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Osteologie 2012; 21(02): 72-76
DOI: 10.1055/s-0037-1621670
Osteonekrose des Kiefers
Schattauer GmbH

Bisphosphonat-assoziierte Kiefernekrosen

Relevante TiermodelleBisphosphonate related osteonecrosis of the jawrelevant animal models
C. Pautke
1   Medizin & Ästhetik, Praxisklinik für Mund-, Kiefer- und plastische Gesichtschirurgie, München
2   Klinisches osteologisches Schwerpunktzentrum (DVO) und Klinik und Poliklinik für Mund-, Kiefer- und Gesichtschirurgie, Universität München
,
S. Otto
2   Klinisches osteologisches Schwerpunktzentrum (DVO) und Klinik und Poliklinik für Mund-, Kiefer- und Gesichtschirurgie, Universität München
,
M. Schieker
3   Klinisches osteologisches Schwerpunktzentrum (DVO) und Spezialsprechstunde für Osteoporose und Alterstraumatologie, Chirurgische Klinik – Innenstadt, Klinikum der LMU München
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Publikationsverlauf

eingereicht: 29. Mai 2012

angenommen: 04. Juni 2012

Publikationsdatum:
04. Januar 2018 (online)

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Zusammenfassung

Stickstoffhaltige Bisphosphonate (BP) werden erfolgreich in der Osteoporose- und der supportiven onkologischen Therapie eingesetzt. Erste Fälle von BP-assoziierten Kiefernekrosen (KN) wurden 2003 in verschiedenen Fallberichten veröffentlicht. Insbesondere unter oraler BP-Therapie bei Osteoporose handelt es sich dabei jedoch um ein sehr seltenes Krankheitsbild. Die Pathogenese der BP-assoziierten KN ist bisher noch nicht vollständig verstanden. Wir glauben, dass letztlich entzündliche Prozesse mit lokal saurem pH-Wert zur Akkumulation von BP im Kieferknochen und lokaler Gewebetoxizität führen. Deshalb reduzieren zahnärztliche Maßnahmen zur Beseitigung von Entzündungsherden signifikant die KN bei onkologischen Patienten unter intravenöser BP-Therapie. Leider gab es bisher keine relevanten Tiermodelle, in denen die Pathogenese und therapeutischen Maßnahmen klinisch relevant getestet werden können. Aktuell haben wir ein Minipig-Modell durch Zahnextraktion und Gabe von i. v.-Zoledronat in der gewichtsadaptierten onkologischen Dosierung etabliert. Mit diesem Modell wird es möglich sein, die Pathogenese von BP- assoziierten KN besser zu verstehen und mögliche Therapieoptionen zu testen.

Summary

Bisphosphonates have been successfully used for almost 20 years to treat osteoporosis or as supportive therapy of bone metastasis. First cases of bisphosphonate related osteonecrosis of the jaw (BRONJ) were reported to the FDA in 2001 and were published as case reports in 2003. To date there are still contradictory publications on the prevalence of BRONJ in literature. However, ONJ is a very rare disease in oral treatment regimen for osteoporosis. The development of BRONJ has a multi- factorial aetiology and the clinical presentation can vary markedly. Moreover, the precise pathogenesis largely remains elusive. Yet, we believe that local tissue acidosis due to local infections in the jaw bone offers a conclusive pathogenesis model and may prove to be the missing link in bisphosphonate related ONJ. Bone-bound bisphosphonates are released at acidic pH, accumulate in jawbone and lead to local tissue toxicity. This might explain why dental procedures to treat foci of inflammation can significantly reduce BRONJ in patients treated with iv-bisphosphonates in oncologic treatment regimens. Unfortunately, relevant large animal models have not been published yet. Most recently we have established a large animal model to induce BRONJ by tooth-extraction and iv-zoledronate treatment in oncologically relevant doses in minipigs. This model gives evidence that bisphosphonates are causally linked to the onset of BRONJ. Moreover, investigations in large animal models will allow for better understanding of the pathogenesis and will allow for testing of new therapeutic strategies for bisphosphonate related ONJ.

Schlüsselwörter

Tiermodell - Kiefernekrose - Bisphosphonate

Keywords

Animal model - osteonecrosis of the jaw - bisphosphonates
 

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