磨损颗粒诱导假体无菌性松动的研究现状

关节置换是临床上治疗终末期关节疾病及老年性股骨颈骨折最常用有效的治疗方法。然而,关节置换病例数目的增加和术后患者使用时间的延长,假体松动成为日益突出的术后并发症[1]。研究表明,无论是髋关节还是膝关节翻修,一半以上都是由假体无菌性松动引起的[2]。目前认为,磨损颗粒诱导的假体周围骨溶解是导致关节无菌性松动的一个最为重要的原因[3]。无菌性松动的本质是机体产生的一种慢性肉芽     

髋关节假体周围微环境与无菌性松动

无菌性松动是髋关节置换术后最常见的远期并发症之一,也限制了关节假体的使用寿命.近年研究表明,假体周围骨溶解是引起关节假体松动的最主要原因.骨水泥型假体、非骨水泥型假体都可发生类似现象.目前认为多种因素参与了骨溶解的发生和发展.该文就髋关节假体周围的物理学和生物学微环境与髋关节置换术后无菌性松动的关系作一综述.     

假体周围骨质溶解细胞分子生物学研究

关节置换术后假体磨损是导致假体周围骨质溶解和假体无菌性松动的主要原因,也是导致关节置换术失败的主导因素.假体磨损颗粒主要作用的靶细胞是巨噬细胞、破骨细胞前体细胞,此外还可能包括成骨细胞、、淋巴细胞等.引起的分子反应包括活化丝裂原蛋白激酶信号转导途径的激活、某些转录因子(如NF-κB)及一些细胞信号抑制因子的激活,导致了促炎症反应的发生和加剧,抑制了一些抗破骨细胞生成的细胞因子(如干扰素-γ)的保护作用.目前对假体周围骨质溶解的研究已转向相关细胞信号转导途径及分子生物学机制的研究,一些研究成果如抑制促炎症反应因子(如TNF-α)和破骨细胞激活及增殖的作用已在动物模型上得到验证,但现阶段对假体周围骨质溶解还没有有效的治疗方法.该文就近年来假体周围骨质溶解细胞分子生物学研究作一系统性综述,并总结不足,以待发现新的研究方向.     

无菌性松动全髋关节假体周围界膜组织中Caspase-3表达和细胞凋亡的研究

目的观察无菌性松动全髋关节假体周围界膜中凋亡调控蛋白Caspase-3表达和细胞凋亡分布的变化,探讨其与假体周围骨溶解之间的关系。方法2001年4月～2006年8月临床上选取16例高分子聚乙烯-金属配伍全髋关节翻修术的患者,其中男10例,女6例;初装年龄45～67岁,翻修年龄55～78岁,使用时间7～13年。根据术前X线片和术中所见,分为松动/非骨溶解组和松动/骨溶解组,每组各8例,取出假体周围各区的假体-骨间界膜组织。另取6例初装人工全髋关节的骨性关节炎患者作为对照组,其中男2例,女4例;年龄54～68岁,病程9～15年;采用免疫组织化学法检测界膜组织中Caspase-3的表达,末端标记法原位检测细胞凋亡,分析并比较Caspase-3和细胞凋亡的阳性表达和分布,与磨损颗粒的局部聚积和骨溶解程度的关系。结果高分子聚乙烯磨损颗粒局部聚积区的Caspase-3阳性细胞率和细胞凋亡指数明显高于金属磨损颗粒;重度磨损细胞凋亡指数高于轻度磨损,差异有统计学意义(P<0.05);松动/骨溶解组Caspase-3阳性细胞率和细胞凋亡指数明显高于松动/非骨溶解组和对照组,差异有统计学意义(P<0.01)。结论假体周围界膜组织Caspase-3的表达和细胞凋亡具有一定规律性,并与磨损微粒的局部聚积和骨溶解程度密切相关,可能是磨损颗粒造成界面骨重建受阻而溶骨大量发生的关键环节之一;细胞凋亡参与了假体无菌性松动的病理过程,且与Caspase-3信号激活有关。     

髋关节置换后假体无菌性松动机制研究

髋关节置换包括全髋和半髋置换,是治疗髋关节严重病损的有效手段,但假体松动作为术后晚期出现的并发症是手术失败的主要原因.早期假体松动归因于应力遮挡引起的骨质重新塑形,晚期假体松动的原因主要是假体微动和磨损碎屑诱导骨溶解.近年研究发现假体松动与运动后假体摩擦产热、吸烟、滑液中IGF-I水平等有关.该文就近几年关于髋关节置换后假体发生无菌性松动的可能发生机制作一综述.     

假体周围生物学微环境与无菌性骨溶解

人工关节置换术是治疗各种终末期关节疾病和老年股骨颈骨折的一种有效的外科手段,能够达到解除关节疼痛、提高患者生活质量的效果,然而人工假体周围发生无菌性骨溶解作为导致人工关节晚期失败的一个主要原因,是始终困扰广大骨科医生的一项重要课题.     

内毒素与人工关节无菌性松动

越来越多的体内外实验提示内毒素在人工关节松动方面起着重要的作用.内毒素与磨损颗粒在很多方面具有相似的作用机制,内毒素可能在磨损颗粒诱导骨溶解的同时发生相互协同作用.该文就内毒素对人工关节无菌性松动的影响作一简要综述.     

人工关节无菌性松动的防治研究进展

从20世纪60年代初,Charley[1]首先采用低磨损人工髋关节置换术到现在,人们对人工关节无菌性松动的发病机理和防治进行了不懈的探索。大家较一致地认为:微动、应力遮挡等机械性因素,磨损颗粒引起的假体(或骨水泥)、骨界面产生的IL1β、IL6、TNFα、PGE2、MCSF、RANKL[2]、和Casp     

人工关节无菌性松动诊断标志物研究进展

影响人工关节中远期使用寿命的无菌性松动最常见的原因是假体周围骨溶解.假体松动的诊断对于有明显临床症状和假体周围骨溶解影像学征象的患者并不困难.但对没有临床症状却也可能存在假体松动和骨溶解的患者.就需要更多灵敏而特异的标志物帮助建立诊断.影像学方法 可直观评估假体周围骨和软组织情况.确定骨溶解区域或炎症反应区域的位置和范围.而很多反映假体磨损或骨代谢的生化因子可间接提示磨损和假体周围骨溶解改变,这两方面研究均有助于确立诊断.对人工关节无菌性松动的诊断相关研究,既可加深对假体松动的认识,又有助于指导及时的临床治疗和疗效评估.     

Markers of connective tissue activation in aseptic hip prosthetic loosening

The fundamental role played by macrophages and fibroblasts of the synovial-like membrane in aseptic hip prosthesis loosening (AHPL) has recently been confirmed by numerous studies. In this study, the activity of these cells in patients with prosthetic loosening was analyzed by evaluating the main markers of fibroblast and macrophage activation in sera and in supernatants of cultured fibroblasts obtained from AHPL patients who underwent revision of a loose total hip arthroplasty implant. In these patients interleukin-I, hyaluronic acid (HA), and type III procollagen peptide were evaluated. The results were compared with those obtained in 13 patients with firmly fixed implants and 13 patients with osteoarthritis. Serum HA levels were significantly higher (779.3 ± 951.6 μg/L) in patients with AHPL as compared with patients with firmly fixed implants (112.9 ± 84.9 μg/L) and osteoarthritis (115.3 ± 107.8 μg/L). Type III procollagen peptide levels were elevated in only 33.3% of patients with AHPL, whereas interleukin-1-beta (IL-1β) was detectable in 4 patients with AHPL but not in patients with firmly fixed implants or osteoarthritis. In supernatants, IL-1β was measurable in 4 of 6 fibroblast cultures, whereas type III procollagen peptide and HA were measurable in all cultures. The data confirm the existence of an inflammatory process in AHPL patients in which macrophages and fibroblasts play a key role. The detection, in these patients, of high circulating levels of IL-1β and HA is very important from a clinical point of view because they could be considered specific markers of inflammation.     

Mechanisms of cellular recruitment in aseptic loosening of prosthetic joint implants

The association of macrophages engaged in polymethylmethacrylate (PMMA) particle phagocytosis with pockets of inflammatory cells is a pathognomonic feature of the aseptically loose interface not present at the well-fixed interface. The mechanism by which the presence of PMMA particles leads to cellular recruitment, bone resorption, and ultimate loosening is poorly understood. Granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin 6 (IL-6), cytokines released by osteoblasts, stimulate the recruitment of macrophages into sites of inflammation. We show that exposure of macrophages to PMMA particles stimulated release of tumor necrosis factor (TNF), but no increase in prostaglandin E2 (PGE-2) or interleukin 1. Incubation of osteoblasts with conditioned medium from macrophages exposed to PMMA particles led to release of GMCSF, IL-6, and PGE-2. Incubation of the PMMA/macrophage medium with antibodies to TNF prior to osteoblast exposure inhibited release of GM-CSF, IL-6, and PGE-2 by the osteoblasts. Our data demonstrate that exposure of macrophages to PMMA particles leads to the release of TNF which then stimulates osteoblasts to produce GMCSF, IL-6, and PGE-2. Based upon the results of this study, we propose that the process of cellular recruitment in aseptic loosening is initiated when the mechanical failure of the cement mantle leads to the production of PMMA particles. These particles are phagocytized by macrophages leading to the production of TNF. TNF stimulates surrounding osteoblasts to produce GM-CSF, IL-6, and PGE-2 which leads to recruitment of macrophages and osteoclasts into the area of the bone-cement interface. The recruitment of these cells potentiates this process leading to bone resorption and ultimately, clinical loosening of prosthetic joint implants.     

Limited influence of prosthetic position on aseptic loosening of elbow replacements

Background?Aseptic loosening of elbow replacements, seen in long-term follow-up, remains a problem. In this study, we attempted to determine the influence of cementing technique, prosthetic position, different component sizes, use of a bone plug, and intraoperative fractures on the development and progression of radiolucent lines and aseptic loosening.

Methods?We studied standard radiographs of 125 primary Souter-Strathclyde total elbow prostheses using the Wrightington method. Additionally, 104 preoperative radiographs were available for analysis. We used a Markow statistical model to detect relationships between all factors described above.

Results?After a mean follow-up time of 5.5 (2–19) years, 21 (17%) prostheses had loosened radiographically (10-year survival: 65%). When the humeral component was tilted more medially or more anteriorly, we found development of radiolucent lines at the medial condyle and at the posterior side of the humeral component. However, the progression of these lines was not influenced by these positions. No other prognostic factors for radiolucent lines or aseptic loosening were found.

Interpretation?Despite the small number of elbows studied, the weak influence of prosthetic position on aseptic loosening gives more ground for a multifactorial cause for aseptic loosening of the Souter-Strathclyde total elbow prosthesis.     

肿瘤型假体无菌性松动翻修术后疗效观察

目的探讨采用普通长柄假体或同种异体骨假体复合物(allograft-prosthesis composite,APC)翻修治疗肿瘤型假体无菌性松动的疗效。方法 2002年1月-2008年6月,收治14例肿瘤型假体无菌性松动患者。男8例,女6例;年龄21～70岁,平均43.9岁。肿瘤部位:股骨远端8例,股骨近端2例,胫骨近端4例。假体置换术后6～31年出现患肢疼痛,负重和行走时加重;6例出现患肢短缩畸形。术前参照美国骨与软组织肿瘤协会(MSTS)功能评分系统行关节功能评分为(16.36±1.50)分。X线片检查见假体明显松动和下沉。出现症状至入院时间为3～9年,平均4.5年。7例骨量严重丢失(骨皮质厚度减少>50%)、假体下沉>2 cm、假体穿破骨皮质或即将穿破骨皮质者采用APC翻修;7例骨量丢失不严重(骨皮质厚度减少<50%)者,采用订制普通长柄假体翻修。结果患者切口均Ⅰ期愈合;2例出现腓总神经一过性麻木,对症治疗后3个月内恢复。患者术后均获随访,随访时间2年2个月～7年,平均3.6年。翻修术后患者术前疼痛症状均缓解,关节功能改善。术后12个月MSTS功能评分为(23.43±2.56)分,与术前比较差异有统计学意义(t=8.910,P=0.024)。X线片检查示,术后12个月2例采用普通长柄假体翻修患者出现骨水泥周围无症状透亮线,无假体松动和周围感染等并发症;其余患者未见明显异常。结论肿瘤型假体无菌性松动后再次行翻修重建肢体功能可行,根据患者骨量丢失情况选择APC或普通长柄假体翻修,可获较好疗效。     

人工髋关节置换术后假体无菌性松动的临床及影像学评估

人工髋关节置换术(THA)后假体无菌性松动问题始终是临床上存在并需要解决的问题。通过临床及放射学检查，观察分析假体松动的表现与过程，对于人工髋关节置换术后假体松动的及时临床处理及预防均有指导意义。本对人工髋关节置换术后假体无菌性松动的临床及影像学评估方法进行了回顾和分析，指出临床及各影像学评估方法的意义，提出正确的评估原则。     

趋化因子与人工关节无菌性松动

趋化因子是一类能趋化细胞定向迁移的分泌性蛋白,在多种生理病理过程中起重要作用。在人工关节无菌性松动过程中,趋化因子不仅是人工关节周围炎症反应的主要参与者,还是调节破骨细胞分化成熟的重要因子。深入研究趋化因子与人工关节无菌性松动的关系,有助于为人工关节无菌性松动的防治研究开辟新途径。该文就近年有关趋化因子与人工关节无菌性松动方面的研究作一综述。     

Multiple biomarkers analysis for the early detection of prosthetic aseptic loosening of hip arthroplasty

Purpose

Our aim was to define the effect of multiple biomarkers of osteolysis or bone remodelling in the early detection of aseptic loosening (AL) of total hip arthroplasty (THA).

Method

One hundred subjects were recruited, including 31 candidates for revision THA (Late AL group), 15 patients who had undergone THA and had clinical and radiographic evidence of AL (early AL group), 19 patients with no sign of AL (stable group), and 40 healthy volunteers. Plasma levels of osteoprotegerin (OPG), receptor activator of nuclear factor-kappaB ligand (RANKL), cross-linked N-terminal telopeptide (NTX), procollagen I C-terminal extension peptide (PICP), tumour necrosis factor-alpha (TNF-α), and interleukin (IL)-1β1 were measured using an immunoenzymatic method. The outcomes of biomarkers were analysed separately and synthetically using Revman software.

Results

The plasma level of OPG, RANKL, NTX, TNF-α, and IL-1β declined from late AL, early AL, stable to the healthy group, while the level of PICP inclined reversely. There was a significant difference in synthetic analysis of six biomarkers between the AL group and the stable group, and between the stable group and the healthy group (both p = 0.02). Heterogeneity of six biomarkers in either comparison was extremely low (both I² =0). Patients who had cemented implants had significantly higher levels of TNF-α than patients with cementless varieties (p = 0.042).

Conclusion

There was significant change in the plasma level of multiple biomarkers in patients with prosthetic AL of THA, especially in the cemented arthroplasties and in patients without traditional clinical or radiographic evidence of AL.     

假体周围组织冰冻切片对诊断髋关节假体无菌性松动的特异性分析

[目的]评价冰冻切片对诊断髋关节假体无菌性松动的作用.[方法]回顾分析了57例(63髋)因髋关节无菌性松动行髋关节翻修的病例,将冰冻切片和石蜡切片结果进行病理学分级,将至少5个高倍镜视野、每个高倍镜视野的中性粒细胞数≥5个视为切片结果阳性；以之前文献报道的无菌性松动的诊断标准为参照标准,计算冰冻切片的特异性、符合率.[结果]冰冻切片的特异性为96.8％,冰冻切片和石蜡切片诊断假体无菌性松动时符合率为96.8％.[结论]在全髋关节翻修术中利用组织冰冻切片进行诊断性检查来确定是否存在感染时要注意冰冻切片和石蜡切片的偏差.