Immunhistochemische Untersuchung von Patienten mit Bisphosphonat-assoziierten Osteonekrosen der Kiefer

Immunohistochemical study of patients with bisphosphonate-related osteonecrosis of the jaw

by Jan Wiegel
Doctoral thesis
Date of Examination:2022-06-16
Date of issue:2022-06-03
Advisor:Prof. Dr. Nicolai Miosge
Referee:PD Dr. Dr. Philipp Kauffmann
Referee:Prof. Dr. Thomas Meyer
Persistent Address: http://dx.doi.org/10.53846/goediss-9280

 

 

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Abstract

English

The aim of this present study was to compare resected mandibula bone segments of patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ) to healthy mandibula bone samples with reference to histological osteogenic factors. Materials and methods: Five human resected segments from the bone of the lower jaw won by surgical necrosectomy treatment of BRONJ patients were compared to four healthy resected bone samples of human mandibular jaws won by wisdom tooth osteotomy. For this purpose, the nine mandibula samples were distributed in two groups of patients (healthy and diseased). There was a systematic and unified pattern of histological preservation and paraffin embedding. Serial sections were created of each bone sample followed by immunohistochemical investigation regarding to the specific proteins neutrophil elastase, collagen type I, RUNX2, SMURF1, SMURF2, SMAD2/3 and RANKL. The histologically finished preperations were scanned and the received images were evaluated with the bioimage analysis software QuPath for a precise cell detection. QuPath enabled a quantitative analysis of the different proteins within the samples of the two patient groups. The final cell detections of the different proteins for the healthy and the diseased group of patients were compared and evaluated. Statistical analysis was performed by using the Mann-Whitney-U-test (p<0.05) and applied in both experimental groups. The comparison showed a significant higher number of inflammation proteins (neutrophil elastase) in BRONJ compounds than in healthy non BRONJ bone samples. In addition RUNX2, SMAD2/3 and RANKL also showed significant more cell detections correlating to more proteins in the diseased group compared to the healthy patient group. No significant difference in cell detections could be found for the proteins Col-I, SMURF1 and SMURF2 by comparing the two patient groups. Summarizing, this study showed that osteogenic factors and specific bone proteins could be found in both patient groups and that there were significant differences of the quantitative cell detections for the proteins neutrophil elastase, RUNX2, SMAD2/3 and RANKL in each group.
Keywords: bisphosphonate; BRONJ; IHC; osteogenic-factors
 
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