糖皮质激素性骨质疏松骨保护素表达与骨密度的相关性

Correlation of osteoprotegerin expression and bone mineral density in rats with glucocorticoid-induced osteoporosis

目的:探讨糖皮质激素性骨质疏松大鼠骨保护素在骨骼局部的表达,及其对骨密度变化的影响。方法:实验于2005-01/2006-03在解放军总医院骨科实验室完成。选择6月龄雄性Wistar大鼠48只,随机数字表法分为实验组和对照组,各24只。实验组大鼠给予地塞米松1mg/kg肌肉注射,1次/d;对照组大鼠给予等量生理盐水肌注。两组大鼠给药后2,4,8,12周各处死6只,取松质骨(腰椎)和皮质骨(股骨干),进行骨密度值测量、骨组织形态学观察及骨保护素免疫组织化学染色,并进行图像处理和统计分析。结果:纳入动物48只,均进入结果分析。①实验组大鼠腰椎骨密度给药后2,4,8,12周与对照组相比均明显下降[分别为(0.175±0.013),(0.212±0.018)g/cm2;(0.152±0.021),(0.211±0.019)g/cm2;(0.129±0.014),(0.213±0.015)g/cm2;(0.113±0.016),(0.212±0.015)g/cm2,P<0.01],给药后12周较2周下降更为显著(P<0.01);股骨干骨密度给药后2周无明显差异(P>0.05),给药后4周开始下降[分别为(0.226±0.013),(0.244±0.015)g/cm2,P<0.05],给药后8,12周均明显下降[分别为(0.204±0.014),(0.238±0.015)g/cm2;(0.186±0.016),(0.240±0.013)g/cm2,P<0.01]。②实验组骨小梁排列稀疏,数目减少,小梁明显变细、间距加宽,股骨干中段骨皮质厚度变薄,12周多视野计数可见破骨细胞增多(P<0.01)。③实验组给药后2周腰椎的骨保护素组织化学染色明显减低,4周股骨干内亦明显减低,并且随着给药时间的延长逐渐减低。结论:糖皮质激素抑制骨骼局部骨保护素表达,并且与局部破骨细胞的增多、骨密度降低密切相关,继发了渐进性骨质丢失,可能参与并促进了骨质疏松的形成。

AIM： To examine the local expressions of osteoprotegerin （OPG） in rats With glueocortieoid-indueed osteoporosis, and study the relationship between bone mineral density （BMD） and OPG expression. METHODS： The experiment was conducted at the Laboratory of Orthopedics Department, Chinese PLA General Hospital from January 2005 to March 2006. Forty-eight male Wistar rats （6 months old） were divided into trail group and control group randomly, with 24 rats in each, The rats of trail group were subjected to dexamethasone administration intramuscularly （1 mg/kg, once a day） while the rats of control group were injected with equal sodium chloride intramuscularly. Six rats of each group were sacrificed at 2, 4, 8 and 12 weeks after administration respectively, Then BMD measurement, histomorphometry observation and OPG immunohistochemistry staining were performed in the cancellous bone （lumbar vertebra） and cortex （femoral shaft）, followed by image processing and statistical analysis. RESULTS： Totally 48 rats were involved in the result analysis. ① Compared with control group, the BMD of lumbar vertebra were significant decreased at 2, 4, 8 and 12 weeks after administration in trail group [（0,175±0.013）, （0.212±0.018） g/cm^2; （0,152±0.021）, （0.211±0.019） g/cm^2; （0.129±0.014）, （0.213±0.015） g/cm^2; （0.113±0.016）, （0.212±0.015） g/cm^2, P 〈 0.01], and the decrease was more obvious at 12 weeks than at 2 weeks （P 〈 0.01）; As for the BMD of femoral shaft, there was no difference after 2 weeks of administration （P 〉 0,05）, but＇BMD began to decrease at 4 weeks [（0.226 ±0.013）, （0.244 ±0,015） g/cm^2, P 〈 0.05], and decreased significantly at 8 weeks and 12 weeks [（0.204±0.014）, （0,238±0.015） g/cm^2; （0.186±0.016）, （0.240±0.013） g/cm^2, P 〈 0.01].②In the trial group, bone trabecula was sparse, thin and declined in number, accompanying the broaden spacing. In addition, the cortical bone in the middle piece of femoral shaft became gracile. The result of multiple perimeter showed the number of osteoclasts was significantly increased at 12 weeks （P 〈 0.01）.③ OPG immunohistochemistry staining were reduced gradually with the administration duration extended, and were obviously decreased in lumbar vertebra at 2 weeks and in femoral shaft at 4 weeks of administration. CONCLUSION： Glueocortieoid can inhibit OPG local expression in the bones, increase the activity and differentiation of osteoelast along with decreasing BMD relatively, followed by gradual bone loss thus induce and accelerate the osteoporosis,