唑来膦酸对骨质疏松性骨折愈合强度影响的实验研究

目的 观察唑来膦酸对骨质疏松性骨折局部骨痂力学强度的影响,探讨其作用机制.方法 将48只24周龄、雌性SD大鼠随机分为对照组CNT以及ZOLD1组、ZOLW1组和ZOLW2组.在骨质疏松性骨折内固定术后1天、1周和2周分别在腹腔注射相当于临床治疗剂量的唑来膦酸.术后第6周和12周取材,进行显微CT三维重建及显微形态计量学测量、生物力学和纳米压痕检测.结果 骨折术后第6周,实验组3组（ZOLD1、ZOLW1和ZOLW2）骨痂骨小梁体积分数（BV/TV）、骨小梁厚度（Tb.Th）以及连接密度（Conn.D）较之CNT组都明显增高（P＜0.05）,骨小梁分离度（Tb.Sp）和骨表面积体积比（BS/BV）明显减低（P＜0.05）,骨痂最大载荷明显增加（P＜0.05）.至第12周,相比CNT组,实验组骨痂能量吸收和最大载荷明显增高（P＜0.05）,ZOLW2组Tb.Sp明显增高,Conn.D明显减低（P＜0.05）.在12周,ZOLD1和ZOLW1骨小梁的弹性模量和硬度都较CNT明显地增高（P＜0.05）,ZOLW2与CNT差异不具有统计学意义（P＞0.05）.结论 唑来膦酸总体上增强了骨质疏松性骨折断端的骨痂结构力学强度.这与该药抑制骨吸收,提高骨痂内部骨小梁数量,维持大量编织骨有关.延迟注射唑来膦酸抑制骨折后期骨痂重建,不会损害编织骨数量,但可能会损害骨痂内部骨小梁力学强度和连接数目.

Effect of Zoledronic Acid on Callus Mechanical Strength through the Process of Fracture Healing in Ovariectomized Rats

Objective The purpose of this work was to test the effect of the use of zoledronic acid （ZOL） on callus mechanical strength properties in an osteoporotic rat model of fracture healing.Methods Ovariectomized（OVX） rats were randomly divided into four treatment groups （n =12 per group）：saline control（CNT） and three systemic zoledronic acid injected groups （0.1 mg/kg） with different administration times of 1 day（ZOLD1） after fracture,1 week after fracture（ZOLW1）,and 2 weeks after fracture （ZOLW2）.Rats were killed at either week 6 or 12 postoperatively for micro-CT scan and 3D-histomorphometry,biomechanics and nanoindentation.Results Treatment with zoledronic acid led to a significant increase in trabecular bone volume fraction（BV/TV）,thickness（Tb.Th） and connection density（Conn.D） within the callus compared to the control at 6 weeks post internal fixation of fracture（P ＜ 0.05）,and a significant decrease in trabecular separation（Tb.Sp） and surface/volume ratio（BS/BV）.Meanwhile,it caused a significant increase in ultimate load （P ＜ 0.05）.At 12 weeks after surgery,the callus treated with zoledronic acid increased energy absorption and ultimate load compared to the control（P ＜ 0.05）.ZOLW2 showed higher trabecular separation（Tb.Sp） and lower connection density（Conn.D） than the control（P ＜ 0.05）.At 12 weeks,ZOLD1 and ZOLW1 had enhanced elastic modulus and hardness （P ＜ 0.05）,while the differences of those between delayed administration （ZOLW2） and control were of no significance （P ＞ 0.05）.Conclusion The superior results obtained with treated groups （ZOLD1,ZOLW1 and ZOLW2） compared to CNT in terms of callus strength of structural mechanics could be the consequence of be a larger number of trabecular bone and woven callus due to the lower bone resorption by zoledronic acid.Mild suppression of callus remodeling by delayed administration（ZOLW2） could not impair the volume of woven callus but the trabecular bone connec