NORD gratefully acknowledges Edward Cheng, MD; Quanjun Cui, MD; Stuart B. Goodman, MD, PhD; Lynne C. Jones, PhD; and Michael A. Mont, MD of ARCO International, a society of clinicians and basic scientists who study bone circulation and related diseases, for assistance in the preparation of this report.
Osteonecrosis, also known as avascular necrosis (AVN), aseptic necrosis or ischemic bone necrosis, is a disease resulting in the death of bone cells. If the process involves the bones near a joint, it often leads to collapse of the joint surface and subsequent arthritis due to an irregular joint surface. The exact cause is unknown.
Although it can happen in any bone, osteonecrosis most commonly affects the ends (epiphysis) of long bones such as the femur (thigh bone). Commonly involved bones are the upper femur (ball part of the hip socket) the lower femur (a part of the knee joint), the upper humerus (upper arm bone involving the shoulder joint), and the bones of ankle joint. The disease may affect just one bone, more than one bone at the same time, or more than one bone at different times. Orthopedic surgeons most often diagnose the disease using either an X-ray of magnetic resonance scan (MRI).
The amount of disability that results from osteonecrosis depends on what part of the bone is affected, how large an area is involved, how far the disease has progressed, and how effectively the bone rebuilds itself. The process of bone rebuilding takes place after an injury as well as during normal growth. Normally, bone continuously breaks down and rebuilds – old bone is reabsorbed and replaced with new bone. The process keeps the skeleton strong and helps it to maintain a balance of minerals. With osteonecrosis, the healing process is usually ineffective and the bone tissues break down faster than the body can repair them. If left untreated, the disease progresses, and the bone may develop a crack whereby the bone can get compressed (collapse) together (similar to compressing a snowball). If this occurs at the end of the bone, it leads to an irregular joint surface, arthritic pain and loss of function of the affected areas.
In the early stages of osteonecrosis, patients may not have any symptoms. As the disease progresses, however, most patients experience joint pain – at first, only when putting weight on the affected joint, and then even when resting. Pain usually develops gradually and may be mild or severe. If osteonecrosis progresses and the bone and surrounding joint surface collapse, pain may develop or increase dramatically. Pain may be severe enough to cause joint stiffness by limiting the range of motion in the affected joint. Disabling osteoarthritis may develop in the affected joint. The period of time between the first symptoms and loss of joint function is different for each patient, ranging from several months to more than a year.
Osteonecrosis has many different causes. Loss of blood supply to the bone may lead to bone cell death and can be caused by an injury (bone fracture or joint dislocation; called traumatic osteonecrosis). At times, there may be no history of injury (non-traumatic osteonecrosis); however, other risk factors are associated with the disease such as some medications (steroids, also known as corticosteroids), alcohol usage or blood coagulation disorders. Increased pressure within the bone also is associated with osteonecrosis. One theory is that the pressure within the bone causes the blood vessels to narrow, making it difficult for blood to circulate through the bone. Osteonecrosis can also be associated with other disorders. The exact reason osteonecrosis develops is not fully understood for some risk factors. Sometimes, osteonecrosis occurs in people with no risk factors (idiopathic). Some people have multiple risk factors. Osteonecrosis most likely develops because of the combination of factors, possibly including genetic, metabolic, self-imposed (alcohol, smoking), and other diseases that you may have and their treatment.
When a joint is injured, as in a fracture or dislocation, the blood vessels may be damaged. This can interfere with the blood circulation to the bone and lead to trauma-related osteonecrosis. Studies suggest that this type of osteonecrosis may develop in more than 20% of people who dislocate their hip joint.
Corticosteroids, such as prednisone, are commonly used to treat diseases in which there is inflammation, such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, and vasculitis. Studies suggest that long-term, high dose systemic (oral or intravenous) corticosteroid use is a major risk factor for non-traumatic osteonecrosis with reports of up to 35 percent of all people with non-traumatic osteonecrosis. However, there is little risk of osteonecrosis associated with the infrequent use of corticosteroids, inhaled corticosteroids, or most steroid injections into joints. Patients should discuss concerns about corticosteroid use with their doctor.
Doctors aren’t sure exactly why the use of corticosteroids sometimes is associated with osteonecrosis. They may have negative effects on different organs and tissues within the body. For example, they may interfere with the body’s ability to build new bones and to break down fatty substances. These substances would then build up in and clog the blood vessels, causing them to narrow. This then would reduce the ability of blood to flow inside a bone.
Excessive alcohol use is another major risk factor for non-traumatic osteonecrosis. Studies have reported that alcohol accounts for about 30% of all people with non-traumatic osteonecrosis. While alcohol can slow down bone remodeling (the balance between forming new bone and removing bone), it is not known why or how alcohol can trigger osteonecrosis.
Other Risk Factors:
Other risk factors or conditions associated with non-traumatic osteonecrosis include Gaucher disease, pancreatitis, autoimmune disease, cancer, HIV infection, decompression disease (Caisson disease), and blood disorders such as sickle cell disease. Certain medical treatments including radiation treatments and chemotherapy can cause osteonecrosis. People who have received a kidney or other organ transplant may also have an increased risk.
Osteonecrosis usually affects people between 30 and 50 years of age; about 10,000 to 20,000 people develop osteonecrosis each year in the United States. Osteonecrosis affects both men and women and affects people of all ages. It is most common among people in their thirties and forties. Depending on a person’s risk factors and whether the underlying cause is trauma, it also can affect younger or older people.
After performing a complete physical examination and asking about the patient’s medical history (for example, what health problems the patient has had and for how long), the doctor may use one or more imaging techniques to diagnose osteonecrosis. As with many other diseases, early diagnosis increases the chances of treatment success.
It is likely that the doctor first will recommend an x-ray. X-rays can help identify many causes of joint pain, such as a fracture or arthritis. If the x-ray is normal, the patient may need to have more tests.
Research studies have shown that magnetic resonance imaging (MRI) is currently the most sensitive method for diagnosing osteonecrosis in the early stages. The tests described below may be used to determine the amount of bone affected and how far the disease has progressed.
An x-ray is a common tool that the doctor may use to help diagnose the cause of joint pain. It is a simple way to produce pictures of bones. The x-ray of a person with early osteonecrosis is likely to be normal because x-rays are not sensitive enough to detect the bone changes in the early stages of the disease. X-rays can show bone damage in the later stages, and once the diagnosis is made, they are often used to monitor the course of the condition.
Magnetic Resonance Imaging (MRI)
MRI is a common method for diagnosing osteonecrosis. Unlike x-rays, bone scans, and CT (computed/computerized tomography) scans, MRI detects chemical changes in the bone marrow and can show osteonecrosis in its earliest stages before it is seen on an x-ray. MRI provides the doctor with a picture of the area affected and the bone rebuilding process. In addition, MRI may show diseased areas that are not yet causing any symptoms. An MRI uses a magnetic field and radio waves to produce cross-sectional images of organs and bodily tissues.
Also known as bone scintigraphy, bone scans should not be used for the diagnosis of osteonecrosis because they may miss 20 to 40% of the bone locations affected.
Computed/Computerized Tomography (CT)
A CT scan is an imaging technique that provides the doctor with a three-dimensional picture of the bone. It also shows “slices” of the bone, making the picture much clearer than x-rays and bone scans. CT scans usually do not detect early osteonecrosis as early as MRI scans but are the best way to show a crack in the bone. Occasionally it may be useful in determining the extent of bone or joint surface collapse.
A biopsy is a surgical procedure in which tissue from the affected bone is removed and studied. It is rarely used for diagnosis, as the other imaging studies are usually sufficiently distinct to make the diagnosis with a high level of confidence.
Appropriate treatment for osteonecrosis is necessary to keep joints from collapsing. If untreated, most patients will experience severe pain and limitation in movement within two years. There is no agreed upon optimal treatment for individuals with osteonecrosis. Early intervention is essential to preserve the joints, but most people are diagnosed late in the disease process.
Several treatments are available that can help prevent further bone and joint damage and reduce pain. To determine the most appropriate treatment, the doctor considers the following aspects of a patient’s disease: the age of the patient; the stage of the disease–early or late; the location and amount of bone affected–a small or large area. The underlying cause has not been shown to influence outcomes of treatment.
The goal in treating osteonecrosis is to improve the patient’s use of the affected joint, stop further damage to the bone, and ensure bone and joint survival. If osteonecrosis is diagnosed early enough, collapse and joint replacement can be prevented. To reach these goals, the doctor may use one or more of the following treatments.
There is no known pharmaceutical cure for osteonecrosis. Several non-operative treatments have been studied including hyperbaric oxygen therapy, shock wave therapy, electrical stimulation, pharmaceuticals (anticoagulants, bisphosphonates, vasodilators, lipid lowering agents), physiotherapy and muscle strengthening exercises, and combinations thereof. There are conflicting results for some of these treatments, therefore, rigorous, randomized controlled trials with large numbers of patients are still needed to determine the effectiveness of these treatments. Non-operative treatment may be part of a wait-and-see approach based on the size of the area of dead bone. Non-operative treatments cannot be labeled as conservative, since many of them do not slow the progression of the disease or lead to avoidance of a total hip arthroplasty. Most are simply pain-relieving at best.
Reduced weight bearing does not alter the course of the disease and is not a treatment. It may be used to simply permit the patient to better cope with pain until appropriate treatment is instituted.
Core decompression – This surgical procedure removes or drills a tunnel into the area of the affected bone, which reduces pressure within the bone. Core decompression works best in people who are in the earliest stages of osteonecrosis, before the collapse of the dead bone. This procedure sometimes can reduce pain and slow the progression of bone and joint destruction in these patients.
Osteotomy – This surgical procedure reshapes the bone to reduce stress on the affected area. There is a lengthy recovery period, and the patient’s activities are very limited for 3 to 12 months after an osteotomy. This procedure is most effective for patients with advanced osteonecrosis and those with a small area of affected bone.
Bone graft – Bone grafts can be used as part of the surgical treatment for osteonecrosis. Bone grafts can use bone from the same patient or donor bone. Bone graft or synthetic bone graft can be inserted into the hole created by the core decompression procedure. A specialized procedure, called vascularized bone grafting, involves moving a piece of bone from another site (often the fibula, one of the bones of the calf, or the iliac crest, a portion of the pelvic bone) with a vascular attachment. This allows for support of the diseased area as well as a new source of blood supply. This is a complex procedure and is performed by surgeons that are specially trained. Another type of bone grafting, involves scraping out all of the dead bone and replacing it with healthier bone graft, often from other portions of the patient’s skeleton.
A unique type of bone graft involves the use of a patient’s own cells that are capable of making new bone. Often these cells are a type of stem cell from the bone marrow or other bodily tissues. There has been increasing interest in the potential of stem cell therapy. This is also being studied for the treatment of osteonecrosis. Mesenchymal stem cells, which are a type of ‘adult’ stem cell, can grow and develop into many different cell types in the body. Physicians take the patient’s own mesenchymal stem cells (autologous transplant) and place them into the affected bone to stimulate bone repair and regeneration.
Arthroplasty/total joint replacement – Total joint replacement is the treatment of choice in late-stage osteonecrosis when the joint is destroyed. In this surgery, the diseased joint is replaced with artificial parts. It may be recommended for people who are not good candidates for other treatments, such as patients who do not do well with repeated attempts to preserve the joint. Various types of replacements are available, and people should discuss specific needs with their doctor.
For most people with osteonecrosis, treatment is an ongoing process. Doctors may first recommend the least complex and invasive procedure, such as protecting the joint by limiting high impact activities, and watch the effect on the patient’s condition.
Other treatments then may be used to prevent further bone destruction and reduce pain such as core decompression with bone graft/stem cell therapy. Eventually patients may need joint replacement if the disease has progressed to collapse of the bone. It is important that patients carefully follow instructions about activity limitations and work closely with their doctor to ensure that appropriate treatments are used.
Scientists, researchers, and physicians continue to pursue a better understanding of how this disease occurs as well as compare the effectiveness of current and newly developed therapies. Often, this requires a clinical trial to answer questions and gain additional knowledge.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
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Some current clinical trials also are posted on the following page on the NORD website:
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For more information about clinical trials conducted in Europe, contact:
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