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

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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.

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References

  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):2–12

    PubMed  Google Scholar 

  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):105–111

    Article  PubMed  Google Scholar 

  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):271–284

    Article  PubMed  Google Scholar 

  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):59–64

    Article  PubMed  Google Scholar 

  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):61–70

    Article  PubMed  Google Scholar 

  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):369–376

    Article  Google Scholar 

  7. Durie BG, Katz M, Crowley J (2005) Osteonecrosis of the jaw and bisphosphonates. N Engl J Med 353:99–102

    Article  PubMed  Google Scholar 

  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. 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):1233–1241

    PubMed  Google Scholar 

  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):479–483

    PubMed  Google Scholar 

  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:b147

    PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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 23:826–836

    Article  PubMed  Google Scholar 

  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 65:415–423

    Article  PubMed  Google Scholar 

  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 6:11

    Article  PubMed Central  PubMed  Google Scholar 

  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 360:679–691

    Article  Google Scholar 

  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 13:330–336

    Article  PubMed  Google Scholar 

  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 23:8580–8587

    Article  Google Scholar 

  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 65:1328–1331

    Article  PubMed  Google Scholar 

  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 112:605–609

    Article  PubMed  Google Scholar 

  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 10:842–848

    Article  PubMed  Google Scholar 

  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 17:1512–1516

    Article  PubMed  Google Scholar 

  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 18:556–560

    Article  Google Scholar 

  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. 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 28

    Article  PubMed  Google Scholar 

  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):117–120

    Article  Google Scholar 

  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):137–145

    Article  Google Scholar 

  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 29

    Article  PubMed  Google Scholar 

  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–e22

    Google Scholar 

  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):43–50

    Article  PubMed  Google Scholar 

  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 45:740

    Article  PubMed  Google Scholar 

  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 45:645–646

    Article  PubMed  Google Scholar 

  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):593–601

    Article  PubMed  Google Scholar 

  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 31

    Article  PubMed  Google Scholar 

  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 26

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Oral Surgery and Radiology, Medical University of Graz, Auenbruggerplatz 12, 8036, Graz, Austria

    Petra Rugani, Norbert Jakse, Barbara Kirnbauer & Stephan Acham

  2. Department of Obstetrics and Gynecology, Auenbruggerplatz 14, 8036, Graz, Austria

    Uwe Lang

  3. Women’s Health Association, Quellengasse 36, 8010, Graz, Austria

    Gero Luschin

Authors
  1. Petra Rugani
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  2. Gero Luschin
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Correspondence to Petra Rugani.

Additional information

Petra Rugani and Gero Luschin contributed equally.

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Rugani, P., Luschin, G., Jakse, N. et al. Prevalence of bisphosphonate-associated osteonecrosis of the jaw after intravenous zoledronate infusions in patients with early breast cancer. Clin Oral Invest 18, 401–407 (2014). https://doi.org/10.1007/s00784-013-1012-5

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  • DOI: https://doi.org/10.1007/s00784-013-1012-5

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