髋假体置入后假体周围松动骨质的病理学变化

背景：磨损颗粒是导致假体周围骨质溶解的重要潜在性因素之一,但引起假体周围骨溶解的原因及其发展过程尚未完全清楚。 目的：复习人工关节置换后翻修病例的病理切片,分析病理检查在人工关节置换后感染诊断中的价值。 方法：由第一作者检索1990/2008 PubMed数据及万方数据库有关髋假体置入后假体周围松动以及假体松动周围骨质的病理学变化方面的文献。 结果与结论：人工假体与骨空隙的产生导致界膜充填,磨损微粒刺激界膜释放炎性细胞因子导致骨溶解而出现假体松动,如果尽可能地减少活动中产生的磨损碎屑可减少炎性递质的释放;减少由充填性界膜向溶骨性界膜的转变,就可从生物学角度降低人工髋关节置换后假体松动的发生率。     

磨损颗粒引起人工关节无菌性松动的研究与进展

背景：研究显示磨损颗粒诱导的假体周围骨溶解是导致人工假体无菌性松动的最主要原因。 目的：对磨损颗粒引起人工关节假体无菌性松动在分子生物学方面的研究现状及新进展作一综述。 方法：应用计算机检索CNKI和Pubmed数据库中1991年1月至2012年3月关于人工关节磨损颗粒的文章,在标题和摘要中以“关节置换,磨损颗粒,假体松动”或“arthroplasty,wear particles,loosening of the prosthesis”为检索词进行检索。最终选择30篇文献进行综述。 结果与结论：假体无菌性松动是人工关节置换后手术失败的最主要原因,在此过程中磨损颗粒起到关键性作用。通过对细胞因子及信号传导途径研究的综述,为预防及药物治疗假体无菌性松动提供理论依据。然而,假体的无菌性松动受多种因素的影响,所以预防应从整体着眼,全面深入研究,为假体的松动防治提供方向。     

磨损颗粒与人工关节无菌性松动

人工关节无菌性松动是影响人工关节长期使用和妨碍人工关节发展的最重要的并发症。许多研究表明,人工关节无菌性松动与假体磨损有着密切关系。磨损颗粒的产生及其所诱发的一系列生物反应是导致假体周围骨溶解及假体无菌性松动的重要因素,其中巨噬细胞、成纤维细胞释放的骨吸收介质和成骨细胞的功能抑制可能是假体无菌性松动发生的重要机制。本文就近年来有关磨损颗粒与人工关节无菌性松动机制的一些研究进展进行综述     

磨损颗粒与人工关节无菌性松动

人工关节无菌性松动是影响人工关节长期使用和妨碍人工关节发展的最重要的并发症。许多研究表明,人工关节无菌性松动与假体磨损有着密切关系。员颗粒的产生及其所诱发的一系列生物反应是导致假体周围骨溶解及本无菌性松动的重要因素,其中巨噬细胞,成纤维细胞释放的骨吸收介质和成骨的功能抑制可能是假体无菌性松动性的重要机制。本语文就近年来有关磨损颗粒与人工关节无菌性松动机制的一些研究进展进行综述。     

人工髋关节无菌性松动失效的生物力学分析与诊断推理

目的研究人工髋关节置换术后无菌性松动失效的力学机理以及引发松动的具体原因,提出对临床中发生无菌性松动事件进行失效诊断的具体方法。方法从骨水泥层强度、界面微动、应力遮挡、磨损与骨溶解等生物力学角度对无菌性松动的成因进行研究,分析无菌性松动失效与产品、临床和患者等因素的关系,并研究翻修术前检测松动的方法。结果提出无菌性松动失效原因推理路线图,成功利用荧光透视分析(fluoroscopic analysis,FSA)技术在翻修术前对无菌性松动进行了在体测定。结论无菌性松动失效分析推理路线图可以帮助展开失效事件的原因挖掘,应用FSA方法可以对松动进行在体测定与确认,辅助医生开展人工髋关节置换术后无菌性松动失效的诊治。     

髋假体高分子聚乙烯磨损的研究进展

人工髋关节假体的磨损不仅能造成关节假体本身的破坏而引起机械性失败，还能产生大量磨损颗粒(wear debris)诱导假体周围骨溶解(osteolysis)。无菌性松动的病例行翻修手术时，在骨与假体之间可见一层纤维结缔组织-界膜(interface membrane)。1983年Goldring等首先对其进行了描述，并证实该界膜组织具有产生骨吸收因子PGE2和胶原酶的能力。     

人工髋关节置换术假体固定与骨溶解的研究

目的探讨人工髋关节置换术后假体的固定与骨溶解之间的关系,以减少术后假体无菌性松动.方法选取我院2005年3月~2011年11月人工关节无菌性松动行髋关节翻修术者28例30髋.首次行全髋关节置换术10髋,年龄38~80岁,平均66岁.分别将金属头与金属臼组合、金属头与高分子聚乙烯臼组合、陶瓷头与高分子聚乙烯臼组合、首次行全髋关节置换术者,设为A、B、C、D四组,每组10髋.手术中取假体周围磨损颗粒及周围各组织,组织学观察成骨情况,颗粒分布及其周围的组织细胞学反应.采用计算机图像分析在OLYMPUS-BX51镜下将组织切片分成若干个视野,测量每个视野中小梁骨面积﹙bone area, BA﹚和该视野组织总面积﹙total tissue area , TTA﹚,并计算BA/TTA比值.所得数据在各处理组间进行比较,以方差分析法作显著性检验﹙a=0.05﹚.结果A、B、C组与D组之间有显著性差异﹙P<0.05﹚,说明A、B、C组均明显抑制周围网织骨形成,并有以巨噬细胞为主的炎症反应及纤维组织大量增生.结论人工髋关节置换后无菌性松动及假体周围磨损颗粒除可激活巨噬细胞为主的炎症产生骨溶解外,还可抑制网织骨形成.其造成的人工髋关节假体—骨界面骨重建障碍可能是骨吸收增加和骨形成减少协同作用的结果.这可能是磨损颗粒刺激下细胞因子介导的骨—假体界面骨代谢异常在人工髋关节无菌性松动中发挥重要作用的关键所在.     

人工关节无菌性松动的早期诊断

背景：人工关节无菌性松动是影响关节假体寿命最主要的因素。 目的：旨在探讨人工关节无菌性松动的早期诊断方法,以利于开展积极的早期治疗。 方法：由第一作者应用计算机检索PubMed、中国期刊全文数据库(CNKI)、维普数据库和万方数据库 1997-05/2010-10相关文献。在标题、摘要、关键词中以“aseptic loosening,artificial joint,prosthesis,osteolysis,early diagnosis”或“无菌性松动,人工关节,假体,骨溶解,早期诊断”为检索词进行检索。选择文章内容与假体无菌性松动有关者,同一领域文献则选择近期发表在权威杂志文章。初检得到182篇文献,根据纳入标准选择关于假体无菌性松动分析及处理的39篇文献进行综述。 结果与结论：假体无菌性松动和骨溶解与骨代谢异常和炎症反应之间的关系密切,所以骨代谢相关指标和磨损颗粒诱导炎症反应的相关细胞因子都可用于早期诊断;核素示踪剂不仅能显示组织器官形态,而且通过显示器官或组织的生理与生化过程来反映组织器官的功能,可早于影像学数周甚至数月发现病变。     

中药淫羊藿苷干预人工关节磨损微粒诱导的骨溶解

背景：人工关节周围产生骨溶解是关节松动失败的重要原因,各国学者都在寻求一种能有效抑制骨溶解反应的药物,以减少假体松动的发生。 目的：观察不同剂量淫羊藿苷干预人工关节磨损微粒诱导骨溶解的效果。 方法：将钛合金及骨水泥磨损微粒制成的混悬液分别置入清洁小鼠颅盖骨进行骨溶解建模后,空白组滴入生理盐水到颅盖骨中,药物干预组给予不同浓度的淫羊藿苷(剂量分别为30,60,120 mg/kg)灌胃,每日1次。建模2周后处死小鼠,在显微镜下观察小鼠颅盖骨的结构。经苏木精-伊红染色和免疫组化分析计算破骨细胞数量和小鼠颅盖骨溶解面积的变化。 结果与结论：与空白组比较,钛合金微粒和骨水泥微粒建模后的小鼠颅盖骨切片上的骨溶解陷窝数量及破骨细胞数明显增加,图像分析骨溶解陷窝面积也增大(P < 0.05)。淫羊藿苷干预后骨溶解面积减小及破骨细胞数量减少  (P < 0.05),以120 mg/kg灌胃组最为显著,其次是60 mg/kg,30 mg/kg。结果可见钛磨损微粒和骨水泥磨损微粒能促进破骨细胞的增殖,诱导骨溶解;淫羊藿苷能抑制磨损微粒诱导的破骨细胞形成,从而抑制骨溶解。中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程全文链接：     

人工关节置换术后假体周围组织的病理学认识及评估

金属人工关节置换术主要的并发症为假体松动,翻修中的假体周围组织由于是非肿瘤性病变,学界对其病理组织形态与临床组织不良反应相关性的关注较少。本文对假体周围组织进行全面且细致的分析,对感染病例探讨术中冷冻及常规石蜡两种方法的诊断价值,分析二者对临床感染诊断的提示意义。对无菌性假体周围组织进行详细的分类描述,包括:滑膜上皮、淋巴细胞、组织细胞及磨损颗粒的分级半定量评估。通过各种无菌性淋巴细胞为主型血管炎评分系统对假体周围组织进行综合评分,从而对人工关节置换术后关节翻修术假体周围组织的评估标准化,为临床人工关节置换术后关节翻修术的评价提供相关的依据。     

Contributions of human tissue analysis to understanding the mechanisms of loosening and osteolysis in total hip replacement

Aseptic loosening and osteolysis are the most frequent late complications of total hip arthroplasty (THA) leading to revision of the prosthesis. This review aims to demonstrate how histopathological studies contribute to our understanding of the mechanisms of aseptic loosening/osteolysis development. Only studies analysing periprosthetic tissues retrieved from failed implants in humans were included. Data from 101 studies (5532 patients with failure of THA implants) published in English or German between 1974 and 2013 were included. “Control” samples were reported in 45 of the 101 studies. The most frequently examined tissues were the bone–implant interface membrane and pseudosynovial tissues. Histopathological studies contribute importantly to determination of key cell populations underlying the biological mechanisms of aseptic loosening and osteolysis. The studies demonstrated the key molecules of the host response at the protein level (chemokines, cytokines, nitric oxide metabolites, metalloproteinases). However, these studies also have important limitations. Tissues harvested at revision surgery reflect specifically end-stage failure and may not adequately reveal the evolution of pathophysiological events that lead to prosthetic loosening and osteolysis. One possible solution is to examine tissues harvested from stable total hip arthroplasties that have been revised at various time periods due to dislocation or periprosthetic fracture in multicenter studies.     

Effects of proteasome inhibitors on cytokines,metalloproteinases and their inhibitors and collagen type-I expression in periprosthetic tissues and fibroblasts from loose arthroplasty endoprostheses

ABSTRACT

Objective: Aseptic loosening is a major problem in total joint replacement. Implant wear debris provokes a foreign body host response and activates cells to produce a variety of mediators and ROS, leading to periprosthetic osteolysis. Elevated ROS levels can harm proteasome function. Proteasome inhibitors have been reported to alter the secretory profile of cells involved in inflammation and also to induce ROS production. In this work, we aimed to document the effects of proteasome inhibitors MG-132 and Epoxomicin, on the production of factors involved in aseptic loosening, in periprosthetic tissues and fibroblasts, and investigate the role of proteasome impairment in periprosthetic osteolysis.

Materials and methods: IL-6 levels in tissue cultures were determined by sandwich ELISA. MMP-1, -3, -13, -14 and TIMP-1 levels in tissue or cell cultures were determined by indirect ELISA. Results for MMP-1 and TIMP-1 in tissue cultures were confirmed by Western blotting. MMP-2 and MMP-9 levels were determined by gelatin zymography. Gene expression of IL-6, MMP-1,-3,-14, TIMP-1 and collagen type-I was determined by RT-PCR.

Results: Results show that proteasome inhibition induces the expression of ΜΜΡ-1, -2, -3, -9 and suppresses that of IL-6, MMP-14, -13, TIMP-1 and collagen type I, enhancing the collagenolytic and gelatinolytic activity already present in periprosthetic tissues, as documented in various studies.

Conclusions: These findings suggest that proteasome impairment could be a contributing factor to aseptic loosening. Protection and enhancement of proteasome efficacy could thus be considered as an alternative strategy toward disease treatment.     

Chronic antigen-specific immune-system activation may potentially be involved in the loosening of cemented acetabular components

Previous studies have attempted to determine whether aseptic loosening and osteolysis are caused by a T cell-mediated type IV hypersensitivity reaction or a nonspecific foreign body reaction involving phagocytic macrophages. The purpose of this study was to examine the role of the B7-CD28 costimulatory pathway (which is indicative of an activated immune response) in loosening and osteolysis of total joint replacements (TJRs). We harvested periprosthetic tissues from 24 loose, cemented, all polyethylene, acetabular components in patients undergoing revision total hip replacement surgery for aseptic loosening. Prostheses were classified radiographically as to whether ballooning, scalloping osteolysis was present or not. Monoclonal antibodies were used to identify macrophages, antigen presenting cells (APCs) expressing B7-1 or B7-2, total T lymphocytes, and T cells expressing CD28 or CTLA-4. The large numbers of positive cells, including macrophages, T cells, and APCs in both groups are substantially higher than previously reported. Macrophages constituted the predominant cell type, the majority of which were APCs. B7-1 was expressed by 18.3% of all cells, and B7-2 was expressed by 61.0% of cells. Despite the fact that there were no statistically significant differences in expression of proteins in the B7-CD28 pathway between the osteolytic and nonosteolytic groups, the magnitude of positive staining suggests that the process of aseptic loosening (not osteolysis) may involve proteins of the B7-CD28 pathway, particularly B7-2. One possible antigenic stimulus is protein-coated particulate wear debris from prosthetic materials.     

Protein expression of MMP-13, uPA, and PAI-1 in pseudocapsular and interface tissue around implants of loose artificial hip joints and in osteoarthritis

Matrix metalloproteinase 13 (MMP-13), urokinase type plasminogen activator (uPA), and plasminogen activator inhibitor type-1 (PAI-1) have been reported to be involved in aseptic loosening of artificial hip joints. This study for the first time presents the protein levels of all of these factors in synovial-like interfaces between bone and prosthesis and in pseudocapsular tissues surrounding the artificial joint in patients with aseptic loosening (n=17) measured by ELISA. No differences were observed in the antigen expression of MMP-13, uPA, and PAI-1, comparing interface and pseudocapsular tissue. Also, no significant correlation between the protein expression of these factors and years from arthroplasty to revision or to type of fixation (cemented vs. cementless) was observed. As control, MMP-13, uPA, and PAI-1 antigen levels were also determined in the synovium of patients with osteoarthritis (n=10). Yet, the antigen levels of MMP-13, uPA, and PAI-1 in tissue specimens from patients with aseptic loosening of artificial hip joints were significantly higher compared to their expression in synovial capsular tissues obtained from patients with osteoarthritis. In conclusion, this study shows that elevated protein levels of uPA, PAI-1, and MMP-13 in periprosthetic pseudocapsular and interface tissues from patients after total hip replacement due to aseptic loosening seem not to be associated with the patient outcome.     

人工关节假体植入后无菌性松动的发病机制

背景：对于人工关节无菌性松动的基础和临床研究很多,但其确切机制仍不甚明确。 目的：综述人工关节假体植入后无菌性松动的发病机制。 方法：由第一作者应用计算机检索PubMed和中国期刊全文数据库2006/2011相关文献。在标题、摘要、关键词中以“artificial prosthesis,aseptic loosening”或“人工关节、无菌性松动”为检索词进行检索。共检索到77篇文献,最终纳入符合标准的文献38篇。 结果与结论：无菌性松动已成为人工关节置换后远期失败的主要原因之一。近年来对人工全髋关节置换后翻修病例回顾性分析的统计显示,无菌性松动位于翻修原因第1位。关于人工关节无菌性松动的机制主要分为机械机制、生物机制及其他机制,它们的共同结果是造成骨吸收、骨溶解,最终导致假体松动。随着研究的进一步深入,以及植入方式及假体材料的不断改进,无菌性松动将最终被最小化,使假体使用寿命更长久。