早期预防性治疗对绝经后骨质疏松症影响的动物实验研究

目的评价早期预防性抗骨吸收治疗对绝经后骨质疏松症骨量、骨代谢指标和骨组织形态的变化特点,提供早期监测和预防绝经后骨质疏松症的依据.方法以去卵巢大鼠为实验对象、抑制骨吸收的唑来膦酸注射液为赋形药物,建立绝经后骨质疏松症的动物模型.选取44只3个月龄雌性SD大鼠,除假手术组行假手术外,其余各组均行双侧卵巢切除.假手术组(sham)、去势对照组(ovx)以安慰剂处理,其余两组分别在去势后3d、1个月给予唑来膦酸注射液(zoledronic acid,ZOL) 500μg/kg静脉单次注射,分别在实验开始、术后1个月及术后3个月测定大鼠股骨骨密度(BMD),收集血清测定I型前胶原氨基端前肽(PINP)、抗酒石酸酸性磷酸酶5b (TRACP-5b)的值变化,并光镜下观察大鼠股骨病理学变化,图像分析系统观察骨形态计量学静态指标骨小梁面积百分率(TBV)、骨小梁厚度(Tb.Th)、骨小梁间距(Tb.sp)的变化.结果应用去卵巢大鼠成功建立绝经后骨质疏松模型.去势对照组在1个月股骨BMD、血清PINP和TRACP-5b、TBV、Tb.Th及Tb.sp等指标变化上和正常对照组存在显著性差异(P＜0.01);去势3d即行ZOL治疗者和假手术对照组的BMD、骨代谢、骨形态学指标比较变化无显著性差异(P＞0.05);1个月后开始ZOL治疗者仅部分恢复骨密度,血清PINP、TRACP5b、骨组织形态指标变化和早期治疗组比较存在非常显著性差异(P＜0.01),且其骨小梁连接有明显的退变.结论骨代谢指标可用于抗骨吸收治疗的疗效监测;去势大鼠早期进行预防性抗骨吸收治疗,能抑制其骨量的丢失,减慢骨小梁退变,恢复骨密度.

An animal experiment on the effects of early preventive treatment on postmenopausal osteoprosis

Objective To evaluate changes of bone mass, bone metabolic index and bone morphology inapplication with anti-bone resorption treatment as early preventive treatment and to provide an evidence for early observation and prevention of postmenopausal osteoporosis. Methods Postmenopausal osteoporosis animal model was created by ovariectomy rats in application with excipient zoledronic acid to inhibit bone resorption. 44 three-month female Sprague-Dawley rats were divided into sham-operated group, ovariectomy （ovx） controlled group, ovx plus early treatment group and ovx plus late treatment group. All groups underwent ovariectomy except sham-operated group that accepted placebo treatment in accompany with ovx controlled group. The ovx plus early treatment group was injected with zoledronic acid （500μg/kg/iv.） at the third day after ovariectomy, while the ovx plus late treatment group at the thirty day after ovariectomy with the identical dosage. Bone mineral density （BMD） of the femur was determined at the beginning, one month and three months after operation. Value changes of PINP and TRACP-5b were measured by analyzing the plasma. Pathological changes of rats＇ femur were observed under the light microscope. Image analyze system was applied to observe changes of static index of bone histomorphometry, that were TBV, Tb. Th and Tb. Sp. Results The postmenopausal OP animal model was created by the excision of ovary on the rats successfully. There was a significant difference （P〈0.01） between the ovx controlled group and the control group in BMD, serum PINP, TRACP5b, TBV, Tb. Th and Tb. Sp 1 month after ovariectomy. There was no significant difference （P〉0.05） between the early treatment group that accepted injection 3 days after ovariectomy and the sham-operated group in terms of BMD, bone metabolism, and bone morphology index. Only part of the patients from ovx plus late treatment groupthat underwent ZOL treatment experienced a recovery of BMD. There was a significant difference （P〈0.01） between the late treatment groups and the early treatment groups in serum P1NP and TRACP5b, TBV, Tb. Th and Tb. Sp. The trabecular connectivity had obvious degeneration. Conclusions Bone metabolic index can be used as a monitor for the therapeutic effect of anti-bone resorption. Preventive treatment of osteoporosis in ovariectomized rats can inhibit bone loss, decelerate the degeneration of trabecular bone and accelerate the recovery of bone mineral density.