唑来膦酸、雷奈酸锶对去势大鼠股骨干骺端缺损修复的效果对比研究

A comparative study on the effects of Zoledronic acid and strontium ranelate on femoral metaphyseal defect repairing in ovariectomized rats

目的研究不同抗骨质疏松药物唑来膦酸、雷奈酸锶对去势大鼠股骨干骺端缺损修复的影响。方法选用SPF级40只健康雌性SD大鼠行手术建立去卵巢模型(OVX组,n=35)和假手术模型(Sham组,n=5)。手术后3个月处死随机选取的5只OVX组大鼠与5只Sham组大鼠,测量其骨密度(BMD)来证实骨质疏松模型建立成功。随后所有的OVX组大鼠在双侧股骨干骺端建立直径为3mm的骨缺损模型后随机分为3组,唑来膦酸治疗组10只(ZA组,1.5μg/w),雷奈酸锶治疗组10只(SR组,625mg/kg,每周5次),空白对照组10只(Control组,等体积的生理盐水)。术后6、12w进行Micro-CT观察、组织病理学观察。结果 6、12w时成骨效果:ZA组和SR组在缺损区HE染色观察均可见大量骨小梁和较多成熟的骨细胞,但12w时Micro-CT显示骨微观结构修复效果ZA组明显好于SR组,新生骨密度也高于SR组。空白对组HE染色观察可见骨组织生成较少,骨小梁排列稀疏紊乱,Micro-CT显示骨微观结构修复效果不佳,新生骨密度也不够理想。结论唑来膦酸较雷奈酸锶能够更好地修复骨质疏松骨缺损。

Objective To investigate the effect of two anti-osteoporosis drug,zoledronic acid and strontium ranelate in bone defects repairing in osteoporotic rats. Methods 40 SPF-grade healthy female SD rats were used to establish ovariectomized（ OVX,n = 35） and sham operation models（ Sham,n = 5）. Three months after the surgery,5 rats randomly selected from OVX group and the 5 rats of the sham operation group were sacrificed,and BMD was measured to confirm the establishment osteoporosis model. In the remaining rats in the OVX group,bilateral femoral metaphyseal bone defect model with a diameter of 3mm were established. These rats were randomized into three groups,Zoledronic acid treatment group（ n = 10）（ ZA group,1. 5 mg / w）,Strontium Ranelate treatment group（ n = 10）（ SR group,625 mg / kg weekly 5 times） and Control group（ n = 10）（ received an equal volume of Physiological saline）. Micro-CT and histopathological assessments were performed at 6 and 12 weeks after operation. Results Osteogenic effect at 6 and 12 weeks： in both ZA and SR groups,HE staining in the defect area was observed with a large number of long spindle shaped bone cells and a large number of trabecular bone. But at 12 weeks,Micro-CT showed that the effect of bone microstructure repairing of the ZA group was significantly better than that of the SR group,and the density of newbone was higher in the ZA group compared with that of the SR group. The Control group＇s HE staining showed that there was less bone formation,and trabecular bone was thin and in disorder. Micro-CT assessment showed that the bone structure repair was poor and the density of newly formed bone is not ideal in the control group. Conclusion Zoledronic acid was more effective than strontium ranelate in bone defect repairing in osteoporotic rats.