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New method predicts hip joint decay from chemotherapy

April 20, 2007

St. Jude study shows that the extent of hip decay is key to predicting which survivors of leukemia/lymphoma who develop osteonecrosis of the femoral head will suffer hip joint collapse requiring surgical repair

Investigators at St. Jude Children's Research Hospital say they have found the best way for predicting when patients will need future surgery to repair hip joints that have deteriorated because of pediatric leukemia or lymphoma treatment.

The investigators found that if more than 30 percent of the head of the bone fitting into the hip socket is deteriorated, it is at high risk of collapsing and requiring reconstructive surgery within two years.

The study is significant because the intensive use of corticosteroid drugs that have been implicated in development of osteonecrosis, or bone deterioration, is a major component of chemotherapy for pediatric leukemia and lymphoma. The drugs have been key to raising the survival rates of children with these cancers, and currently there is no adequate substitute for their use. Therefore, it is important for clinicians to monitor patients during treatment and identify those at highest risk for this complication. Eventually, genetic or other tests may be developed to help predict these patients. This is a subject of ongoing study.

A report on this work appears in the April 20 issue of "Journal of Clinical Oncology."

Hip collapse occurs following deterioration of the ball-like top part of the upper leg bone, or femur, which fits into the hip socket. Degeneration of this area, called osteonecrosis of the capital femoral epiphysis, is a common problem among children undergoing chemotherapy for leukemia or lymphoma.

"Being able to predict which children are likely to experience serious bone deterioration in the future will help investigators identify and monitor survivors who are at particularly high risk for developing this problem," said Sue Kaste, D.O., a member of the Radiological Sciences department at St. Jude. Kaste is the paper's senior author.

Collapse of the femur causes severe pain that might leave the patient wheelchair bound, according to Evguenia Jane Karimova, M.D., Radiological Sciences department at St. Jude and the paper's first author. To ease the pain, many patients require arthroplasty, or surgery to rebuild the hip joint.

"Hip collapse and joint replacement carry a worse prognosis in a young person," Karimova said. "Young patients tend to engage in more strenuous activity than older patients with hip replacements, and that can damage the replacement and further complicate recovery. Many of these patients are expected to require further surgery in the future to replace their prostheses, which have a limited life span."

"Osteonecrosis has become one of the most important side effects of therapy that affects the quality of life of these long-term survivors," Kaste said. "We want the survivors to have the best quality of life possible. Therefore, we analyzed the extensive amount of data on such patients accumulated at St. Jude over the years to determine which factors cause joint collapse and make it likely that the patient will need arthroplasty."

The St. Jude team reviewed the medical records and MRI images of 80 patients who developed osteonecrosis of the capital femoral epiphysis to identify factors that appeared to be linked to the future collapse of the bone's surface and the need for arthroplasty. A total of 23 of the 80 patients, or 29 percent, eventually underwent arthroplasty for one or both hips at an average of 1.3 years after diagnosis of osteonecrosis. In cases in which necrosis involved more than 30 percent of the head of the hip, 80 percent of the hips collapsed within two years after osteonecrosis was identified, with 50 percent requiring arthroplasty. The age of the patient at the time of the first arthroplasty ranged from 15.1 to 35.4 years.

The investigators plan to conduct prospective studies to determine if it is possible to develop a treatment that prevents this damage and preserves hip function.

St. Jude Children's Research Hospital