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Bisphosphonate incadronate prevents total gastrectomy-induced osteopenia in rats

双膦酸盐英卡膦酸可预防大鼠全胃切除术引起的骨质减少

基本信息

批准号：
13671257
负责人：
SUZUKI Yutaka
金额：
$ 1.98万
依托单位：
Jikei University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671257/
关键词：
Rat Osteoporosis Osteomalasia Bisphosphonate Osteocalcin Total gastrectomy Osteocalcin Deoxypyridinoline 胃全摘後骨障害

项目摘要

PURPOSE : Total gastrectomy(GX) leads to osteopenia. We examined the effects of bisphosphonate incadronate(INC), a potent inhibitor of bone resorption, on bone characteristics in rats that underwent total GX. EXPERIMENTAL DESIGN : Male Wistar rats were divided into 4 groups : (1)sham-operation (n=10), (2)total GX control (n=6), (3)total GX with 0.3 mg/kg/day oral administration of INC (n=7), and (4)total GX with 3.0 mg/kg/day oral administration of INC (n=7). RESULTS : Total GX significantly impaired bone mineral density ; these effects were prevented by treatment with INC. Similarly, in GX control rats, morphometrical changes of femoral metaphysis stained with Villanueva's and Villanueva-Goldner's : bone volume, tissue volume, mineral apposition rate, labeled/bone surface, bone formation rate, osteoid volume, mineralization lag time as well as serum osteocalcin, and urinary deoxypyridinoline demonstrated simultaneous existences of both osteomalacia and osteopenia ; these impairments were also prevented by INC. However, GX-induced decrease in serum levels of calcium as well as 25-hydroxyvitamin D/24,25-dihydroxyvitamin D and the increase in 1,25-dihydroxyvitamin D were not prevented by administration of INC. CONCLUSIONS : These results enhance the understanding of unique pathophysiology of both osteomalacia and osteoporosis induced by total GX and suggest the possibility of INC preventive therapy for osteopenia in GX-treated patients.

目的：全胃切除术（GX）导致骨质减少。我们研究了一种有效的骨吸收抑制剂二膦酸盐（INC）对接受全GX治疗的大鼠骨骼特征的影响。实验设计：雄性Wistar大鼠分为4组：(1)假手术组（n=10），(2)总GX对照组（n=6），(3)总GX组（0.3 mg/kg/d）口服INC (n=7),(4)总GX组（3.0 mg/kg/d）口服INC （n=7）。结果：总GX显著影响骨密度；用INC治疗可预防这些影响。同样，在GX对照大鼠中，Villanueva’s染色和Villanueva- goldner’s染色的股骨干骺部形态学变化：骨体积、组织体积、矿物质附着率、标记/骨表面、骨形成率、类骨体积、矿化滞后时间以及血清骨钙素和尿脱氧吡dinoline显示骨软化症和骨质减少同时存在；INC也可以防止这些损伤。然而，gx诱导的血清钙、25-羟维生素D/24,25-二羟维生素D水平的降低和1,25-二羟维生素D水平的升高并没有被INC阻止。结论：这些结果增强了对总GX诱导的骨软化症和骨质疏松症的独特病理生理的理解，并提示了对GX治疗患者骨质减少的INC预防性治疗的可能性。