Naoto O'uchi, Haruko Nishikawa, Hiroyuki Motoie and Hisataka Shikama
(*)
Metabolic Diseases Research, Pharmacology Laboratories, Institute for
Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka,
Tsukuba, Ibaraki 305-8585, Japan
(*) To whom correspondence should be addressed.
Abstract: We examined mechanisms by which incadronate disodium
(YM175) prevented bone resorption in ovariectomized dogs with dietary calcium
restriction using the morphometrical method. YM175 (0.01 - 1.0 mg/kg) was
given to ovariectomized dogs for 18 months. Because lumbar bone mineral
density remained constant at month 17, we assumed that the trabecular bone
resorption rate was equal to the bone formation rate and that wall thickness
equaled resorption cavity depth. YM175 decreased both the bone resorption
rate per number of osteoclasts and resorption cavity depth of cancellous
pockets which were increased in ovariectomized dogs. These results suggest
that YM175 reduces bone loss by decreasing the resorbing activity of osteoclasts.
Keywords: Histomorphometry, Bone resorption, YM175