Entstehung einer Osteonekrose des Kiefers unter Bisphosphonat-Therapie

Abstract

Aim: The use of bisphosphonates (BP) has been linked to the development of an osteonecrosis of the jaw (ONJ). This doctoral dissertation initially aimed to clinically describe this new disease. Then followed an epidemiologic analysis of BP prescription in Germany. Based on that, the major goal was to identify individual risk factors towards an ONJ among patients with underlying malignancies or osteoporosis. Methods: A register (Register) for all cases of ONJ in Germany was installed at the Charite University Hospital and between 2005-2012, a total of 1229 cases were collected. Epidemiological information on BP use were analyzed from insurance claims data in a joint project with the University of Bremen. The Register itself served for detailed analysis of clinical aspects and to compare the duration of BP-treatment until an ONJ occurred for the different BPs and the various underlying diseases. If possible, all analyses were stratified by gender and age. Results: Approximately 0.1% of the German public was treated with an i.v. BP per year. Men received i.v. BPs more often, but those under treatment died significantly earlier than women. An ONJ occured after a median i.v. treatment time of 25 months. Ibandronate and Zoledronate users suffered from their ONJ significantly earlier than Pamidronate users. A sequential intake of two different BPs could significantly prolong treatment time. Age and a concomitant osteoporosis had no influence on treatment duration. In comparison to epidemiological data, the Register showed an unexpected accumulation of women, patients with multiple myeloma, and those treated with Zoledronate. Dental anamnesis showed a tooth extraction under BP-treatment in 67% of patients but 11% developed their ONJ spontaneously. The ONJ-free survival was poorest for patients with kidney cancer. Gender appears to be an additional risk factor for males in that subgroup. The incidence of an ONJ for patients with osteoporosis was 0,001%. Conclusion: Life expectancy influences the duration of BP treatment and, hence, raises the chance of developing an ONJ. How soon an ONJ occurs depends on various risk factors such as the type of the underlying disease, the type and application of the BP, and sometimes on gender. The information gained from this doctoral thesis will help doctors to individually advise their patients on the risk to develop an ONJ under BP-treatment.