利塞膦酸钠对大鼠骨质疏松性非典型性骨折愈合的影响

Effect of risedronate sodium on osteoporotic atypical fracture healing in rats

目的探讨利塞膦酸钠对大鼠骨质疏松性非典型性骨折愈合的影响。方法选取健康6月龄SD雌性大鼠60只,随机分为正常对照组(A组)、去卵巢模型+股骨干骨折模型+利塞膦酸钠灌胃治疗组(B组)、去卵巢模型+股骨干骨折模型+生理盐水灌胃组(C组),每组20只。骨折模型建模后第3周和第6周时动态观察股骨骨密度(bone mineral density,BMD)、骨矿物质含量(bone mineral content,BMC)、影像学及骨组织显微形态学的改变。结果①通过X线检查结果可知,B组在第3、第6周时,骨折处骨痂形成,局部骨密度越来越高,前3周骨折出现愈合加速,后3周出现明显延迟愈合情况;同时期B组、C组骨折处相比较,前3周B组大鼠出现骨折处骨连续性较A组、C组好,但在第6周时,B组大鼠出现骨折处骨连续性较A组、C组差,骨折处局部出现骨折延迟愈合情况;②同时期各组大鼠病理切片结果对比,B组大鼠在前3周骨折处增殖的软骨细胞较A组、C组多,骨小梁较密集,骨小梁相互之间连接性较好,骨皮质厚度更大,骨折愈合情况更好;但在后3周时,B组大鼠较A组、C组骨折处增殖的软骨细胞少,骨小梁稀疏,骨小梁相互之间连接性差,骨皮质厚度变化不明显,出现骨折愈合延迟现象;在同时期前后对比中,B组大鼠在前3周局部骨折处出现明显加速现象,后3周则出现明显延迟愈合现象;③各组大鼠BMD、BMC组间、组内对比中,结果具有统计学意义,说明利塞膦酸钠在前3周可显著提高大鼠骨折处BMD、降低大鼠骨折处BMC,且显著提高骨折处BMD增加速度,延缓骨折处BMC降低速度,但在后3周出现延迟骨折愈合情况。结论早期骨质疏松性非典型性骨折患者愈合过程中建议使用利塞膦酸钠,中、后期则不建议使用。

Objective To investigate the effect of risedronate on the healing of atypical osteoporotic fracture in rats.Methods In this study,60 healthy female SD rats of 6 months old were randomly divided into three groups(20 in each group)including normal control group(group A),ovariectomized model+femoral shaft fracture model+risedronate sodium gavage treatment group(group B)and ovariectomized model+femoral shaft fracture model+saline gavage group(group C).Femoral bone density(BMD),bone mineral content(BMC),imaging and microstructural changes in bone tissue were observed dynamically at 3 and 6 weeks after fracture model modeling.Results①According to the results of X-ray examination,in group B,at 3 and 6 weeks the callus was formed at the fracture site,and the local bone density kept on increasing.The fracture healing accelerated in the first 3 weeks,but delayed healing occurred in the last 3 weeks.At the same time,comparing the fracture site of the B and C groups,in the first 3 weeks,the bone continuity of the fracture site in the B group was better than that in the A and C groups.However,at the 6th week the bone continuity of the fracture site in the B group was worse,and delayed fracture healing occurred locally in the fracture site compared with the A and C groups.②Comparing the results of pathological sections of rats at the same period,rats in group B had more chondrocytes proliferating than those in the A and C groups in the first 3 weeks;the trabecular bone was denser,the trabecular bones were better connected to each other,the thickness of the cortical bone was larger,and the fracture healing was better.However,in the last 3 weeks,compared with rats in the A and C groups,rats in the B group had less cartilage cells,sparse trabeculae,poor connectivity between trabecular bone and no obvious changes in cortical bone thickness,and had delayed fracture healing at the fracture site.For before and after comparison of the same period,the rats in group B showed obviously accelerated healing of local fractures in the first 3 weeks,but significantly delayed healing in the last 3 weeks;③For the between and within group comparison of BMD and BMC,the results were statistically significant,indicating that in the first 3 weeks risedronate sodium could significantly increase BMD and decrease BMC in the fracture site,and significantly increase the rate of BMD increase at the fracture site and slow down the BMC reduction rate,but in the last 3 weeks delayed fracture healing occurred.Conclusion It is recommended to use risedronate at the early stage of healing in patients with osteoporotic atypical fractures.It is not recommended to use risedronate in the middle and late stages.