A known complication that can occur in patients using bisphosphonates (BPs) is osteonecrosis of the jaw (ONJ). ONJ features bone exposure that may be associated with severe pain, swelling, local infection, and pathological fracture of the jaw. Current literature indicates that a complex combination of factors is necessary to induce ONJ. Several hypotheses about the pathophysiology of ONJ were previously reported. Here, we review these hypotheses and introduce new ideas and suggestions on this topic, focusing on bone site-specific cells, and the effect that BPs and other anti-resorptive drugs have on those cells. Gaining more insight into bone site-specific effects may help to better understand the pathogenesis ONJ, and contribute to the development of new bone site-specific anti-resorptive drugs.
Keywords: Bisphosphonates; Bone marrow; Jaw; Microenvironment; ONJ; Osteoclast; Osteonecrosis.