国产羟乙膦酸钠抗去势大鼠骨质疏松实验研究

Experimental Study on Effect of Etidronate Disodium against Osteoporosis in Ovariectomized Rats

目的:探讨国产羟乙膦酸钠对去势大鼠骨质疏松的疗效。方法:将4月龄wistar雌性大鼠55只随机分为6组:卵巢切除(OVX)组、假手术(SHAM)组、雌二醇阳性对照(E)组、羟乙膦酸钠灌服低剂量(IGL)组、中剂量(IGM)组、高剂量(IGH)组,共给药12周。主要测定动物骨重及钙、磷含量和骨形态计量等。结果:去势大鼠骨干重、灰重及钙、磷含量显著降低,骨小梁体积及宽度明显减小,破骨细胞及成骨细胞活性均增加,但破骨显著大于成骨,羟乙膦酸钠各剂量组均恢复至接近正常水平。结论:国产羟乙膦酸钠能有效防治去势大鼠骨质疏松,并对子宫无副作用。

Objective： To investigate the effect of etidronate disodium on osteoporosis in ovariectomized rats. Methods： Fifty-five female wistar rats aged 4 months were mandomly divided into 6 groups： the SHAM group （subjected to the sham operation）, the OVX group （subjected to bilateral ovariectomy）, the E group （subjected to bilateral ovariectomy and treated postoperatively with estrogen 4 mg/kg twice a week for 12 weeks）, and the etidronate disodium group （subjected to bilateral ovariectomy and treated postoperatively with etidronate disodium synthesized first by School of Pharmaceutical Sciences,Sichuan University）, which was divided into 3 groups, i.e., the IGL group, the IGM group, and the IGH group according to the different doses of etidronate disodium given. The IGL, IGM, and IGH groups were given etidronate disodium 75, 150, and 300 mg/kg, respectively via gavage once a day for 12 weeks. Results： In the OVX group, the dry weight, ashweight, calcium content, and phosphorus content of the left femur, and the trabecular bone volume and mean trabecular thickness of the tibia were all reduced significantly. This bone loss was associated with an increase in the osteoclast index, osteoblast index, osteoid surface, and serum ALP activity. The distances between the tetracycline double labelings were also markedly elevated. All of the indices showed that there was an increase in the bone turnover and that there was much more bone resorption than bone formation. The bone mass in the three etidronate disodium groups recovered nearly to the condition of the SHAM group and the E group. A marked inhibition of resorption was also observed. Conclusion： The results indicate that the domestic etidronate disodium can provide an effective protection against osteoporosis in ovarietomized rats.