Kieferosteonekrosen in der Osteoonkologie

Zusammenfassung

Osteoprotektive Medikamente (Bisphosphonate und RANKL-Antikörper) sind integrale Bestandteile der Therapie von Knochenmetastasen. Osteoprotektiva reduzieren die Zahl skelettaler Komplikationen, wie Hyperkalzämie, Frakturen und Knochenschmerzen, bzw. verzögern deren Auftreten. Das entscheidende Therapieziel ist die Verbesserung der Lebensqualität der betroffenen Patienten. Während Bisphosphonate seit ca. 25 Jahren eingesetzt werden, steht der RANKL–Antikörper in der Onkologie erst seit 2011 zur Verfügung. Beide Substanzklassen sind durch unterschiedliche Nebenwirkungen gekennzeichnet, teilen allerdings das Risiko für das Auftreten von Kieferosteonekrosen (ONJ). In drei großen Phase–III–Studien mit 5723 Patienten mit soliden Tumoren und Knochenmetastasen oder multiplem Myelom wurden zum ersten Mal prospektiv Daten zur Inzidenz von ONJ gewonnen. Die Patienten wurden entweder mit Zoledronsäure oder Denosumabüber median 17 Monate behandelt. Obwohl die Häufigkeit von ONJ im Bisphosphonatkollektiv numerisch unter der der Denosumabgrup-pe lag (37 vs. 52) waren die Ergebnisse statistisch nicht signifikant unterschiedlich und lagen zwischen 1,3 und 1,8 %. Weitere Untersuchungen mit osteoprotektiven Medikamenten in der adjuvanten Situation legen nahe, dass die Inzidenz mit der „onkologischen Dosierung” zu einer Steigerung von Kieferosteonekrosen um 1–1,5 % pro Behandlungsjahr führt. Die Jahresdosis zur Behandlung von Knochenmetastasen liegt um den Faktor 10–12 höher als in der Therapie der Osteoporose. Derzeit sind von vielen Fachgesellschaften Leitlinien und Empfehlungen zur Vermeidung und Therapie von Kieferosteonekrosen formuliert und publiziert worden. Ob die Berücksichtigung prophylaktischer Maßnahmen zu einer Reduktion der Erkrankungshäufigkeit führen wird, muss prospektiv in zukünftigen Studien untersucht werden.

Summary

Osteoprotective drugs (bisphosphonates and RANKL-antibodies) are integral components of the treatment of metastatic bone disease. Os teoprotective medications reduce the number of skeletal complications, like hypercalcemia, fractures and bone pain, or delay their manifestation significantly. The major goal of this therapy is the improvement of the patients' quality of life. While bisphosphonates have been used for approximately 25 years, the RANKL-antibody denosumab has been labeled in oncology only since 2011. Both classes of substances are characterized by different side effects, but share the risk for the occurence of osteonecrosis of the jaw (ONJ). In the last two years, for the first time, data for the incidence of ONJ were prospectively generated in three large phase-III studies including 5,723 patients with solid tumors and bone metastases or multiple myeloma. The patients were treated with either zoledronic acid or denosumab for a median of 17 months. Though the frequency of ONJ in the bisphosphonate group was numerically lower compared with the denosumab group (37 vs. 52), the results were statistically not different and were between 1.3 % and 1.8 %, respectively. Further studies with osteoprotective drugs in adjuvant treatment in oncology suggest that using the „tumor-dose” leads to an increase of 1–1.5 % per annum in the incidence of ONJ. The annual dose for the treatment of bone metastases is approximately 10–12 higher than in the therapy of the osteoporosis. At present, many scientific societies have generated and published guidelines and recommendations for the avoidance and therapy of ONJ. Whether prophylactic measures will lead to a reduction of the morbidity of ONJ, should be investigated prospectively in future studies.

Schlüsselwörter

Knochenmetastasen - Bisphosphonate - Denosumab - Osteoprotektion - Kieferosteonekrosen

Keywords

Bone metastases - bisphosphonates - Denosumab - osteonecrosis of the jaw - ONJ - osteo – protection

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