Batty Lachlan M, Mackenzie Christopher, Landwehr Chelsea, Webster Kate E, Feller Julian A
OrthoSport Victoria Research Unit, Melbourne, Victoria, Australia.
School of Allied Health, Human Services and Sport, La Trobe University, Melbourne, Victoria, Australia.
Orthop J Sports Med. 2024 Oct 7;12(10):23259671241275072. doi: 10.1177/23259671241275072. eCollection 2024 Oct.
Anterior cruciate ligament (ACL) injury is frequently associated with injuries to other parts of the knee, including the menisci and articular cartilage. After ACL injury and reconstruction, there may be progressive chondral degradation. Biomarkers in blood, urine, and synovial fluid can be measured after ACL injury and reconstruction and have been proposed as a means of measuring the associated cellular changes occurring in the knee.
To systematically review the literature regarding biomarkers in urine, serum, or synovial fluid that have been associated with an outcome measure after ACL reconstruction.
Systematic review; Level of evidence, 3.
This review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The MEDLINE, Embase, CINAHL, and Web of Science databases were searched to identify studies published before September 2023 that reported on patients undergoing ACL reconstruction where a biomarker was measured and related to an outcome variable. Of 9360 results, 16 studies comprising 492 patients were included. Findings were reported as descriptive summaries synthesizing the available literature.
A total of 45 unique biomarkers or biomarker ratios were investigated (12 serum, 3 urine, and 38 synovial fluid; 8 biomarkers were measured from >1 source). Nineteen different outcome measures were identified, including the International Knee Documentation Committee Subjective Knee Form, Knee injury and Osteoarthritis Outcome Score, numeric pain scores, radiological outcomes (magnetic resonance imaging and radiography), rates of arthrofibrosis and cyclops lesions, and gait biomechanics. Across the included studies, 17 biomarkers were found to have a statistically significant association ( < .05) with an outcome variable. Serum interleukin 6 (s-IL-6), serum and synovial fluid matrix metalloproteinase-3 (s-MMP-3 and sf-MMP-3), urinary and synovial fluid C-terminal telopeptide of type 2 collagen (u-CTX-II and sf-CTX-II), and serum collagen type 2 cleavage product (s-C2C) showed promise in predicting outcomes after ACL reconstruction, specifically regarding patient-reported outcome measures (s-IL-6 and u-CTX-II), gait biomechanical parameters (s-IL-6, sf-MMP-3, s-MMP-3, and s-C2C), pain (s-IL-6 and u-CTX-II), and radiological osteoarthritis (ratio of u-CTX-II to serum procollagen 2 C-propeptide).
The results highlight several biomarkers that have been associated with clinically important postoperative outcome measures and may warrant further research to understand if they can provide meaningful information in the clinical environment.
前交叉韧带（ACL）损伤常与膝关节其他部位的损伤相关，包括半月板和关节软骨。ACL损伤和重建后，可能会出现软骨进行性退变。ACL损伤和重建后可测量血液、尿液和滑液中的生物标志物，这些生物标志物被认为是测量膝关节中相关细胞变化的一种手段。
系统回顾关于尿液、血清或滑液中与ACL重建后结局指标相关的生物标志物的文献。
系统回顾；证据等级为3级。
本综述按照PRISMA（系统评价和Meta分析的首选报告项目）指南进行。检索MEDLINE、Embase、CINAHL和Web of Science数据库，以识别2023年9月之前发表的报告对接受ACL重建的患者进行生物标志物测量并与结局变量相关的研究。在9360个结果中，纳入了16项研究，共492例患者。研究结果以综合现有文献的描述性总结形式报告。
共研究了45种独特的生物标志物或生物标志物比值（12种血清标志物、3种尿液标志物和38种滑液标志物；8种生物标志物从>1种来源进行测量）。确定了19种不同的结局指标，包括国际膝关节文献委员会主观膝关节量表、膝关节损伤和骨关节炎结局评分、数字疼痛评分、放射学结局（磁共振成像和X线摄影）、关节纤维化和独眼病变的发生率以及步态生物力学。在所纳入的研究中，发现17种生物标志物与结局变量存在统计学显著关联（P<0.05）。血清白细胞介素6（s-IL-6）、血清和滑液基质金属蛋白酶-3（s-MMP-3和sf-MMP-3）、尿液和滑液Ⅱ型胶原C末端肽（u-CTX-II和sf-CTX-II）以及血清Ⅱ型胶原裂解产物（s-C2C）在预测ACL重建后的结局方面显示出前景，特别是在患者报告的结局指标（s-IL-6和u-CTX-II）、步态生物力学参数（s-IL-6、sf-MMP-3、s-MMP-3和s-C2C）、疼痛（s-IL-及u-CTX-II）以及放射学骨关节炎（u-CTX-II与血清前胶原2 C-端前肽的比值）方面。
研究结果突出了几种与临床上重要的术后结局指标相关的生物标志物，可能值得进一步研究以了解它们是否能在临床环境中提供有意义的信息。
