The aim of the present study was to assess the effects of ipriflavone administration in the prevention of the rapid bone loss that follows ovariectomy in women. After 10-30 days from bilateral ovariectomy, patients received either the sole calcium supplementation (500 mg/day, n = 16) or ipriflavone (600 mg/day, n = 16) in addition to the same daily calcium supplement for 12 months. In calcium-treated subjects urinary hydroxyproline excretion, serum alkaline phosphatase and plasma bone Gla protein levels showed a substantial (p < 0.01) increase, while radial bone density significantly (p < 0.01) decreased 6 months after surgery. In ipriflavone treated group the patterns of biochemical markers indicated that ipriflavone can restrain the bone remodeling processes and radial bone density showed no significant modification during the 12 month study period. These results demonstrate that ipriflavone administration prevents the rapid bone loss that follows ovariectomy. Thus, ipriflavone can represent an attractive alternative for the prevention of osteoporosis in postmenopausal women who present contraindications to the estrogen replacement therapy.