Cell therapy of hip osteonecrosis with autologous bone marrow grafting

One of the reasons for bone remodeling leading to an insufficient creeping substitution after osteonecrosis in the femoral head may be the small number of progenitor cells in the proximal femur and the trochanteric region. Because of this lack of progenitor cells, treatment modalities should stimulate and guide bone remodeling to sufficient creeping substitution to preserve the integrity of the femoral head. Core decompression with bone graft is used frequently in the treatment of osteonecrosis of the femoral head. In the current series, grafting was done with autologous bone marrow obtained from the iliac crest of patients operated on for early stages of osteonecrosis of the hip before collapse with the hypothesis that before stage of subchondral collapse, increasing the number of progenitor cells in the proximal femur will stimulate bone remodeling and creeping substitution and thereby improve functional outcome.

Between 1990 and 2000, 342 patients (534 hips) with avascular osteonecrosis at early stages (Stages I and II) were treated with core decompression and autologous bone marrow grafting obtained from the iliac crest of patients operated on for osteonecrosis of the hip. The percentage of hips affected by osteonecrosis in this series of 534 hips was 19% in patients taking corticosteroids, 28% in patients with excessive alcohol intake, and 31% in patients with sickle cell disease. The mean age of the patients at the time of decompression and autologous bone marrow grafting was 39 years (range: 16-61 years). The aspirated marrow was reduced in volume by concentration and injected into the femoral head after core decompression with a small trocar. To measure the number of progenitor cells transplanted, the fibroblast colony forming unit was used as an indicator of the stroma cell activity.

Patients were followed up from 8 to 18 years. The outcome was determined by the changes in the Harris hip score, progression in radiographic stages, change in volume determined by digitizing area of the necrosis on the different cuts obtained on MRI, and by the need for hip replacement. Total hip replacement was necessary in 94 hips (evolution to collapse) among the 534 hips operated before collapse (Stages I and II). Sixty-nine hips with stage I osteonecrosis of the femoral head at the time of surgery demonstrated total resolution of osteonecrosis based on preoperative and postoperative MRI studies; these hips did not show any changes on plain radiographs. Before treatment, these 69 osteonecrosis had only a marginal band like pattern as abnormal signal and a volume less than 20 cubic centimeters. The intralesional area had kept a normal signal as regards the signal of the femoral head outside the osteonecrosis area. For the 371 other hips without collapse at the most recent follow up (average 12 years), the mean preoperative volume of the osteonecrosis was 26 cm(3) (minimum 12, maximum 30 cm(3)). The mean volume of the abnormal signal measured on MRI at the most recent follow up (mean 12 years) was 12 cm(3). The abnormal signal persisting as a sequelae was seen on T1 images as an intralesional area of low intensity signal with a disappearance of the marginal band like pattern.

According to our experience, best indication for the procedure is symptomatic hips with osteonecrosis without collapse. In some patients who had Steinberg stage III osteonecrosis (subchondral lucency, no collapse) successful outcomes (no further surgery) has been obtained between 5 to 10 years. Therefore in selected patients, even more advanced disease can be considered for core decompression. Patients who had the greater number of progenitor cells transplanted in their hips had better outcomes.