The oral mucosa is initially involved. As the damage progresses, underlying alveolar bone is also involved and the clinical presentation of ONJ becomes evident
Impaired immune homeostasis-macrophage impaired function
Dendritic cells, macrophages, cytotoxic and helper T-lymphocytes are affected by bisphosphonates. Chemokines, like tumor necrosis factor-alpha, inteleukins IL-1a, IL-1b, IL-6 and IL-8 are also impaired by bisphosphonates. Impaired immune response is responsible for continued inflammation resulting in osteomyelitis. Impaired function of macrophages due to RANKL inhibition is a key phenomenon in the defective topical immune response