Bisphosphonate incadronate prevents total gastrectomy-induced osteopenia in rats

目的：全胃切除术(GX)导致骨量减少。我们研究了一种有效的骨吸收抑制剂--双磷酸盐inadronate(INC)对接受总GX治疗的大鼠骨特性的影响。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)，(7)总GX组(3.0 mg/kg/d)。结果：总GX显著损害骨密度；这些影响可被INC预防。类似地，在GX对照组大鼠，用Villanueva‘s和Villanueva-Goldner’s染色的股骨干骺端的形态计量学变化：骨体积、组织体积、矿物沉积率、标记/骨表面、骨形成率、类骨质体积、矿化滞后时间以及血清骨钙素和尿脱氧吡啶酚同时存在骨软化和骨量减少，这些损害也被Inc.预防。然而，给予Inc.并不能阻止GX引起的血清钙和25-羟基维生素D/24，25-二羟基维生素D水平的降低和1，25-二羟基维生素D水平的升高。结论：这些结果加深了对总GX所致骨软化和骨质疏松症的独特病理生理机制的理解，并提示了INC预防治疗GX患者骨量减少的可能性。

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.