中药防治假体周围骨溶解的研究进展

现如今人工关节置换术越来越多的应用于重建关节功能改善关节疾病患者的生活质量,但是术后并发症严重影响了手术的效果,人工假体周围骨溶解及假体无菌性松动又是人工关节置换术后失败的主要原因之一,所以如何预防以及发病后如何去治疗成为现今关节医生面临的重要课题。OPG/RANKL/RANK系统,炎性因子的产生,破骨细胞、成骨细胞这些都是影响人工假体术后产生无菌性松动,和引发假体周围骨溶解的重要因素,有效药物的干预治疗成为现如今关节置换术后以及围手术期的热门话题,中药因其副作用小,疗效独特,及深入的研究逐渐受到广大医生的注意,因此中药在治疗人工假体松动及骨溶解方面也得到了重大突破,本文从中医肾藏精,精生髓,髓能养骨理论着手总结中药作用于OPG/RANKL/RANK系统,抑制炎性因子、破骨细胞及促进成骨细胞增殖的研究现状。     

二磷酸盐促进假体周围骨溶解后假体翻修骨整合的实验研究

目的:评价阿仑膦酸钠对新西兰大白兔假体周围发生骨溶解后,再进行对新西兰大白兔假体翻修骨整合的影响。方法:选取雄性新西兰大白兔30只,随机分成3组(正常组,实验组,对照组,每组10只)。正常组在胫骨松质骨区域植入钛合金假体,实验组和对照组分别植入钛合金假体和钛颗粒,饲养8周后,三组统一进行假体翻修。实验组用阿仑磷酸钠治疗8周后取材,对照组和正常翻修组也分别进行取材。通过假体推出力学实验、硬组织切片观察,评价阿仑磷酸钠对假体周围翻修后骨整合的影响。结果:假体推出力学实验结果显示,实验组假体最大推出载荷明显大于对照组(P0.01)。硬组织学切片通过苦味酸--品红染色,利用图像分析仪器统计假体周围骨整合的面积实验组假体周围骨量明显优于对照组假体周围骨量(P0.05)。结论:二磷酸盐-阿仑磷酸钠可以提高假体翻修后假体周围骨整合。     

原花青素对磷酸三钙磨损颗粒所致小鼠颅骨溶解的干预作用及其机制

目的:研究原花青素对磷酸三钙(TCP)磨损颗粒诱导小鼠颅骨溶解的保护作用,并探讨其机制。方法:48只雄性ICR小鼠,随机分为假手术(Sham)组、TCP磨损颗粒(TCP)组、原花青素(0.2mg/kg,1mg/kg,5mg/kg)组,每组12只。将TCP磨损颗粒30mg包埋于小鼠颅骨顶部构建假体周围模型,于术后第2日颅顶局部注射原花青素,隔日1次。2周后处死小鼠采血、取颅骨。抗酒石酸酸性磷酸酶(TRAP)染色和HE染色观察假体周围骨溶解和破骨细胞生成情况;实时荧光定量PCR检测假体周围骨组织中破骨细胞调控基因TRAP、capthesinK、c-Fos和NFATc1的mRNA水平;化学比色法检测血清中丙二醛(MDA)和总抗氧化能力(T-AOC)含量及超氧化物歧化酶(SOD)活性;Westernblot法检测小鼠假体周围骨组织中自噬标志蛋白Beclin-1和微管相关蛋白1轻链3(LC-3)表达变化。结果:与Sham组比较,TCP组假体周围骨溶解面积、破骨细胞生成及其调控基因mRNA水平显著增加(P<0.05),血清MDA含量均明显升高、T-AOC水平和SOD活性明显降低(P<0.05),假体周围骨组织中Beclin-1和LC-3均表达显著上调、LC-3I向LC-3II转换明显增加(P<0.05)。与TCP组比较,原花青素组假体周围骨溶解面积、破骨细胞生成及其上述调控基因、血清MDA含量明显减少(P<0.05),血清T-AOC含量和SOD活性显著增加(P<0.05)且Beclin-1和LC-3等蛋白表达及LC-3I向LC-3II转换也明显下调。结论:原花青素对TCP磨损颗粒所致的假体周围骨溶解具有明显保护作用,其机制可能与减轻氧化应激反应和自噬的活化密切相关。     

磷酸三钙磨损颗粒诱导小鼠假体周围骨细胞损伤的作用

目的：研究磷酸三钙（TCP）磨损颗粒是否能诱导小鼠颅骨假体周围骨细胞损伤,并探讨其作用机制。方法：36只雄性ICR小鼠随机分为3组（n=12）：假手术组（Sham）、模型（TCP）组和3-甲基腺嘌呤（3-MA）组,采用TCP磨损颗粒30 mg置于小鼠颅骨中缝骨膜外缝合皮肤构建小鼠颅骨溶解模型。3-MA处理组小鼠于术后第2天颅顶皮下注射自噬的特异性抑制剂3-MA （1.0 mg/kg）,2 d 1次,2周后处死动物取血清和颅骨。Micro-CT分析各组小鼠颅骨骨密度（BMD）、骨体积分数（BVF）和骨吸收孔（porosity）数;HE染色和流式细胞术检测各组假体周围骨细胞活性及凋亡情况;ELISA法检测各组血清中骨细胞特征蛋白牙本质基质蛋白（DMP-1）和骨硬化蛋白（SOST）水平;Western blot法检测各组假体周围骨细胞中DMP-1、SOST和自噬关键分子Beclin-1及微管相关蛋白1轻链3（LC-3）等蛋白的表达。结果：与Sham组比较,TCP组假体周围骨细胞活性明显降低,骨细胞死亡及凋亡显著增加（P<0.05）,血清SOST水平及其蛋白表达明显增加,而血清DMP-1水平及其蛋白表达显著减少（P<0.05）,Beclin-1表达增加,LC-3I向LC-3Ⅱ转换明显增加;与TCP组比较,3-MA组假体周围骨细胞损伤明显加重,骨细胞凋亡显著增加（P<0.05）。结论：TCP磨损颗粒可通过激活凋亡和自噬而诱导假体周围骨细胞损伤,促进假体周围骨溶解和关节无菌性松动。     

新型非骨水泥柄设计特征及临床应用效果

目的:探讨一种新型的适合于儿童的非骨水泥固定型股骨柄设计特征,并通过随访获得其临床效果。方法:选取2010年9月~2013年4月在我科植入新型非骨水泥股骨柄的6名儿童患者,其中男1例,女5例;年龄8.5±3.2岁(5~11岁)。病理诊断结果骨肉瘤患者5例,恶性神经鞘瘤患者1例;右股骨下端患者5例,左股骨下端患者1例;其中一例患者术前有病理骨折。6例患者在我科行双动半膝关节置换术,其中股骨下端均采用了新型非骨水泥假体柄。采用Enneking骨肌肉肿瘤置换后下肢功能评定标准对患肢行功能评价,影像学重点评估股骨柄在髓腔放置位置是否得当、股骨柄假体有无松动、有无应力遮挡、骨溶解等现象,并测量术后患者患肢短缩畸形数据。结果:6例患者随访时间32个月(14~54个月),除1例5岁女童术前肢体条件较差在术后14个月行膝关节融合手术,其余无翻修病例,置换关节均无感染、折断等现象。MSTS评分21.33分;射线片示所有患者股骨髓腔内假体柄放置位置满意,股骨侧及胫腓骨侧假体周围未见骨溶解。结论:新型非骨水泥固定型股骨柄设计合理,早期稳定性可,后期可取得满意的生物固定效果。     

氧化应激对磷酸三钙磨损颗粒诱导的假体周围骨溶解的影响及其机制

目的：探讨氧化应激对磷酸三钙（TCP）磨损颗粒诱导的假体周围骨溶解的影响及其作用机制。方法：36只雄性ICR小鼠随机分为3组（n=12）：假手术（Sham）组、TCP磨损颗粒（TCP）组和N-乙酰-L-半胱氨酸（NAC）组。将TCP磨损颗粒30 mg包埋于小鼠颅骨顶部构建假体周围骨溶解模型,于术后第2天颅顶骨膜局部注射NAC（1.0 mg/kg）,隔日1次,持续2周后处死动物采血、取颅骨。抗酒石酸酸性磷酸酶（TRAP）染色观察小鼠颅骨假体周围骨溶解情况;ELISA和化学比色法检测血清中肿瘤坏死因子-α（TNF-α）、白介素-1β（IL-1β）、白介素-6（IL-6）和总抗氧化能力（T-AOC）含量及超氧化物歧化酶（SOD）活性;Western blot检测假体周围骨组织中内质网应激标志蛋白葡萄糖调节蛋白78（GRP78）、蛋白激酶R样内质网激酶（PERK）、磷酸化PERK（p-PERK）、真核细胞翻译起始因子2α（eIF2α）和磷酸化eIF2α（p-eIF2α）的表达。结果：与Sham组比较,TCP组小鼠血清TNF-α、IL-1β和IL-6水平及假体周围骨溶解面积显著增加（P<0.05）,T-AOC含量和SOD活性明显降低（P<0.05）,GRP78蛋白质表达、p-PERK/PERK和p-eIF2α/eIF2α值显著升高。与TCP组比较,NAC组小鼠血清TNF-α、IL-1β和IL-6水平及骨溶解面积明显减少（P<0.05）,血清T-AOC含量和SOD活性明显增加（P<0.05）,GRP78蛋白质表达、p-PERK/PERK和p-eIF2α/eIF2α值明显降低。结论：抑制氧化应激可阻止TCP磨损颗粒诱导的假体周围骨溶解,其机制可能与PERK/eIF2α通路的失活有关。     

阿仑膦酸钠联合阿法骨化醇对预防全髋关节置换术后患者骨矿物质流失的疗效

目的：探讨初次行全髋关节置换术后使用阿仑膦酸钠单一用药或阿仑膦酸钠与阿法骨化醇联合用药对患者假体周围骨矿物 质流失的疗效。方法：将60 名患者按照随机数字表法分为阿仑膦酸钠单一药物治疗组（n=18）、阿仑膦酸钠和阿法骨化醇联合治 疗组（n=20）和无药物治疗组（n=22）。术后1、12、24 和48 周,对患者假体周围骨矿物质密度（BMD）和生化标志物进行检测,比较 检测区域测量值的变化。结果：单个测量周期中,单一药物治疗组和联合药物治疗组在股骨矩区域的BMD 均高于无药物治疗组 （P＜0.01）。单一药物治疗组和联合药物治疗组尿Ⅰ型胶原N端肽的血浆浓度与骨碱性磷酸酶浓度显著低于无药物治疗组（P＜ 0.01）。结论：单一药物治疗和联合治疗能显著预防假体周围的骨矿物质流失,尤其对预防股骨矩位置的骨矿物质流失效果显著。     

人工关节假体无菌性松动动物模型的快速建立

目的:人工关节置换手术发展至今,取得了非常大的成功,已在临床解决了许多终末期的关节疾患。研究表明,假体无菌性松动的患者,其假体周围处于高骨更新状态。因此骨-假体界面的早期整合对于阻止磨屑颗粒和细胞因子的迁移至关重要,而限制人工关节假体使用寿命的一个主要原因是磨屑颗粒诱导的假体无菌性松动。在本研究中,我们旨在尝试使用107个UHMWPE颗粒快速建立人工关节假体无菌性松动的兔动物模型,以便为进一步探讨假体无菌性松动的机制及防治奠定实验基础。方法:我们用雌性新西兰大白兔建立动物模型,随机均分为实验组和对照组,在两组动物的左侧胫骨髓腔内植入羟基磷灰石(hydroxyapatite,HA)涂层假体。在实验组中,分别于假体表面和膝关节腔内植入0.5×10~7超高分子量聚乙烯(Ultra-high molecular weight polyethylene,UHMWPE)颗粒。结果:同对照组相比,实验组动物的关节内压力更高、骨组织形态学参数更差、假体生物力学固定强度更低,同时,促炎细胞因子和骨更新标志均显著高于对照组。结论:我们使用很少的UHMWPE颗粒成功快速地建立了人工关节假体无菌性松动的兔动物模型,从而为今后人工关节假体无菌性松动的进一步研究奠定了实验基础。     

人工全髋关节置换术中Delta陶瓷的界面选择

目的:Delta陶瓷较Forte陶瓷在材料复合方面进步明显,并采用了36 mm大直径球头的设计,其组成的界面具有耐磨性好,关节活动度大,稳定性佳,不易脱位等优点,适合年轻及活动量大的患者,但其价格较其他界面更为高昂.观察采用Delta陶瓷-陶瓷界面与Delta陶瓷-高交联聚乙烯界面假体行全髋关节置换术的患者术后效果的差异.方法:选取2009年10月-2012年10月在我院选择Delta陶瓷-高交联聚乙烯界面行全髋关节置换术的35例患者(A组),以同期在我院选择Delta陶瓷-陶瓷界面26例行全髋关节置换术的患者(B组)作为对照.通过随访影像学复查,以及术后Harris功能评分进行临床效果的评价.结果:所有患者均得到随访,随访时间6个月到2年.所有患者在影像学方面,未发现松动下沉,脱位以及碎裂等现象.假体周围未见骨溶解所致透亮线形成以及异位骨化.两组患者行人工全髋关节置换术后Harris评分较术前均有显著提高,但两组之间无显著差异.结论:Delta陶瓷作为最新一代的生物陶瓷,其优异性能毋庸置疑.采用Delta陶瓷-陶瓷界面及Delta陶瓷-高交联聚乙烯界面在短期内未见明显差异,其中长期效果仍有待进一步随访观察.     

运用偏振光观测聚乙烯磨屑颗粒诱导人工关节假体无菌性松动

目的:探讨运用偏振光显微镜来观测无菌性松动人工关节假体周围的聚乙烯颗粒分布,评估其在研究磨屑颗粒诱导假体无菌性松动机制及防治措施等实验研究中的可行性。方法:我们用雌性新西兰大白兔建立动物模型,在左侧胫骨髓腔内植入羟基磷灰石(hydroxyapatite,HA)涂层假体。并分别于假体表面和膝关节腔内植入0.5×107超高分子量聚乙烯(Ultra-high molecular weight polyethylene,UHMWPE)颗粒。术后行四环素荧光双标记。膝关节滑膜组织苏木精-伊红(hematoxylin-eosin,HE)染色、骨组织改良丽春红染色后分别用普通光镜和偏振光镜观察,未染色的骨组织行荧光显微镜和偏振光镜观察。结果:在聚乙烯颗粒刺激下,膝关节滑膜组织增生明显,骨-假体结合差,假体周围骨小梁稀疏,偏振光显微镜可清晰显示双折光性的聚乙烯颗粒在膝关节分布于滑膜及其深层结缔组织中,在骨-假体间隙间大量充填,阻碍骨-假体整合。结论:运用偏振光显微镜可以清晰而简便地观察滑膜和假体周围的聚乙烯颗粒分布,与传统实验方法相比,更加直观、简便和经济。     

Periprosthetic osteolysis and its association with RANKL expression

Extensive osteolysis adjacent to orthopedic implants is often associated with wear particles of prosthetic material. The activation of the RANKL/RANK/OPG system is considered to be a likely cause of periprosthetic osteolysis leading to implant failure. The aim of this study was to examine the possible correlation between the clinical extent of osteolysis, the number of wear particles and expression of the osteoclastic mediator RANKL (receptor activator of nuclear factor kappa B ligand) in the tissues around aseptically loosened cemented and non-cemented total hip replacements. Periprosthetic tissues were harvested from 59 patients undergoing revision of hip replacement for aseptic loosening. We observed RANKL-positive cells in 23 of our 59 patients, their presence was noted predominantly in tissues with a loosened cemented endoprosthesis. We have found that RANKL is present only in tissues with a large amount of wear debris and predominantly in cases involving loosened cemented implants.     

CoCrMo‐Nanoparticles induced peri‐implant osteolysis by promoting osteoblast ferroptosis via regulating Nrf2‐ARE signalling pathway

ObjectivesAseptic loosening (AL) is the most common reason of total hip arthroplasty (THA) failure and revision surgery. Osteolysis, caused by wear particles released from implant surfaces, has a vital role in AL. Although previous studies suggest that wear particles always lead to osteoblast programmed death in the process of AL, the specific mechanism remains incompletely understood and osteoblast ferroptosis maybe a new mechanism of AL.Materials and MethodsCoCrMo nanoparticles (CoNPs) were prepared to investigate the influence of ferroptosis in osteoblasts and calvaria resorption animal models. Periprosthetic osteolytic bone tissue was collected from patients who underwent AL after THA to verify osteoblast ferroptosis.ResultsOur study demonstrated that CoNPs induced significant ferroptosis in osteoblasts and particles induced osteolysis (PIO) animal models. Blocking ferroptosis with specific inhibitor Ferrostatin‐1 dramatically reduced particle‐induced ferroptosis in vitro. Moreover, in osteoblasts, CoNPs significantly downregulated the expression of Nrf2 (nuclear factor erythroid 2‐related factor 2), a core element in the antioxidant response. The overexpression of Nrf2 by siKeap1 or Nrf2 activator Oltipraz obviously upregulated antioxidant response elements (AREs) and suppressed ferroptosis in osteoblasts. Furthermore, in PIO animal models, the combined utilization of Ferrostatin‐1 and Oltipraz dramatically ameliorated ferroptosis and the severity of osteolysis.ConclusionsThese results indicate that CoNPs promote osteoblast ferroptosis by regulating the Nrf2‐ARE signalling pathway, which suggests a new mechanism underlying PIO and represents a potential therapeutic approach for AL.

CoCrMo‐Nanoparticles induced peri‐implant osteolysis by promoting osteoblast ferroptosis via regulating Nrf2‐ARE signalling pathway. Blocking ferroptosis with Ferrostatin‐1 and Oltipraz significantly ameliorated osteolysis induced by implanted particles, which suggests a new mechanism underlying particle‐induced osteolysis and represents a potential therapeutic approach for aseptic loosening.     

Influence of demographic, surgical and implant variables on wear rate and osteolysis in ABG I hip arthroplasty

Periprosthetic osteolysis is associated with accelerated wear rates. The goal of this study was to investigate the influence of demographic and technical variables on wear rates and size of osteolytic lesions. Eighty retrieved ABG I prostheses were analyzed according to prospectively established criteria. There were 22 men and 58 women with an average age of 52 years (34-65) at the time of revision. The average time from index surgery to revision was 67 months (26 to 106). Polyethylene wear measurements were performed using a Universal-type measuring microscope. The average linear wear and volumetric wear rate was 0.363 mm per year (0-0.939, SD 0.241) and 161 mm(3) per year (0-467, SD 118.2), respectively. The wear rates were significantly higher (a) in patients with primary osteoarthritis in comparison with postdysplastic hips, (b) in hips where zirconia prosthetic heads articulated against the polyethylene liner, and (c) in cups placed laterally to Kohler's line. Risk that linear wear rate could be more than 0.2 mm per year was three times higher in patients who were operated in 1997 and later (OR 3.0, 95 % CI 1.126-7.993, p = 0.03). A strong association was revealed between magnitude of wear and size of femoral osteolysis.     

Poor survival of ABG I hip prosthesis in younger patients

Background: Hydroxyapatite coated (HAC) hip implants have been used in clinical practice for more than two decades. However, the majority of studies have reported only intermediate term outcomes that are not reliable for predicting long-term behavior in all implants. The aim of this study was to determine the performance of HAC total hip arthroplasty in younger patients over a 10-year follow-up period. Methods and Results: This was an observational retrospective study of a 137 consecutive hips with the ABG I prosthesis. Of these, 128 were available for the last investigation. Median duration of follow-up was 10.9 years. The mean age at time of index surgery was 46+/-6.7 years. Probability of implant survival was estimated using the Kaplan-Meier method. The overall 12-year cumulative survival was 0.55 (95% CI, 0.443-0.659). Periprosthetic osteolysis (57 %) was the most frequent reason for failure followed by aseptic loosening (28 %). When only aseptic loosening was included in the analysis, the same figures for cup and stem were 0.873 (95% CI, 0.808-0.938) and 0.992 (95% CI, 0.976- 1.0), respectively. Patients with a smaller cup size were those at high risk for revision due to wear-related complications (odds ratio, OR=4.3; 95% CI, 1.734-10.555). Conclusion: This study reports one of the poorest 12-year survivorship data for cementless acetabular component in the literature. The main reason for premature failure was osteolysis, strongly related to high wear rate of polyethylene.     

A novel sensor concept for optimization of loosening diagnostics in total hip replacement

The main reason for the revision of total hip replacements is aseptic loosening, caused by stress shielding and wear particle induced osteolysis. In order to detect an implant loosening early, the osseointegration of endoprosthetic implants must be measured exactly. Currently applied diagnostic methods, such as standard radiographs and clinical symptomatology, often result in an imprecise diagnosis. A novel radiation-free method to improve the diagnostic investigation of implant loosening is presented. The osseointegration of an implant can be identified using mechanical magnetic sensors (oscillators), which impinge on small membranes inside an implant component, e.g., the femoral hip stem. The maximum velocity after impingement of the oscillator depends on the osseointegration of the implant. Excitation of the oscillator is realized by a coil outside the human body. Another external coil is used to detect the velocity of the oscillator. To demonstrate the principle of the novel loosening sensor, an overdimensioned test device was designed to measure simulated loosening phases in the first experimental tests with different material layers. The overdimensioned test device of the loosening sensor showed significant differences in the various phases of fixation. Analysis of the membrane without any material layer in the case of advanced loosening resulted in a 23% higher maximum velocity compared to an attached artificial bone layer. Based on these preliminary results, the sensor system shows potential for the detection of implant loosening. Moreover, the proposed system could be used in experimental applications to determine the quality of bioactive coatings and new implant materials.     

Volumetric computerized tomography as a measurement of periprosthetic acetabular osteolysis and its correlation with wear

Osteolysis, which is considered to be a major source of morbidity following total hip joint replacement, has been notoriously difficult to measure accurately, particularly in the acetabular area. In order to study periacetabular osteolysis, specialized software for computerized tomography (CT) scan image analysis has been developed. This software (3D-CT) eliminates metal artifacts, allows three-dimensional segmentation of the CT image, and reconstructs the segmented image to provide an accurate representation and measurement of volume for osteolytic lesions. In the present study, 20 patients underwent periacetabular osteolytic volume determination using 3D-CT, functional assessment (using the Harris Hip Scale, the Western Ontario and McMaster University Osteoarthritis Index, and the short form 36 questionnaire), and two-dimensional analysis of volumetic polyethylene wear using digitalized plain films. Periacetabular osteolysis correlated directly with the polyethylene wear rate (relative risk [RR] = 0.494, P = 0.027). If one patient with an acetabular revision, one patient with recurrent dislocation, and one patient with a Biomet prosthesis are excluded, then the correlation between wear and osteolysis is improved (RR = 0.685, P = 0.002). In summary, the current study demonstrates both the feasibility of CT imaging of periacetabular osteolysis and the correlation between polyethylene wear and osteolytic volume, providing a potential outcome measure for clinical trials that are designed to examine interventions in this complex disease process.     

Volumetric computerized tomography as a measurement of periprosthetic acetabular osteolysis and its correlation with wear

Osteolysis, which is considered to be a major source of morbidity following total hip joint replacement, has been notoriously difficult to measure accurately, particularly in the acetabular area. In order to study periacetabular osteolysis, specialized software for computerized tomography (CT) scan image analysis has been developed. This software (3D-CT) eliminates metal artifacts, allows three-dimensional segmentation of the CT image, and reconstructs the segmented image to provide an accurate representation and measurement of volume for osteolytic lesions. In the present study, 20 patients underwent periacetabular osteolytic volume determination using 3D-CT, functional assessment (using the Harris Hip Scale, the Western Ontario and McMaster University Osteoarthritis Index, and the short form 36 questionnaire), and two-dimensional analysis of volumetic polyethylene wear using digitalized plain films. Periacetabular osteolysis correlated directly with the polyethylene wear rate (relative risk [RR] = 0.494, P = 0.027). If one patient with an acetabular revision, one patient with recurrent dislocation, and one patient with a Biomet prosthesis are excluded, then the correlation between wear and osteolysis is improved (RR = 0.685, P = 0.002). In summary, the current study demonstrates both the feasibility of CT imaging of periacetabular osteolysis and the correlation between polyethylene wear and osteolytic volume, providing a potential outcome measure for clinical trials that are designed to examine interventions in this complex disease process.     

The role played by cell-substrate interactions in the pathogenesis of osteoclast-mediated peri-implant osteolysis

Prosthetic wear debris-induced peri-implant osteolysis is a major cause of aseptic loosening after total joint replacement. In this condition, wear particles released from the implant components induce a granulomatous inflammatory reaction at the interface between implant and adjacent bone, leading to progressive bone resorption and loss of fixation. The present study was undertaken to characterize definitively the phenotype of osteoclast-like cells associated with regions of peri-implant focal bone resorption and to compare the phenotypic features of these cells with those of mononucleated and multinucleated cells associated with polyethylene wear particles. Peri-implant tissues were obtained from patients undergoing hip revision surgery for aseptic loosening after total joint replacement. Cells were examined for the expression of several markers associated with the osteoclast phenotype using immunohistochemistry, histochemistry, and/or in situ hybridization. CD68 protein, a marker expressed by multiple macrophage lineage cell types, was detected in mononucleated and multinucleated cells associated with polyethylene particles and the bone surface. Cathepsin K and tartrate-resistant acid phosphatase were expressed highly in both mononucleated and multinucleated cells associated with the bone surface. Levels of expression were much lower in cells associated with polyethylene particles. High levels of β₃ integrin protein were detected in cells in contact with bone. Multinucleated cells associated with polyethylene particles exhibited faint positive staining. Calcitonin receptor mRNA expression was detected solely in multinucleated cells present in resorption lacunae on the bone surface and was absent in cells associated with polyethylene particles. Our findings provide further evidence that cells expressing the full repertoire of osteoclast phenotypic markers are involved in the pathogenesis of peri-implant osteolysis after total joint replacement. They also demonstrate that foreign body giant cells, although believed to be phenotypically and functionally distinct from osteoclasts, express many osteoclast-associated genes and gene products. However, the levels and patterns of expression of these genes in the two cell types differ. We speculate that, in addition to the role of cytokines and growth factors, the substrate with which these cells interact plays a critical role in their differential phenotypic and functional properties.     

Wear in the prosthetic shoulder: association with design parameters

Total replacement of the glenohumeral joint provides an effective means for treating a variety of pathologies of the shoulder. However, several studies indicate that the procedure has not yet been entirely optimized. Loosening of the glenoid component remains the most likely cause of implant failure, and generally this is believed to stem from either mechanical failure of the fixation in response to high tensile stresses, or through osteolysis of the surrounding bone stock in response to particulate wear debris. Many computational studies have considered the potential for the former, although only few have attempted to tackle the latter. Using finite-element analysis an investigation, taking into account contact pressures as well as glenohumeral kinematics, has thus been conducted, to assess the potential for polyethylene wear within the artificial shoulder. The relationships between three different aspects of glenohumeral design and the potential for wear have been considered, these being conformity, polyethylene thickness, and fixation type. The results of the current study indicate that the use of conforming designs are likely to produce slightly elevated amounts of wear debris particles when compared with less conforming joints, but that the latter would be more likely to cause material failure of the polyethylene. The volume of wear debris predicted was highly influenced by the rate of loading, however qualitatively it was found that wear predictions were not influenced by the use of different polyethylene thicknesses nor fixation type while the depth of wearing was. With the thinnest polyethylene designs (2 mm) the maximum depth of the wear scar was seen to be upwards of 20% higher with a metal-backed fixation as opposed to a cemented design. In all-polyethylene designs peak polymethyl methacrylate tensile stresses were seen to reduce with increasing polyethylene thickness. Irrespective of the rate of loading of the shoulder joint, the current study indicates that it is possible to optimize glenoid component design against abrasive wear through the use of high conformity designs, possessing a polyethylene thickness of at least 6 mm.     

A Resorbable Antibiotic-Eluting Polymer Composite Bone Void Filler for Perioperative Infection Prevention in a Rabbit Radial Defect Model

Nearly 1.3 million total joint replacement procedures are performed in the United States annually, with numbers projected to rise exponentially in the coming decades. Although finite infection rates for these procedures remain consistently low, device-related infections represent a significant cause of implant failure, requiring secondary or revision procedures. Revision procedures manifest several-fold higher infection recurrence rates. Importantly, many revision surgeries, infected or not, require bone void fillers to support the host bone and provide a sufficient tissue bed for new hardware placement. Antibiotic-eluting bone void fillers (ABVF), providing both osteoconductive and antimicrobial properties, represent one approach for reducing rates of orthopedic device-related infections. Using a solvent-free, molten-cast process, a polymer-controlled antibiotic-eluting calcium carbonate hydroxyapatite (HAP) ceramic composite BVF (ABVF) was fabricated, characterized, and evaluated in vivo using a bacterial challenge in a rabbit radial defect window model. ABVF loaded with tobramycin eliminated the infectious burden in rabbits challenged with a clinically relevant strain of Staphylococcus aureus (inoculum as high as 10⁷ CFU). Histological, microbiological, and radiographic methods were used to detail the effects of ABVF on microbial challenge to host bone after 8 weeks in vivo. In contrast to the HAP/BVF controls, which provided no antibiotic protection and required euthanasia 3 weeks post-operatively, tobramycin-releasing ABVF animals showed no signs of infection (clinical, microbiological, or radiographic) when euthanized at the 8-week study endpoint. ABVF sites did exhibit fibrous encapsulation around the implant at 8 weeks. Local antibiotic release from ABVF to orthopedic sites requiring bone void fillers eliminated the periprosthetic bacterial challenge in this 8-week in vivo study, confirming previous in vitro results.