不同双膦酸盐类药物在骨代谢的实验研究

The comparison of different bisphosphonates in bone metabolism using animal models

目的合理选择双膦酸盐类药物为临床治疗骨质疏松提供依据。方法通过实验兔肌肉注射地塞米松磷酸钠注射液方法制作骨质疏松动物模型,并对骨质疏松模型分别进行"99Tc-MDP"、"阿仑膦酸钠"和"博宁"治疗后的疗效研究,实验室分析指标:病理骨组织学、骨密度、生物力学试验、骨形态计量、放射性"99mTc-MDP"骨骼显像ROI比值、X线、CT摄片及血清骨碱性磷酸酶(BALP)、骨钙素(BGP)。并与骨质疏松模型对照组比较,评判各组间的差异。采用SPSS13.0软件进行统计学处理分析。结果经肌肉注射盐酸地塞米松方法制作骨质疏松模型试验,在病理骨组织学、骨密度、生物力学试验、BGP等指标均出现骨质疏松征象,证实骨质疏松模型成立。在骨质疏松的基础上,经"99Tc-MDP"、"阿仑膦酸钠"和"博宁"各治疗组的治疗,均有较明显的改善,但存在不同程度的差异,改善程度依次为"99Tc-MDP"治疗组、"阿仑膦酸钠"治疗组和"博宁"治疗组。结论不同的双膦酸盐类药物在骨组织生理代谢不一样,所产生的疗效也不同。"阿仑膦酸钠"是在"博宁"的基础上研制的新一代治疗骨质疏松症的双膦酸盐,所以抑制骨吸收优于"博宁"。而"99Tc-MDP"可能对骨组织还具有免疫调节价值。对不同的双膦酸盐在骨组织生理代谢作用的治疗价值将可为临床治疗方向提供依据。

Objective To validate the optimal bisphosphonate in the treatment of osteoporosis using animal models and provide evidence for more appropriate clinical uses of bisphosphonates.Me thod First we established osteoporotic rabbit models by injecting dexamethasone sodium phosphate intramuscularly.And then the animal models were divided into four different groups and treated with99Tc-MDP,alendronate and pamironate disodium respectively.The effects of the three different drugs were investigated by comparing with the control group and by analyzing laboratory test,bone histology,bone density,biomechanical test,ROI ratio of99mTc-MDP bone scintigraphy,X ray,CT tomography,BALP as well as BGP.The statistical analysis was carried out using SPSS13.0.Re sult Although all the three methods had relieved the osteoporosis in our experimental groups,99Tc-MDP is the most effective therapy when compared with alendronate or pamironate disodium.Conclusion Depending on different mechanisms in bone metabolism,the effects of bisphosphonates vary among different therapies.Alendronate is the newly developed bisphosphonate based on pamironate disodium,as a result,it behaves much better when inhibiting bone absorbing in treating osteoporosis.In addition,99Tc-MDP may exerting therapeutic effects through immunization routes.Our research will provide value for more appropriate treatment of osteoporosis.