Objective To observe the biomechanical changes of subchondral bone in the early stage of knee joint instability and effect of diphosphonate therapy so as to investigate the role of the early biomechanical changes of subchondral bone in the onset and development of osteoarthritis (OA).Methods Sixty healthy male New Zealand white rabbits were assigned to model group (n =24),diphosphonate group (n =24) and control group (n =12) according to random number table.Joint destabilization by anterior cruciate ligament transection of the right knee of the rabbits was performed to induce OA models.Rabbits in diphosphonate group received subcutaneous injection of 0.01 mg/kg diphosphonate (risedronate) per day,and isotonic saline solution of the same volume was subcutaneously given to rabbits in model and control groups.Half the animals in each group were killed by aeroembolism at postoperative 4 weeks and 12 weeks respectively.Surgical knee joint with preservation of each 2 cm bone above and below joint surface was dissected to perform gross scoring.Thereafter,two-dimensional image profile was achieved by Micro-CT examination and converted into Ansys for limit element analysis after fitting in Mimics software.Results At four weeks,bone volume fraction (BVF),elastic modulus (EM),reaction force (RF),and mean Von Mises stress were all declined in three groups,the lowest level in the model group (P ＜ 0.01).The diphosphonate group also had lower levels than the control group,with insignificant difference.Bone mineral density (BMD) in the model group was obviously declined in contrast with the diphosphonate and control groups (P ＜ 0.01),but there were no significant difference between the diphosphonate group and the control group.At 12 weeks,the model group showed higher level of BVF and BMD,but lower level of EM,RF and Von Mises stress in comparison with the control and diphosphonate groups (P ＜ 0.01).EM,RF,and Von Mises stress were lower in the diphosphonate group than those in the control group as well,but the difference was statistically insignificant.The model group showed that BVF,BMD,EM,RF,and Von Mises stress at 12 weeks were improved from those at 4 weeks (P ＜ 0.01).Conclusions Biomechanical properties of subchondral bone are affected in the early stage of knee joint instability and a notable decrease of EM is observed in the early stage,followed by an enhancement in late stage.It means that the biomechanical changes of subchondra,l bone in the early stage of knee joint instability may be connected with the bone resorption resulting from abnormal stress.On the contrary,diphosphonate may markedly improve EM of subchondral bone through inhibiting bone resorption.%目的 观察膝关节不稳早期软骨下骨力学性能的改变及二磷酸盐的干预作用,以探讨骨性关节炎(osteoarthritis,OA)早期软骨下骨力学性能的改变在疾病发生发展中的作用. 方法 健康雄性新西兰大白兔60只,按随机数字表法分成模型组(24只)、二磷酸盐组(24只)、对照组(12只).采用兔关节不稳模型(切断前交叉韧带)右膝造模.二磷酸盐组每天皮下注射二磷酸盐(利塞磷酸钠)0.01 mg/kg,模型组和对照组给予等体积的等渗盐水皮下注射.分别于术后4,12周空气栓塞处死动物,其中模型组12只,二磷酸盐组12只,对照组6只.分别切取保留关节面上下各2 cm骨的手术侧膝关节,进行大体评分.后行Micro-CT检查,得到二维图像文件,导入Mimics软件中进行拟合,并导入到Ansys中进行有限元处理. 结果 造模后4周,模型组、二磷酸盐组、对照组骨体积分数(bone volume fraction,BVF)、弹性模量(elastic modulus,EM)、反应力(reaction force,RF)、平均Von Mises应力参数均下降,模型组较二磷酸盐组、对照组低(P＜0.01)；二磷酸盐组与对照组比较也下降,但差异无统计学意义.模型组骨密度(bone mineral density,BMD)较二磷酸盐组及对照组明显降低(P＜0.01)；而二磷酸盐组与对照组比较差异无统计学意义.12周时模型组BVF、BMD明显增加,EM、RF、Von Mises应力较对照组和二磷酸盐组低(P＜0.01)；二磷酸盐组亦较对照组低,但差异无统计学意义.模型组12周与4周各参数比较,BVF、BMD、EM、RF、Von Mises应力均升高(P＜0.01). 结论 膝关节不稳早期软骨下骨发生力学性能改变,早期弹性模量明显降低,后期升高.表明关节不稳早期软骨下骨力学性能的改变可能和异常应力引起的骨吸收有关,而二磷酸盐可通过抗骨吸收明显提高软骨下骨的弹性模量.
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