Prevention of Bone Loss by Bisphosphonate YM175 in Ovariectomized Dogs with Dietary Calcium Restriction

The Japanese Journal of Pharmacology

Takashi Fujikura¹  Stig Ogata¹  Hiroyuki Motoie¹  Kosei Kawamuki¹  Hiroyuki Kanoh¹  Hisataka Shikama¹ 

[1] Endocrinology and Metabolic Disease Research Laboratory, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.

关键词: Bisphosphonate;    YM175;    Bone mineral density;    Dietary calcium restriction;    Ovariectomy;   

DOI  :  10.1254/jjp.71.239

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(34)Cited-By(10)We have evaluated the effects of YM175 {disodium dihydrogen (cycloheptylamino) methylenebisphosphonate monohydrate}, a novel bisphosphonate, on bone mineral densities (BMD) at the lumbar spine and forelimb in ovariectomized beagles with dietary calcium restriction. Groups 1 and 2 were given a sham operation and Groups 3—6 were ovariectomized. One month later (month 0), a low calcium diet was given to Groups 2—6. Groups 4—6 were orally treated with YM175 at doses of 0.01, 0.1 and 1.0 mg/kg, respectively, for 18 months. Changes in BMD at the lumbar spine and left forelimb were determined serially by dual energy X-ray absorptiometry. Calcium restriction decreased lumbar BMD by 19% at month 2 and by up to 30% at month 17 compared to its baseline value, but ovariectomy itself had a minimal effect on bone mass in dogs with restricted calcium intake. YM175 (1 mg/kg) prevented the bone loss at month 2 and YM 175 at 0.1 mg/kg or more inhibited the BMD reduction at month 17. The magnitude of BMD reduction of the forelimb was less remarkable as compared to that of the lumbar spine. Urinary hydroxyproline excretion and plasma osteocalcin levels were increased by calcium restriction, indicating a high turnover of bone. YM 175 reduced hydroxyproline excretion but not osteocalcin levels. These results indicate that YM 175 prevents bone loss induced by calcium restriction and ovariectomy through partially normalizing high bone turnover.

【 授权许可】

Unknown