SYSTEMIC IMPLICATIONS OF TOTAL JOINT REPLACEMENT

越来越多的人认识到，从长远来看，完全联合 替代(TJR)可能与不利的局部和远程组织相关 假体降解产物介导的反应 材料。人们对金属的兴趣格外浓厚 苏氨酸的降解产物，因为已知的毒性 构成植入合金的金属元素。在这一长期内 研究，我们一直在调查金属的释放，运输，储存和 全髋关节和膝关节置换术后患者的排泄量。在 在目前的授权期内，我们已经证明(1)血清中的升高 钛和铬可以在健康状况良好的人身上检测到 功能性全髋关节和膝关节置换术；(2)最高铬 在金属对金属患者中观察到钴水平 轴承；(3)广泛多孔性涂层钴的被动溶解- 基托合金股骨柄不是金属释放的主要模型； 相反，股骨组件在模块连接处的微动腐蚀是 与血清铬的升高更密切相关；(4)钴- 以及TJR产生的钛合金颗粒降解产物 扩散到腹主动脉旁淋巴结、肝和脾，尤其是在 有失败的TJR的个人；以及(5)有迹象表明 血清金属含量升高的个体可能与 肝细胞损伤。 我们建议在这些研究的基础上扩展到(1)量化金属在 术后7~12年的前瞻性研究组， 与植入物相关的并发症更多的时间间隔 流行；(2)前瞻性随访患者长达8年 血清水平显著升高的翻修手术患者 金属含量用于确定血清金属转运是否随 时间；(3)扩展我们的尸检检索程序，不仅表征 颗粒磨屑的组织金属水平和系统分布 以及这些降解的组织和细胞定位 产品；及(4)进行生物利用度及生物反应性研究 腐蚀和磨损导致的循环金属-蛋白质络合物 关节替换部件的数量。 这是矫形外科生物材料研究员获得的四项资助之一- 名为“安全与安全”的互动研究项目资助 永久性骨替代种植体的疗效“研究 在此建议解决安全问题，并被认为是关键，以便 了解接受全关节置换术患者的潜在风险 关节成形术。

There is an increasing recognition that, in the long term, total joint replacement (TJR) may be associated with adverse local and remote tissue responses that are mediated by the degradation products of prosthetic materials. There has been particular interest in the metallic degradation products of THR because of the known toxicities of the metallic elements that comprise the implant alloys. In this long term study, we have been investigating metal release, transport, storage and excretion in patients with total hip and knee replacements. In the current grant period, we have demonstrated that (1) elevations in serum titanium and chromium can be detected in individuals with well functioning total hip and knee replacements; (2) the highest chromium and cobalt levels have been observed in patients with metal-on-metal bearings; (3) passive dissolution from extensively porous coated cobalt- base alloy femoral stems is not a dominant model of metal release; rather, fretting corrosion of femoral components at modular junctions is more closely associated with elevations in serum chromium; (4) cobalt- and titanium-alloy particulate degradation products from TJR commonly disseminate to paraaortic lymph nodes, liver and spleen, particularly in individuals who have had a failed TJR; and (5) there are indications that individuals with elevated serum metal content may have associated liver cell injury. We propose to expand on these studies to (1) quantify metal release in the prospective study group which will be 7 to 12 years postoperative, an interval in which complications related to the implant are more prevalent; (2) prospectively follow patients up to 8 years after revision surgery who have demonstrated significant elevations in serum metal content to determine if serum metal transport diminishes with time; (3) expand our autopsy retrieval program to characterize not only tissue metal levels and systemic distribution of particulate wear debris but also the tissue and cellular localization of these degradation products; and (4) conduct bioavailability and bioreactivity studies of circulating metal-protein complexes which result from corrosion and wear of joint replacement components. This is one of four grants in an Orthopaedic Biomaterials Investigator- Initiated Interactive Research Project Grant entitled "Safety and Efficacy of Permanent Skeletal Replacement Implants". The studies proposed here address safety issues and are deemed critical in order to understand the prospective risks to patients undergoing total joint arthroplasty.