Biedermann Lara, Bandick Evgeniya, Ren Yi, Tsitsilonis Serafeim, Donner Stefanie, Müller Michael, Duda Georg, Perka Carsten, Kienzle Arne
Clinic for Orthopedics, Center for Musculoskeletal Surgery, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Julius Wolff Institute and Center for Musculoskeletal Surgery, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
JB JS Open Access. 2023 Jan 10;8(1). doi: 10.2106/JBJS.OA.22.00101. eCollection 2023 Jan-Mar.
Despite the general success of total knee arthroplasty (TKA), addressing periprosthetic joint infection (PJI) and the resulting long-term complications is a growing medical need given the aging population and the increasing demand for arthroplasty. A larger proportion of patients face revision surgery because of the long-term complication of aseptic loosening despite clearance of the infection. The pathomechanisms leading to prosthetic loosening are not understood as it has been widely assumed that the bone stock recovers after explantation revision surgery. While clinical observations suggest a reduced osteogenic potential in patients with PJI, knowledge regarding the relevant biology is sparse. In the present study, we investigated the inflammatory impact of PJI on the bone and bone marrow in the vicinity of the joint. Additionally, we evaluated changes in the local inflammatory environment in a 2-stage exchange at both explantation and reimplantation.
In this study, we analyzed 75 human bone and bone-marrow specimens (obtained from 65 patients undergoing revision arthroplasty with cement for the treatment of PJI) for markers of inflammation. Samples were analyzed using hematoxylin and eosin overview staining, fluorescent immunohistochemical staining, flow cytometry, and polymerase chain reaction (PCR).
Leukocyte prevalence was significantly elevated at explantation (femur, +218.9%; tibia, +134.2%). While leukocyte prevalence decreased at reimplantation (femur, -49.5%; tibia, -34.2%), the number of cells remained significantly higher compared with the control group (femur, +61.2%; tibia, +54.2%). Expression of inflammatory markers interleukin (IL)-1α (femur, +2,748.7%; tibia, +1,605.9%), IL-6 (femur, +2,062.5%; tibia, +2,385.7%), IL-10 (femur, +913.7%; tibia, +897.5%), IL-12 (femur, +386.1%; tibia, +52.5%), IL-18 (femur, +805.3%; tibia, +547.7%), and tumor necrosis factor (TNF)-α (femur, +296.9%; tibia, +220.9%) was significantly elevated at prosthesis explantation in both femoral and tibial specimens. Expression remained significantly elevated at reimplantation for all inflammatory markers except IL-12 compared with the control group. Conversely, there were only limited inflammatory changes in the bone marrow environment.
The present study demonstrated a strong and lasting upregulation of the proinflammatory environment in the joint-surrounding osseous scaffold in patients with PJI. Our data suggest that modulating the inflammatory environment has substantial potential to improve the clinical outcome in affected patients.
尽管全膝关节置换术（TKA）总体上取得了成功，但鉴于人口老龄化和关节置换需求的增加，解决假体周围关节感染（PJI）及其导致的长期并发症已成为日益增长的医疗需求。尽管感染已清除，但仍有较大比例的患者因无菌性松动这一长期并发症而面临翻修手术。导致假体松动的病理机制尚不清楚，因为人们普遍认为在翻修手术取出假体后骨量会恢复。虽然临床观察表明PJI患者的成骨潜能降低，但相关生物学知识却很匮乏。在本研究中，我们调查了PJI对关节附近骨骼和骨髓的炎症影响。此外，我们评估了在两阶段置换中，即取出假体和重新植入时局部炎症环境的变化。
在本研究中，我们分析了75份人类骨骼和骨髓标本（从65例接受用于治疗PJI的骨水泥翻修关节置换术的患者中获取）的炎症标志物。样本采用苏木精和伊红总体染色、荧光免疫组织化学染色、流式细胞术和聚合酶链反应（PCR）进行分析。
取出假体时白细胞患病率显著升高（股骨，+218.9%；胫骨，+134.2%）。虽然重新植入时白细胞患病率下降（股骨，-49.5%；胫骨，-34.2%），但与对照组相比细胞数量仍显著更高（股骨，+61.2%；胫骨，+54.2%）。炎症标志物白细胞介素（IL）-1α（股骨，+2748.7%；胫骨，+1605.9%）、IL-6（股骨，+2062.5%；胫骨，+2385.7%）、IL-10（股骨，+913.7%；胫骨，+897.5%）、IL-12（股骨，+386.1%；胫骨，+52.5%）、IL-18（股骨，+805.3%；胫骨，+547.7%）和肿瘤坏死因子（TNF）-α（股骨，+296.9%；胫骨，+220.9%）在股骨和胫骨标本的假体取出时表达均显著升高。与对照组相比，除IL-12外，所有炎症标志物在重新植入时表达仍显著升高。相反，骨髓环境中的炎症变化有限。
本研究表明PJI患者关节周围骨支架中的促炎环境存在强烈且持久的上调。我们的数据表明，调节炎症环境对改善受影响患者的临床结局具有巨大潜力。
