Download PDF
Osteologie 2012; 21(04): 291-295
DOI: 10.1055/s-0037-1621963
Osteonekrosen
Schattauer GmbH

Bisphosphonat-assoziierte Kiefer nekrosen[1]

AktuelleÜbersicht zu Definition, klinischer Präsention, Risikofaktoren, Pathogenese, Prophylaxe und TherapieBis phosphonate-related osteonecrosis of the jaw
S. Otto
1   Klinikum der Universität München, Osteologisches Schwerpunktzentrum (DVO), Klinik und Poliklinik für Mund, Kiefer und Gesichtschirurgie, München
,
C. Pautke
1   Klinikum der Universität München, Osteologisches Schwerpunktzentrum (DVO), Klinik und Poliklinik für Mund, Kiefer und Gesichtschirurgie, München
2   Medizin& Ästhetik, Praxisklinik für Mund, Kiefer und plastische Gesichtschirurgie, München
,
M. Schieker
3   Klinikum der Universität München, Osteologisches Schwerpunktzentrum (DVO), Chirurgische Klinik und Poliklinik, Spezialsprechstunde für Osteoporose und Alterstraumatologie, München
› Author Affiliations
Further Information

Publication History

eingereicht: 01 October 2012

angenommen: 09 October 2012

Publication Date:
04 January 2018 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Bisphosphonate spielen eine entscheidende Rolle in der Osteologie und Onkologie. Sie vermindern die Häufigkeit unerwünschter skelettaler Ereignisse und verbessern somit die Lebensqualität der Patienten. Bis phosphonate gelten insgesamt als nebenwirkungsarm. Doch seit der Beschreibung Bisphosphonat-assoziierter Kiefernekrosen haben sich diese zu einem ernsthaften klinischen Problem entwickelt. Sie treten hauptsächlich bei Patienten mit langjähriger intravenöser Applikation von stickstoffhaltigen Bisphosphonaten in onkologischer Dosierung auf. Deutlich seltener tritt diese Komplikation jedoch auch im Rahmen der Osteoporosebehandlung auf. Eine wesentliche Ursache für die Entstehung Bisphosphonat-assoziierter Kiefernekrosen wird in lokal entzündlichen Veränderungen sowie häufig daraus resultierenden dentoalveolär chirurgischen Eingriffen gesehen, so dass wesentliche prophylaktische Bemühungen stets auf die Eliminierung von akuten oder chronisch entzündlichen Veränderungen im Bereich der Kiefer vor bzw. unter der Behandlung mit Bisphosphonaten gerichtet sein sollten. Hinsichtlich der Therapie Bisphosphonat-assoziierter Kiefernekrosen setzen sich chirurgische Behandlungskonzepte mehr und mehr durch, wobei insbesondere die innovative fluoreszenzorientierte Knochenabtragung vielversprechend erscheint.

Summary

Bisphosphonates play a key role in the prophylaxis and treatment of osteoporosis and metastatic bone disease. They reduce the frequency of skeletal related events especially fractures and thereby they increase the quality of life of the patients. Bisphosphonates show a favorable risk profile but ever since the description of bisphosphonate-related osteonecrosis of the jaw this side effects has become a major clinical problem which is difficult to treat. The majority of cases occurred in patients suffering from metastatic bone disease who received long term intravenous administrations of nitrogen-containing bisphosphonates. Far less frequently it has also been described in osteoporotic patients receiving oral or intravenous administration of nitrogen-containing bisphosphonates. Bisphosphonate-related osteonecrosis of the jaws is defined by exposed necrotic bone in the maxillofacial region in patients under previous or ongoing bisphosphonate treatment and without history of irradiation of the jaw bones. The clinical hallmark of the disease is exposed necrotic bone in the oral cavity which can be accompanied by signs of infection such as pain, swelling, abscess or fistula formation. The majority of cases were preceded by local inflammations and or dento -alveolar surgeries especially tooth extractions and implant insertions. Therefore care should be taken to eliminate or avoid dental infections prior to or under ongoing bisphosphonate treatment. Once bisphosphonate-related osteonecrosis of the jaw has manifested surgical treatment schemes have shown to be superior when compared to conservative treatment protocols. Especially the fluorescence-guided bone resection seems to be an innovative and promising technique.

Schlüsselwörter

Bisphosphonate - Kiefernekrosen - Bisphosphonat-assoziierte Kiefernekrosen

Keywords

Bisphosphonates - osteonecrosis of the jaw - bisphosphonate-related osteonecrosis of the jaw (ONJ)

1 Die Arbeit beruht in wesentlichen Teilen auf dem Exposee und den Ergebnissen des Habilitationsprojektes von Dr. med. Dr. med. dent. Sven Otto


 

  • Literatur

  • 1 Rodan GA, Fleisch HA. Bisphosphonates: mechanisms of action. J Clin Invest 1996; 97: 2692.
    CrossrefPubMedGoogle Scholar
  • 2 Russell RG, Watts NB, Ebetino FH, Rogers MJ. Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy. Osteoporos Int 2008; 19: 733.
    CrossrefPubMedGoogle Scholar
  • 3 Black DM, Schwartz AV, Ensrud KE. et al. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Longterm Extension (FLEX): a randomized trial. JAMA 2006; 296: 2927.
    CrossrefPubMedGoogle Scholar
  • 4 Sambrook P, Cooper C. Osteoporosis. Lancet 2006; 367: 2010.
    CrossrefPubMedGoogle Scholar
  • 5 Kyle RA, Yee GC, Somerfield MR. et al. American Society of Clinical Oncology 2007 clinical practice guideline update on the role of bisphosphonates in multiple myeloma. J Clin Oncol 2007; 25: 2464.
    CrossrefPubMedGoogle Scholar
  • 6 Berenson JR, Yellin O, Boccia RV. et al. Zoledronic acid markedly improves bone mineral density for patients with monoclonal gammopathy of undetermined significance and bone loss. Clin Cancer Res 2008; 14: 6289.
    CrossrefPubMedGoogle Scholar
  • 7 Wang J, Goodger NM, Pogrel MA. Osteonecrosis of the jaws associated with cancer chemotherapy. J Oral Maxillofac Surg 2003; 61: 1104.
    CrossrefPubMedGoogle Scholar
  • 8 Migliorati CA. Bisphosphonates and oral cavity avascular bone necrosis. J Clin Oncol 2003; 21: 4253.
    PubMedGoogle Scholar
  • 9 Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. J Oral Maxillofac Surg 2003; 61: 1115.
    CrossrefPubMedGoogle Scholar
  • 10 American Association of Oral and Maxillofacial. Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws. J Oral Maxillofac Surg 2007; 65: 369.
    CrossrefPubMedGoogle Scholar
  • 11 Ruggiero SL, Dodson TB, Assael LA. et al. American Association of Oral and Maxillofacial Surgeons position paper on bisphosphonate-related osteonecrosis of the jaws—2009 update. J Oral Maxillofac Surg 2009; 67: 2.
    CrossrefPubMedGoogle Scholar
  • 12 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: 1567.
    CrossrefPubMedGoogle Scholar
  • 13 Badros A, Weikel D, Salama A. et al. Osteonecrosis of the jaw in multiple myeloma patients: clinical features and risk factors. J Clin Oncol 2006; 24: 945.
    CrossrefPubMedGoogle Scholar
  • 14 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: 5356-5362.
    CrossrefPubMedGoogle Scholar
  • 15 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: 303.
    CrossrefPubMedGoogle Scholar
  • 16 Khosla S, Burr D, Cauley J. et al. Bisphosphonateassociated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 2007; 22: 1479.
    CrossrefPubMedGoogle Scholar
  • 17 Otto S, Abu-Id MH, Fedele S. et al. Osteoporosis and bisphosphonates-related osteonecrosis of the jaw: Not just a sporadic coincidence—a multicentre study. J Craniomaxillofac Surg 2011; 39: 272.
    CrossrefPubMedGoogle Scholar
  • 18 Dimopoulos MA, Kastritis E, Bamia C. et al. Reduction of osteonecrosis of the jaw (ONJ) after implementation of preventive measures in patients with multiple myeloma treated with zoledronic acid. Ann Oncol 2009; 20: 117.
    PubMedGoogle Scholar
  • 19 Abu-Id MH, Warnke PH, Gottschalk J. et al. “Bisphossy jaws”—high and low risk factors for bisphosphonate-induced osteonecrosis of the jaw. J Craniomaxillofac Surg 2008; 36: 95.
    CrossrefPubMedGoogle Scholar
  • 20 Allen MR, Burr DB. The pathogenesis of bisphosphonate-related osteonecrosis of the jaw: so many hypotheses, so few data. J Oral Maxillofac Surg 2009; 67: 61.
    PubMedGoogle Scholar
  • 21 Otto S, Hafner S, Mast G. et al. Bisphosphonaterelated osteonecrosis of the jaw: is pH the missing part in the pathogenesis puzzle?. J Oral Maxillofac Surg 2010; 68: 1158.
    CrossrefPubMedGoogle Scholar
  • 22 Bauss F, Pfister T, Papapoulos S. Ibandronate uptake in the jaw is similar to long bones and vertebrae in the rat. J Bone Miner Metab 2008; 26: 406.
    CrossrefPubMedGoogle Scholar
  • 23 O'Ryan FS, Khoury S, Liao W. et al. Intravenous bisphosphonate-related osteonecrosis of the jaw: bone scintigraphy as an early indicator. J Oral Maxillofac Surg 2009; 67: 1363.
    CrossrefPubMedGoogle Scholar
  • 24 Sedghizadeh PP, Kumar SK, Gorur A. et al. Identification of microbial biofilms in osteonecrosis of the jaws secondary to bisphosphonate therapy. J Oral Maxillofac Surg 2008; 66: 767.
    CrossrefPubMedGoogle Scholar
  • 25 Hansen T, Kunkel M, Weber A, James Kirkpatrick C. Osteonecrosis of the jaws in patients treated with bisphosphonates—histomorphologic analysis in comparison with infected osteoradionecrosis. J Oral Pathol Med 2006; 35: 155.
    CrossrefPubMedGoogle Scholar
  • 26 Reid IR, Bolland MJ, Grey AB. Is bisphosphonateassociated osteonecrosis of the jaw caused by soft tissue toxicity?. Bone 2007; 41: 318.
    CrossrefPubMedGoogle Scholar
  • 27 Hoffmann T, John M, Kerschbaum T. et al. Oral Epidemiology. In: Micheelis W, Schiffner U. eds. Institute of German Dentists: Fourth German Oral Health Study (DMS IV). Köln: Deutscher Zahnärzte Verlag D ÄV; 2006
    Google Scholar
  • 28 Otto S, Pautke C, Opelz C. 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.
    CrossrefPubMedGoogle Scholar
  • 29 Sato M, Grasser W, Endo N. et al. Bisphosphonate action. Alendronate localization in rat bone and effects on osteoclast ultrastructure. J Clin Invest 1991; 88: 2095.
    CrossrefPubMedGoogle Scholar
  • 30 Lesclous P, Abi Najm S, Carrel JP. et al. Bisphosphonate-associated osteonecrosis of the jaw: a key role of inflammation?. Bone 2009; 45: 843.
    CrossrefPubMedGoogle Scholar
  • 31 Oizumi T, Funayama H, Yamaguchi K. et al. Inhibition of necrotic actions of nitrogen-containing bisphosphonates (NBPs) and their elimination from bone by etidronate (a non-NBP): a proposal for possible utilization of etidronate as a substitution drug for NBPs. J Oral Maxillofac Surg 2010; 68: 1043.
    CrossrefPubMedGoogle Scholar
  • 32 Pautke C, Kreutzer K, Weitz J. et al. Bisphosphonate related osteonecrosis of the jaw: A minipig large animal model. Bone 2012; 51: 592.
    CrossrefPubMedGoogle Scholar
  • 33 Otto S, Schuler K, Ihrler S. et al. Osteonecrosis or metastases of the jaw or both? Case report and review of the Literature. J Oral Maxillofac Surg 2010; 68: 1185.
    CrossrefPubMedGoogle Scholar
  • 34 Pautke C, Bauer F, Bissinger O. et al. Tetracycline bone fluorescence: a valuable marker for osteonecrosis characterization and therapy. J Oral Maxillofac Surg 2010; 68: 125.
    CrossrefPubMedGoogle Scholar
  • 35 Pautke C, Bauer F, Otto S. et al. Fluorescenceguided bone resection in bisphosphonate-related osteonecrosis of the jaws: first clinical results of a prospective pilot study. J Oral Maxillofac Surg 2011; 69: 84.
    CrossrefPubMedGoogle Scholar
  • 36 Marx RE. Reconstruction of defects caused by bisphosphonate-induced osteonecrosis of the jaws. J Oral Maxillofac Surg 2009; 67: 107-119.
    PubMedGoogle Scholar
  • 37 Stockmann P, Vairaktaris E, Wehrhan F. et al. Osteotomy and primary wound closure in bisphosphonate-associated osteonecrosis of the jaw: a prospective clinical study with 12 months followup. Support Care Cancer 2010; 18: 449.
    CrossrefPubMedGoogle Scholar
  • 38 Filleul O, Crompot E, Saussez S. Bisphosphonateinduced osteonecrosis of the jaw: a review of 2,400 patient cases. J Cancer Res Clin Oncol 2010; 136: 1117-1124.
    CrossrefPubMedGoogle Scholar
  • 39 Van den Wyngaert T, Claeys T, Huizing MT. et al. Initial experience with conservative treatment in cancer patients with osteonecrosis of the jaw (ONJ) and predictors of outcome. Ann Oncol 2009; 20: 331.
    PubMedGoogle Scholar
  • 40 Pautke C, Bauer F, Tischer T. et al. Fluorescenceguided bone resection in bisphosphonate-associated osteonecrosis of the jaws. J Oral Maxillofac Surg 2009; 67: 471.
    CrossrefPubMedGoogle Scholar