OSTEONECROSIS: A SOURCE OF BONE PAIN AND LOSS OF FUNCTION IN CHILDHOOD CANCER SURVIVORS

by Nina Kadan-Lottick, M.D. Source: Spring 2006 CCCF Newsletter

Osteonecrosis is a bone condition that can be a long term complication of childhood cancer therapy. It results from the temporary or permanent interruption in the flow of blood to the affected bone. Because of the loss of blood supply, the bone tissue dies and causes the bone to collapse. When this happens near a joint, the joint surface can collapse. Other names for osteonecrosis include the following: “avascular necrosis,”  “asceptic necrosis,” and “ischemic bone necrosis.”

WHAT ARE THE SYMPTOMS?

The clinical spectrum varies from person to person and over time. In the early stages of osteonecrosis, a person may have no symptoms. This is called sub-clinical osteonecrosis and may only be detectable by an x-ray or another diagnostic imaging test. As the condition progresses, the person develops pain when putting weight on the affected bone or joint. Later, there may be joint swelling pain even when resting. Typically the pain develops gradually and the severity varies from person to person. Also, the period of time between the first symptoms and loss of joint function differs between individuals and may range from months to years. Osteonecrosis which develops in children with cancer typically occurs during the first one to two years after starting therapy and often affects multiple bone/joint sites. Usually a weight bearing joint is affected, like the hip or ankle or knee.

WHO GETS OSTEONECROSIS?

Osteonecrosis has several causes. In fact, most osteonecrosis is found in people who have not had cancer. In the general population, risk factors for developing osteonecrosis include the following:

• Sickle cell disease
• Injury to the bone through fracture or dislocation
• Excessive alcohol use
• Long-term corticosteroids  for both non-cancer  and cancer diseases

Among individuals with a history of cancer, corticosteroid therapy is considered the major risk factor for the development of osteonecrosis. Survivors with a history of acute lymphoblastic leukemia (ALL) and various types of lymphoma represent most of the individuals who previously received corticosteroid therapy. Previous studies have estimated that somewhere between 1.7 and 7.9% of acute lymphoblastic leukemia (ALL) survivors develop osteonecrosis in the first 3-5 years after diagnosis.  Among ALL patients who receive corticosteroid therapy, the following patient characteristics are particularly associated with an increased risk of developing osteonecrosis:

• Age >10 years at diagnosis of cancer
• Female gender
• More intense therapy: for example high risk acute lymphoblastic leukemia (ALL) patients have a higher risk than low risk ALL patients.

The most common corticosteroids used in cancer therapy are prednisone and dexamethasone. It is not known exactly how corticosteroids cause osteonecrosis. Some investigators think that corticosteroids interfere with the body’s ability to break down fatty substances. Then the fatty substances can build up and clog blood vessels which supply blood to the bone. Some studies also suggest that corticosteroids directly kill bone cells.

HOW IS OSTEONECROSIS DIAGNOSED?

Diagnosis usually begins with an evaluation by a physician who does a detailed history about any bone pain (?when ?where ?how long) and a thorough physical examination. A physician who is worried about the possibility of osteonecrosis will then recommend an imaging test. Often the first done is an x-ray to make sure that there is not a fracture or arthritis or other causes of bone pain. X-rays are not sensitive enough to diagnose early osteonecrosis, but are useful to monitor the progression of advanced osteonecrosis. If the x-ray is normal, the doctor may arrange magnetic resonance imaging (MRI). Research has shown that MRI is the most sensitive method for diagnosing early osteonecrosis. Bone scan (also known as bone scintigraphy) can also be done, but is not sensitive for early disease. Biopsy, the surgical removal of a small amount of bone tissue for study under the microscope, is rarely needed.

Currently, the Children”s Oncology Group (COG) Late Effects Committee Consensus Guidelines recommends screening for osteonecrosis by assessing for bone pain and loss of limb mobility at regular checkups. Symptomatic individuals are advised to be referred for diagnostic imaging (x-ray and/or MRI) and orthopedic consultation.

HOW IS OSTEONECROSIS TREATED?

In general, all survivors with osteonecrosis should avoid activities which put considerable stress on the joints (running, jumping, football, volleyball). Activities that are good for joints with osteonecrosis are swimming and bicycling.

People with osteonecrosis are typically managed by an orthopedist specialist. Their care is usually individualized according to the following factors:

• Age of patient
• Stage of the osteonecrosis (early or late)
• Location and amount of bone affected
• Degree of pain and immobility

Several treatments are available, depending on the individual situation.  The goal is to improve use of the affected joint and to stop further bone damage. Doctors typically first recommend the least invasive therapy and follow the patient’s condition closely to determine if/when other therapies should be tried. Potential therapies that the doctor my recommend include the following:

Conservative Therapy Options: (rarely results in lasting improvement, but can delay surgery)

• Lipid lowering agents to reduce fatty substances that increase with corticosteroid treatment
• Nonsteroidal anti-inflammatory drugs to reduce pain
• Restriction of weight-bearing, useful if early osteonecrosis
• Physical therapy with range of motion exercises
• Electrical stimulation to induce bone growth
• Bisphosphonate therapy: medicine which increases bone formation

Surgery Options: (eventually needed by most patients )

• Core decompression: surgical procedure to remove inner layer of bone, reduce pressure within bone, and increase blood flow to bone. This procedure works best in early osteonecrosis
• Osteotomy: major surgical procedure to reshape the bone to reduce stress on the affected area. This usually works best with advanced disease.
• Bone graft: major surgical procedure which involves taking healthy bone from one part of the patient and transplanting it to the affected area.
• Joint replacement: major surgical procedure which involves replacing a diseased joint with artificial parts. This is the treatment of choice in advanced osteonecrosis.

FUTURE RESEARCH

Research is ongoing to better determine which cancer survivors will develop osteonecrosis, preventative strategies, and the most effective therapies.

RESOURCES:

CureSearch, a combined effort of the National Childhood Cancer Survivorship Foundation and the Childrens Oncology Group

National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH or 877-226-4267 (toll free)

American Academy of Orthopaedic Surgeons or 1-800-824-2663