Bcl-xL expression in osteoclasts of patients with medication-related osteonecrosis of the jaw: a comparison with osteoradionecrosis and osteomyelitis

Abstract

Objective: The pathological mechanism of medication-related osteonecrosis of the jaw (MRONJ) is still unknown now. Osteoclasts are cells directly influenced by MRONJ, which might be the key mediator of pathological mechanism. This study aimed to evaluate the histological features of MRONJ, investigate the morphology and quantity of osteoclasts in MRONJ as well as expression of Bcl-xl, and compare it with ORN, OM, and normal jaw bone.

Methods: In this study, 57 subjects, including patients with MRONJ, osteoradionecrosis of the jaw (ORN), osteomyelitis of the jaw (OM), and normal jaw bone were studied. Hematoxylin and eosin-stained slides of these diagnosed cases were reviewed to investigate the histologic features and osteoclasts’ characteristics. Immunohistochemistry was performed to observed the function (TRAP staining) and Bcl-xL expression of osteoclasts. These characteristics of osteoclasts were also evaluated in the relationship with the histological features using statistical analysis.

Results: The results showed that MRONJ, ORN, and OM shared the characteristic feature of necrotic bone. The significant difference found between MRONJ and ORN was the presence of fibrous tissue (p<0.05), and between MRONJ and OM was the status of bacterial colonies (p<0.05). Osteoclasts in MRONJ enhance activity by increasing the size and the quantity (p<0.05). The regression analysis showed a strong correlation between the presence of osteoblasts, inflammatory cells, and bacterial colonies with the change in morphology and the number of osteoclasts (p<0.05). However, the TRAP-positive mean number and the TRAP intensity of osteoclasts in MRONJ did not show a significant difference with those in other groups (p>0.05); and Bcl-xL did not express in osteoclasts of MRONJ.

Conclusion: Osteoclasts in MRONJ showed an enhanced response to increase size and number that might relate to the presence of osteoblasts, inflammation and bacteria. This finding supports the idea that osteoclasts might be the main key to investigate MRONJ pathogenesis.