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阿仑膦酸钠对去卵巢大鼠腰椎间盘退变伴骨质流失的影响。

Effects of alendronate on lumbar intervertebral disc degeneration with bone loss in ovariectomized rats.

作者信息

Song Huiping, Luo Yang, Wang Wenya, Li Shuyang, Yang Kai, Dai Muwei, Shen Yong, Zhang Yingze, Zhang Liu

机构信息

Department of Orthopaedic Surgery, The Affiliated Hospital of North China University of Science and Technology, 73 Jianshe Rd, Tangshan 063000, China.

Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, 139 Ziqiang Rd, Shijiazhuang, 050051, China.

出版信息

Spine J. 2017 Jul;17(7):995-1003. doi: 10.1016/j.spinee.2017.03.002. Epub 2017 Mar 10.

DOI:10.1016/j.spinee.2017.03.002
PMID:28288923
Abstract

BACKGROUND CONTEXT

Osteoporosis adversely affects disc degeneration cascades, and prophylactic alendronate (ALN) helps delay intervertebral disc degeneration (IDD) in ovariectomized (OVX) rats. However, there remains no information regarding whether ALN affects IDD with bone loss.

PURPOSE

This study aimed to observe the effects of ALN on degenerative discs with bone loss induced by OVX in rats.

STUDY DESIGN

This study used controlled in vivo experiments in rodents.

METHODS

Thirty female Sprague-Dawley rats were randomly assigned to undergo sham surgery (n=10) or OVX surgery (n=20); 3 months later, the OVX animals were injected with either ALN (OVX+ALN, 15 µg/kg/2w, n=10) or normal saline (OVX+vehicle treatment [V], n=10). At 3 months after the ALN intervention, van Gieson staining and immunohistochemistry were used to investigate histologic and metabolic changes in the discs. Bone mineral density (BMD), micro-computed tomography, and biomechanical tests were conducted to determine the biological properties of the vertebrae.

RESULTS

The OVX+ALN group exhibited significantly reduced morphologic degenerative alterations in both the nucleus pulposus and annulus fibrosus, with a markedly lower IDD score than that of the OVX+V group. The OVX+ALN samples showed increased disc height and decreased cartilage end plate thickness and bony area compared with the OVX+V group. Compared with saline, ALN administration markedly inhibited the type I collagen, matrix metalloprotease (MMP)-1, and MMP-13 expression levels while increasing the type II collagen and aggrecan expression levels in the disc matrix. Compared with the OVX+V group, OVX+ALN vertebrae revealed significantly enhanced BMD with increased biomechanical strength, as well as increased percent bone volume and trabecular thickness.

CONCLUSIONS

ALN has favorable effects on disc degeneration with bone loss and helps to alleviate IDD while enhancing the biological and mechanical properties of vertebrae and end plates.

摘要

背景

骨质疏松对椎间盘退变级联反应有不利影响,预防性使用阿仑膦酸盐(ALN)有助于延缓去卵巢(OVX)大鼠的椎间盘退变(IDD)。然而,关于ALN是否影响伴有骨质流失的IDD尚无相关信息。

目的

本研究旨在观察ALN对OVX诱导的伴有骨质流失的大鼠退变椎间盘的影响。

研究设计

本研究采用啮齿动物体内对照实验。

方法

30只雌性Sprague-Dawley大鼠随机分为假手术组(n=10)或OVX手术组(n=20);3个月后,对OVX动物注射ALN(OVX+ALN,15µg/kg/2周,n=10)或生理盐水(OVX+载体处理[V],n=10)。在ALN干预3个月后,采用范吉森染色和免疫组织化学方法研究椎间盘的组织学和代谢变化。进行骨密度(BMD)、微计算机断层扫描和生物力学测试以确定椎体的生物学特性。

结果

OVX+ALN组髓核和纤维环的形态学退变改变明显减少,IDD评分明显低于OVX+V组。与OVX+V组相比,OVX+ALN组样本的椎间盘高度增加,软骨终板厚度和骨面积减小。与生理盐水相比,给予ALN显著抑制了椎间盘基质中I型胶原蛋白、基质金属蛋白酶(MMP)-1和MMP-13的表达水平,同时提高了II型胶原蛋白和聚集蛋白聚糖的表达水平。与OVX+V组相比,OVX+ALN组椎体的BMD显著提高,生物力学强度增加,骨体积百分比和小梁厚度也增加。

结论

ALN对伴有骨质流失的椎间盘退变具有良好的作用,有助于减轻IDD,同时增强椎体和终板的生物学和力学性能。

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