A Multicenter Study of Early Anti-inflammatory Treatment in Patients With Acute Anterior Cruciate Ligament Tear
A Multicenter Study of Early Anti-inflammatory Treatment in Patients With Acute Anterior Cruciate Ligament Tear
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DOI：
10.1177/0363546516666818
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发表时间：
2017-02-01
影响因子：
4.8
通讯作者：
Spindler, Kurt P.
中科院分区：
文献类型：
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作者：
Lattermann, Christian;Jacobs, Cale A.;Spindler, Kurt P.
背景资料：越来越多的人认识到，关节的生化异常早于创伤后骨关节炎（PTOA）的放射学异常长达数十年。越来越多的证据强烈表明，从前交叉韧带（ACL）损伤到PTOA的进展是多因素的，涉及关节软骨的生物力学紊乱和生化稳态之间的相互作用。目的：使用急性ACL损伤模型的该随机研究的目的是（1）评价炎症和软骨变性生物标志物的自然进展，（2）评估疼痛的主观报告与炎症和软骨退行性生物标志物之间的关系，（3）确定损伤后关节穿刺术和皮质类固醇注射是否能够改变这种生化级联反应。研究设计：随机对照试验;证据等级：2.方法：共49例患者随机分为4组：组1（ACL损伤后4天皮质类固醇，2周安慰剂注射盐水），组2（ACL损伤后4天安慰剂，2周皮质类固醇），第3组（在两个时间间隔注射皮质类固醇）或安慰剂组（在两个时间间隔注射盐水）。在损伤后约4天、11天和5周收集患者报告的结局指标和滑膜生物标志物。使用Wilcoxon检验评估所有变量的时间点之间的变化，并通过计算斯皮尔曼来评估结局评分变化与生物标志物之间的关系。使用Kruskal-Wallis tests.Results的结果和生物标志物也进行了比较4组之间：没有不良事件或感染观察到任何研究患者。除基质金属蛋白酶1（MMP-1）和肿瘤坏死因子诱导基因6（TSG-6）外，软骨退行性标志物在前5周内恶化，而所有患者报告的结局在此期间均改善，与治疗组无关。接受皮质类固醇注射的患者和安慰剂组之间的患者报告结果没有差异。然而，与II型胶原分解相关的II型胶原C端肽（CTX-II）的增加在安慰剂组中显著更大（1.32 ± 1.10 ng/mL），高于损伤后最初几天内接受皮质类固醇注射的任何一组（第1组：0.23 ± 0.27 ng/mL [P = 0.01];第3组：0.19 ± 0.34 ng/mL [P = 0.01]）。然而，令人鼓舞的是，抗炎剂的早期干预能够影响软骨退化的生物标志物。如果早期干预导致症状性PTOA的发作或严重程度发生有意义的变化，则ACL损伤患者的当前治疗模式可能必须重新构建，以包括早期抽吸和关节内干预。ClinicalTrials.gov
Background: It is increasingly recognized that biochemical abnormalities of the joint precede radiographic abnormalities of posttraumatic osteoarthritis (PTOA) by as much as decades. A growing body of evidence strongly suggests that the progression from anterior cruciate ligament (ACL) injury to PTOA is multifactorial, involving the interplay between biomechanical disturbances and biochemical homeostasis of articular cartilage.Purpose: The purposes of this randomized study using an acute ACL injury model were to (1) evaluate the natural progression of inflammatory and chondrodegenerative biomarkers, (2) evaluate the relationship between subjective reports of pain and inflammatory and chondrodegenerative biomarkers, and (3) determine if postinjury arthrocentesis and corticosteroid injection offer the ability to alter this biochemical cascade.Study Design: Randomized controlled trial; Level of evidence, 2.Methods: A total of 49 patients were randomized to 4 groups: group 1 (corticosteroid at 4 days after ACL injury, placebo injection of saline at 2 weeks), group 2 (placebo at 4 days after ACL injury, corticosteroid at 2 weeks), group 3 (corticosteroid at both time intervals), or a placebo group (saline injections at both time intervals). Patient-reported outcome measures and synovial biomarkers were collected at approximately 4 days, 11 days, and 5 weeks after injury. The change between the time points was assessed for all variables using Wilcoxon tests, and the relationship between changes in outcome scores and biomarkers were assessed by calculating Spearman . Outcomes and biomarkers were also compared between the 4 groups using Kruskal-Wallis tests.Results: No adverse events or infections were observed in any study patients. With the exception of matrix metalloproteinase 1 (MMP-1) and tumor necrosis factor-inducible gene 6 (TSG-6), chondrodegenerative markers worsened over the first 5 weeks while all patient-reported outcomes improved during this time, regardless of treatment group. Patient-reported outcomes did not differ between patients receiving corticosteroid injections and the placebo group. However, increases in C-telopeptide of type II collagen (CTX-II), associated with collagen type II breakdown, were significantly greater in the placebo group (1.32 1.10 ng/mL) than in either of the groups that received the corticosteroid injection within the first several days after injury (group 1: 0.23 0.27 ng/mL [P = .01]; group 3: 0.19 +/- 0.34 ng/mL [P = .01]).Conclusion: PTOA begins at the time of injury and results early on in dramatic matrix changes in the knee. However, it is encouraging that early intervention with an anti-inflammatory agent was able to affect biomarkers of chondral degeneration. Should early intervention lead to meaningful changes in either the onset or severity of symptomatic PTOA, the current treatment paradigm for patients with ACL injury may have to be restructured to include early aspiration and intra-articular intervention.Trial Registration: ClinicalTrials.gov identifier: NCT01692756.