Osteonecrosis of bone associated with combination chemotherapy without corticosteroids

Osteonecrosis (aseptic or avascular necrosis of bone) is an entity with many causes that can occur at a variety of sites. It is a known complication of corticosteroid therapy, either alone or combined with other drugs in the treatment of malignancy. Osteonecrosis associated with chemotherapy that does not include corticosteroids is rare; three such cases have been reported in the English literature. One received cyclophosphamide alone, another vinblastine and bleomycin, while the third received cyclophosphamide, methotrexate, and 5-fluorouracil. The authors report a 40-year-old woman who had a left radical mastectomy in 1978 and a right radical mastectomy in 1980 for infiltrating ductal adenocarcinoma of the breasts. She received melphalan following the first surgery and a combination of doxorubicin, cyclophosphamide, and 5-fluorouracil after the second operation. In 1984 she noted pain in both knees that slowly increased in severity. A bone scan revealed increased periarticular activity in the medial and lateral femoral condyles of both knees compatible with bilateral osteonecrosis. There was no evidence of metastatic carcinoma on the bone scan. The patient was treated surgically with drilling and autologous bone grafting. A bone biopsy at the time of surgery revealed osteonecrosis but no metastatic adenocarcinoma.