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Posttraumatic knee osteoarthritis following anterior cruciate ligament injury: Potential biochemical mediators of degenerative alteration and specific biochemical markers.

ABSTRACT: As a common injury, anterior cruciate ligament (ACL) injury is unable to heal itself naturally, which possibly increases knee instability, accelerates the risk of joint degeneration and leads to knee osteoarthritis (OA) in the ACL-injured knee. Thus, ACL reconstruction using an autograft or allograft tendon is proposed to maintain the biomechanical stability of the knee joint. However, previous studies demonstrate that surgical management of ACL reconstruction failed to abrogate the development of OA completely, indicating that biochemical disturbance is responsible for the osteoarthritic changes observed following ACL injury. Inflammatory mediators are elevated subsequent to ACL injury or rupture, inducing matrix metalloproteinase production, proteoglycan degradation, collagen destruction, chondrocyte necrosis and lubricin loss. These potential biochemical mediators may aid in the development of effective biological management to reduce the onset of future posttraumatic OA. Furthermore, during the degenerative process of cartilage, there are a number of cartilage-specific biomarkers, which play a critical step in the loss of structural and functional integrity of cartilage. The present review illustrates several specific biomarkers in the ACL-injured knee joint, which may provide effective diagnostic and prognostic tools for investigating cartilage degenerative progression and future posttraumatic OA of ACL-injured patients.

SUBMITTER: Li H

PROVIDER: S-EPMC4360874 | biostudies-other | 2015 Mar

REPOSITORIES: biostudies-other

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Posttraumatic knee osteoarthritis following anterior cruciate ligament injury: Potential biochemical mediators of degenerative alteration and specific biochemical markers.

Li Hong H Chen Chen C Chen Shiyi S

Biomedical reports 20141217 2

As a common injury, anterior cruciate ligament (ACL) injury is unable to heal itself naturally, which possibly increases knee instability, accelerates the risk of joint degeneration and leads to knee osteoarthritis (OA) in the ACL-injured knee. Thus, ACL reconstruction using an autograft or allograft tendon is proposed to maintain the biomechanical stability of the knee joint. However, previous studies demonstrate that surgical management of ACL reconstruction failed to abrogate the development ...[more]

PMID: 25798238

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Project description:BackgroundWe aimed to evaluate clinical and radiological results after simultaneous open-wedge high tibial osteotomy (HTO) and anterior cruciate ligament (ACL) reconstruction in patients with ACL deficiency combined with medial uni-compartmental osteoarthritis (OA) and varus deformity.MethodsThis retrospective study was performed using data collected from 2005 to 2011 on a total of 24 patients who were diagnosed with ACL injury and medial unicompartmental OA with varus deformity, and who subsequently underwent simultaneous open-wedge HTO and arthroscopic ACL reconstruction. The mean follow-up duration was 5.2 years. For clinical outcomes, we evaluated Lysholm score, Tegner activity score, range of motion, Lachmann test, and pivot-shift test, and for radiological outcomes, we evaluated the degree of varus deformity, progression of medial OA, tibial posterior slope, anterior instability, and postoperative complication.ResultsThere were no limitations in range of motion found in any cases. Three patients showed progressive osteoarthritis on the medial compartment. The mechanical femorotibial angle was significantly corrected from varus 7.0 degrees to valgus 1.2 degrees, and the tibial posterior slope was not significantly changed. The Lysholm and Tegner activity scores were significantly improved after surgery (from 58 to 94 points on the Lysholm scale and from 4.0 to 5.3 points on the Tegner activity scale). Although the Lachman test and the pivot-shift test showed significant improvements after surgery, instability greater than Gr II was observed in three patients on the Lachman test and in four patients on the pivot-shift test. The side-to-side difference improved from 9.6 mm to 4.2 mm postoperatively as assessed using a Telos® arthrometer. There were no cases of nonunion or fixation loss.ConclusionsSimultaneous open-wedge HTO and ACL reconstruction in patients with ACL injury with medial compartmental OA showed satisfactory functional outcomes and postoperative activity level scores. However, some patients showed residual instability and progression of OA.

Project description:Anterior cruciate ligament (ACL) injury predisposes individuals to early-onset knee joint osteoarthritis (OA). Abnormal joint loading is apparent after ACL injury and reconstruction. The relationship between altered joint biomechanics and the development of knee OA is unknown.Altered knee joint kinetics and medial compartment contact forces initially after injury and reconstruction are associated with radiographic knee OA 5 years after reconstruction.Case-control study; Level of evidence, 3.Individuals with acute, unilateral ACL injury completed gait analysis before (baseline) and after (posttraining) preoperative rehabilitation and at 6 months, 1 year, and 2 years after reconstruction. Surface electromyographic and knee biomechanical data served as inputs to an electromyographically driven musculoskeletal model to estimate knee joint contact forces. Patients completed radiographic testing 5 years after reconstruction. Differences in knee joint kinetics and contact forces were compared between patients with and those without radiographic knee OA.Patients with OA walked with greater frontal plane interlimb differences than those without OA (nonOA) at baseline (peak knee adduction moment difference: 0.00 ± 0.08 N·m/kg·m [nonOA] vs -0.15 ± 0.09 N·m/kg·m [OA], P = .014; peak knee adduction moment impulse difference: -0.001 ± 0.032 N·m·s/kg·m [nonOA] vs -0.048 ± 0.031 N·m·s/kg·m [OA], P = .042). The involved limb knee adduction moment impulse of the group with osteoarthritis was also lower than that of the group without osteoarthritis at baseline (0.087 ± 0.023 N·m·s/kg·m [nonOA] vs 0.049 ± 0.018 N·m·s/kg·m [OA], P = .023). Significant group differences were absent at posttraining but reemerged 6 months after reconstruction (peak knee adduction moment difference: 0.02 ± 0.04 N·m/kg·m [nonOA] vs -0.06 ± 0.11 N·m/kg·m [OA], P = .043). In addition, the OA group walked with lower peak medial compartment contact forces of the involved limb than did the group without OA at 6 months (2.89 ± 0.52 body weight [nonOA] vs 2.10 ± 0.69 body weight [OA], P = .036).Patients who had radiographic knee OA 5 years after ACL reconstruction walked with lower knee adduction moments and medial compartment joint contact forces than did those patients without OA early after injury and reconstruction.

Project description:BackgroundThough anterior cruciate ligament (ACL) tear has been widely accepted as an important accelerator for knee osteoarthritis (KOA), the role of intrinsic ACL degeneration in developing KOA has not been fully investigated.PurposeTo determine whether ACL degeneration, in the absence of ACL tear, is associated with incident KOA over 4 years.Study designCohort study; Level of evidence, 2.MethodsParticipants' knees in this nested case-control study were selected from the Osteoarthritis Initiative (OAI) study, with Kellgren-Lawrence grading (Kellgren-Lawrence grading) of 0 or 1 at baseline (BL). Case knees which had incident KOA (KLG ≥2) over 4 years, were matched 1:1 with control knees by gender, age and radiographic status. ACL signal intensity alteration (0-3 scale) and volume were assessed as compositional feature and morphology of ACL degeneration, using knee MRI at P0 (time of onset of incident KOA), P-1 (1 year prior to P0) and baseline. Conditional logistic regression was applied to analyze the association between measures of ACL degeneration and incident KOA.Results337 case knees with incident KOA were matched to 337 control knees. Participants were mostly female (68.5%), with an average age of 59.9 years old. ACL signal intensity alterations at BL, P-1 and P0 were significantly associated with an increased odds of incident KOA respectively (all P for trend ≤0.001). In contrast, ACL volumes were not significantly associated with incident KOA at any time points.ConclusionsACL signal intensity alteration is associated with increased incident KOA over 4 years, whereas ACL volume is not.The translational potential of this article: This paper focused on ACL signal intensity alteration which could better reflect ACL degeneration rather than ACL tear during the progression of KOA and explored this topic in a nested case-control study. Utilizing MR images from KOA participants, we extracted the imaging features of ACL. In addition, we established a semi-quantitative score for ACL signal intensity alteration and found a significant correlation between it and KOA incidence. Our findings confirmed that the more severe the ACL signal intensity alteration, the stronger relationship with the occurrence of KOA. This suggests that more emphasis should be placed on ACL degeneration rather than ACL integrity in the future.

Project description:BackgroundThe long-term prevalence of knee osteoarthritis (OA) after anterior cruciate ligament (ACL) injury is unknown, especially in patients without a history of ACL surgery.PurposeTo (1) describe the prevalence of radiographic OA, symptomatic OA, and knee replacement surgery 32 to 37 years after acute ACL injury and to (2) compare the prevalence of radiographic OA, symptomatic OA, and knee symptoms between patients allocated to early ACL surgery or no ACL surgery and patients who crossed over to ACL surgery.Study designCohort study; Level of evidence, 2.MethodsParticipants aged 15 to 40 years at the time of ACL injury were allocated to surgical (augmented or nonaugmented ACL repair) or nonsurgical ACL treatment within 14 days of injury. At 32 to 37 years after the initial injury, 153 participants were followed up with plain weightbearing radiographs and completed 4 subscales from the Knee injury and Osteoarthritis Outcome Score (KOOS). Radiographic OA was defined as Kellgren and Lawrence grade 2 or higher. Symptomatic OA was defined as radiographic OA plus knee symptoms measured with the KOOS.ResultsParticipants allocated to ACL surgery (n = 64) underwent surgery at a mean ± SD of 5 ± 4 days (range, 0-11 days) after injury. Of the 89 participants allocated to no ACL surgery, 53 remained nonsurgically treated, 27 had ACL surgery within 2 years, and 9 had ACL surgery between 3 and 21 years after injury. In the total sample, 95 participants (62%) had radiographic tibiofemoral OA, including 11 (7%) who had knee replacement. The prevalence of radiographic tibiofemoral OA was lower in the group allocated to ACL surgery compared with the group who never had ACL surgery (50% vs 75%; P = .005). The prevalence of symptomatic OA (50% in the total sample) and patellofemoral radiographic OA (35% in the total sample) was similar between groups.ConclusionPatients allocated to early ACL surgery, performed a mean 5 days after injury, had a lower prevalence of tibiofemoral radiographic OA at 32 to 37 years after injury compared with patients who never had ACL surgery. The prevalences of symptomatic OA, radiographic patellofemoral OA, and knee symptoms were similar irrespective of ACL treatment. Overall, the prevalence of OA after ACL injury was high.RegistrationNCT03182647 (ClinicalTrials.gov identifier).

Project description:Although anterior cruciate ligament (ACL) reconstruction is the treatment gold standard for ACL injury, it does not reduce the risk of posttraumatic osteoarthritis. Therefore, new treatments that minimize this postoperative complication are of interest. Bioenhanced ACL repair, in which a bioactive scaffold is used to stimulate healing of an ACL transection, has shown considerable promise in short-term studies. The long-term results of this technique and the effects of the bioenhancement on the articular cartilage have not been previously evaluated in a large animal model.(1) The structural (tensile) properties of the porcine ACL at 6 and 12 months after injury are similar when treated with bioenhanced ACL repair, bioenhanced ACL reconstruction, or conventional ACL reconstruction, and all treatments yield results superior to untreated ACL transection. (2) After 1 year, macroscopic cartilage damage following bioenhanced ACL repair is similar to that in bioenhanced ACL reconstruction and less than in conventional ACL reconstruction and untreated ACL transection.Controlled laboratory study.A total of 64 Yucatan mini-pigs underwent ACL transection and randomization to 4 experimental groups: no treatment, conventional ACL reconstruction, bioenhanced ACL reconstruction using a bioactive scaffold, and bioenhanced ACL repair using a bioactive scaffold. The biomechanical properties of the ligament or graft were examined and macroscopic assessments of the cartilage surfaces were performed after 6 and 12 months of healing.The structural properties (ie, linear stiffness, yield, and maximum loads) of the ligament after bioenhanced ACL repair were not significantly different from those in bioenhanced ACL reconstruction or conventional ACL reconstruction but were significantly greater than those in untreated ACL transection after 12 months of healing. Macroscopic cartilage damage after bioenhanced ACL repair was significantly less than that in untreated ACL transection and bioenhanced ACL reconstruction, and there was a strong trend (P = .068) for less macroscopic cartilage damage than in conventional ACL reconstruction in the porcine model at 12 months.Bioenhanced ACL repair produces a ligament that is biomechanically similar to an ACL graft and provides chondroprotection to the joint after ACL surgery.Bioenhanced ACL repair may provide a new, less invasive treatment option that reduces cartilage damage following joint injury.

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Posttraumatic knee osteoarthritis following anterior cruciate ligament injury: Potential biochemical mediators of degenerative alteration and specific biochemical markers.

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Posttraumatic knee osteoarthritis following anterior cruciate ligament injury: Potential biochemical mediators of degenerative alteration and specific biochemical markers.

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