In vitro effect of KCA-098, a derivative of coumestrol, on bone resorption of fetal rat femurs.
The effects of 3,9-bis(N,N-dimethylcarbamoyloxy)-5H-benzofuro[3,2-c]quinoli ne-6-one (KCA-098), a derivative of coumestrol, on bone resorption was studied in organ cultures of 20-day fetal rat femora. KCA-098 increased the length, dry weight, and calcium and phosphorus contents of parathyroid hormone (PTH)-treated fetal rat femur. As PTH significantly reduced the calcium and phosphorus contents of the femora, probably by stimulating bone resorption, KCA-098 seems to inhibit bone resorption. In fact, KCA-098 inhibited the PTH-induced release of 45Ca from pre-labeled fetal rat femora into the medium in organ culture. Coumestrol also inhibited the release of 45Ca from bone into the medium. However, KCA-098 did not increase the uterine weight of ovariectomized rats, whereas coumestrol did so. Thus KCA-098 is a unique, new inhibitor of bone resorption that has no estrogenic activity.
Central Research Laboratories, Kissei Pharmaceutical Co., Ltd., Nagano, Japan.
N
N
Tsutsumi
K
K
Kawashima
N
N
Arai
H
H
Nagata
M
M
Kojima
A
A
Ujiie
H
H
Endo
D000818:Animals; D001862:Bone Resorption / Q000196:embryology*; D002113:Calcification, Physiologic; D002118:Calcium / Q000378:metabolism; D003375:Coumestrol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005269:Femur / Q000196:embryology* / Q000502:physiology; D009924:Organ Culture Techniques; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000494:pharmacology; D010758:Phosphorus / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D014599:Uterus / Q000033:anatomy & histology
D010281:Parathyroid Hormone; C088191:KCA 098; D010758:Phosphorus; D004958:Estradiol; D002118:Calcium; D003375:Coumestrol