Abstract：
Progressive osteolysis can occur at the cement-bone interface of joint replacements and the associated loss of fixation can lead to clinical loosening. We previously developed a rat hemiarthroplasty model that exhibited progressive loss of fixation with the development of cement-bone gaps under the tibial tray that mimicked patterns found in human arthroplasty retrievals. Here we explored the ability of a bisphosphonate (zoledronic acid, ZA) to attenuate cement-bone osteolysis and maintain implant stability. Sprague-Dawley rats (n = 59) received a poly(methylmethacrylate) cemented tibial component and were followed for up to 12 weeks. Treatment groups included peri-operative administration of ZA (ZA group), administration of ZA at 6 weeks postop (late ZA group), or vehicle (Veh group). There was a 60% reduction in the rate of cement-bone gap formation for the ZA group (0.15 mm3/week) compared to Veh group (0.38 mm3/week, p = 0.016). Late ZA prevented further progression of gap formation but did not reverse bone loss to the level achieved in the ZA group. Micromotion from five times body weight toggle loading was positively correlated with cement-bone gap volume (p = 0.009) and negatively correlated with the amount of cement in the metaphysis (p = 0.005). Reduced new bone formation and enduring nonviable bone in the epiphysis for the ZA group were found. This suggests that low bone turnover in the epiphysis may suppress the early catabolic response due to implantation, thereby maintaining better fixation in the epiphysis. This preclinical model presents compelling supporting data documenting improved maintenance of the cement-bone fixation with the use of peri-operative bisphosphonates.
摘要：
关节置换的骨水泥-骨界面可发生进行性骨溶解，相关的固定丢失可导致临床松动。我们先前开发了一种大鼠半髋关节置换术模型，该模型表现出固定的进行性丧失，胫骨盘下的水泥-骨间隙的发展模仿了人类关节置换术中发现的模式。在这里，我们探索了双膦酸盐(唑来膦酸，ZA）以减轻水泥-骨骨溶解并保持植入物的稳定性。Sprague-Dawley大鼠（n=59）接受了聚（甲基丙烯酸甲酯）胶结的胫骨组件，并随访长达12周。治疗组包括围手术期给予ZA（ZA组），在术后6周给予ZA（晚期ZA组），或车辆（Veh组）。与Veh组相比，ZA组（0.15mm3/周）的骨水泥-骨间隙形成率降低了60％（0.38mm3/周，p=0.016)。晚期ZA阻止了间隙形成的进一步进展，但并未将骨丢失逆转至ZA组的水平。来自五倍体重肘节载荷的微动与骨水泥-骨间隙体积呈正相关（p=0.009），与干phy端中的骨水泥量呈负相关（p=0.005）。发现ZA组的骨phy中新骨形成减少和持久的无活力骨。这表明骨phy的低骨转换可能会抑制植入引起的早期分解代谢反应。从而在骨phy中保持更好的固定。该临床前模型提供了令人信服的支持数据，证明了围手术期使用双膦酸盐改善了水泥-骨固定的维护。
