Circulating levels of proinflammatory mediators as potential biomarkers of post-traumatic knee osteoarthritis development.

BACKGROUND: The identification of biomarkers of post-traumatic osteoarthritis (PTOA) progression is of clinical importance. The aims of this study were: (1) to assess the abilities of various soluble proinflammatory mediators in plasma to distinguish patients with knee PTOA from controls; (2) to determine the correlations between the mediators in plasma and those mediators in synovial fluid (SF); and (3) to explore the associations of the mediators with radiographic PTOA severity. MATERIALS AND METHODS: The concentrations of IL-1ß, IL-6, IL-18, TNFα, and leptin were measured using ELISA. Nitric oxide was determined as nitrite/nitrate (NO x ) using the Griess reaction. RESULTS: We included 171 subjects (134 PTOA patients and 37 controls) and excluded patients with rheumatoid arthritis or gout. The ROC curve of plasma NO x had the highest AUC, a specificity of 100%, and a sensitivity of 84.4%. The combination of IL-6 and leptin proved to be the most discriminatory, with an AUC value of 0.933, a specificity of 96.7%, and a sensitivity of 85.7%. The levels of NO x , IL-6, IL-18, and leptin in plasma were significantly correlated with their levels in SF. Leptin levels in both plasma (p = 0.036) and SF (p = 0.041) and the synovial IL-18 level (p = 0.045) were correlated with the Kellgren-Lawrence (KL) grade. Early-stage PTOA (KL 1-2) was associated with a high concentration of IL-1ß in plasma before and after (OR 6.235, 95% CI 1.362 to 28.552, p = 0.018) adjusting for age, gender, and BMI. CONCLUSIONS: Circulating NO x level and a combination of IL-6 and leptin permitted the strongest discrimination of patients with PTOA from controls. PTOA severity was correlated with leptin levels in plasma and SF and with the synovial IL-18 level. Early PTOA was associated with the circulating level of IL-1ß. LEVEL OF EVIDENCE: III (case-control study).

[PROINFLAMMATORY CYTOKINE GENE POLYMORPHISMS AND THE PLASMA AND SYNOVIAL FLUID LEVELS OF CYTOKINES IN PATIENTS WITH POST-TRAUMATIC KNEE OSTEOARTHRITIS].

Post-traumatic knee osteoarthritis patients (n=117) and healthy people (n=94) were investigated to determine the genotypic and allelic frequency distribution of polymorphic loci Т-31С, С+3953Т IL-1ß and G-308A TNF-α. The plasma and synovial fluid levels of proinflammatory cytokines IL-1ß and TNF-α were measured in 31 patients. The research demonstrated that the blood and synovial fluid levels of IL-1ß but not TNF-α were increased in patients with post-traumatic knee osteoarthritis. Also, the linkage between TNF-α level and polymorphic locus G-308A TNF-α was shown: the presence of allele -308А was associated with decreased TNF-α level. We demonstrated that polymorphic loci Т-31С, С+3953Т IL-1ß and G-308A TNF-α do not predict the higher risk of post-traumatic knee osteoarthritis development in Russian population of Rostov-on-Don region.

Prolonged quadriceps latency during gait early after anterior cruciate ligament injury predicts radiographic knee osteoarthritis 6-years after anterior cruciate ligament reconstruction.

BACKGROUND: The purpose was to explore quadriceps electromechanical function (quadriceps latency) during gait after anterior cruciate ligament injury as a predictor for radiographic knee osteoarthritis 6-years after anterior cruciate ligament reconstruction. Change in latency after preoperative physical therapy was also examined. METHODS: Quadriceps latency (time between peak knee moment and quadriceps electromyography) was calculated before preoperative physical therapy (2.4 [0.5-7.5] months after anterior cruciate ligament injury) and after preoperative physical therapy in 24 athletes. Participants were dichotomized into osteoarthritis (Kellgren and Lawrence grade ≥ 2) and non-osteoarthritis groups at 6-years. Forward selection logistic regression was performed using z-score normalized quadriceps latency and demographics. A 2 × 2 repeated measure ANOVA was performed for quadriceps latency between groups before and after preoperative physical therapy. FINDINGS: Quadriceps latency before preoperative physical therapy was the only predictor of 6-year radiographic osteoarthritis (p = 0.014, odds ratio [95% confidence interval] = 5.859 [1.435-23.924]). Time by group interaction was observed for quadriceps latency (p = 0.039, η2p = 0.179). In the osteoarthritis group, latency may reduce after training (before preoperative physical therapy = 115.7 ± 20.6 ms, after preoperative physical therapy = 99.5 ± 24.0 ms, p = 0.082). INTERPRETATION: Prolonged latency after anterior cruciate ligament injury may predict post-traumatic knee osteoarthritis 6-years after anterior cruciate ligament reconstruction. Latency may shorten with preoperative physical therapy, yet athletes still moved on to develop osteoarthritis. Quadriceps function may need intervention immediately following anterior cruciate ligament injury for prevention of post-traumatic knee osteoarthritis.

Chronic ACLD Knees with Early Developmental Cartilage Lesions Exhibited Increased Posterior Tibial Translation during Level Walking.

OBJECTIVE: Early articular cartilage lesion (CL) is a vital sign in the onset of posttraumatic knee osteoarthritis (PTOA) in patients with anterior cruciate ligament deficiency (ACLD). Researchers have suggested that altered kinematics could accelerate CLs and, therefore, lead to the onset of PTOA. However, little is known about whether specific knee kinematics exist that lead to early CL in chronic ACLD knees. Level walking is the most frequent and relevant in vivo activity, which greatly impacts knee health. We hypothesized that the knee kinematics during level walking in chronic ACLD knees with early tibiofemoral CL would significantly differ from those of chronic ACLD knees without early tibiofemoral CL. METHODS: Thirty patients with a chronic ACLD history, including 18 subjects with CLs and 12 subjects without CLs, and 35 healthy control subjects were recruited for the study from July 2020 to August 2022. The knee kinematic data during level walking were collected using a three-dimensional motion analysis system. The kinematic differences between groups were compared using statistical parametric mapping with one dimension for One-Way ANOVA. The cartilage statuses of the ACLD knees were assessed via MRI examination. The CLs distribution of subjects was evaluated using a modified Noyes scale and analyzed by chi-square tests. RESULTS: ACLD knees with CLs had significantly greater posterior tibial translation (7.7-8.0mm, 12%-18% gait cycle GC, p = 0.014) compared to ACLD knees without CLs during level walking. ACLD knees with CLs had greater posterior tibial translation (4.6-5.5mm, 0%-23% GC, p < 0.001; 5.8-8.0mm, 86%-100% GC, p < 0.001) than healthy controls during level walking. In the group of ACLD knees with CLs, CL is mainly located in the back of the tibia plateau and front of load bearing area of the medial femoral condyle (p < 0.05). CONCLUSION: Chronic anterior cruciate ligament deficient knees with cartilage lesions have increased posterior tibial translation compared to anterior cruciate ligament deficient knees without cartilage lesions and healthy subjects. The posterior tibial translation may play an important role in knee cartilage degeneration in ACLD knees. The increased posterior tibial translation and cartilage lesion characteristics may improve our understanding of the role of knee kinematics in cartilage degeneration and could be a helpful potential reference for anterior cruciate ligament deficient therapy, such as physical training to improve abnormal kinematic behavior.

Post-traumatic knee osteoarthritis; the role of inflammation and hemarthrosis on disease progression.

Knee injuries such as anterior cruciate ligament ruptures and meniscal injury are common and are most frequently sustained by young and active individuals. Knee injuries will lead to post-traumatic osteoarthritis (PTOA) in 25-50% of patients. Mechanical processes where historically believed to cause cartilage breakdown in PTOA patients. But there is increasing evidence suggesting a key role for inflammation in PTOA development. Inflammation in PTOA might be aggravated by hemarthrosis which frequently occurs in injured knees. Whereas mechanical symptoms (joint instability and locking of the knee) can be successfully treated by surgery, there still is an unmet need for anti-inflammatory therapies that prevent PTOA progression. In order to develop anti-inflammatory therapies for PTOA, more knowledge about the exact pathophysiological mechanisms and exact course of post-traumatic inflammation is needed to determine possible targets and timing of future therapies.

The effect of a longitudinal tear of the medial meniscus on medial meniscal extrusion in anterior cruciate ligament injury patients.

PURPOSE: The purpose of this study was to investigate the effect of a longitudinal tear of the medial meniscus (MM) and its meniscal repair on MM extrusion in anterior cruciate ligament (ACL)-injured patients. The hypothesis underlying this study was that a longitudinal tear of the MM is correlated with MM extrusion, and that the extrusion would persist after ACL reconstruction with concomitant MM repair. METHODS: Forty-three ACL-injured patients with a concomitant MM longitudinal tear were included in the MM tear group. Thirty-four solely ACL-injured patients without any meniscal injuries were included in the Control group. Medial meniscus extrusion width (MEW) was measured pre-operatively and three months after surgery on magnetic resonance imaging. RESULTS: Pre-operative MEW in the MM tear group was significantly larger than that in the Control group (MM tear group: 1.5 mm, Control: 0.3 mm, P < 0.001). The MEW change in the MM tear group was significantly greater than that in the Control group three months after operation (MM tear group: 0.8 mm, Control: -0.2 mm, P < 0.001). The number of sutures required for repair was correlated with MEW both pre-operatively and postoperatively in the MM tear group (pre-operative: P = 0.005, R = 0.42, postoperative: P < 0.001, R = 0.54). CONCLUSION: Longitudinal tear of the MM was correlated with MM extrusion and the MM extrusion persisted after ACL reconstruction with concomitant MM repair in the MM tear group. The initial meniscal tear size was directly correlated with the pre-operative MEW. Therefore, meniscal extrusion after longitudinal tears of the medial meniscus should be taken into careful consideration.

Arthroscopically assisted reduction and internal fixation (ARIF) versus open reduction and internal fixation (ORIF) for lateral tibial plateau fractures: a comparative retrospective study.

BACKGROUND: This study aims to explore if the arthroscopically assisted reduction and internal fixation (ARIF) technique is superior to the traditional open reduction and internal fixation (ORIF) technique in the treatment of tibial lateral plateau fractures. METHODS: Forty patients with tibial plateau fractures (Schatzker type I-III) treated with ARIF or ORIF from 2012 to 2017 were included in this retrospective study. All patients received pre-operative radiographs and CT scans. The patients were divided into two groups (ARIF or ORIF). All patients had a minimum follow-up of 12 months and an average follow-up of 44.4 months. The clinical and radiographic outcomes were evaluated according to the Knee Society Score (KSS) and the modified Rasmussen radiological score. RESULTS: Satisfactory clinical and radiological results were found in 39 out of 40 (97.5%) patients. KSS and modified Rasmussen radiological score were significantly better in ARIF group. The mean KSS was 92.37 (± 6.3) for the ARIF group and 86.29 (± 11.54) for the ORIF group (p < 0.05). The mean modified Rasmussen radiographic score was 8.42 (± 2.24) for the ARIF group and 7.33 (± 1.83) for the ORIF group (p = 0.104). Worst clinical and radiological results were related to concomitant intra-articular lesions (p < 0.05). Meniscal tears were found and treated in 17 out of 40 (42.5%) patients. The overall complication rate was 10%. CONCLUSIONS: Both ARIF and ORIF provided a satisfactory outcome for the treatment of Schatzker I-III tibial plateau fractures. However, ARIF led to better clinical results than ORIF. No statistically significant differences were found in perioperative complications, radiological results, and post-traumatic knee osteoarthritis. LEVEL OF EVIDENCE: Level III.

Myrtol improves post-traumatic knee osteoarthritis by regulation of reactive oxygen species, transforming growth factor ß1 and apoptosis in a mouse model.

The present study tested whether myrtol improves post-traumatic knee osteoarthritis (PTKO) by regulating the reactive oxygen species (ROS), transforming growth factor ß1 (TGF-ß1) and apoptosis in a mouse model. PTKO model mice were administered with 150, 300 or 450 mg/kg myrtol for 8 weeks. ELISA analysis was used to measure tumor necrosis factor-α, interleukin-6, malondialdehyde, superoxide dismutase, reactive oxygen species and TGF-ß1 levels. Caspase-3 and Bax protein expressions were analyzed using western blot analysis. In the current study, treatment with myrtol improved the tissue damage and osteoarthritis score, while it also reversed the subchondral bone thickness, subchondral bone density, trabecular bone volume/relative trabecular bone volume ratio and trabecular bone spacing in PTKO mice. The activity of tumor necrosis factor α, interleukin-6, TGF-ß1, malondialdehyde, superoxide dismutase and ROS were effectively inhibited, and the protein expression of caspase-3 and Bax were clearly suppressed by treatment with myrtol in a mouse model of PTKO. In conclusion, the results demonstrated that myrtol treatment improved PTKO through the suppression of inflammation, oxidative stress, ROS, TGF-ß1 and Bax/caspase-3 in mice, and myrtol may be a potential agent for clinical therapy.

Ten-year survival and complications of total knee arthroplasty for osteoarthritis secondary to trauma or surgery: A French multicentre study of 263 patients.

BACKGROUND: Previous surgical procedures raise technical challenges in performing total knee arthroplasty (TKA) and may affect TKA outcomes. Survival rates of TKA done after trauma or surgery to the knee have not been accurately determined in large populations. The objectives of this retrospective study in 263 patients with TKA after knee trauma or surgery and a follow-up of 10 years were to assess survival, functional outcomes, and the nature and frequency of complications. HYPOTHESIS: Knee trauma or surgery before TKA increases the risk of complications and decreases implant survival. MATERIAL AND METHODS: Two hundred and sixty-three patients (122 [47%] females and 141 [53%] males) underwent TKA between 2005 and 2009 at nine centres in France. Mean age at surgery was 61 years. The patients had knee osteoarthritis secondary to a fracture (n=66), osteotomy (n=131), or ligament injury (n=66). Mean time from trauma or surgery to TKA was 145 months (range, 72-219 months). RESULTS: Major complications were infection (n=12, 4.5%), skin problems (n=8, 3%), and stiffness (n=8, 3%). Ten-year survival to implant exchange for any reason was 89%±2.8%. Flexion range increased by 2.5°±17° (p=0.02) to a mean of 110° (range, 30° to 140°); extension range increased by 4°±7° (p<0.001) to a mean of -1.19 (range, -20° to 0°). Of the 263 patients, 157 (60%) reported little or no pain at last follow-up. Mean postoperative hip-knee-ankle angle was 179°±3.2° (range, 171°-188°). CONCLUSION: TKA performed after knee injury or surgery carries a risk of specific complications (infection, skin problems, and stiffness) and may have a lower survival rate compared to primary TKA. LEVEL OF EVIDENCE: IV, retrospective cohort study.

Early Intervention with Therapeutic Low-Intensity Pulsed Ultrasound in Halting the Progression of Post-traumatic Osteoarthritis in a Rat Model.

Anterior cruciate ligament (ACL) and meniscus injuries are highly correlated with post-traumatic knee osteoarthritis (PTOA). The aim of this study was to examine whether early intervention with low-intensity pulsed ultrasound (LIPUS) at an intensity of 0.1 W/cm2 helps delay PTOA progression. A PTOA model was established by ACL transection and meniscectomy in male Sprague-Dawley rats. LIPUS intervention (1.0 MHz, 0.1 W/cm2) started on the third day after surgery and continued for 4 consecutive wk. Histopathological analyses and immunoassays of collagen type II and matrix metallopeptidase 13 in joints were conducted. Results indicated that compared with the sham treatment, LIPUS significantly reduced Mankin scores, inflammatory cells and matrix metallopeptidase 13 expression and increased collagen type II expression in rats with PTOA (p < 0.05). Early intervention with LIPUS has beneficial effects on delaying cartilage degradation by reducing synovial inflammation and matrix metallopeptidase 13 expression, as well as enhancing collagen type II expression in cartilage.

Sivelestat sodium hydrate improves post-traumatic knee osteoarthritis through nuclear factor-κB in a rat model.

As a specific inhibitor of neutrophil elastase, sivelestat sodium hydrate has primarily been used in the treatment of acute lung injury caused by various factors since its approval in 2002. Sivelestat sodium hydrate also improves post-traumatic knee osteoarthritis (KOA), although its underlying mechanisms of action have yet to be elucidated. The aim of the current study was to determine if sivelestat sodium hydrate improves post-traumatic KOA through nuclear factor (NF)-κB in a rat model. Treatment with sivelestat sodium hydrate significantly inhibited the induction of structural changes and significantly increased the vertical episode count and ipsilateral static weight bearing of the joint in KOA rats (all P<0.01). Sivelestat sodium hydrate significantly inhibited tumor necrosis factor-α and interleukin-6 production, serum nitrite levels, inducible nitric oxide synthase protein expression and high mobility group box 1 (HMGB1) secretion in KOA rats compared with the model group (all P<0.01). Sivelestat sodium hydrate also significantly suppressed p50/p65 DNA binding activity and NF-κB and phosphorylated inhibitor of κB protein expression in the joints of KOA rats compared with the model group (all P<0.01). These results suggest that sivelestat sodium hydrate improves post-traumatic KOA through HMGB1 and NF-κB in rats.