Unit:
Κατεύθυνση Οδοντοφατνιακή ΧειρουργικήΒιβλιοθήκη Οδοντιατρικής
Author:
Paschalidi Polytimi
Supervisors info:
Νικητάκης Νικόλαος, Καθηγητής, Τμήμα Οδοντιατρικής, Σχολή Επιστημών Υγείας, ΕΚΠΑ
Περισανίδης Χρήστος, Καθηγητής, Τμήμα Οδοντιατρικής, Σχολή Επιστημών Υγείας, ΕΚΠΑ
Τσιχλάκης Κωνσταντίνος, Καθηγητής, Τμήμα Οδοντιατρικής, Σχολή Επιστημών Υγείας, ΕΚΠΑ
Original Title:
The role of macrophages in Medication Related Osteonecrosis of the Jaws. An immunohistochemical study
Translated title:
The role of macrophages in Medication Related Osteonecrosis of the Jaws. An immunohistochemical study
Summary:
Medication-related osteonecrosis of the jaw (MRONJ) is an adverse side effect of long-term administration of antiresorptives, mainly bisphosphonates and denosumab. Although macrophage polarization has been reported to be an important mediator of MRONJ, the detailed potential mechanism of MRONJ remains unclear. The main aim of this study was to investigate the link between M1 and M2 macrophage polarization and disease progression in patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ) and denosumab-related osteonecrosis of the jaw (DRONJ).
The study material comprised mucosal tissues near osteonecrotic areas of 30 MRONJ patients with stage I-III, obtained at the Department of Oral and Maxillofacial Surgery of Dental School, National and Kapodistrian University of Athens (NKUoA), Greece. As controls, inflamed mucosal tissues from participants without MRONJ who received either bisphosphonates or denosumab and participants who did not received antiresorptive therapy were used.
For M1 and M2 macrophage identification, double CD68/iNOS and CD68/CD206 immunofluorescence staining were performed respectively. Each slide was evaluated for the intension of staining with specific software (Image J, NIH) in computer and after the use of specific filters (threshold) for each antibody. For the remaining secreted cytokines (IL6, IL10), the region of interest was selected, a minimal and maximal threshold were set and total expression was calculated. Statistical analysis was performed using the SPSS.
Our analysis showed that there was a statistically significant increase in CD68+/iNOS+ M1 macrophage density (p <0.001) and M1/M2 ratio (p <0.001) between the different MRONJ stages and controls. We found a statistically significant higher M1 macrophage density and increased M1/M2 ratio in MRONJ patients with stages 2 and 3 compared to controls receiving antiresorptive therapy and controls not receiving antiresorptive therapy (p <0.05 for all pairwise comparisons). Our results showed that M1 and M2 macrophage density were statistically significant higher in patients receiving bisphosphonates compared to those receiving denosumab (p = 0.005, p = 0.002 respectively). We observed a significant increase in expression of IL-6 in MRONJ patients with advanced stages 2 and 3 as well as a significant higher IL-10 expression in MRONJ patients with stage 1 compared to controls (p <0.05 for all pairwise comparisons).
In conclusion, our study reveals the role of macrophage polarization in MRONJ patients with advanced disease. We demonstrate that a higher density of M1 macrophages and increased M1/M2 ratio as well as enhanced expression of IL-6 in mucosal tissues surrounding necrotic bone are associated with advanced stage in both BRONJ and DRONJ patients.
Main subject category:
Health Sciences
Keywords:
Osteonecrosis, Macrophages polarization, Bisphosphonates, Denosumab, Αntiresorptives
Number of references:
122
