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. 人们对金属降解特别感兴趣， 由于已知的金属元素的毒性， 包括植入物合金。 在这项长期研究中，我们 研究患者体内金属的释放、运输、储存和排泄 全髋关节（THR）和全膝关节（TKR）置换术。 在我们的第一笔赠款中 期间，我们已经证明i）钛基托松动的患者 合金THR显示血清钛显著升高 与关节磨损相关的浓度; ii）在某些情况下，这些 高浓度可以比低浓度高一到两个数量级。 对照值; iii）在TKR患者中，髌骨分层 部件和碳纤维增强聚乙烯关节面， 与血清钛显著升高相关; iv）血清钴 水平升高，并与失败的腐蚀程度相关。 组配式股骨THR部件; v）THR功能良好的患者， 在前瞻性随访中，TKR显示血清钛升高 纵向方式;以及vi）在具有功能良好的植入物的患者中， 组织金属含量局部升高， 脾脏、肝脏和局部淋巴结内的金属。 这些发现 综合起来表明，金属释放运输的幅度和 与TJR组件相关的存储容量大于 预期。 我们建议扩大这些研究，以（l）量化金属释放的 术后3 - 8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 普遍;（2）表征局部和全身金属的关联 组配式THR中的浓度和腐蚀组织反应 部件;（3）前瞻性随访翻修手术后 已经证明血清金属含量显著升高， 确定血清金属转运是否随时间减少;和（4）扩大 我们的尸检回收程序不仅能描述组织金属含量 以及微粒磨损碎屑的全身分布， 以及这些降解产物的细胞定位。 这些研究被认为是至关重要的，以了解前瞻性 对接受全关节置换术的患者的风险。

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 the implant alloys. In this long term study, we have been investigating metal release, transport, storage and excretion in patients with total hip (THR) and knee (TKR) replacements. In our first grant period, we have demonstrated that i) patients with loose titanium base alloy THR demonstrate significant elevations in serum titanium concentration that correlate with articular wear; ii) in some cases, these elevated concentrations can be one to two orders of magnitude higher than control values; iii) in patients with TKRs, delaminated patellar components and carbon fiber reinforced polyethylene articular surfaces are associated with dramatic elevations of serum titanium; iv) serum cobalt levels are elevated and correlated to the degree of corrosion in failed modular femoral THR components; v) patients with well-functioning THR and TKR demonstrated elevated serum titanium when followed in a prospective longitudinal manner; and vi) in patients with well-functioning implants, there is local elevation in tissue metal content as will as deposition of metal within the spleen, liver and regional lymph nodes. These findings taken together suggest that the magnitude of metal release transport and storage associated with TJR components is greater than what was anticipated. We propose to expand on these studies to (l) quantify metal release in the prospective study group which will be three to eight years post-operative - an interval in which complications related to the implant are more prevalent; (2) characterize the association of local and systemic metal concentration and tissue reaction with corrosion in modular THR components; (3) prospectively follow patients after revision surgery who have demonstrated significant elevations in serum metal content to determine if serum metal transport diminishes with time; and (4) 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. These studies are deemed critical in order to understand the prospective risks to patients undergoing total joint arthroplasty.