SYSTEMIC IMPLICATIONS OF TOTAL JOINT REPLACEMENT

越来越多的人认识到，从长远来看， 置换（TJR）可能与局部和远端组织不良反应相关 由假体降解产物介导的反应 材料.人们对金属材料特别感兴趣， 由于THR的已知毒性， 包括植入物合金的金属元素。在这个长期的 研究，我们一直在调查金属释放，运输，储存和 全髋关节和膝关节置换术患者的排泄。在 目前的补助期，我们已经证明，（1）血清中的升高， 钛和铬可以在个体中检测到， 功能全髋关节和膝关节置换术;（2）最高铬 在金属对金属的患者中观察到钴水平 关节面;（3）广泛多孔涂层钴的被动溶解- 基础合金股骨柄不是金属释放的主要模型; 相反，股骨部件在组配式连接处的微动腐蚀， 与血清铬升高更密切相关;（4）钴- TJR的钛合金颗粒降解产物通常 扩散至主动脉旁淋巴结、肝脏和脾脏，特别是在 （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 我们建议扩大这些研究，以（1）量化金属释放， 前瞻性研究组将在术后7至12年， 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， 已证实血清中的 金属含量，以确定血清金属转运是否随着 时间;（3）扩大我们的尸检检索程序，不仅表征 组织金属水平和微粒磨损碎屑的全身分布 而且这些降解的组织和细胞定位 产品;及（4）进行生物利用度和生物活性研究 循环的金属蛋白复合物， 关节置换组件。 这是骨科生物材料研究者的四项赠款之一- 启动了题为“安全和 永久性颅骨置换植入物的有效性”。研究 此处提出的建议解决了安全问题，并被视为至关重要， 了解接受全关节置换术的患者的预期风险 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.