The bone-marrow activity in the iliac crest of eleven patients who had idiopathic osteonecrosis of the hip and thirty patients who had osteonecrosis of the hip that was related to corticosteroid therapy (fourteen patients) or to alcohol abuse (sixteen patients) was compared with that in two groups of control subjects who did not have osteonecrosis (thirty-three healthy bone-marrow donors and thirty-four patients who had been managed with bone-marrow grafting for a non-union). Cultures of granulocyte-macrophage progenitor cells and fibroblast colony-forming units were performed to assess the activity of hematopoietic stem cells and stromal cells.The activity of stem cells in both the hematopoietic and the stromal compartment of the bone marrow was decreased in the patients who were receiving corticosteroids or who abused alcohol, as compared with that in the two groups of control subjects. The patients who had idiopathic osteonecrosis also had a decrease in bone-marrow activity compared with the control subjects.CLINICAL RELEVANCE: Our findings suggest that patients who are receiving corticosteroid therapy or who abuse alcohol have decreased activity of bone-marrow cells. Whether this decrease is related to the osteonecrosis could not be determined, as our study did not include control subjects who had a history of alcohol abuse or who were receiving corticosteroids but did not have osteonecrosis. However, it is possible that the reduced bone-marrow activity was related to the osteonecrosis, as patients who had idiopathic osteonecrosis also had decreased bone-marrow activity. The study of pathological alterations in the bone marrow outside the necrotic zone may provide important insights into the pathophysiology of osteonecrosis.