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Mechanical factors have been implicated in the development of osteoarthritis after anterior cruciate ligament (ACL) reconstruction. This study tested for associations between ambulatory joint loading (total joint moment [TJM] and vertical ground reaction force [vGRF]) and changes in serum levels of cartilage oligomeric matrix protein (COMP) in response to a mechanical stimulus (30‐min walk) in individuals with ACL reconstruction. Twenty‐five subjects (mean age: 34.5 ± 9.8 years; 2.2 ± 0.2 years post‐surgery) with primary unilateral ACL reconstruction underwent gait analysis for assessment of peak vGRF and TJM first (TJM1) and second (TJM2) peaks. Serum COMP concentrations were measured by enzyme‐linked immunosorbent assay immediately before, 3.5 h, and 5.5 h after a 30‐min walk. Pearson correlation coefficients and backward stepwise multiple linear regression analysis, with adjustments for age, sex, body mass index, and between‐limb speed difference, assessed associations between changes in COMP and between‐limb differences in joint loading parameters. Greater TJM1 (R = 0.542, p = 0.005), TJM2 (R = 0.460, p = 0.021), and vGRF (R = 0.577, p = 0.003) in the ACL‐reconstructed limb as compared to the contralateral limb were associated with higher COMP values 3.5 h following the 30‐min walk. Change in COMP at 5.5 h became a significant predictor of the between‐limb difference in TJM1 and vGRF in multivariate analyses after accounting for the between‐limb speed difference. These results demonstrate that higher TJM and vGRF in the ACLR limb as compared to the contralateral limb are associated with higher relative COMP levels 3.5 and 5.5 h after a 30‐min walk. Future work should investigate the effect of therapies to alter joint loading on the biological response in individuals after ACL reconstruction. [ABSTRACT FROM AUTHOR]

Disruptions in knee biomechanics during walking following anterior cruciate ligament (ACL) injury have been suggested to lead to the development of premature knee osteoarthritis (OA) and to be potential markers of OA risk and targets for intervention. This study investigated if side‐to‐side differences in early stance peak vertical ground reaction force (vGRF) during walking 2 years after ACL reconstruction are associated with longer‐term (10 years post‐reconstruction) changes in patient‐reported outcomes. Twenty‐eight participants (mean age: 28.7 ± 6.4 years) with primary unilateral ACL reconstruction underwent gait analysis for assessment of peak vGRF and completed Knee Injury and Osteoarthritis Outcome Score (KOOS) and International Knee Documentation Committee (IKDC) surveys at 2 years post‐surgery (2.2 ± 0.3 years) and completed surveys at follow‐up 10 years post‐surgery (10.5 ± 0.9 years). Associations between changes (10–2 years) in patient‐reported outcomes and between limb‐differences in vGRF were assessed with Pearson or Spearman's ρ correlation coefficients and exploratory backwards elimination multiple linear regression analyses. Differences in vGRF between symptomatic progressors and non‐progressors were also assessed. The side‐to‐side difference in vGRF was related to the variability in longer‐term changes in patient‐reported outcome metrics and distinguished symptomatic progressors from non‐progressors. Participants with higher vGRF in the reconstructed (ACLR) limb versus the contralateral limb had worsening of IKDC (R = −0.391, p = 0.040), KOOS pain (ρ = −0.396, p = 0.037), KOOS symptoms (ρ = −0.572, p = 0.001), and KOOS quality of life (R = −0.458, p = 0.014) scores at follow‐up. Symptomatic progressors had greater vGRF in the ACLR limb as compared to the contralateral limb at baseline than non‐progressors (p = 0.023). These data highlight associations between a simple‐to‐measure gait metric and the development of long‐term clinical symptoms after an ACL injury. [ABSTRACT FROM AUTHOR]

This study aimed to determine if changes in knee adduction moment (KAM) after 6 months of variable‐stiffness shoe wear are associated with changes in symptoms or serum levels of cartilage oligomeric matrix protein (COMP) following a mechanical stimulus in subjects with medial knee osteoarthritis (OA). Twenty‐five subjects were enrolled in the study and assigned a variable‐stiffness shoe, and 19 subjects completed the 6‐month follow‐up. At baseline and follow‐up subjects underwent gait analysis in control and variable‐stiffness shoes, completed Western Ontario and McMaster Universities (WOMAC) questionnaires, and serum COMP concentrations were measured immediately before, 3.5 and 5.5 hours after a 30‐minute walking activity. Relationships between changes in KAM (first peak and impulse) and changes in (a) COMP levels in response to the 30‐minute walking activity and (b) WOMAC scores from baseline to 6‐month follow‐up were assessed by Pearson correlation coefficients. Changes in first peak KAM were associated with changes in COMP levels 5.5 hours postactivity from baseline to follow‐up (R =.564, P =.045). Subjects with greater reductions in KAM had larger decreases in COMP (expressed as a percent of preactivity levels) at follow‐up. Subjects with greater reductions in KAM impulse had significantly greater improvements in WOMAC Pain (R = −.56, P =.015) and Function (R = −.52, P =.028) scores at follow‐up. The study results demonstrated the magnitude of reduction in the KAM wearing a variable‐stiffness shoe is associated with decreases in mechanically stimulated COMP levels and pain/function. This work suggests that interactions between COMP and joint loading during walking should be further investigated in future studies of treatment outcomes in OA. [ABSTRACT FROM AUTHOR]

ABSTRACT: Progression of medial compartment knee osteoarthritis (OA) has been associated with repetitive mechanical loading during walking, often characterized by the peak knee adduction (KAM) and knee flexion moments (KFM). However, the relative contributions of these components to the knee total joint moment (TJM) can change as the disease progresses since KAM and KFM are influenced by different factors that change over time. This study tested the hypothesis that the relative contributions of KAM, KFM, and the rotational moment (KRM) to the TJM change over time in subjects with medial compartment knee OA. Patients with medial compartment knee OA (n = 19) were tested walking at their self‐selected speed at baseline and a 5‐year follow‐up. For each frame during stance, the TJM was calculated using the KAM, KFM, and KRM. The peaks of the TJM and the relative contributions of the moment components at the time of the peaks of the TJM were tested for changes between baseline and follow‐up. The percent contribution of KFM to the first peak of the TJM (TJM1) significantly decreased (p < 0.001) and the percent contribution of KAM to TJM1 significantly increased (p < 0.001), while the magnitude of the TJM1 did not significantly change over the 5‐year follow‐up. These gait changes with disease progression appear to maintain a constant TJM1, but the transition from a KFM to a KAM dominance appears to reflect gait changes associated with progressing OA and pain. Thus, the TJM and its component analysis captures a comprehensive metric for total loading on the knee over time. Published 2018. This article is a U.S. Government work and is in the public domain in the USA. 36:2373–2379, 2018. [ABSTRACT FROM AUTHOR]

ABSTRACT: The objective of the study was to test the hypothesis that serum levels of cartilage oligomeric matrix protein (COMP) would decrease and serum levels of tumor‐necrosis factor alpha (TNF‐α) and selected matrix metalloproteinases (MMPs) would increase in response to bed rest (BR) and that these changes are unaffected by the intake of potassium bicarbonate or whey protein. Seven and nine healthy male subjects participated in two 21‐day 6° head down tilt crossover BR‐studies with nutrition interventions. Serum samples were taken before, during, and after BR and biomarker concentrations were measured using commercial enzyme‐linked immunosorbent assays. MMP‐3 during BR was significantly lower than at baseline (reduction greater 20%; p < 0.001). MMP‐3 increased significantly from 14 to 21 days of BR (+7%; p = 0.049). COMP during BR was significantly lower than at baseline (reduction greater 20%; p < 0.001). MMP‐3 and COMP returned to baseline within 1 day after BR. MMP‐9 on day 3 of BR was significantly lower than at baseline (−31%; p < 0.033) and on days 3, 5, and 14 of BR significantly lower than at the end of and after BR (reduction greater 35%; p < 0.030). The nutritional countermeasures did not affect these results. The observed changes in cartilage biomarkers may be caused by altered cartilage metabolism in response to the lack of mechanical stimulus during BR and inflammatory biomarkers may play a role in changes in biomarker levels. Clinical relevance: Immobilization independently from injury can cause altered cartilage biomarker concentration. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1465–1471, 2018. [ABSTRACT FROM AUTHOR]

ABSTRACT: The purpose of this study was to longitudinally investigate changes in knee joint kinematics and kinetics from 2 to 8 years post‐ACLR. Seventeen subjects with primary unilateral transtibial ACLR performed bilateral gait analysis approximately 2 years and 8 years post‐ACLR. Seventeen matched healthy control subjects were also analyzed. Kinematic and kinetic comparisons between the ACLR and contralateral limbs over time were completed using a 2 × 2 (time, limb) repeated‐measures ANOVA. Unpaired Student's t‐tests were used to compare the ACLR and contralateral kinematics and kinetics to the control group. The ACLR and contralateral limbs had similar gait changes over time. Kinetic changes over time included a reduction in first (p = 0.048) and second (p < 0.001) peak extension moments, internal rotation moment (p < 0.001), adduction moment (first peak: p = 0.002, second peak: p = 0.009, impulse: p = 0.004) and an increase in peak knee flexion moment (p = 0.002). Kinematic changes over time included increases in peak knee flexion angle in the first half of stance (p = 0.026), minimum knee flexion angle in the second half of stance (p < 0.001), and average external rotation angle during stance (p = 0.007), and a reduction in average anterior femoral displacement during stance (p = 0.006). Comparison to healthy controls demonstrated improvement in some gait metrics over time. The results demonstrated longitudinal changes from 2 to 8 years after ACLR in knee joint kinetics and kinematics that have been related to clinical outcome after ACLR and the progression of knee OA, and support future larger and comprehensive investigations into long‐term changes in joint mechanics in the ACLR population. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1478–1486, 2018. [ABSTRACT FROM AUTHOR]

ABSTRACT: Using serum biomarkers to assess osteoarthritis (OA) disease state and risks of progression remain challenging. This study tested the hypothesis that changes to serum biomarkers in response to a mechanical stimulus in patients with medial knee OA signal cartilage thickness changes 5 years later. Specifically, serum concentrations of a collagen degradation marker (C1,2C) and a chondroitin sulfate synthesis marker (CS846) were measured 0.5 and 5.5 hours after a 30‐min walk in 16 patients. Regional cartilage thickness changes measured from magnetic resonance images obtained at study entry and at 5‐year follow‐up were tested for correlations with baseline biomarker changes after mechanical stimulus, and for differences between groups stratified based on whether biomarker levels increased or decreased. Results showed that an increase in the degradation biomarker C1,2C correlated with cartilage thinning of the lateral tibia (R = −0.63, p = 0.009), whereas an increase in the synthesis marker CS846 correlated with cartilage thickening of the lateral femur (R = 0.76, p = 0.001). Changes in C1,2C and CS846 were correlated (R2 = 0.28, p = 0.037). Subjects with increased C1,2C had greater (p = 0.05) medial tibial cartilage thinning than those with decreased C1,2C. In conclusion, the mechanical stimulus appeared to metabolically link the biomarker responses where biomarker increases signaled more active OA disease states. The findings of medial cartilage thinning for patients with increases in the degradation marker and correlation of cartilage thickening in the less involved lateral femur with increases in the synthetic marker were consistent with progression of medial compartment OA. Thus, the mechanical stimulus facilitated assessing OA disease states using serum biomarkers. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:891–897, 2018. [ABSTRACT FROM AUTHOR]

Reduced quadriceps contraction has been suggested as an adaptation to prevent anterior tibial translation in anterior cruciate ligament (ACL)-deficient knees. This theory has been supported by a recent study that peak knee flexion moment (thought to be created by a decrease of quadriceps contraction) during walking was negatively correlated with patellar ligament insertion angle (PLIA) in ACL-deficient knees, but not in contralateral, uninjured knees. In addition, the PLIA was significantly smaller in ACL-deficient knees than in contralateral, uninjured knees. However, it is unknown whether ACL reconstruction restores the PLIA or whether the relationship between the PLIA and knee flexion moments previously observed in ACL-deficient knees disappears. This study tested the following hypotheses: (1) The PLIA of ACL-reconstructed knees is significantly smaller than the PLIA of uninjured contralateral knees; (2) Peak knee flexion moment (balanced by net quadriceps moment) during walking is negatively correlated with the PLIA in ACL-reconstructed knees. The PLIA of 24 ACL-reconstructed and contralateral knees were measured using MRI, and peak knee flexion moments during walking were measured. Results showed that the PLIA of ACL-reconstructed (22.9 ± 4.4°) knees was not significantly smaller ( p = 0.09, power = 0.99) than the PLIA of contralateral (24.1 ± 4.8°) knees. Peak knee flexion moment was not correlated with the PLIA following ACL reconstruction ( R2 = 0.016, power = 0.99). However, the magnitude of the knee flexion moment remained significantly lower in ACL-reconstructed knees. In summary, this study has shown that the PLIA of ACL-reconstructed knees returned to normal and that patients no longer adapt their gait in response to the PLIA, though quadriceps function did not return to normal levels. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 730-735, 2009 [ABSTRACT FROM AUTHOR]