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We previously found that 3,9-bis(N,N-dimethylcarbamoyloxy)-5H- benzofuro[3,2-c]quinoline-6-one (KCA-098) inhibited bone resorption in organ culture. In this study, to determine if KCA-098 is therapeutically applicable for the treatment of osteoporosis, we compared the effect of KCA-098 on bone tissues with that of ipriflavone, a drug that is clinically used for the treatment of osteoporosis. Both KCA-098 and ipriflavone inhibited parathyroid hormone-, prostaglandin E2-, 1 alpha,25-dihydroxyvitamin D3- and interleukin 1 beta-induced bone resorption of fetal rat bones, but the inhibitory activity of KCA-098 was more potent than that of ipriflavone. In fact, the effective concentrations of KCA-098 were 10 to 100 times lower than those of ipriflavone. Oral administration of KCA-098 (1 and 3 mg/kg) or ipriflavone (100 mg/kg) to ovariectomized rats on a low-calcium diet increased the breaking force and bone density of the femora, indicating that KCA-098 is an effective on the whole animal as ipriflavone. Furthermore, KCA-098 increased the length and calcium content of 9-day chick embryonic femora cultured in vitro, whereas ipriflavone did not, suggesting that KCA-098 had a direct stimulatory effect on bone mineralization. Therefore, KCA-098 seems to be more potent than ipriflavone in stimulating bone tissue formation and may thus be expected to become a useful agent for the treatment of osteoporosis.

Effects of KCA-098 on Bone Metabolism: Comparison with Those of Ipriflavone