Risikofaktoren und Therapie von Antiresorptiva-assoziierten Kiefernekrosen, eine retrospektive Analyse an der Universitätsmedizin Göttingen

Risk factors and treatment of antiresorptive-associated necrosis of the jaw, a retrospective analysis at the University Medical Center Göttingen

by Johanna Gollasch née Richels
Doctoral thesis
Date of Examination:2023-05-10
Date of issue:2023-04-20
Advisor:PD Dr. Dr. Philipp Kauffmann
Referee:PD Dr. Dr. Philipp Kauffmann
Referee:PD Dr. Dr. Philipp Kanzow
Persistent Address: http://dx.doi.org/10.53846/goediss-9847

 

 

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Abstract

English

Antiresorptives (bisphosphonates and denosumab) are nowadays an integral part of the therapy and prophylaxis of osteoporosis and osseous metastasised bone tumours. A feared side effect of these drugs is antiresorptive-associated osteonecrosis of the jaw (ARONJ), which can have a far-reaching impact on the quality of life of patients. The aim of this study was to identify risk factors for the development of ARONJ by means of a retrospective study design and to evaluate the success of conservative therapy and surgical therapy, especially for individual indication groups. 128 patients (88 with ARONJ) were recruited from October 2012 to April 2021 from the antiresorptive consultation of the Department of Oral and Maxillofacial Surgery at the University Medical Center Göttingen and potential risk factors were recorded. The stages of necrosis were assessed after three, six and twelve months after therapy. Stage 0 was considered a successful therapy. Of the 88 patients with ARONJ, 53.4% were female and 46.6% male. The average age was 72.77 years  10.47 years. The main indications for AR in ARONJ patients were osteoporosis (26.1 %), prostate cancer (25.0 %), breast cancer (18.2 %), multiple myeloma (12.5 %), renal cell cancer (8.0 %), lung cancer (3.4 %), thyroid cancer (2.3 %), CUP (2.3 %), endometrial cancer (1.1 %) and malignant melanoma (1.1 %). There was a significant association between the development of ARONJ and the presence of metastases (p < 0.001), chemotherapy (p < 0.001), radiotherapy (p = 0.004) and anti-hormonal therapy (p = 0.007). Study participants with a higher Charlson comorbidity index had more ARONJ (p < 0.0001, Man-Whitney U test). In the ARONJ group, zolendronate (45.5 %) was most common, followed by denosumab (31.8 %), pamidronate (10.2 %), alendronate (8 %), ibandronate (3.4 %) and risendronate (1.1 %). On median, patients receiving zolendronate (n = 39) developed ARONJ after 36 months ( 21.53 mo), denosumab (n = 28) after 26.50 months ( 20.35 mo) and alendronate (n = 6) after 45 months ( 27.52 mo) (not significant). The risk profile of developing ARONJ (p < 0.001) showed a distribution of 57 % (high risk profile), 26.6 % (intermediate risk profile) and 16.4 % (low risk profile) for the total collective (n = 128). With regard to the necrosis lesions, 63.5 % were located in the mandible. In relation to the treatment of ARONJ, subjects were divided into three cohorts: conservative (n = 9), surgical (n = 31) and mixed (n = 21, surgical and conservative). Patients who received a purely surgical intervention were more likely to have treatment success and downstaging than subjects in the mixed or conservative cohort (local irrigation, antibiotic administration). This study underlines the importance of surgery for the healing of ARONJ, in order to decisively influence the success of the therapy through the complete removal of necrotic bone areas.
Keywords: Antiresorptives; bisphosphonates; denosumab; antiresorptive-associated osteonecrosis; risk factors for the development of ARONJ
Schlagwörter: Antiresorptiva; Bisphosphonate; Denosumab; Antiresorptiva-assoziierte Kiefernekrose; Risikofaktoren für die Entstehung einer ARONJ
 
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