Purdue P Edward, Koulouvaris Panagiotis, Potter Hollis G, Nestor Bryan J, Sculco Thomas P
Hospital for Special Surgery, New York, NY, USA.
Clin Orthop Relat Res. 2007 Jan;454:251-61. doi: 10.1097/01.blo.0000238813.95035.1b.
The generation of prosthetic implant wear after total joint arthroplasty is recognized as the major initiating event in development of periprosthetic osteolysis and aseptic loosening, the leading complication of this otherwise successful surgical procedure. We review current concepts of how wear debris causes osteolysis, and report ideas for prevention and treatment. Wear debris primarily targets macrophages and osteoclast precursor cells, although osteoblasts, fibroblasts, and lymphocytes also may be involved. Molecular responses include activation of MAP kinase pathways, transcription factors (including NFkappaB), and suppressors of cytokine signaling. This results in up-regulation of proinflammatory signaling and inhibition of the protective actions of antiosteoclastogenic cytokines such as interferon gamma. Strategies to reduce osteolysis by choosing bearing surface materials with reduced wear properties should be balanced by awareness that reducing particle size may increase biologic activity. There are no approved treatments for osteolysis despite the promise of therapeutic agents against proinflammatory mediators (such as tumor necrosis factor) and osteoclasts (bisphosphonates and molecules blocking receptor activator of NFkappaB ligand [RANKL] signaling) shown in animal models. Considerable efforts are underway to develop such therapies, to identify novel targets for therapeutic intervention, and to develop effective outcome measures.
全关节置换术后假体植入物磨损的产生被认为是假体周围骨溶解和无菌性松动发展过程中的主要起始事件，而假体周围骨溶解和无菌性松动是这种原本成功的外科手术的主要并发症。我们回顾了磨损碎屑导致骨溶解的当前概念，并报告了预防和治疗的思路。磨损碎屑主要作用于巨噬细胞和破骨细胞前体细胞，不过成骨细胞、成纤维细胞和淋巴细胞也可能参与其中。分子反应包括丝裂原活化蛋白激酶途径、转录因子（包括核因子κB）以及细胞因子信号转导抑制因子的激活。这导致促炎信号上调，并抑制抗破骨细胞生成细胞因子（如干扰素γ）的保护作用。通过选择具有较低磨损特性的承重表面材料来减少骨溶解的策略，应与意识到减小颗粒尺寸可能会增加生物活性相平衡。尽管在动物模型中显示出针对促炎介质（如肿瘤坏死因子）和破骨细胞（双膦酸盐和阻断核因子κB受体活化因子配体[RANKL]信号传导的分子）的治疗药物有前景，但目前尚无批准用于治疗骨溶解的方法。目前正在做出巨大努力来开发此类疗法、确定治疗干预的新靶点并制定有效的疗效评估指标。
