During the prefibrotic phase, injury to endothelial cells secondary to radiation causes destruction of local vasculature, and recruitment of inflammatory cells and fibroblasts via pro-inflammatory cytokines like TNF-α, FGF-β and TGF-β1. In addition, osteoblasts within the bone are damaged and destroyed, leading to decreased production of normal bone tissue. In the constitutive organized phase, fibroblasts persist and are converted to myofibroblasts by these same cytokines, that begin to fibrous extracellular matrix (ECM) within the affected bone. Consequently, the increased production of ECM by myofibroblasts coupled with decreased production of osteoid by osteoblasts results in weakened bony tissue. Finally, during the late fibroatrophic phase, the affected bone becomes hypocellular as myofibroblasts begin to die and leave behind weak, fibrotic tissue. Ultimately, these tissues are fragile and susceptible to damage by trauma or infection with little ability to repair or defend themselves due to the lack of vasculature caused during the pre-fibrotic phase. Given this understanding of the pathophysiology of ORN, current treatments are targeted at decreasing inflammatory cytokines and reducing free radical damage to DNA. Risk factors
Risk factors for osteoradionecrosis include:

Size and location of tumor; the risk of developing ORN increases with larger tumors, since they require higher doses of radiation to achieve cure, subsequently exposing nearby tissues to higher doses. While radiation therapy has become more targeted and precise, patients with tumors located closer to the mandible (e.g. oral cavity) or maxilla (e.g. nasopharynx) will more commonly develop ORN since the bone is more likely fall within the radiation field.
Other signs and symptoms include:

Pain
Swelling
Non-healing sore or ulcer in the mouth
Trismus
An extra-oral fistula (from jaw to skin)
Infection in gums/teeth
Extra-oral draining sinuses
Lymphadenopathy
Malocclusion
Jaw fracture
Sequestrum (most commonly found below the mandible)If symptoms are evident, these should be reported to the patients doctor or healthcare team as soon as possible. Epidemiology and etiology
Epidemiology
The epidemiology of osteoradionecrosis has proven difficult to estimate, with previous studies reporting incidence of disease between 4.74-37.5%. More recent reports have estimated the incidence to 2%, which is likely attributable to improvements in radiation therapy. Pathophysiology
Radiation therapy destroys cancer primarily by causing DNA damage that promotes cell death. Tumor cells within a cancer are especially susceptible to damage by radiation as they frequently develop mutations in the DNA repair mechanisms that allow normal, healthy cells to recover from radiation damage. However, excessive radiation doses can cause even normal cells to be overwhelmed by DNA damage and lead to local tissue changes and necrosis. Scientists have been conducting investigations into the exact mechanisms of these changes to help create treatments since osteoradionecrosis (ORN) was first described by Regaud in 1922. Several competing theories have emerged over the years with resultant changes to accepted treatments. Initially, it was believed that ORN arose from a combination of radiation, trauma and infection. According to this belief, radiation damage to the bone caused the bone to weaken, making it susceptible to microfractures caused by trauma and allowing bacteria to invade. This theory placed ORN on a spectrum of disease with osteomyelitis, so it was primarily treated with antibiotics.