1P308 Effects of Clodronate on postmenopause like bone loss by malnmary carcinoma Walker 256/S in rat

• Published in: Journal of Pharmacological Sciences Vol. 91; no. suppl.1; p. 164
• Main Authors: Kou Kayamori, Yoshihiro Waki, Kazuhiro Aoki, Keiichi Ohya
• Format: Journal Article
• Language: Japanese
• Published: The Japanese Pharmacological Society 2003
• ISSN: 1347-8613

Walker 256/S (W256/S) is an ectopic hormone (LH-RH) producing tumor. Excess LH-RH Ieads negative feedback and at last lowering serum estrogen level. When subcateneously inoculated into female Wistar-Imamichi (WI) rats, W256/S caused postmenopause-like bone loss; a decrease in the trabecular bone, Ioss of bone weight and bone-mineral density (BMD). Clodronate (dichloromethylene-bisphosphonate) is known to prevent bone resorption without imparing bone mineralization. The purpose of this study is to clarify the effects of clodronate on the bone loss by W256/S. In in vitro cell culture, clodronate (10^-10M-10^-4M) showed no effects on proliferation of W256/S cells. For in vivo experiments, clodronate was subcateneously injected to female WI rats (7 weeks old) at the dose of 2mgP/kg/day and 4mgP/kg/day from Day 7 to 13 after tumor inoculation. BMD was significantly decreased in rats bearing W256/S at 14 days after inoculation. Clodronate 2mgP/kg/day recovered the BMD to the level of non-inoculated healthy control and prevented bone resorption especially in distal femur and in proximal tibia. Clodronate 4mgP/kg/day showed similar recovery effects in bone loss to that of 2mgP. From these results, clodronate shows the inhibitory effects on postmenopausal-like bone loss by W256/S and has a remarkable potency for treatment of osteoporosis induced by estrogen deficiency.