and in vivo antitumor effects of bisphosphonates. Curr Med Chem 10:173–180

    PubMed  CAS  Google Scholar 

  6. Lin JH (1996) Bisphosphonates: a review of their pharmacokinetic properties. Bone 18:75–85

    Article  PubMed  CAS  Google Scholar 

  7. Perry CM, Figgitt DP (2004) Zoledronic acid: a review of its use in patients with advanced cancer. Drugs 64:1197–1211

    Article  PubMed  CAS  Google Scholar 

  8. Leyvraz S, Hess U, Flesch G, Bauer J, Hauffe S, Ford JM, Burckhardt P (1992) Pharmacokinetics of pamidronate in patients with bone metastases. J Natl Cancer Inst 84:788–792

    Article  PubMed  CAS  Google Scholar 

  9. Amin D, Cornell SA, Gustafson SK, Needle SJ, Ullrich JW, Bilder GE, Perrone MH (1992) Bisphosphonates used for the treatment of bone disorders inhibit squalene synthase and cholesterol biosynthesis. J Lipid Res 33:1657–1663

    PubMed  CAS  Google Scholar 

  10. Amin D, Cornell SA, Perrone MH, Bilder GE (1996) 1-Hydroxy-3-(methylpentylamino)-propylidene-1,1-bisphosphonic acid as a potent inhibitor of squalene synthase. Arzneimittelforschung 46:759–762

    PubMed  CAS  Google Scholar 

  11. Marx RE (2003) Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of jaws: a growing epidemic. J Oral Maxillofac Surg 61:1115–1117

    Article  PubMed  Google Scholar 

  12. Carter GD, Goss AN (2003) Bisphosphonates and avascular necrosis of the jaws. Aust Dent J 48:268

    Article  PubMed  CAS  Google Scholar 

  13. Migliorati CA (2003) Bisphosphanates and oral cavity avascular bone necrosis. J Clin Oncol 21:4253–4254

    Article  PubMed  Google Scholar 

  14. Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL (2004) Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg 62:527–534

    Article  PubMed  Google Scholar 

  15. Grötz KA, Diel IJ (2005) Osteonekrose des Kiefers unter Bisphosphonat Langzeittherapie. Im Focus Onkologie 8:52–55

    Google Scholar 

  16. Fournier P, Boissier S, Filleur S, Guglielmi J, Cabon F, Colombel M, Clezardin P (2002) Bisphosphonates inhibit angiogenesis in vitro and testosterone-stimulated vascular regrowth in the ventral prostate in castrated rats. Cancer Res 62:6538–6544

    PubMed  CAS  Google Scholar 

  17. Santini D, Vincenzi B, Avvisati G, Dicuonzo G, Battistoni F, Gavasci M, Salerno A, Denaro V, Tonini G (2002) Pamidronate induces modifications of circulating angiogenetic factors in cancer patients. Clin Cancer Res 8:1080–1084

    PubMed  CAS  Google Scholar 

  18. Wood J, Bonjean K, Ruetz S, Bellahcene A, Devy L, Foidart JM, Castronovo V, Green JR (2002) Novel antiangiogenic effects of the bisphosphonate compound zoledronic acid. J Pharmacol Exp Ther 302:1055–1061

    Article  PubMed  CAS  Google Scholar 

  19. Hughes DE, Wright KR, Uy HL, Sasaki A, Yoneda T, Roodman GD, Mundy GR, Boyce BF (1995) Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. J Bone Miner Res 10:1478–1487

    Article  PubMed  CAS  Google Scholar 

  20. Pan B, Farrugia AN, To LB, Findlay DM, Green J, Lynch K, Zannettino AC (2004) The nitrogen-containing bisphosphonate, zoledronic acid, influences RANKL expression in human osteoblast-like cells by activating TNF-alpha converting enzyme (TACE). J Bone Miner Res 19:147–154

    Article  PubMed  CAS  Google Scholar 

  21. Plotkin LI, Aguirre JI, Kousteni S, Manolagas SC, Bellido T (2005) Bisphosphonates and estrogens inhibit osteocyte apoptosis via distinct molecular mechanisms downstream of extracellular signal-regulated kinase activation. J Biol Chem 280:7317–7325

    Article  PubMed  CAS  Google Scholar 

  22. Hansen T, Kunkel M, Weber A, James Kirkpatrick C (2006) Osteonecrosis of the jaws in patients treated with bisphosphonates—histomorphologic analysis in comparison with infected osteoradionecrosis. J Oral Pathol Med 35:155–160

    Article  PubMed  Google Scholar 

  23. Dearden WF (1899) Fragilitas ossium amongst workers in Lucifer match factories. BMJ 2:270

    Article  Google Scholar 

  24. Bernardi D, Barzan L, Franchin G, Cinelli R, Balestreri L, Tirelli U, Vaccher E (2005) Treatment of head and neck cancer in elderly patients: state of the art and guidelines. Crit Rev Oncol Hematol 53:71–80

    PubMed  Google Scholar 

  25. Macdonald AG, Bissett JD (2001) Avascular necrosis of the femoral head in patients with prostate cancer treated with cyproterone acetate and radiotherapy. Clin Oncol (R Coll Radiol) 13:135–137

    CAS  Google Scholar 

  26. Dawson LK, Nussey F, Oliver TB, Marks RC, Leonard RC (2001) Osteonecrosis of the femoral head following adjuvant chemotherapy for breast cancer. Breast 10:447–449

    Article  PubMed  CAS  Google Scholar 

  27. Tarassoff P, Csermak K (2003) Avascular necrosis of the jaws: risk factors in metastatic cancer patients. J Oral Maxillofac Surg 61:1238–1239

    Article  PubMed  Google Scholar 

  28. Kluth EV, Jain PR, Stuchell RN, Frich JC Jr (1988) A study of factors contributing to the development of osteoradionecrosis of the jaws. J Prosthet Dent 59:194–201

    Article  PubMed  CAS  Google Scholar 

  29. Curi MM, Dib LL (1997) Osteoradionecrosis of the jaws: a retrospective study of the background factors and treatment in 104 cases. J Oral Maxillofac Surg 55:540–544 (Discussion 545–546)

    Article  PubMed  CAS  Google Scholar 

  30. Reuther T, Schuster T, Mende U, Kubler A (2003) Osteoradionecrosis of the jaws as a side effect of radiotherapy of head and neck tumour patients-a report of a thirty year retrospective review. Int J Oral Maxillofac Surg 32:289–295

    Article  PubMed  CAS  Google Scholar 

  31. Robinson NA, Yeo JF (2004) Bisphosphonates-a word of caution. Ann Acad Med Singapore 33:48–49

    PubMed  CAS  Google Scholar 

  32. Wagner W, Kuffner HD, Hartmann U (1986) Der bestrahlte Patient als Risikopatient bei zahnärztlich—chirurgischen Eingriffen. Dtsch Zahnarztl Z 41:440–443

    PubMed  CAS  Google Scholar 

  33. Hoskin PJ (2003) Bisphosphonates and radiation therapy for palliation of metastatic bone disease. Cancer Treat Rev 29:321–327

    Article  PubMed  CAS  Google Scholar 

  34. Algur E, Macklis RM, Hafeli UO (2005) Synergistic cytotoxic effects of zoledronic acid and radiation in human prostate cancer and myeloma cell lines. Int J Radiat Oncol Biol Phys 61:535–542

    Article  PubMed  CAS  Google Scholar 

  35. Schwartz HC (2004) Osteonecrosis and bisphosphonates: correlation versus causation. J Oral Maxillofac Surg 62:763–764

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Klinik für Mund-, Kiefer- und Gesichtschirurgie, Johannes Gutenberg-Universität Mainz, Augustusplatz 2, 55131, Mainz, Germany

    Christian Walter, Knut A. Grötz, Martin Kunkel & Bilal Al-Nawas

Authors
  1. Christian Walter
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Knut A. Grötz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Martin Kunkel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bilal Al-Nawas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Christian Walter.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Walter, C., Grötz, K.A., Kunkel, M. et al. Prevalence of bisphosphonate associated osteonecrosis of the jaw within the field of osteonecrosis. Support Care Cancer 15, 197–202 (2007). https://doi.org/10.1007/s00520-006-0120-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00520-006-0120-z

Keywords

Search

Navigation