Systemic Implications of Total Joint Replacement

全关节置换术的系统影响

• 批准号: 7012313
• 负责人: Joshua J Jacobs
• 金额: $ 27.94万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-05-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7012313
• 关键词: X ray; aluminum oxide; atomic absorption spectrometry; biological transport; biomaterial compatibility; biomaterial evaluation; blood chemistry; chromium; clinical research; cobalt; corrosions; hip prosthesis; human subject; joint prosthesis; knee; longitudinal human study; manganese; medical implant science; metal poisoning; nanotechnology; nickel; orthopedics; patient oriented research; postoperative complications; scanning electron microscopy; titanium; urinalysis; vanadium

DESCRIPTION (provided by applicant): 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 TJR because of the known toxicities of the metallic elements that comprise implant alloys. In this long-term study, metal release, transport, storage and excretion in patients with TJRs habs been investigated. In the current grant period, it has been demonstrated that (1) elevations in serum Ti, Co and Cr can be detected in individuals with well functioning total hip and knee replacements up to 84 months postoperative; (2) the highest Cr and Co levels have been observed in patients with metal-on-metal bearings; (3) passive dissolution from extensively porous coated Co-base alloy femoral stems is not a dominant mode of metal release; rather, fretting corrosion of femoral components at modular junctions is more closely associated with elevations in serum Cr; (4) in patients with TJR and elevated serum metal concentrations, two molecular weight ranges were found to bind Cr (at approximately 70 kD and approximately 180 kD) whereas a single molecular weight range (at approximately 70 kD) was found to bind Ti; (5) following revision surgery for a failed total hip replacement, circulating metal levels diminish, but remain chronically elevated up to 60 months post-revision; (6) Co- and Ti-alloy particulate degradation products, usually from sources other than the bearing surface, commonly disseminate to paraaortic lymph nodes, liver and spleen, particularly in individuals who have had a failed TJR; and (7) the bioreactivity of metal degradation products is governed by its' physiochemical nature and protein adducts: a Cr-containing 180 kD metal-protein complex was the most stimulatory in these studies. This proposal expands on these findings by addressing the following Specific Aims: (1) to quantify metal release in the prospective primary THR study groups which will be 10 to 15 years postoperative, an interval in which complications related to the implant are more prevalent; (2) to prospectively follow patients with Co-alloy metal-on-metal hip replacements to determine the prevalence of metal hypersensitivity in correlation with the serum and urine metal content; (3) to expand the autopsy retrieval program to characterize not: only the systemic distribution of particulate wear debris but also the tissue metal levels and the cellular localization; and (4) to conduct bioavailability and bioreactivity studies of circulating metal-protein complexes which result from corrosion and wear of joint replacement components.

描述（由申请人提供）：人们越来越认识到，从长远来看，全关节置换术（TJR）可能与由假体材料的降解产物介导的不利的局部和远端组织反应相关。由于已知构成植入合金的金属元素具有毒性，因此人们对 TJR 的金属降解产物特别感兴趣。在这项长期研究中，对 TJRs hab 患者的金属释放、运输、储存和排泄进行了调查。在目前的资助期内，已经证明：(1) 在功能良好的全髋关节和膝关节置换术后长达 84 个月的个体中，可以检测到血清 Ti、Co 和 Cr 的升高； (2) 在金属对金属轴承的患者中观察到最高的 Cr 和 Co 水平； (3)大孔涂层钴基合金股骨柄的被动溶解不是金属释放的主要模式；相反，股骨组件在模块连接处的微动腐蚀与血清 Cr 的升高更为密切相关； (4) 在 TJR 和血清金属浓度升高的患者中，发现两个分子量范围与 Cr 结合（约 70 kD 和约 180 kD），而单个分子量范围（约 70 kD）与 Ti 结合； (5) 在全髋关节置换术失败的修复手术后，循环金属水平降低，但在修复后 60 个月内仍长期保持升高状态； (6) 钴合金和钛合金颗粒降解产物通常来自轴承表面以外的来源，通常会扩散到主动脉旁淋巴结、肝脏和脾脏，特别是在 TJR 失败的个体中； (7) 金属降解产物的生物反应性由其理化性质和蛋白质加合物决定：含 Cr 的 180 kD 金属-蛋白质复合物在这些研究中最具刺激性。该提案通过解决以下具体目标扩展了这些发现：(1) 量化术后 10 至 15 年的前瞻性主要 THR 研究组中的金属释放，在此期间与植入物相关的并发症更为普遍； (2) 对接受钴合金金属对金属髋关节置换术的患者进行前瞻性随访，以确定金属过敏的患病率与血清和尿液金属含量的相关性； (3) 扩大尸检检索程序，不仅可以表征颗粒磨损碎片的全身分布，还可以表征组织金属水平和细胞定位； (4) 对因关节置换部件的腐蚀和磨损而产生的循环金属-蛋白质复合物进行生物利用度和生物反应性研究。