Progression of collapse in osteonecrosis of the femoral head is related to the repair response, especially bone resorption around the necrotic region. A preliminary clinical study was done to determine whether systemic alendronate would prevent collapse and lead to pain relief in patients with osteonecrosis of the femoral head. Fourteen patients (20 hips) with osteonecrosis of the femoral head received daily administration of 5 mg alendronate (alendronate group) for 1 year. Eight patients (13 hips) with osteonecrosis of the femoral head did not receive alendronate (control group). All patients had measurements of biochemical markers of bone turnover at entry into the study, and the patients in the alendronate group repeated the measurements at 3 months, 6 months, and 12 months. All patients had clinical and plain radiographic examinations at entry into the study and at 3 months, 6 months, and 12 months. The alendronate group showed a greater decrease of biochemical marker of bone resorption than biochemical marker of bone formation. The alendronate group showed a lower frequency of collapse of the femoral head and reported less hip pain than the control group. Our results suggest alendronate has the potential to prevent collapse of the femoral head, even with extensive necrosis, presumably by inhibiting bone resorption in the necrotic region.