Incadronate inhibits osteoporosis in ovariectomized rats.
Incadronate is a highly effective inhibitor of stimulated bone resorption as demonstrated in a hypercalcemia model in rats, bone metastasis models in mice and rats, and an osteoporosis model in dogs. In this study, the effect of incadronate on osteoporosis in ovariectomized rats was examined. Incadronate dose-dependently inhibited decreases in second lumbar vertebrae bone mineral density (BMD) following oral administration for 4 or 12 weeks. Significant inhibition was observed at doses of more than 0.3 mg/kg. Incadronate dose-dependently inhibited the loss of distal femur metaphyseal compressive strength following 12 weeks of oral administration, and this was significant at a 3 mg/kg daily dose. Incadronate also dose-dependently inhibited the increases in urinary deoxypyridinoline levels after 4-or 12-week oral administrations. While incadronate had no effect on serum osteocalcin levels after 4 weeks of oral administration, it did dose-dependently reduce levels after 12 weeks of oral administration. These results suggested that incadronate may be a useful drug for osteoporosis due to stimulated bone resorption.
Teramura
Kyoko
K
Pharmacology Department, Institute for Drug Development Research, Yamanouchi Pharmaceutical Co, Ltd, 1-8, Azusawa 1-chome, Itabashi, Tokyo 174-8511, Japan. teramurk@yamanouchi.co.jp
Fukushima
Shinji
S
Iwai
Takaya
T
Nozaki
Kazutoshi
K
Kokubo
Satoshi
S
Takahashi
Koichiro
K
D000284:Administration, Oral; D000596:Amino Acids / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000652:urine; D015519:Bone Density / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D019245:Compressive Strength / Q000187:drug effects; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015675:Osteocalcin / Q000097:blood; D010024:Osteoporosis / Q000188:drug therapy* / Q000209:etiology; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley
D000596:Amino Acids; D015415:Biomarkers; D004164:Diphosphonates; D010281:Parathyroid Hormone; D015675:Osteocalcin; C071542:cimadronate; C036020:deoxypyridinoline