The Role of the Immune Response in the Development of Medication-Related Osteonecrosis of the Jaw.

Weidong Zhang,Wenhao Ren,Shaoming Li,Shasha Li,Chunmiao Jiang,Ling Gao,Jingjing Zheng,Shuying Yang,Keqian Zhi

doi:10.3389/fimmu.2021.606043

Abstract

Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious adverse drug effect. There are multiple hypotheses to explain the development of MRONJ. Reduced bone remodeling and infection or inflammation are considered central to the pathogenesis of MRONJ. In recent years, increasing evidence has shown that bisphosphonates (BPs)-mediated immunity dysfunction is associated with the pathophysiology of MRONJ. In a healthy state, mucosal immunity provides the first line of protection against pathogens and oral mucosal immune cells defense against potentially invading pathogens by mediating the generation of protective immunoinflammatory responses. In addition, the immune system takes part in the process of bone remodeling and tissue repair. However, the treatment of BPs disturbs the mucosal and osteo immune homeostasis and thus impairs the body's ability to resist infection and repair from injury, thereby adding to the development of MRONJ. Here, we present the current knowledge about immunity dysfunction to shed light on the role of local immune disorder in the development of MRONJ.

Highlights

Medication-related osteonecrosis of the jaw (MRONJ) is a severe medication-induced necrotic bone disease [1]
The in vitro differentiation of neutrophils was not affected, their life span was shortened by BPs. These results suggested that BPs have the potential to suppress the innate immune system, which possibly contributed to the pathogenesis of MRONJ [80]
We focused on the role of the immune response in the pathogenesis of MRONJ

Summary

Introduction

Medication-related osteonecrosis of the jaw (MRONJ) is a severe medication-induced necrotic bone disease [1]. Disruption of the oral mucosal barrier is induced by potential risk factors and by the toxic effect of BPs on soft tissue (Figure 1). BPs, on the one hand, can induce an immunosuppressive condition by suppressing immune cell activation, on the other hand, it can render an imbalance between anti-inflammatory and pro-inflammatory cytokines, thereby resulting in intense inflammation and tissue damage.

Results

Conclusion