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Bisphosphonatassoziierte Osteonekrose des Kiefers

Bisphosphonate-associated osteonecrosis of the jaw

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Zusammenfassung

Hintergrund

Im Jahr 2003 wurde erstmals über den Zusammenhang zwischen Bisphosphonaten (BP) und Osteonekrosen der Kiefer (ONJ) berichtet. Seitdem gab es zahlreiche Meldungen, die dieses neue Krankheitsbild als therapeutisch schwer beeinflussbare Erkrankung beschreiben. Wegen ihrer hemmenden Wirkung auf die osteoklastäre Knochenresorption werden BP in zunehmender Zahl bei Patienten mit skeletalen Komplikationen maligner Erkrankungen und Osteoporose eingesetzt. Wir präsentieren einen Literaturüberblick, die Ergebnisse einer Befragung unter Kliniken für Mund-, Kiefer- und Gesichtschirurgie und unsere eigenen Patienten.

Material und Methoden

Es wurden 349 Fälle aus der Literatur, 54 Falldokumentationen von Kliniken für Mund-, Kiefer- und Gesichtschirurgie und 19 eigene Fälle nach BP- und Komedikation, Grund- und Begleiterkrankung, Lokalisation, Histologie sowie Therapie analysiert (n=73).

Ergebnisse

Von den 73 untersuchten Patienten erhielten 68 (93%) Pamidronat und/oder Zoledronat. 69 Patienten (94%) wurden BP wegen einer malignen Grunderkrankung, 3 (5%) wegen Osteoporose und 1 Patient (1%) wegen eines Mb Paget verabreicht. Die ONJ traten bei 54 Patienten (74%) im Unterkiefer, bei 12 (16%) im Oberkiefer und 4 (5%) in beiden Kiefern auf. Bei 38 Patienten (52%) waren Zahnextraktionen vorausgegangen, bei 35 (48%) entwickelte sich die ONJ spontan. Histologisch fanden sich chronisch-fibrosierende und floride, eitrige Osteomyelitiden, auffällig häufig auch Actinomyceskolonien im Knochen. 9 Patienten (12%) wurden rein konservativ behandelt, 52 (71%) unterzogen sich teils mehrfach begrenzten chirurgischen Maßnahmen (z. B. Dekortikation) und bei 19 Patienten (26%) erfolgten Kieferteilresektionen. Insgesamt konnte nur bei 55% der Patienten eine Heilung der ONJ erzielt werden. Die höchste Erfolgsrate (88%) wurde bei den Patienten mit Resektionen beobachtet.

Diskussion

Im Verhältnis zur millionenfachen Anwendung der BP treten ONJ nur selten auf, bei Tumorpatienten kommt es unter Pamidronat und Zoledronat bei 4–10% zur ONJ. Wegen der Ähnlichkeit mit der Phosphornekrose („phossy jaw“) nennen einige Autoren die Erkrankung „bis-phossy jaw“. Anhand der vorliegenden Daten kann aber eine Kausalität zwischen BP und ONJ nur vermutet werden; wir empfehlen die Bezeichnung bisphosphonatassoziierte Osteonekrose. Die Therapie der Wahl ist die chirurgische Nekroseentfernung und sichere plastische Deckung. Eine kontinuierliche und systematische Prophylaxe ist notwendig. Die Zusammenarbeit von Onkologen, Zahnärzten und Mund-, Kiefer- und Gesichtschirurgen muss ein zentraler Aspekt sein.

Abstract

Background

Bisphosphonates (BP) are widely used in patients with osteoporosis or malignant tumors with bony metastases such as breast cancer and plasmocytoma because of their potency to affect osteoclasts and bone resorption. Osteonecrosis of the jaw (ONJ) has been described as a potential side effect since 2003. After a review of the literature we present results of a questionnaire, which was sent to departments of oral and maxillofacial surgery (OMFS) in German-speaking countries.

Material and methods

We present 349 patients from the literature, 54 patients from the departments of OMFS and 19 cases from our own department. These patients ware analyzed depending on their disease, their medication, localization of the affected area, histological signs and therapeutic outcome.

Results

Of 73 patients, 68 (93%) were treated with pamidronate or zoledronate; 69 (94%) patients suffered from malignant diseases, 3 (5%) had osteoporosis, and 1 (1%) had Paget’s disease. In 57 (78%) patients the ONJ affected the mandible, in 12 (16%) the maxilla and in 4 (5%) both jaws. A previous tooth extraction was reported in 38 (52%) patients, and in 35 (48%) ONJ occurred spontaneously. Histological findings were similar to osteomyelitis with a high number of actinomyces colonies. Nine (12%) patients received non-surgical treatment only, 52 (71%) patients underwent minor surgical procedures (e. g. decortication) and 19 (26%) patients underwent marginal or segmental resection of the jaw. Considering all treatment modalities, healing was achieved in 55; the most effective was marginal and segmental resection (88%).

Discussion

Though millions of patients receive BP treatment only a few suffer from ONJ. The incidence in cancer patients with pamidronate and zoledronate therapy is 4%–10%. Because of the similarity to “phossy jaw”, seen in patients dealing with white phosphorus in the nineteenth century, some authors call the new entity “bis-phossy jaw”. As the pathogenesis of ONJ is not clear we recommend that the descriptive term bisphosphonate-associated osteonecrosis should be used. Bone resection and safe soft tissue closure is the treatment of choice. We recommend systematic dental care for patients receiving BP medication. Information exchange between oncologists, oral and maxillofacial surgeons and dentists is important.

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Authors and Affiliations

  1. Abteilung für Mund-, Kiefer- und Gesichtschirurgie, Plastische Operationen, Asklepios Klinik Nord, Hamburg

    M. H. Abu-Id & T. Kreusch

  2. Klinik für Mund-, Kiefer- und Gesichtschirurgie, Universitätsklinikum Schleswig-Holstein, Campus Kiel

    Y. Açil

  3. Abteilung für Pathologie und Neuropathologie, Asklepios Klinik Nord, Hamburg

    J. Gottschalk

  4. Abteilung für Mund-, Kiefer- und Gesichtschirurgie, Plastische Operationen, Kopfzentrum Asklepios Klinik Nord, Tangstedter Landstraße 400, 22417, Hamburg

    M. H. Abu-Id

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  1. M. H. Abu-Id
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Correspondence to M. H. Abu-Id.

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Abu-Id, M.H., Açil, Y., Gottschalk, J. et al. Bisphosphonatassoziierte Osteonekrose des Kiefers. Mund Kiefer GesichtsChir 10, 73–81 (2006). https://doi.org/10.1007/s10006-005-0670-0

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