Investigation of medication-­related osteonecrosis of the jaw by real-­time in vitro assays, histologic examination, and radiographic evaluation

Abstract

Although medication-related osteonecrosis of the jaw (MRONJ) was first reported over fifteen years ago, to date the pathogenesis of the disease remains unclear. As a result, there is no consensus on a unified treatment or prevention protocol. Treatment of MRONJ is difficult and costly, and disease sequela can include pain, infection, inability to eat, extraoral fistula, and pathologic fracture, all of which significantly impact the quality of life for patients. This project aimed to provide a more profound picture of how bisphosphonates and denosumab could influence the expression patterns of human gingival fibroblasts and participating immune cells and mediators using real-time in vitro assays. The composition of the bone in the MRONJ disease process was also examined in additional histologic and radiographic examinations to correlate the altered bone structure with different disease variants and degree of antiresorptive exposure. Our results lead us to suggest that the etiology of MRONJ could be attributed to a multifactorial process involving soft tissue toxicity, mechanical damage and surgical trauma, local inflammation, immune suppression and dysfunction, infection and biofilm alteration, dysfunctional bone resorption, over-­ossification and a limited osteocyte network, and impaired wound healing leading to necrotic bone exposure