Avascular necrosis (AVN), also called osteonecrosis or bone infarction, is death of bone tissue due to interruption of the blood supply. Early on, there may be no symptoms. Gradually joint pain may develop which may limit the ability to move. Complications may include collapse of the bone or nearby joint surface. Risk factors include bone fractures, joint dislocations, alcoholism, and the use of high-dose steroids. The condition may also occur without any clear reason. The most commonly affected bone is the femur. Other relatively common sites include the upper arm bone, knee, shoulder, and ankle. Diagnosis is typically by medical imaging such as X-ray, CT scan, or MRI. Rarely biopsy may be used. Treatments may include medication, not walking on the affected leg, stretching, and surgery. Most of the time surgery is eventually required and may include core decompression, osteotomy, bone grafts, or joint replacement. About 15,000 cases occur per year in the United States. People 30 to 50 years old are most commonly affected. Males are more commonly affected than females. Signs and symptoms In many cases, there is pain and discomfort in a joint which increases over time. While it can affect any bone, about half of cases show multiple sites of damage. Avascular necrosis most commonly affects the ends of long bones such as the femur. Other common sites include the humerus, knees, shoulders, ankles and the jaw. Causes The main risk factors are bone fractures, joint dislocations, alcoholism, and the use of high-dose steroids. Other risk factors include radiation therapy, chemotherapy, and organ transplantation. Osteonecrosis is also associated with cancer, lupus, sickle cell disease, HIV infection, Gaucher's disease, and Caisson disease (dysbaric osteonecrosis). The condition may also occur without any clear reason. Bisphosphonates are associated with osteonecrosis of the mandible. Prolonged, repeated exposure to high pressures (as experienced by commercial and military divers) has been linked to AVN, though the relationship is not well understood. In children, avascular osteonecrosis can have several causes. It can occur in the hip as part of Legg–Calvé–Perthes syndrome, and it can also occur as a result after malignancy treatment such as acute lymphoblastic leukemia and allotransplantation. Pathophysiology The hematopoietic cells are most sensitive to low oxygen and are the first to die after reduction or removal of the blood supply, usually within 12 hours. Experimental evidence suggests that bone cells (osteocytes, osteoclasts, osteoblasts etc.) die within 12–48 hours, and that