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氯膦酸盐对低钙饮食的去卵巢大鼠皮质骨和小梁骨的影响。

Effects of clodronate on cortical and trabecular bone in ovariectomized rats on a low calcium diet.

作者信息

Kaastad T S, Reikerâs O, Madsen J E, Narum S, Stromme J H, Obrant K J, Nordsletten L

机构信息

Institute for Surgical Research, Rikshospitalet The National Hospital, N-0027 Oslo, Norway.

出版信息

Calcif Tissue Int. 1997 Aug;61(2):158-64. doi: 10.1007/s002239900315.

DOI:10.1007/s002239900315
PMID:9236265
Abstract

The aim of this study was to evaluate the contribution of a low calcium diet to the cortical and trabecular osteoporosis seen in ovariectomized rats after 7 weeks on a low calcium diet and to investigate the effects of the bisphosphonate clodronate on this development of osteoporosis. Thirty-six mature, female Wistar rats were randomized into four groups: Ovx-B (bisphosphonate) and Ovx-C (control) were ovariectomized, and Sham-Ca (low calcium) and Sham+Ca (normal calcium) were sham operated. The first three groups were fed a low calcium diet (0.01%) and Sham+Ca normal rat chow (Ca 1.1%). The Ovx-B received 10 mg/kg s.c. clodronate daily for nine weeks, and Ovx-C, Sham-Ca, and Sham+Ca received the same volumes of saline. Bone mineral turnover measured as 85Sr-uptake was increased in all low calcium groups compared to Sham+Ca. The Sham+Ca femora had higher dry weight and ash weight than the other groups, and Ovx-C had higher dry weight compared with Ovx-B and Sham-Ca. Calcium content was lower in both Ovx groups compared to both Sham groups. Magnesium was lower in all groups compared to Sham+Ca and higher in Ovx-B compared with Ovx-C. In the femoral shaft, Sham+Ca had significantly higher ultimate bending moment, energy absorption, and deflection compared to the other three groups. Ultimate bending moment was higher in Sham-Ca than in Ovx-C. Stiffness was increased in both Sham+Ca and Ovx-B compared to Ovx-C. The maximum stress in the femoral midshaft was higher in Sham+Ca than in the other groups, and higher in Ovx-B than in Ovx-C. Histomorphometry showed increased medullary area in all low calcium groups compared to Sham+Ca and larger cortical area in Sham+Ca and Ovx-B compared to Ovx-C. Compared to Sham+Ca the trabecular bone volume was decreased to 30% in Sham-Ca and to 9% in Ovx-C, but was unchanged in Ovx-B. The low calcium diet generally increased bone mineral turnover and reduced the tibial bone volume. Femoral changes led to a reduction of cortical fracture strength and maximal stress. Ovariectomy in addition to a low calcium diet reduced femoral strength even more. Daily injections of clodronate to ovariectomized rats on a low calcium diet increased femoral shaft stiffness and maximum stress, and clodronate preserved both trabecular and cortical tibial bone volume completely.

摘要

本研究的目的是评估低钙饮食对低钙饮食7周后去卵巢大鼠皮质和小梁骨质疏松症的影响,并研究双膦酸盐氯屈膦酸对骨质疏松症发展的作用。36只成熟雌性Wistar大鼠被随机分为四组:Ovx-B(双膦酸盐)组和Ovx-C(对照组)去卵巢,Sham-Ca(低钙)组和Sham+Ca(正常钙)组进行假手术。前三组给予低钙饮食(0.01%),Sham+Ca组给予正常大鼠饲料(钙含量1.1%)。Ovx-B组每天皮下注射10mg/kg氯屈膦酸,持续9周,Ovx-C组、Sham-Ca组和Sham+Ca组注射相同体积的生理盐水。与Sham+Ca组相比,所有低钙组以85Sr摄取量衡量的骨矿物质周转率均升高。Sham+Ca组股骨的干重和灰分重量高于其他组,Ovx-C组的干重高于Ovx-B组和Sham-Ca组。与两个假手术组相比,两个去卵巢组的钙含量均较低。与Sham+Ca组相比,所有组的镁含量均较低,Ovx-B组的镁含量高于Ovx-C组。在股骨干中,与其他三组相比,Sham+Ca组的极限弯矩、能量吸收和挠度显著更高。Sham-Ca组的极限弯矩高于Ovx-C组。与Ovx-C组相比,Sham+Ca组和Ovx-B组的刚度均增加。股骨干中部的最大应力,Sham+Ca组高于其他组,Ovx-B组高于Ovx-C组。组织形态计量学显示,与Sham+Ca组相比,所有低钙组的髓腔面积增加,与Ovx-C组相比,Sham+Ca组和Ovx-B组的皮质面积更大。与Sham+Ca组相比,Sham-Ca组的小梁骨体积减少至30%,Ovx-C组减少至9%,但Ovx-B组无变化。低钙饮食通常会增加骨矿物质周转率并减少胫骨骨体积。股骨的变化导致皮质骨折强度和最大应力降低。除低钙饮食外,去卵巢进一步降低了股骨强度。每天给低钙饮食的去卵巢大鼠注射氯屈膦酸可增加股骨干刚度和最大应力,氯屈膦酸完全保留了小梁和皮质胫骨骨体积。

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