Effects of KCA-098 on bone metabolism: comparison with those of ipriflavone.

Abstract

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.

• Authors: N Tsutsumi, K Kawashima, H Nagata, J Tsuyuki, F Itoh, N Arai, M Kojima, A Ujiie, H Endo
• Journal: Japanese journal of pharmacology (Jpn J Pharmacol) Vol. 65 Issue 4 Pg. 343-9 (Aug 1994) ISSN: 0021-5198 [Print] Japan
• PMID: 7990272 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Calcium, Dietary
• Interleukin-1
• Isoflavones
• Parathyroid Hormone
• KCA 098
• 24,25-Dihydroxyvitamin D 3
• ipriflavone
• Dinoprostone
• Calcium
• Coumestrol

Topics

• 24,25-Dihydroxyvitamin D 3 (pharmacology)
• Animals
• Bone Density (drug effects)
• Bone Resorption (metabolism)
• Bone and Bones (drug effects, metabolism)
• Calcification, Physiologic (drug effects)
• Calcium (metabolism)
• Calcium, Dietary (administration & dosage)
• Chick Embryo
• Coumestrol (analogs & derivatives, pharmacology)
• Dinoprostone (pharmacology)
• Female
• Femur (drug effects, embryology, metabolism)
• Interleukin-1 (pharmacology)
• Isoflavones (pharmacology)
• Osteoporosis (metabolism)
• Ovariectomy
• Parathyroid Hormone (pharmacology)
• Rats
• Rats, Wistar