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）：越来越多的认识是，从长期来看，总关节置换（TJR）可能与不利的局部和远程组织反应有关，这些反应是由假体材料的退化产物介导的。 TJR的金属降解产物特别感兴趣，因为构成植入合金的金属元素的已知毒性。在这项长期研究中，研究了TJRS HAB患者的金属释放，运输，存储和排泄。在当前的赠款期间，已经证明（1）在术后84个月内长达84个月的髋关节和膝关节替换良好的个体中，血清Ti，CO和CR的升高可以检测到； （2）在金属金属轴承患者中观察到最高的CR和CO水平； （3）从广泛的多孔涂层的共基合金股骨茎中被动溶解不是金属释放的主要模式；相反，模块化连接处的股骨成分的碎腐蚀与血清CR的升高密切相关。 （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结合Cr（在约70 kD和约180 kD时），而单个分子量量范围（约70 kD）被发现以结合Ti； （5）在修订手术后，总髋关节置换术失败，循环金属水平降低，但长期升高到林中后60个月； （6）通常来自轴承表面以外的其他来源的共同和Ti-Aloy颗粒物降解产物，通常将其传播到副淋巴结，肝脏和脾脏，尤其是在失败TJR的个体中； （7）金属降解产物的生物反应性受其“生理化学性质和蛋白质加合物：含CR的180 kD金属蛋白质蛋白复合物的生物反应性是最刺激性的。该提案通过解决以下具体目的来扩展这些发现：（1）量化前瞻性原发性THR研究组中的金属释放，该研究小组将在术后10到15年，这是一个间隔，其中与植入物相关的并发症更为普遍； （2）前瞻性地跟随具有同事金属对金属髋关节置换的患者，以确定金属超敏反应与血清和尿液金属含量相关的患病率； （3）扩大尸检检索程序以不表征：仅颗粒磨损碎片的全身分布，而是组织金属水平和细胞定位； （4）对循环金属 - 蛋白质复合物进行生物利用度和生物反应性研究，这些研究是由关节置换成分的腐蚀和磨损产生的。