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Clinical Oral Investigations

, Volume 18, Issue 2, pp 401–407 | Cite as

Prevalence of bisphosphonate-associated osteonecrosis of the jaw after intravenous zoledronate infusions in patients with early breast cancer

  • Petra RuganiEmail author
  • Gero Luschin
  • Norbert Jakse
  • Barbara Kirnbauer
  • Uwe Lang
  • Stephan Acham
Original Article

Abstract

Objectives

The definite incidence rate of bisphosphonate-related osteonecrosis of the jaws (BRONJ) is still unknown. The aim of this study was to investigate prevalence of BRONJ in a group of breast cancer patients applying the classification of the Association of Oral and Maxillofacial Surgeons 2009.

Patients and methods

Between 2000 and 2008, 63 premenopausal early breast cancer patients who were free of metastases were treated with 4 mg zoledronic acid every 6 months over 3 years as participants of a multicenter, randomized, controlled, adjuvant breast cancer medication trial. Patients were not informed about the risk of jaw necrosis. None reported tooth or jaw complaints during the breast cancer follow-up examinations. In 2010, 48 patients of this cohort were investigated concerning BRONJ by clinical and radiological examinations.

Results

No advanced stages (AAOMS 2009)were detected. However, five patients (10.4 %) presented purulent (2) and nonpurulent (3) fistulas and radiological signs correlating to BRONJ stage 0.

Conclusion

Although no case of advanced BRONJ was detected, the study revealed a high prevalence of BRONJ stage 0. This supports the need for tight cooperation between dentists and medical specialists prescribing bisphosphonates including dental pre-therapeutic and follow-up examinations. Adaption of the BRONJ classification taking account to bone exposure via fistulas is recommended.

Clinical relevance

BRONJ is said to be a complication linked to high-dosage bisphosphonate therapy. The study demonstrates that even after application of zoledronate in a low-dose protocol, early BRONJ occurred. Radiological signs solely are not sufficient to confirm BRONJ; clinical signs are mandatory.

Keywords

Bisphosphonates Osteonecrosis Osteochemonecrosis Early breast cancer Bisphosphonate osteonecrosis of the jaw BRONJ 

Notes

Conflict of interest

None.

References

  1. 1.
    Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B, American Association of Oral and Maxillofacial Surgeons (2009) American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws—2009 update. J Oral Maxillofac Surg 67(5 Suppl):2–12PubMedGoogle Scholar
  2. 2.
    Ziebart T, Pabst A, Klein MO, Kammerer P, Gauss L, Brullmann D, Al-Nawas B, Walter C (2011) Bisphosphonates: restrictions for vasculogenesis and angiogenesis: inhibition of cell function of endothelial progenitor cells and mature endothelial cells in vitro. Clin Oral Investig 15(1):105–111PubMedCrossRefGoogle Scholar
  3. 3.
    Hoefert S, Schmitz I, Tannapfel A, Eufinger H (2010) Importance of microcracks in etiology of bisphosphonate-related osteonecrosis of the jaw: a possible pathogenetic model of symptomatic and non-symptomatic osteonecrosis of the jaw based on scanning electron microscopy findings. Clin Oral Investig 14(3):271–284PubMedCrossRefGoogle Scholar
  4. 4.
    Rustemeyer J, Bremerich A (2010) Bisphosphonate-associated osteonecrosis of the jaw: what do we currently know? A survey of knowledge given in the recent literature. Clin Oral Investig 14(1):59–64PubMedCrossRefGoogle Scholar
  5. 5.
    Allen MR, Burr DB (2009) The pathogenesis of bisphosphonate-related osteonecrosis of the jaw: so many hypotheses, so few data. J Oral Maxillofac Surg 67(5 Suppl):61–70PubMedCrossRefGoogle Scholar
  6. 6.
    Advisory Task Force on Bisphosphonate-Related Ostenonecrosis of the Jaws, American Association of Oral and Maxillofacial Surgeons (2007) American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg 65(3):369–376CrossRefGoogle Scholar
  7. 7.
    Durie BG, Katz M, Crowley J (2005) Osteonecrosis of the jaw and bisphosphonates. N Engl J Med 353:99–102PubMedCrossRefGoogle Scholar
  8. 8.
    DÖSAK (2011)StrkuturierteDatenerfassung der Bisphosphonat-assoziiertenKiefernekrosen (BP-ONJ). https://bp-onj-datenbank.de/downloads/E-081125_Fragebogen-OJN-DOESAK.pdf Accessed:29 January 2012
  9. 9.
    Almăşan HA, Băciuţ M, Rotaru H, Bran S, Almăşan OC, Băciuţ G (2011) Osteonecrosis of the jaws associated with the use of bisphosphonates. Discussion over 52 cases. Rom J Morphol Embryol 52(4):1233–1241PubMedGoogle Scholar
  10. 10.
    Bantis A, Zissimopoulos A, Sountoulides P, Kalaitzis C, Giannakopoulos S, Deftereos S, Tsakaldimis G, Thomaidis V, Touloupidis S (2011) Bisphosphonate-induced osteonecrosis of the jaw in patients with bone metastatic, hormone-sensitive prostate cancer. Risk factors and prevention strategies. Tumori 97(4):479–483PubMedGoogle Scholar
  11. 11.
    Bonacina R, Mariani U, Villa F, Villa A (2011) Preventive strategies and clinical implications for bisphosphonate-related osteonecrosis of the jaw: a review of 282 patients. J Can Dent Assoc 77:b147PubMedGoogle Scholar
  12. 12.
    Schubert M, Klatte I, Linek W, Müller B, Döring K, Eckelt U, Hemprich A, Berger U, Hendricks J (2011) The Saxon Bisphosphonate Register—therapy and prevention of bisphosphonate-related osteonecrosis of the jaws. Oral Oncol 48(4):349–354. doi: 10.1016/j.oraloncology.2011.11.004 PubMedCrossRefGoogle Scholar
  13. 13.
    Hoff AO, Toth BB, Altundag K, Johnson MM, Warneke CL, Hu M, Nooka A, Sayegh G, Guarneri V, Desrouleaux K, Cui J, Adamus A, Gagel RF, Hortobagyi GN (2008) Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates. J Bone Miner Res 23:826–836PubMedCrossRefGoogle Scholar
  14. 14.
    Mavrokokki T, Cheng A, Stein B, Goss A (2007) Nature and frequency of bisphosphonate-associated osteonecrosis of the jaws in Australia. J Oral Maxillofac Surg 65:415–423PubMedCrossRefGoogle Scholar
  15. 15.
    Walter C, Al-Nawas B, Frickhofen N, Gamm H, Beck J, Reinsch L, Blum C, Grötz KA, Wagner W (2010) Prevalence of bisphosphonate associate osteonecrosis of the jaws in multiple myeloma patients. Head Face Med 6:11PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Gnant M, Mlineritsch B, Stoeger H, Luschin-Ebengreuth G, Heck D, Menzel C, Jakesz R, Seifert M, Hubalek M, Bjelic-Radisic V, Samonigg H, Tausch C, Eidtmann H, Steger G, Kwasny W, Dubsky P, Fridrik M, Fitzal F, Stierer M, Rücklinger E, Greil R, ABCSG-12 Trial Investigators, Marth C (2008) Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med 360:679–691CrossRefGoogle Scholar
  17. 17.
    Ibrahim T, Barbanti F, Giorgio-Marrano G, Mercatali L, Ronconi S, Vicini C, Amadori D (2008) Osteonecrosis of the jaw in patients with bone metastases treated with bisphosphonates: a retrospective study. Oncologist 13:330–336PubMedCrossRefGoogle Scholar
  18. 18.
    Bamias A, Kastritis E, Bamia C, Moulopoulos LA, Melakopoulos I, Bozas G, Koutsoukou V, Gika D, Anagnostopoulos A, Papadimitriou C, Terpos E, Dimopoulos MA (2005) Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors. J ClinOncol 23:8580–8587CrossRefGoogle Scholar
  19. 19.
    Wang EP, Kaban LB, Strewler GJ, Raje N, Troulis MJ (2007) Incidence of osteonecrosis of the jaw in patients with multiple myeloma and breast or prostate cancer on intravenous bisphosphonate therapy. J Oral Maxillofac Surg 65:1328–1331PubMedCrossRefGoogle Scholar
  20. 20.
    Fehm T, Beck V, Banys M, Lipp HP, Hairass M, Reinert S, Solomayer EF, Wallwiener D, Krimmel M (2009) Bisphosphonate-induced osteonecrosis of the jaw (ONJ): incidence and risk factors in patients with breast cancer and gynecological malignancies. Gynecol Oncol 112:605–609PubMedCrossRefGoogle Scholar
  21. 21.
    Guarneri V, Donati S, Nicolini M, Giovannelli S, D'Amico R, Conte PF (2005) Renal safety and efficacy of i.v. bisphosphonates in patients with skeletal metastases treated for up to 10 Years. Oncologist 10:842–848PubMedCrossRefGoogle Scholar
  22. 22.
    Sanna G, Preda L, Bruschini R, CossuRocca M, Ferretti S, Adamoli L, Verri E, Franceschelli L, Goldhirsch A, Nolè F (2006) Bisphosphonates and jaw osteonecrosis in patients with advanced breast cancer. Ann Oncol 17:1512–1516PubMedCrossRefGoogle Scholar
  23. 23.
    AguiarBujanda D, Bohn Sarmiento U, Cabrera Suarez MA, Aguiar Morales J (2007) Assessment of renal toxicity and osteonecrosis of the jaws in patients receiving zoledronic acid for bone metastasis. Ann Oncol 18:556–560CrossRefGoogle Scholar
  24. 24.
    Grötz KA, Piesold J, Al-Nawas B(2012)Bisphosphonat-assoziierteKiefernekrose (BP-ONJ) und andereMedikamenten-assoziierteKiefernekrosen. S3 Leitlinie der DGMKG. AWMF online. http://www.awmf.org/uploads/tx_szleitlinien/007-091l_S3_Bisphosphonat-assoziierte_Kiefernekrose_2012-04.pdf. Accessed: 22 June 2012
  25. 25.
    Fedele S, Porter SR, D'Aiuto F, Aljohani S, Vescovi P, Manfredi M, Arduino PG, Broccoletti R, Musciotto A, Di Fede O, Lazarovici TS, Campisi G, Yarom N (2010) Nonexposed variant of bisphosphonate-associated osteonecrosis of the jaw: a case series. Am J Med 123(11):1060–1064, Epub 2010 Sep 28PubMedCrossRefGoogle Scholar
  26. 26.
    Dimopoulos MA, Kastritis E, Bamia C, Melakopoulos I, Gika D, Roussou M, Migkou M, Eleftherakis-Papaiakovou E, Christoulas D, Terpos E, Bamias A (2009) Reduction of osteonecrosis of the jaw (ONJ) after implementation of preventive measures in patients with multiple myeloma treated with zoledronic acid. Ann Oncol Off J Eur Soc Med Oncol/ESMO 20(1):117–120CrossRefGoogle Scholar
  27. 27.
    Ripamonti CI, Maniezzo M, Campa T, Fagnoni E, Brunelli C, Saibene G, Bareggi C, Ascani L, Cislaghi E (2009) Decreased occurrence of osteonecrosis of the jaw after implementation of dental preventive measures in solid tumour patients with bone metastases treated with bisphosphonates. The Experience of the National Cancer Institute of Milan. Ann Oncol Off J Eur Soc Med Oncol/ESMO 20(1):137–145CrossRefGoogle Scholar
  28. 28.
    Treister NS, Friedland B, Woo SB (2010) Use of cone-beam computerized tomography for evaluation of bisphosphonate-associated osteonecrosis of the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 109(5):753–764, Epub 2010 Mar 29PubMedCrossRefGoogle Scholar
  29. 29.
    Cohen D, Bhattacharyya I, Dashti H, Kuklani R, Fitzpatrick S, Islam MN, Magliocca K (2010) Radiographic features of oral bisphosphonate-related osteonecrosis of the jaw. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 110(6):e21–e22Google Scholar
  30. 30.
    Elad S, Gomori MJ, Ben-Ami N, Friedlander-Barenboim S, Regev E, Lazarovici TS, Yarom N (2010) Bisphosphonate-related osteonecrosis of the jaw: clinical correlations with computerized tomography presentation. Clin Oral Investig 14(1):43–50PubMedCrossRefGoogle Scholar
  31. 31.
    Woo SB, Mawardi H, Treister N (2009) Letter to the Editor. Comments on “Osteonecrosis of the jaws in intravenous bisphosphonate use: proposal for a modification of the clinical classification”. Oral Oncol 45:740PubMedCrossRefGoogle Scholar
  32. 32.
    Bagan JV, Jimenez Y, Diaz JM, Murillo J, Sanchis JM, Poveda R, Carbonell E, Gavalda C, Scully C (2009) Letter to the Editor. Osteonecrosis of the jaws in intravenous bisphosphonate use: proposal for a modification of the clinical classification. Oral Oncol 45:645–646PubMedCrossRefGoogle Scholar
  33. 33.
    Mawardi H, Treister N, Richardson P, Anderson K, Munshi N, Faiella RA, Woo SB (2009) Sinus tracts—an early sign of bisphosphonate-associated osteonecrosis of the jaws? J Oral Maxillofac Surg 67(3):593–601PubMedCrossRefGoogle Scholar
  34. 34.
    Nicolatou-Galitis O, Papadopoulou E, Sarri T, Boziari P, Karayianni A, Kyrtsonis MC, Repousis P, Barbounis V, Migliorati CA (2011) Osteonecrosis of the jaw in oncology patients treated with bisphosphonates: prospective experience of a dental oncology referral center. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 112(2):195–202, Epub 2011 May 31PubMedCrossRefGoogle Scholar
  35. 35.
    Van den Wyngaert T, Claeys T, Huizing MT, Vermorken JB, Fossion E (2009) Initial experience with conservative treatment in cancer patients with osteonecrosis of the jaw (ONJ) and predictors of outcome. Ann Oncol 20(2):331–336, Epub 2008 Oct 26PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Petra Rugani
    • 1
    Email author
  • Gero Luschin
    • 3
  • Norbert Jakse
    • 1
  • Barbara Kirnbauer
    • 1
  • Uwe Lang
    • 2
  • Stephan Acham
    • 1
  1. 1.Department of Oral Surgery and RadiologyMedical University of GrazGrazAustria
  2. 2.Department of Obstetrics and GynecologyGrazAustria
  3. 3.Women’s Health AssociationGrazAustria

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