Supraphysiologic Fluid Shear Stress as an Alternative Cause of Short-term Aseptic Loosening in Total Knee Replacements

超生理流体剪切应力是全膝关节置换术中短期无菌性松动的另一个原因

基本信息

批准号：
9115459
负责人：
Karen I Cyndari
金额：
$ 3.5万
依托单位：
UPSTATE MEDICAL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-01 至 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9115459
关键词：
Address Affect Arthritis Autopsy Biological Factors Biology Bone Cements Bone Resorption Cell Count Cell Line Cells Client satisfaction Clinical Coculture Techniques Complement Complex Deposition Devices Disease Economic Burden Environment Failure Funding Gene Expression Goals Human Immigration Implant In Vitro Investigation Joints Knee Knowledge Link Liquid substance Location Marrow Mechanics Mediating Medicare Minerals Morbidity - disease rate Operative Surgical Procedures Osteoblasts Osteoclasts Osteolysis Pain Patients Physiological Polarization Microscopy Polyethylenes Procedures Process Pump Replacement Arthroplasty Research Retrieval Services Surface Synovial Fluid System Testing Time United States Work base bone economic cost experience fluid flow improved in vitro activity joint loading joint mobilization knee pain knee replacement arthroplasty meetings particle prevent public health relevance research study response sample fixation shear stress standard of care substantia spongiosa success

项目摘要

DESCRIPTION (provided by applicant): Cemented Total Knee Replacement (TKR) is an established and reliable procedure that seeks to restore joint mobility and relieve pain associated with rheumatoid or osteo-arthritis. While over 600,000 knees are implanted with great success annually, a substantial portion (~15%) fail prematurely. Most long-term failures are due to a process known as aseptic loosening, where the mechanical interlock between trabecular bone and cement weakens due to the erosion (osteolysis) of bone. This allows the implant to migrate and become painful, necessitating a revision surgery. Aseptic loosening is most often attributed to osteolysis caused by the body's response to articulating surface polyethylene (PE) wear accumulation at the implant-bone interface. Importantly, short-term failures can and do occur, and these may not be related to PE debris since the amount of debris created is proportional to time in service. Recent studies of postmortem retrieved, clinically- successful, human TKRs point to an additional, contributing factor in aseptic loosening: in the short-term, there is >50% resorption of the trabeculae that initially interlock with the bone cement, but this occurs without much wear to the PE articulating surface. This suggests early loss of fixation is caused by an alternate mechanism. In the postmortem studies, it was observed that when joint loads are applied to the TKRs, synovial fluid and/or marrow is pumped through small gaps between the interlocked trabeculae and cement. The fluid shear stresses (FSS) generated from the fluid pumping is estimated to be supraphysiologic, and will likely have an effect on the osteoblasts and osteoclasts that line the surface of trabecular bone. The overall goal of this study is to show that these supraphysiologic fluid shear stresses are sufficient to cause resorption of the trabeculae that interlock with cement, and that this can occur without PE debris. The Specific Aims of this project are to show: 1) trabecular resorption at the interface occurs in the absence of PE debris, 2) supraphysiologic FSS can affect resorption by increasing osteoclast activity (mineral resorption) while decreasing osteoblast activity (mineral deposition), and 3) PE debris accumulation and supraphysiologic FSS act in concert to produce more resorption than either process alone. We will first identify the location and amount of PE debris at the cement-bone in postmortem retrieved, clinically successful, human tibial components of TKA with short term (<5 years) and long term (>10 years) use. We expect short-term devices to contain little to no wear at the interface, but have extensive bone resorption. In contrast, we expect long-term devices to have both substantial PE wear and resorption. Next, we will elucidate the effects of FSS ranging from sub to supraphysiologic levels on in vitro cell lines of osteoclasts and osteoblasts, with or without PE debris. These experiments will allow us to first, quantify PE debris in direct, physical relation to the cement-trabeculae interface of retrievals, and second, differentiate the effects of high FSS from PE debris. Overall, the goal of this work is to extend the long-term success of TKRs.

描述（由申请人提供）：骨水泥全膝关节置换术 (TKR) 是一种既定且可靠的手术，旨在恢复关节活动性并缓解与类风湿或骨关节炎相关的疼痛，虽然每年有超过 600,000 个膝关节植入并取得了巨大成功，但其中有相当多的人获得了成功。部分（~15%）过早失效。大多数长期失效是由于无菌松动的过程造成的，即骨小梁和骨水泥之间的机械互锁。由于骨骼侵蚀（骨质溶解）而减弱，这使得植入物移位并变得疼痛，需要进行修复手术。无菌性松动通常是由于身体对关节表面聚乙烯（PE）磨损累积的反应引起的骨质溶解。重要的是，短期故障可能并且确实发生，并且这些可能与 PE 碎片无关，因为产生的碎片量与死后回收的、临床上成功的、使用时间成正比。人类 TKR 指出了无菌性松动的另一个影响因素：短期内，最初与骨水泥咬合的小梁有 >50% 的吸收，但这种情况的发生对 PE 关节表面没有太大磨损。在尸检研究中，观察到当关节负载施加到 TKR 上时，滑液和/或骨髓会通过 TKR 之间的小间隙泵出。流体泵送产生的流体剪切应力（FSS）估计是超生理的，并且可能对小梁骨表面的成骨细胞和破骨细胞产生影响。表明这些超生理流体剪切应力足以引起与骨水泥联锁的小梁的吸收，并且这可以在没有 PE 碎片的情况下发生。表明：1）界面处的小梁吸收在没有 PE 碎片的情况下发生，2）超生理 FSS 可以通过增加破骨细胞活性（矿物质吸收）同时降低成骨细胞活性（矿物质沉积）来影响吸收， 3) PE 碎片积累和超生理 FSS 协同作用，比单独任何一个过程产生更多的吸收。我们将首先在尸后回收的、临床上成功的 TKA 人类胫骨组件中确定 PE 碎片在水泥骨上的位置和数量。短期（<5 年）和长期（>10 年）使用，我们预计短期装置在界面处几乎没有磨损，但会出现广泛的骨吸收，相反，我们预计长期装置会有磨损。两个都接下来，我们将阐明 FSS 从亚生理水平到超生理水平对体外破骨细胞和成骨细胞系的影响，无论有或没有 PE 碎片，这些实验将使我们能够首先直接量化 PE 碎片。，与回收的骨水泥-小梁界面的物理关系，其次，区分高 FSS 与 PE 碎片的影响总体而言，这项工作的目标是。延长 TKR 的长期成功。