Etiology and Prevention of Loss of Fixation in Cemented Knee Replacements

项目摘要/摘要 在美国，每年进行的全膝关节置换术(TKA)超过75万例，预计需求将 到2030年增长到每年300多万。尽管这些设备取得了成功，但修订率仍保持不变 高得令人无法接受；据估计，男性终身翻修的风险为14.9%，男性为17.4% 女性。在当前的资金周期中，我们发现 随着服役时间的延长，骨水泥和骨量增加，在老年TKA捐赠者中更加广泛。损失的损失 互锁与较弱的接口相关，并且结构更有可能在 机械过载的情况。 最近的临床回顾研究表明，TKA术后应用双膦酸类药物 可能会降低修订率。然而，这种治疗可能影响界面的机制 种植体周围骨的情况也不得而知。本研究的总体目标是提供一种机械性和功能性的 了解骨水泥与骨之间的机械锁定在TKA固定中的作用，并确定是否 植入物的固定可以通过使用已有的药物疗法来减轻互锁的损失而得到改善。 在这一竞争性更新中，我们将在大鼠中开发一种骨水泥胫骨置换模型，该模型可重现 人体关节成形术中的骨水泥交错锁。我们将：1)调查 TKA骨水泥联锁的形态和细观力学随时间的变化及体内使用 研究动态骨重建和细胞反应作为交锁内固定位置的函数 构建，3)确定衰老/骨质疏松症对形态、微观力学和 卵巢摘除(OVX)模型下骨水泥-骨交锁术中细胞变化的研究 在正常和OVX病例中，剂量的抗吸收药物(唑来膦酸)可以防止TKA联锁的丢失， 以及5)确定在TKA中局部使用PMMA水泥中的唑来膦酸是否可以带来积极的效果 类似于全身给药。 总而言之，这项工作将提供一个导致TKA微观损失的过程的机械理解 联锁和固定。这项工作还将产生(或驳斥)使用局部或系统的科学理由 抗吸收药物，以防止因种植体固定丢失而导致的临床松动。

Project Summary/Abstract Over 750,000 total knee arthroplasties (TKA) are performed annually in the US and demand is expected to grow to over 3 million annually by 2030. Despite the success with these devices, revision rates remain unacceptably high; the lifetime risk of revision has been estimated to be 14.9% for males and 17.4% for females. During the current funding cycle, we found that there was loss of mechanical interlock between the cement and bone that increased with time in service and was more extensive in older TKA donors. The loss of interlock was associated with weaker interfaces, and the constructs were more likely to be damaged in the case of a mechanical overload. Recent clinical retrospective studies have indicated that administration of bisphosphonates after TKA surgery may reduce revision rates. However, the mechanism by which this treatment may be affecting the interfaces and peri-implant bone is not known. The overall goal of this study is to provide a mechanistic and functional understanding of the role of mechanical interlock between cement and bone in TKA fixation, and determine if implant fixation can be improved by mitigating the loss of interlock through use of an established drug therapy. In this competitive renewal, we will develop a cemented tibial replacement model in the rat that recapitulates the cement-bone interlock that occurs in human arthroplasty. We will: 1) investigate alterations in the morphology and micro-mechanics of TKA cement-bone interlock as a function of time with in vivo service, 2) investigate dynamic bone remodeling and cellular response as a function of position in the interlocked construct, 3) determine the longitudinal effect aging/osteoporosis on morphology, micro-mechanics, and cellular changes of cement-bone interlock for TKA using an ovariectomy (OVX) model, 4) determine if systemic dosing of an antiresorptive agent (zoledronic acid) can prevent loss of TKA interlock in normal and OVX cases, and 5) determine if local dosing of zoledronic acid from PMMA cement in TKA can confer a positive effect as similar to systemic dosing. In summary, this work will provide a mechanistic understanding of the processes leading to loss of TKA micro- interlock and fixation. The work will also produce (or refute) a scientific rationale for the use of local or systemic anti-resorptive agents to prevent clinical loosening due to loss of implant fixation.