- Author: Jeanne K Tofferi, MD, MPH, FACP; Chief Editor: Herbert S Diamond, MD more...
Avascular necrosis (AVN) is defined as cellular death of bone components due to interruption of the blood supply; the bone structures then collapse, resulting in bone destruction, pain, and loss of joint function.
AVN usually involves the epiphysis of long bones, such as the femoral and humeral heads and the femoral condyles, but small bones can also be affected. In clinical practice, AVN is most commonly encountered in the hip.[1, 2] Most available data regarding the natural history, pathology, pathogenesis, and treatment of AVN pertains to femoral head necrosis.
AVN is associated with numerous conditions. Patients taking corticosteroids and organ transplant recipients are particularly at risk of developing AVN. AVN of the jaw has been described in patients taking bisphosphonates and, more recently, in 1.7% of cancer patients taking denosumab.[3, 4] For full discussion of this entity, see Bisphosphonate-Related Osteonecrosis of the Jaw.
Early diagnosis and appropriate intervention can delay the need for joint replacement. However, most patients present late in the disease course. Without treatment, the process is almost always progressive, leading to joint destruction within 5 years.
Although the pathophysiology of AVN is not fully understood, the final common pathway is interruption of blood flow to the bone. AVN affects bones with a single terminal blood supply, such as the femoral head, carpals, talus, and humerus. These bones have limited collateral circulation. Interruption of the vascular supply and resultant necrosis of marrow, medullary bone, and cortex are theorized to be caused by the mechanisms listed below. However, individual patients usually have more than one risk factor; this indicates that the pathogenesis of AVN is likely multifactorial.
Altered lipid metabolism: Animal studies have led to the hypothesis that increased levels of serum lipids leads to lipid deposition in the femoral head, causing femoral hypertension and ischemia.  Lipid-level–lowering drugs in animals reverse this process. Corticosteroid administration was associated with fat emboli in the femoral heads of rabbits. 
Intravascular coagulation: Disorders of the coagulation system have been implicated in the pathogenesis of AVN. Typically, it is a secondary event triggered by a familial thrombophilia, hypercholesterolemia, allograft organ rejection, other disorders (eg, infection, malignancy), or pregnancy.
Healing process: Necrotic bone triggers a process of repair that includes osteoclasts, osteoblasts, histiocytes, and vascular elements. Osteoblasts build new bone on top of the dead bone, leading to a thick scar that prevents revascularization of the necrotic bone, with resultant abnormal joint remodeling and joint dysfunction.
Primary cell death: Osteocyte death without other features of AVN has been seen in renal transplant patients, as well as in patients receiving steroids and those who consume significant amounts of alcohol.
Mechanical stress: Animal studies have shown an association between increased weight bearing and an increased incidence of AVN of the femoral head.
The frequency of AVN depends on the site involved. The most common site is the hip; other locations include the carpals, talus, femur, metatarsal, mandible, and humerus. In the United States, approximately 15,000 new cases of AVN are reported each year. AVN accounts for more than 10% of total hip replacement surgeries performed in the United States. Most recently, 380 cases of osteonecrosis of the jaw associated with bisphosphonate use have been reported. Most patients with osteonecrosis of the jaw also had an ongoing malignancy and/or had undergone a recent dental procedure.[7, 3, 8]
In most countries, the incidence and prevalence of AVN are unknown. A Japanese survey estimated that 2500-3300 cases of AVN of the hip occur each year; of these, 34.7% were due to corticosteroid use, 21.8% to alcohol abuse, and 37.1% to idiopathic mechanisms.
Data on mortality rates associated with AVN are not available. Most data involve AVN of the hip. Mortality rates are very low and vary based on the operative procedure used to treat AVN.
Morbidity rates are high and depend on the underlying cause. Morbidity rates associated with AVN of the hip are high; the prevalence of long-term disability is significant. Despite advances in orthopedic procedures, most patients with advanced AVN require more than one hemiarthroplasty or total hip replacement during their lifetime.
AVN has no racial predilection except for cases associated with sickle cell disease and hemoglobin S and SC disease, which predominantly occur in people of African and Mediterranean descent.
With the exception of AVN associated with systemic lupus erythematosus, AVN is more common in men, with an overall male-to-female ratio of 8:1.
AVN is a disease of middle age that most often occurs during the fourth or fifth decade of life and is bilateral in 55% of cases.
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