Raloxifene, estrogen, and alendronate affect the processes of fracture repair differently in ovariectomized rats
Raloxifene, estrogen, and alendronate affect the processes of fracture repair differently in ovariectomized rats
复制标题
DOI：
10.1359/jbmr.2002.17.12.2237
复制
发表时间：
2002-12-01
影响因子：
6.2
通讯作者：
Norimatsu, H
中科院分区：
文献类型：
--
作者：
Cao, YP;Mori, S;Norimatsu, H
我们研究了骨吸收抑制剂(雌激素、雷洛昔芬和阿仑膦酸盐)对去卵巢大鼠骨折修复过程的影响。将140只3月龄雌性SD大鼠分为假手术组、雌激素组(雌激素组，0.1 mg/kg)、雷洛昔芬(Rix组，1.0 mg/kg)、阿仑膦酸组(Aln，0.01 mg/kg)。手术后立即开始治疗。术后4周处死骨折前对照组，行双侧股骨中段截骨术，髓内钢丝固定。继续治疗，在骨折后6周和16周切除骨折痂，通过X射线摄影、定量计算机体层摄影(QCT)、生物力学测试和组织形态计量学进行评估。在骨折后6周，Aln和OVX组的骨痂比其他组大。Sham组和OVX组的极限负荷高于EE2和RLX组，Aln组与对照组无明显差异。ALN骨痂中的矿物质含量(骨矿物质含量[BMC])也高于其他组。在骨折后16周，OVX骨痂小于6周，Aln的大小没有改变。ALN的BMC和极限载荷均高于OVX、EE2和RLX。EE2和RLX具有相似的生物力学特性，与假手术相似。有趣的是，OVX和Aln动物在所有时间点都比其他组重；因此，极限负荷按体重归一化，以显示两组之间在骨折后6周或16周的整个骨痂强度没有显著差异。但AlN对骨痂的重塑有较强的抑制作用，与其他组相比，骨痂中编织骨的含量最高，原始骨折线的可见度最高，板层骨的含量最低。因此，较大的Aln骨痂似乎是一种显著的形态适应，以固定劣质材料的骨折。总之，OVX刺激的骨转换导致骨折修复进展最快，而Aln治疗延迟最多，这与明显抑制骨吸收和形成活动是一致的。雌激素和RLX的作用与假手术大致相似，表明这些药物轻度抑制骨转换对骨折修复的进展影响不大。
We investigated the effects of inhibitors of bone resorption (estrogen, raloxifene, and alendronate) on the processes of fracture repair in ovariectomized (OVX) rats. One hundred forty female Sprague-Dawley rats at 3 months of age were either OVX or sham-operated and divided into five groups: sham control, OVX control, estrogen (17alpha-ethynyl estradiol [EE2], 0.1 mg/kg), raloxifene (RIx, 1.0 mg/kg), and alendronate (Aln, 0.01 mg/kg) groups. Treatment began immediately after the surgery. Four weeks postovariectomy, prefracture controls were killed and bilateral osteotomies were performed on the femoral midshafts and fixed with intramedullary wires. Treatment was continued and fracture calluses were excised at 6 weeks and 16 weeks postfracture for evaluation by X-ray radiography, quantitative computed tomography (QCT,) biomechanical testing, and histomorphometry. At 6 weeks postfracture, Aln and OVX had larger calluses than other groups. Sham and OVX had higher ultimate load than EE2 and Rlx, with Aln not different from either control. Aln calluses also contained more mineral (bone mineral content [BMC]) than all other groups. By 16 weeks postfracture, OVX calluses were smaller than at 6 weeks and the dimensions for Aln had not changed. Aln had higher BMC and ultimate load than OVX, EE2, and Rlx. EE2 and Rlx had similar biomechanical properties, which were similar to sham. Interestingly, OVX and Aln animals were heavier than other groups at all time points; therefore, ultimate load was normalized by body weight to show no significant differences in strength of the whole callus between groups at either 6 weeks or 16 weeks postfracture. However, Aln strongly suppressed remodeling of the callus, resulting in the highest content of woven bone, persistent visibility of the original fracture line, and lowest content of lamellar bone, compared with other groups. Therefore, the larger Aln callus appeared to be a remarkable, morphological adaptation to secure the fracture with inferior material. In conclusion, OVX-stimulated bone turnover resulted in the fastest progression of fracture repair that was most delayed with Aln treatment, consistent with marked suppression of bone resorption and formation activity. Estrogen and Rlx had similar effects that were generally similar to sham, indicating that mild suppression of bone turnover with these agents has insignificant effects on the progression of fracture repair.