Incadronate inhibits osteoporosis in ovariectomized rats

• Published in: European journal of pharmacology Vol. 457; no. 1; pp. 51 - 56
• Main Authors: Teramura, Kyoko, Fukushima, Shinji, Iwai, Takaya, Nozaki, Kazutoshi, Kokubo, Satoshi, Takahashi, Koichiro
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 13.12.2002; Elsevier
• Subjects: Administration, Oral; Amino Acids - urine; Animals; Biological and medical sciences; Biomarkers - urine; Bisphosphonate; Bone Density - drug effects; Bone mineral density; Bones, joints and connective tissue. Antiinflammatory agents; Chromatography, High Pressure Liquid; Compressive Strength - drug effects; Deoxypyridinoline; Diphosphonates - administration & dosage; Diphosphonates - pharmacology; Dose-Response Relationship, Drug; Female; General and cellular metabolism. Vitamins; Medical sciences; Osteocalcin - blood; Osteoporosis; Osteoporosis - drug therapy; Osteoporosis - etiology; Ovariectomy; Parathyroid Hormone - blood; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Deoxypyridinoline; Osteoporosis; Bisphosphonate; Bone mineral density; Ovariectomy; Rat; Diseases of the osteoarticular system; Diphosphonic acid derivatives; Bone disease; Osteoclast; Antihypercalcemic agent; Bisphosphonates; Dose activity relation; Prevention; Mechanism of action; Osteocalcin; Treatment efficiency; Rodentia; Oral administration; Resorption; Incadronic acid; Vertebrata; Chemotherapy; Mammalia; Treatment; Animal; Bone
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(02)02659-6

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.