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BACKGROUND: Menstrual cycle phase has been correlated with risk of noncontact anterior cruciate ligament injury in women. The mechanism by which hormonal cycling may affect injury rate is unknown. HYPOTHESES: Jumping and landing activities performed during different phases of the menstrual cycle lead to differences in foot strike knee flexion, as well as peak knee and hip loads, in women not taking an oral contraceptive but not in women taking an oral contraceptive. Women will experience greater normalized joint loads than men during these activities. STUDY DESIGN: Controlled laboratory study. METHODS: Twenty-five women (13 using oral contraceptives) and 12 men performed repeated trials of a horizontal jump, vertical jump, and drop from a 30-cm box on the left leg. Lower limb kinematics (foot strike knee flexion) and peak externally applied moments were calculated (hip adduction moment, hip internal rotation moment, knee flexion moment, knee abduction moment). Men were tested once. Women were tested twice for each phase of the menstrual cycle (follicular, luteal, ovulatory), as determined from serum analysis. An analysis of variance was used to examine differences between phases of the menstrual cycle and between groups (alpha = .05). RESULTS: No significant differences in moments or knee angle were observed between phases in either female group or between the 2 female groups or between either female group and the male controls. CONCLUSIONS: Variations of the menstrual cycle and the use of an oral contraceptive do not affect knee or hip joint loading during jumping and landing tasks. CLINICAL RELEVANCE: Because knee and hip joint loading is unaffected by cyclic variations in hormone levels, the observed difference in injury rates is more likely attributable to persistent differences in strength, neuromuscular coordination, or ligament properties. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study tested the hypothesis that gait changes related to knee osteoarthritis (OA) of varied severity are associated with increased loads at the ankle, knee, and hip. METHODS: Forty-two patients with bilateral medial compartment knee OA and 42 control subjects matched for sex, age, height, and mass were studied. Nineteen patients had Kellgren/Lawrence (K/L) radiographic severity grades of 1 or 2, and 23 patients had K/L grades of 3 or 4. Three-dimensional kinematics and kinetics were measured in the hip, knee, and ankle while the subjects walked at a self-selected speed. RESULTS: Patients with more severe knee OA had greater first peak knee adduction moments than their matched control subjects (P = 0.039) and than patients with less severe knee OA (P < 0.001). All patients with knee OA made initial contact with the ground with the knee in a more extended position than that exhibited by control subjects. An increased axial loading rate was present in all joints of the lower extremity. Patients with more severe knee OA had lower hip adduction moments compared with their matched control subjects. CONCLUSION: The secondary gait changes observed among patients with knee OA reflect a potential strategy to shift the body's weight more rapidly from the contralateral limb to the support limb, which appears to be successful in reducing the load at the knee in only patients with less severe knee OA. The increased loading rate in the lower extremity joints may lead to a faster progression of existing OA and to the onset of OA at joints adjacent to the knee. Interventions for knee OA should therefore be assessed for their effects on the mechanics of all joints of the lower extremity. [ABSTRACT FROM AUTHOR]

BACKGROUND: Increased valgus loading at the knee has been previously identified as a possible risk factor for noncontact anterior cruciate ligament injuries, which are common in sports. Arm position variation may affect risk of injury by altering valgus knee loading. HYPOTHESIS: Sport-dependent variations in arm position increase valgus loading of the knee during run-to-cut maneuvers. STUDY DESIGN: Controlled laboratory study. METHODS: Eleven subjects performed a sidestep cutting maneuver, first with no arm constraints and then with 3 sports-related arm positions in random order (holding a lacrosse stick, holding a football on the plant side, and holding a football on the cut side). The analysis focused on the knee valgus moment relative to the arm positions during the landing phase of the activity. RESULTS: Arm position significantly influenced the valgus moment with an increase in the lacrosse trials and in the plant-side football trials but not in the cut-side football trials (alpha = .05). CONCLUSIONS: Constraining the plant-side arm results in increased valgus loading at the knee during run-to-cut maneuvers, which suggests the possibility of greater risk of anterior cruciate ligament injury during these conditions. CLINICAL RELEVANCE: These results suggest that training methods that consider arm position as a risk factor could help reduce the risk of anterior cruciate ligament noncontact injury. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine whether reducing walking speed is a strategy used by patients with knee osteoarthritis (OA) of varying disease severity to reduce the maximum knee adduction moment. METHODS: Self-selected walking speeds and maximum knee adduction moments of 44 patients with medial tibiofemoral OA of varying disease severity, as assessed by using the Kellgren/Lawrence grade, were compared with those of 44 asymptomatic control subjects matched for sex, age, height, and weight. RESULTS: Differences in self-selected normal walking speed explained only 8.9% of the variation in maximum knee adduction moment for the group of patients with knee OA. The severity of the disease influenced the adduction moment-walking speed relationship; the individual slopes of this relationship were significantly greater in patients with less severe OA than in asymptomatic matched control subjects. Self-selected walking speed did not differ between patients with knee OA, regardless of the severity, and asymptomatic control subjects. However, knees with more-severe OA had significantly greater adduction moments (mean +/- SD 3.80 +/- 0.89% body weight x height) and were in more varus alignment (6.0 +/- 4.5 degrees ) than knees with less-severe OA (2.94 +/- 0.70% body weight x height; and 0.0 +/- 2.9 degrees, respectively). CONCLUSION: Patients with less-severe OA adapt a walking style that differs from that of patients with more-severe OA and controls. This walking style is associated with the potential to reduce the adduction moment when walking at slower speeds and could be linked to decreased disease severity. [ABSTRACT FROM AUTHOR]

This article discusses methods for evaluating the progression of osteoarthritis through dynamic functional imaging as opposed to current static techniques. Comparison is made between static and dynamic methods of evaluating knee alignment. The correlation between dynamic knee moments during gait and bone mineral content is discussed. Knee loading is considered in terms of high tibial osteotomy, knee braces, pain, and non-steroidal anti-inflammatory drugs. New image-processing techniques for quantitating cartilage loss are described, and computational methods for generating true three-dimensional (3-D) maps of cartilage thickness are developed. Finally, new approaches to cross-correlate magnetic resonance images with kinematic measurements are described. These new techniques promise to become powerful diagnostic tools to detect and characterize pathological load distributions across articular cartilage. [ABSTRACT FROM AUTHOR]

Five patients with symptomatic knee hyperextension thrusting patterns due to posterolateral ligament complex injury underwent gait analysis before and after a gait retraining program. Patients were trained to avoid knee hyperextension by 1) walking with their knees slightly flexed throughout stance, 2) maintaining ankle dorsiflexion in early stance, and 3) maintaining an erect trunk-hip attitude during stance. Kinematic and kinetic measurements were obtained using automated gait analysis. Four of the five patients significantly reduced hyperextension at the knee and abnormal motion patterns at the hip and ankle. Patients showed increases in knee flexion throughout stance conversions of knee flexion-extension moments to more normal biphasic patterns with a 79% decrease in extension moments at terminal extension, and a 22% decrease in knee adduction moments. Posttraining values also showed a 30% decrease in the calculated medial tibiofemoral loads (P < 0.05). At the hip, there were significant decreases in abduction and adduction moments (36% and 18%, respectively, P< 0.01). Ankle plantar flexion motion decreased significantly by 42% (P < 0.01). Gait retraining can alter the biomechanics of hip, knee, and ankle function to approximately normal levels, and therefore is recommended before ligament reconstruction because abnormal knee motions, if resumed postoperatively, can stretch soft tissue reconstructions. [ABSTRACT FROM AUTHOR]

Thirty-two patients with an ACL-deficient knee and lower limb varus alignment and 16 healthy controls were analyzed during level walking using a force-plate and optoelectronic system. The forces and moments of the lower limb and knee joint were measured and knee joint loads and ligament tensile forces were calculated using a mathematical model. The majority of patients (20 of 32) had an abnormally high adduction moment at the affected knee. The adduction moment showed a statistically significant correlation to high medial tibiofemoral compartment loads and high lateral soft tissue forces, but not to the degree of varus alignment on standing roentgenograms. Fifteen of 32 knees had abnormally high lateral soft tissue forces. We interpreted these gait findings as indicative of a medial shift in the center of maximal joint pressure and an increase in lateral soft tissue forces to achieve coronal plane stability. Further, there is the likelihood of separation of the lateral tibiofemoral joint and 'condylar lift-off' during periods of the stance phase. If this occurs, all of the load-bearing forces would shift to the medial tibiofemoral joint and relatively large tensile forces would occur in the lateral soft tissue restraints. The flexion moment, as related to the quadriceps muscle force, was significantly lower than the control knees in 40% of the involved knees, and the extension moment, as related to the hamstring muscle force, was significantly higher in 50% of the involved knees. We interpret this finding as a gait adaptation tending to diminish quadriceps muscle activity and enhance hamstring muscle activity to provide dynamic anteroposterior stability of the knee joint. The fundamental assumption of this paper is that any combination of conditions leading to higher medial joint forces is associated with factors leading to more rapid degeneration of the medial compartment in patients with ACL deficiency, varus deformity, and lax lateral ligaments. [ABSTRACT FROM AUTHOR]

The percent force changes in the posterior cruciate ligament were calculated using a previously validated computerized knee model after the femoral insertion sites were varied 2.5 and 5.0 mm in an anterior, posterior distal, anterior distal, and posterior distal direction. The tibial insertion sites were also varied 2.5 amd 5.0 mm in the medial, lateral, proximal, and distal directions. Percent force changes were measured over a range of 0 degrees to 90 degrees. These insertion sites simulated potential surgical placement errors. Results of this study demonstrated that the greatest percent force changes in the posterior cruciate ligament were at full extension. The greatest absolute percent force change between 0 degrees and 90 degrees of flexion was with a femoral insertion of the posterior cruciate ligament placed 5 mm anterior to its normal attachment site, which resulted in a 39% change in the posterior cruciate ligament force. Distal femoral site attachment had the least effect (10% at 5.0 mm). Alterations at the tibial attachment site were less sensitive than on the femur; the greatest absolute percent force changes occurred with medial and lateral attachment sites (14% and 15%, respectively, at 5.0 mm). A minimal amount of percent force changes were seen between 45 degrees and 75 degrees of knee flexion in all positions tested for both tibial and femoral attachment sites. This model suggests that, like the anterior cruciate ligament, the force in the posterior cruciate ligament is also sensitive to attachment site position. As in anterior cruciate ligament studies, the femoral attachment site was found to be more sensitive. The greatest percent force changes for the posterior cruciate ligament were seen at the extremes of the knee motion tested (i.e., 0 degreees and 90 degrees). The posterior cruciate ligament sensitivity to graft placement lends credence to the importance of anatomic reconstruction. Results of this study can also be extrapolated to help in designing early continuous passive motion and rehabilitation programs, with the safest range of knee motion between 45 degrees and 75 degrees. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to test the hypothesis that proinflammatory cytokines correlate with knee loading mechanics during gait following a mechanical walking stimulus in subjects 2 years after anterior cruciate ligament reconstruction. Elevated systemic levels of proinflammatory cytokines can be sustained for years after injury. Considering roughly 50% of these patients progress to Osteoarthritis 10-15 years after injury, a better understanding of the role of proinflammatory cytokines such as tumor necrosis factor-α and Interleukin-1β on Osteoarthritis risk is needed., Methods: Serum proinflammatory cytokines concentrations were measured in 21 subjects 2 years after unilateral ACLR from blood drawn at rest and 3.5 h after 30 min of walking. An optoelectronic system and a force plate measured subjects' knee kinetics. Correlations were tested between inflammatory marker response and knee extension and knee adduction moments., Findings: Changes in proinflammatory cytokines due to mechanical stimulus were correlated (R = 0.86) and showed substantial variation between subjects in both cytokines at 3.5 h post-walk. Knee loading correlated with 3.5-h changes in tumor necrosis factor-α concentration (Knee extension moment: R = -0.5, Knee adduction moment: R = -0.5) and Interleukin-1β concentration (Knee extension moment: R = -0.44). However, no significant changes in concentrations were observed in tumor necrosis factor-α and Interleukin-1β when comparing baseline and post walking stimulus conditions., Interpretation: The significant associations between changes in serum proinflammatory markers following a mechanical stimulus and gait metrics in subjects at risk for developing Osteoarthritis underscore the importance of investigating the interaction between biomarkers and biomechanical factors in Osteoarthritis development., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To characterize ambulatory knee moments with respect to medial knee osteoarthritis (OA) severity comprehensively and to assess the possibility of developing a severity index combining knee moment parameters. Methods: Nine parameters (peak amplitudes) commonly used to quantify three-dimensional knee moments during walking were analyzed for 98 individuals (58.7 ± 9.2 years old, 1.69 ± 0.09 m, 76.9 ± 14.5 kg, 56% female), corresponding to three medial knee osteoarthritis severity groups: non-osteoarthritis ( n = 22), mild osteoarthritis ( n = 38) and severe osteoarthritis ( n = 38). Multinomial logistic regression was used to create a severity index. Comparison and regression analyses were performed with respect to disease severity. Results: Six of the nine moment parameters differed statistically significantly among severity groups ( p ≤ 0.039) and five reported statistically significant correlation with disease severity (0.23 ≤ | r | ≤ 0.59). The proposed severity index was highly reliable (ICC = 0.96) and statistically significantly different between the three groups ( p < 0.001) as well as correlated with disease severity ( r = 0.70). Conclusion: While medial knee osteoarthritis research has mostly focused on a few knee moment parameters, this study showed that other parameters differ with disease severity. In particular, it shed light on three parameters frequently disregarded in prior works. Another important finding is the possibility of combining the parameters into a severity index, which opens promising perspectives based on a single figure assessing the knee moments in their entirety. Although the proposed index was shown to be reliable and associated with disease severity, further research will be necessary particularly to assess its validity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ulrich, Erhart-Hledik, Asay, Omoumi, Andriacchi, Jolles and Favre.)

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., (© 2021 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

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., (© 2021 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Osteoarthritis (OA) is a leading cause of pain and disability for which disease-modifying treatments remain lacking. This is because the symptoms and radiographic changes of OA occur after the onset of likely irreversible changes. Defining and treating earlier disease states are therefore needed to delay or to halt OA progression. Taking this concept a step further, studying OA pathogenesis before disease onset by characterizing potentially reversible markers of increased OA risk to identify a state of "pre-osteoarthritis (pre-OA)" shifts the paradigm towards OA prevention. The purpose of this review is to summarize the 42 studies comprising the 2019 Kappa Delta Elizabeth Lanier Award where conceptualization of a systems-based definition for "pre-osteoarthritis (pre-OA)" was followed by demonstration of potentially reversible markers of heightened OA risk in patients after anterior cruciate ligament (ACL) injury and reconstruction. In the process, these efforts contributed a new magnetic resonance imaging method of ultrashort echo time (UTE) enhanced T2* mapping to visualize joint tissue damage before the development of irreversible changes. The studies presented here support a transformative approach to OA that accounts for interactions between mechanical, biological, and structural markers of OA risk to develop and evaluate new treatment strategies that can delay or prevent the onset of clinical disease. This body of work was inspired by and performed for patients. Shifting the paradigm from attempting to modify symptomatic radiographic OA towards monitoring and reversing markers of "pre-OA" opens the door for transforming the clinical approach to OA from palliation to prevention., (© 2021 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Background: Reduced quadriceps function and proprioception can cause decreased mobility during stair navigation in patients with knee pain. Patients can benefit from interventions to mitigate pain and restore quadriceps function. Activating the somatosensory system via intermittent vibrational stimulation has the potential to improve stair navigation mobility in patients with knee pain by moderating quadriceps inhibition and enhancing proprioception., Research Question: What are the effects of intermittent vibrational stimulus synchronized to stair ambulation on muscle activity, kinematics, kinetics, and pain using a randomized controlled clinical trial design., Methods: Thirty-eight patients with knee pain were enrolled into a blinded cross-over study, and twenty-nine patients completed all assessments and analyses. Subjects were randomly assigned sequentially to both an active Treatment A (active) and passive Treatment B (passive) worn at the knee during ambulation for 4 weeks with a 2-week washout period between treatments., Results: Knee pain during stair navigation was significantly reduced only with Treatment A (P = 0.007). During ascent, Treatment A (active) significantly increased vastus lateralis activation (P = 0.01), increased knee flexion moment (P = 0.04) and decreased trunk flexion angles (P = 0.015) between baseline and 4-week follow-up. After using passive Treatment B, there were no significant differences in pain (P = 0.19), knee flexion moment (P = 0.09), and trunk flexion angles (P = 0.23). Changes in muscle function correlated significantly with changes in knee flexion moment and trunk flexion with Treatment A (P < 0.015). Descending differed from ascending in response to Treatment A with significantly decreased knee flexion moment(P = 0.04), hip(P = 0.02) and ankle(P = 0.04) flexion angles. Treatment B significantly reduced hip flexion angles (P = 0.005) but not knee flexion moment (P = 0.85)., Significance: The results of this study suggest that intermittent vibration can improve joint motion and loading during stair navigation by enhancing quadriceps function during stair ascent and improving movement control during stair descent by modifying an adaptive flexed movement pattern in the lower limb., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: To address the need for early knee osteoarthritis (OA) markers by testing if longitudinal cartilage thickness changes are associated with specific biomechanical and biological measures acquired at a baseline test in asymptomatic aging subjects., Design: Thirty-eight asymptomatic subjects over age 45 years were studied at baseline and at an average of 7-9 year follow-up. Gait mechanics and knee MRI were measured at baseline and MRI was obtained at follow-up to assess cartilage thickness changes. A subset of the subjects (n = 12) also had serum cartilage oligomeric matrix protein measured at baseline in response to a mechanical stimulus (30-min walk) (mCOMP). Baseline measures, including the knee extension (KEM), flexion (KFM), adduction (KAM) moments and mCOMP, were tested for associations with cartilage thickness changes in specific regions of the knee., Results: Cartilage change in the full medial femoral condyle (p = 0.005) and external medial femoral region (p = 0.041) was negatively associated with larger early stance peak KEM. Similarly, cartilage change in the full medial femoral region (p = 0.009) and medial femoral external region (p = 0.043) was negatively associated with larger first peak KAM, while cartilage change in the anterior medial tibia was positively associated with larger first peak KAM (p = 0.003). Cartilage change in the anterior medial tibia was also significantly associated (p = 0.011) with mCOMP levels 5.5-h post-activity (percentage of pre-activity levels)., Conclusions: Interactions found between gait, mechanically-stimulated serum biomarkers, and cartilage thickness in an at-risk aging asymptomatic population suggest the opportunity for early detection of OA with new approaches that bridge across disciplines and scales., Competing Interests: Declaration of competing interest There are no conflicts of interest for any of the authors., (Copyright © 2021. Published by Elsevier Ltd.)

Background : This study compares knee kinematics in two groups of patients who have undergone primary total knee arthroplasty (TKA) using two different modern designs: medially congruent (MC) and posterior-stabilized (PS). The aim of the study is to demonstrate only minimal differences between the groups. Methods : Ten TKA patients (4 PS, 6 MC) with successful clinical outcomes were evaluated through 3D knee kinematics analysis performed using a multicamera optoelectronic system and a force platform. Extracted kinematic data included knee flexion angle at heel-strike (KFH), peak midstance knee flexion angle (MSKFA), maximum and minimum knee adduction angle (KAA), and knee rotational angle at heel-strike. Data were compared with a group of healthy controls. Results: There were no differences in preferred walking speed between MC and PS groups, but we found consistent differences in knee function. At heel-strike, the knee tended to be more flexed in the PS group compared to the MC group; the MSKFA tended to be higher in the PS group compared to the MC group. There was a significant fluctuation in KAA during the swing phase in the PS group compared to the MC group, PS patients showed a higher peak knee flexion moment compared to MC patients, and the PS group had significantly less peak internal rotation moments than the MC group. Conclusions: Modern, third-generation TKA designs failed to reproduce normal knee kinematics. MC knees tended to reproduce a more natural kinematic pattern at heel-strike and during axial rotation, while PS knees showed better kinematics during mid-flexion.

Background: Patellofemoral joint degeneration and dysfunction after anterior cruciate ligament reconstruction (ACLR) are increasingly recognized as contributors to poor clinical outcomes., Purpose: To determine if greater deep cartilage matrix disruption at 2 years after ACLR, as assessed by elevated patellofemoral magnetic resonance imaging (MRI) ultrashort echo time-enhanced T2* (UTE-T2*), is correlated with (1) worse patient-reported knee function and pain and (2) gait metrics related to patellofemoral tracking and loading, such as greater external rotation of the tibia at heel strike, reduced knee flexion moment (as a surrogate of quadriceps function), and greater knee flexion angle at heel strike., Study Design: Cross-sectional study; Level of evidence, 3., Methods: MRI UTE-T2* relaxation times in patellar and trochlear deep cartilage were compared with patient-reported outcomes and ambulatory gait metrics in 60 patients with ACLR at 2 years after reconstruction. ACLR gait metrics were compared with those of 60 uninjured reference patients matched by age, body mass index, and sex. ACLR UTE-T2* values were compared with those of 20 uninjured reference patients., Results: Higher trochlear UTE-T2* values were associated with worse Knee injury and Osteoarthritis Outcome Scores (KOOS) Sport/Recreation subscale scores (rho = -0.32; P = .015), and showed a trend for association with worse KOOS Pain subscale scores (rho = -0.26; P = .045). At 2 years after ACLR, greater external rotation of the tibia at heel strike was associated with higher patellar UTE-T2* values ( R = 0.40; P = .002); greater knee flexion angle at heel strike was associated with higher trochlear UTE-T2* values (rho = 0.39; P = .002); and greater knee flexion moment showed a trend for association with higher trochlear UTE-T2* values (rho = 0.30; P = .019). Patellar cartilage UTE-T2* values, knee flexion angle at heel strike, and external rotation of the tibia at heel strike were all elevated in ACLR knees as compared with reference knees ( P = .029, .001, and .044, respectively)., Conclusion: Patellofemoral deep cartilage matrix disruption, as assessed by MRI UTE-T2*, was associated with reduced sports and recreational function and with gait metrics reflective of altered patellofemoral loading. As such, the findings provide new mechanistic information important to improving clinical outcomes related to patellofemoral dysfunction after ACLR.

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., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Alterations in cartilage thickness (CTh) are a hallmark of knee osteoarthritis, which remain difficult to characterize at high resolution, even with modern magnetic resonance imaging (MRI), due to a paucity of standardization tools. This study aimed to assess a computational anatomy method producing standardized two-dimensional femorotibial CTh maps. The method was assessed with twenty knees, processed following three common experimental scenarios. Cartilage thickness maps were obtained for the femorotibial cartilages by reconstructing bone and cartilage mesh models in tree-dimension, calculating three-dimensional CTh maps, and anatomically standardizing the maps. The intra-operator accuracy (median (interquartile range, IQR) of -0.006 (0.045) mm), precision (0.152 (0.070) mm), entropy (7.02 (0.71) and agreement (0.975 (0.020))) results suggested that the method is adequate to capture the spatial variations in CTh and compare knees at varying osteoarthritis stages. The lower inter-operator precision (0.496 (0.132) mm) and agreement (0.808 (0.108)) indicate a possible loss of sensitivity to detect differences in a setting with multiple operators. The results confirmed the promising potential of anatomically standardized maps, with the lower inter-operator reproducibility stressing the need to coordinate operators. This study also provided essential reference data and indications for future research using CTh maps.

Background: Pain and proprioception deficits are often associated with knee pathologies and resultant quadriceps muscle inhibition. There is a need for new approaches to mitigate active knee pain and restore muscle function during walking. Activating properties of the somatosensory system with common pain and sensory pathways offers a novel opportunity to enhance quadriceps function during walking., Research Question: Conduct a controlled clinical trial that investigates the effects of applying intermittent vibrational cutaneous stimulation during walking on knee pain and symptoms and their correlations to gait parameters., Methods: This longitudinal controlled cross-over clinical study included thirty-two patients randomly and blindly assigned to active Treatment A and passive Treatment B for 4 weeks with a 2-week washout period between treatments., Results: Subjects when wearing active Treatment A for 4 weeks had significant (p = 0.04) improvement in patient reported outcomes, while they had no significant differences with passive Treatment B (p > 0.7) compared to the no treatment condition. For Treatment A, subjects with low knee flexion moment and knee flexion angle in no-treatment condition exhibited the greatest increase in knee flexion moment/angle in the active treatment condition (R > 0.57, p < 0.001). These changes in gait measures were correlated significantly to changes in pain., Significance: This clinical trial indicates that knee pain can be reduced, and gait improved in a manner that enhances quadriceps function by applying intermittent cutaneous stimulation during gait in patients following knee injury or disease. The correlation between decreased pain and improved gait suggests that rehabilitation and exercise therapy may benefit from this treatment., Competing Interests: Declaration of Competing Interest On behalf of my co-authors, I declare that this manuscript “Utilizing the Somatosensory System via Vibratory Stimulation to Mitigate Knee Pain during Walking: Randomized Clinical Trial” is original work, has not been published before and is not currently being considered for publication elsewhere. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: This study aimed to improve our understanding of the relationship between bone and cartilage by characterizing the morphological coupling between these mechanosensitive tissues exposed to the same mechanical environment within each knee. Specifically, it reanalyzed a prior dataset to test the hypothesis that the locations of thickest cartilage and densest subchondral bone are correlated in non-osteoarthritic femoral condyles., Method: Anatomically standardized maps of cartilage thickness (CTh) and subchondral bone mineral density (sBMD) were calculated for 50 non-osteoarthritic distal femurs based on computed tomography arthrography examinations. The locations of thickest CTh and densest sBMD were identified in the load-bearing region of the medial and lateral compartments, and correlation analyses were performed to quantify the associations between these locations, with inclusion of age, gender, femoral bone size and femorotibial angle as cofounding variables. Paired Student's t-tests were also performed to compare CTh and sBMD locations., Results: Locations of thickest CTh and densest sBMD were positively correlated along the anteroposterior direction in both compartments ( r  ≥ 0.45, p  ≤ 0.001). Furthermore, thickest CTh was more posterior than densest sBMD in the medial ( p  = 0.014) and lateral ( p  < 0.001) compartments, and more lateral than densest sBMD in the lateral compartment ( p  < 0.001). On average, these location differences were of 1.3, 5.3 and 2.1% of the subchondral bone size., Conclusion: The positive spatial relationship between the locations of thickest CTh and densest sBMD supports the idea of a functional cartilage/subchondral bone unit with morphological coupling conditioned by the individual loading pattern., Competing Interests: None., (© 2020 The Authors.)

Objective: To stimulate future research directions that seek solutions for osteoarthritis (OA) at the interface between diverse disciplines and address osteoarthritis (OA) as a serious disease with a complexity that has presented a barrier to finding safe effective solutions., Methods: Sessions were conducted at the 2019 meetings of the Orthopaedic Research Society (ORS) and Osteoarthritis Research Society International (OARSI) that included presentations and questions/comments submitted from leading OA researchers representing imaging, mechanics, biomarkers, phenotyping, clinical, epidemiology, inflammation and exercise., Results: Solutions for OA require a paradigm shift in research and clinical methods in which OA is contextualized as a complex whole-body/person disease. New OA definition(s)/phenotype(s) and OA markers/signals are needed to address the interplay between genetic and environmental factors of the disease as well as capture the mechanosensitivity of the disease. The term "Mechanokines" was proposed to highlight the importance of incorporating whole body mechanics as a marker of early OA. New interventions and apparent paradoxical observations/questions (e.g. exercise vs. load modification) were also discussed in the context of considering OA as a complex system., Conclusion: To advance new OA treatments that are safe and effective, OA should be considered as a "Whole Person" disease. This approach requires a concerted effort to bridge disciplines and include interactions across scales from the molecule to the whole body, including psychosocial aspects., Competing Interests: The authors have nothing to disclose regarding the content of this manuscript., (© 2020 The Authors.)

Background: Anterior cruciate ligament (ACL) injury is often followed by quadriceps deficits that are apparent with gait analysis. The deficit frequently remains after ACL reconstruction (ACLR). As such, evaluation of ACLR patients could be enhanced by a simple method to detect quadriceps deficits. Analyzing forward trunk flexion during stair ascent has been suggested as an assessment of quadriceps function that can be visualized with relatively simple instrumentation., Aim: The purpose of this study was to determine if trunk flexion angle (TFA) during stair ascent is associated with quadriceps function (as measured by the peak knee flexion moment (KFM)) at 2 and 8 years post-ACLR and if changes are associated with patient-reported outcomes (PRO)., Methods: Fourteen subjects with unilateral primary ACLR performed three stair-ascending trials at two-time periods: 2 years (baseline) and 8 years (follow-up) post-ACLR. Paired Student t-tests determined differences in KFM and TFA. Associations between KFM, TFA, and PRO were determined through Pearson correlations., Results: Peak KFM during stair ascent significantly increased from baseline to follow-up (p = 0.01). Though there was no significant difference in TFA (p = 0.84) compared to baseline, 50% of subjects showed decreases in TFA. Further, subjects with reduced TFA during stair ascent at follow-up had significantly increased peak KFM (p = 0.029) and improvements in PRO (p = 0.001)., Discussion: The results suggest that TFA during stair ascent can provide a simple method to assess changes in quadriceps function and pain over time following ACLR. Further analysis is needed to draw conclusions between knee osteoarthritis development and increases in TFA., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Quadriceps muscle rehabilitation following knee injury or disease is often hampered by pain, proprioception deficits or instability associated with inhibition of quadriceps activation during walking. The cross-modal plasticity of the somatosensory system with common sensory pathways including pain, pressure and vibration offers a novel opportunity to enhance quadriceps function during walking. This study explores the effectiveness of an active knee brace that used intermittent cutaneous vibration during walking to enhance the peak knee flexion moment (KFM) during early stance phase as a surrogate for net quadriceps moment (balance between knee extensor and flexor muscle moments). The stimulus was turned on prior to heel strike and turned off at mid-stance of the gait cycle. Twenty-one subjects with knee pathologies known to inhibit quadriceps function were tested walking under three conditions: control (no brace), a passive brace, and an active brace. Findings show that compared to the control, subjects wearing an active brace during gait exhibited a significant (p < 0.001) increase in peak KFM and no significant difference when wearing a passive brace (p = 0.17). Furthermore, subjects with low KFM and knee flexion angle (KFA) in control exhibited the greatest increase in KFA at loading response in the active brace condition (R = 0.47, p < 0.05). Intermittent cutaneous stimulation during gait, therefore, provides an efficient method for increasing the KFM in patients with knee pathologies. This study's results suggest that intermittent vibration stimulus can activate the cross-modalities of the somatosensory system in a manner that gates pain stimulus and possibly restores quadriceps function in patients with knee pain., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To introduce an integrated joint system (IJS) model of joint health and osteoarthritis (OA) pathophysiology through a systematic review of the cross-sectional relationships among three knee properties (cartilage thickness, gait mechanics, and subchondral bone mineral density)., Methods: Searches using keywords associated with the three knee properties of interest were performed in PubMed, Scopus, and Ovid databases. English-language articles reporting cross-sectional correlations between at least two knee properties in healthy or tibiofemoral OA human knees were included. A narrative synthesis of the data was conducted., Results: Of the 5600 retrieved articles, 13 were included, eight of which reported relationships between cartilage thickness and gait mechanics. The 744 tested knees were separated into three categories based on knee health: 199 healthy, 340 at-risk/early OA, and 205 late OA knees. Correlations between knee adduction moment and medial-to-lateral cartilage thickness ratios were generally positive in healthy, inconclusive in at-risk/early OA, and negative in late OA knees. Knee adduction moment was positively correlated with medial-to-lateral tibial subchondral bone mineral density ratios in knees of all health categories. One study reported a positive correlation between lateral tibial subchondral bone mineral density and femoral cartilage thickness in at-risk/early OA knees., Conclusions: The correlations identified between knee properties in this review agreed with the proposed relationship-based IJS model of OA pathophysiology. Accordingly, the IJS model could provide insights into overcoming current barriers to developing disease-modifying treatments by considering multiple aspects of OA disease, aspects that could be assessed simultaneously at an in vivo system level., (Copyright © 2018 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

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., (Published 2018. This article is a U.S. Government work and is in the public domain in the USA.)

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., (© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

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., (© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Objective: Quantitative magnetic resonance imaging (MRI) ultrashort echo time (UTE) T2* is sensitive to cartilage deep tissue matrix changes after anterior cruciate ligament reconstruction (ACLR). This study was performed to determine whether UTE-T2* profile analysis is a useful clinical metric for assessing cartilage matrix degeneration. This work tests the hypotheses that UTE-T2* depthwise rates of change (profile slopes) correlate with clinical outcome metrics of walking mechanics and patient reported outcomes (PRO) in patients 2 years after ACLR., Design: Thirty-six patients 2 years after ACLR completed knee MRI, gait analysis, and PRO. UTE-T2* maps were generated from MRI images and depthwise UTE-T2* profiles were calculated for weight-bearing cartilage in the medial compartment. UTE-T2* profiles from 14 uninjured subjects provided reference values. UTE-T2* profile characteristics, including several different measures of profile slope, were tested for correlation to kinetic and kinematic measures of gait and also to PRO., Results: Decreasing UTE-T2* profile slopes in ACLR knees moderately correlated with increasing knee adduction moments (r = 0.41, P < 0.015), greater external tibial rotation (r = 0.44, P = 0.007), and moderately negatively correlated with PRO (r = -0.36, P = 0.032). UTE-T2* profiles from both ACLR and contralateral knees of ACLR subjects differed from that of uninjured controls (P < 0.015)., Conclusions: The results of this study suggest that decreasing UTE-T2* profile slopes reflect cartilage deep tissue collagen matrix disruption in a population at increased risk for knee osteoarthritis (OA). That UTE-T2* profiles were associated with mechanical and patient reported measures of clinical outcomes support further study into a potential mechanistic relationship between these factors and OA development., (Copyright © 2018. Published by Elsevier Ltd.)

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 (R 2  = 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., (© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Background: Anterior cruciate ligament (ACL) injury increases risk for posttraumatic knee osteoarthritis (OA). Quantitative ultrashort echo time enhanced T2* (UTE-T2*) mapping shows promise for early detection of potentially reversible subsurface cartilage abnormalities after ACL reconstruction (ACLR) but needs further validation against established clinical metrics of OA risk such as knee adduction moment (KAM) and mechanical alignment., Hypothesis: Elevated UTE-T2* values in medial knee cartilage 2 years after ACLR correlate with varus alignment and higher KAM during walking., Study Design: Cohort study (diagnosis); Level of evidence, 2., Methods: Twenty patients (mean age, 33.1 ± 10.5 years; 11 female) 2 years after ACLR underwent 3.0-T knee magnetic resonance imaging (MRI), radiography, and gait analysis, after which mechanical alignment was measured, KAM during walking was calculated, and UTE-T2* maps were generated. The mechanical axis and the first and second peaks of KAM (KAM1 and KAM2, respectively) were tested using linear regressions for correlations with deep UTE-T2* values in the central and posterior medial femoral condyle (cMFC and pMFC, respectively) and central medial tibial plateau (cMTP). UTE-T2* values from ACL-reconstructed patients were additionally compared with those of 14 uninjured participants (mean age, 30.9 ± 8.9 years; 6 female) using Mann-Whitney U and standard t tests., Results: Central weightbearing medial compartment cartilage of ACL-reconstructed knees was intact on morphological MRI. Mean UTE-T2* values were elevated in both the cMFC and pMFC of ACL-reconstructed knees compared with those of uninjured knees ( P = .003 and P = .012, respectively). In ACL-reconstructed knees, UTE-T2* values of cMFC cartilage positively correlated with increasing varus alignment ( R = 0.568). Higher UTE-T2* values in cMFC and cMTP cartilage of ACL-reconstructed knees also correlated with greater KAM1 ( R = 0.452 and R = 0.463, respectively) and KAM2 ( R = 0.465 and R = 0.764, respectively) and with KAM2 in pMFC cartilage ( R = 0.602)., Conclusion: Elevated deep UTE-T2* values of medial knee cartilage 2 years after ACLR correlate with 2 clinical markers of increased risk of medial knee OA. These results support the clinical utility of MRI UTE-T2* for early diagnosis of subsurface cartilage abnormalities. Longitudinal follow-up of larger cohorts is needed to determine the predictive and staging potential of UTE-T2* for posttraumatic OA.

Objective: To test long-term effectiveness of neuromuscular exercise (NEMEX) with instructions in optimized pharmacological treatment (PHARMA) on activities of daily living (ADL) in patients with early knee osteoarthritis., Design: 12-months follow-up from a randomized controlled trial. Participants with mild-to-moderate medial tibiofemoral knee osteoarthritis were randomly allocated to 8 weeks NEMEX or PHARMA. The primary outcome measure was the ADL-subscale of the Knee Injury and Osteoarthritis Outcome Score (KOOS). Secondary outcome measures included the other four KOOS-subscales, the University of California Activity Score (UCLA) and the European Quality of Life-5 Dimensions., Results: Ninety-three patients (57% women, 58 ± 8 years, body mass index 27 ± 4 kg/m 2 ) were randomized to NEMEX (n = 47) or PHARMA group (n = 46) with data from 85% being available at 12-months follow-up. Good compliance was achieved for 49% of the participants in NEMEX (≥12 sessions) and 7% in PHARMA (half the daily dose of acetaminophen/NSAIDs ≥ 28 days). Within-group improvements in NEMEX were considered to be clinically relevant (≥10 points) for all KOOS-subscales, except Sport/Rec whereas, no between-groups difference in the primary outcome KOOS ADL (3.6 [-2.1 to 9.2]; P = 0.216) was observed. For KOOS Symptoms, a statistically significant difference of 7.6 points (2.6-12.7; P = 0.004) was observed in favor of NEMEX with 47% improving ≥10 points., Conclusions: No difference in improvement in difficulty with ADL was observed. NEMEX improved knee symptoms to a greater extent with half of patients reporting clinically relevant improvements. CLINICALTRIALS., Gov Identifier: NCT01638962 (July 3, 2012)., Ethical Committee: S-20110153., (Copyright © 2017 Osteoarthritis Research Society International. All rights reserved.)

While cartilage thickness alterations are a central element of knee osteoarthritis (OA), differences among disease stages are still incompletely understood. This study aimed to quantify the spatial-variations in cartilage thickness using anatomically standardized thickness maps and test if there are characteristic patterns in patients with different stages of medial compartment knee OA. Magnetic resonance images were acquired for 75 non-OA and 100 OA knees of varying severities (Kellgren and Lawrence (KL) scores 1-4). Three-dimensional cartilage models were reconstructed and a shape matching technique was applied to convert the models into two-dimensional anatomically standardized thickness maps. Difference thickness maps and statistical parametric mapping were used to compare the four OA and the non-OA subgroups. This analysis showed distinct thickness patterns for each clinical stage that formed a coherent succession from the non-OA to the KL 4 subgroups. Interestingly, the only significant difference for early stage (KL 1) was thicker femoral cartilage. With increase in disease severity, typical patterns developed, including thinner cartilage in the anterior area of the medial condyle (significant for KL 3 and 4) and thicker cartilage in the posterior area of the medial and lateral condyles (significant for all OA subgroups). The tibial patterns mainly consisted of thinner cartilage for both medial and lateral compartments (significant for KL 2-4). Comparing anatomically standardized maps allowed identifying patterns of thickening and thinning over the entire cartilage surface, consequently improving the characterization of thickness differences associated with OA. The results also highlighted the value of anatomically standardized maps to analyze spatial variations in cartilage thickness. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2442-2451, 2017., (© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

This study aimed to determine if active feedback gait retraining to produce a medial weight transfer at the foot significantly reduces the knee adduction moment in subjects with medial compartment knee osteoarthritis. Secondarily, changes in peak knee flexion moment, frontal plane knee and ankle kinematics, and center of pressure were investigated. Ten individuals with medial compartment knee osteoarthritis (9 males; age: 65.3 ± 9.8 years; BMI: 27.8 ± 3.0 kg/m 2 ) were tested at self-selected normal and fast speeds in two conditions: Intervention, with an active feedback device attached to the shoe of their more affected leg, and control, with the device de-activated. Kinematics and kinetics were assessed using a motion capture system and force plate. The first peak, second peak, and impulse of the knee adduction moment were significantly reduced by 6.0%, 13.9%, and 9.2%, respectively, at normal speed, with reductions of 10.7% and 8.6% in first peak and impulse at fast speed, respectively, with the active feedback system, with no significant effect on the peak knee flexion moment. Significant reductions in peak varus knee angle and medialized center of pressure in the first half of stance were observed, with reductions in peak varus knee angle associated with reductions in the knee adduction moment. This study demonstrated that active feedback to produce a medial weight-bearing shift at the foot reduces the peaks and impulse of the knee adduction moment in patients with medial compartment knee osteoarthritis. Future research should determine the long-term effect of the active feedback intervention on joint loading, pain, and function. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2251-2259, 2017., (© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

The increased use of gait analysis has raised the need for a better understanding of how walking speed and demographic variations influence asymptomatic gait. Previous analyses mainly reported relationships between subsets of gait features and demographic measures, rendering it difficult to assess whether gait features are affected by walking speed or other demographic measures. The purpose of this study was to conduct a comprehensive analysis of the kinematic and kinetic profiles during ambulation that tests for the effect of walking speed in parallel to the effects of age, sex, and body mass index. This was accomplished by recruiting a population of 121 asymptomatic subjects and analyzing characteristic 3-dimensional kinematic and kinetic features at the ankle, knee, hip, and pelvis during walking trials at slow, normal, and fast speeds. Mixed effects linear regression models were used to identify how each of 78 discrete gait features is affected by variations in walking speed, age, sex, and body mass index. As expected, nearly every feature was associated with variations in walking speed. Several features were also affected by variations in demographic measures, including age affecting sagittal-plane knee kinematics, body mass index affecting sagittal-plane pelvis and hip kinematics, body mass index affecting frontal-plane knee kinematics and kinetics, and sex affecting frontal-plane kinematics at the pelvis, hip, and knee. These results could aid in the design of future studies, as well as clarify how walking speed, age, sex, and body mass index may act as potential confounders in studies with small populations or in populations with insufficient demographic variations for thorough statistical analyses., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: To test if sagittal plane gait mechanics parameters and serum inflammation levels differ between healthy asymptomatic subjects and asymptomatic subjects with magnetic resonance imaging (MRI) evidence of cartilage loss., Design: Gait mechanics and resting serum tumor necrosis factor-α (TNFα) concentrations were measured for two groups of asymptomatic subjects recruited for a previous study: Pre-Osteoarthritis (OA) subjects had MRI evidence of partial- or full-thickness knee cartilage loss in at least one compartment (n = 52 (30 female), 1.7 ± 0.1 m, 85.3 ± 18.9 kg, 44 ± 11 years); Control subjects had no MRI features of cartilage loss, osteophytes, bone marrow lesions, nor meniscal pathology in either knee (n = 26 (13 female), 1.7 ± 0.1 m, 74.6 ± 14.9 kg, 34 ± 10 years). Discrete measures of sagittal plane gait kinematics and kinetics were compared between subject groups and adjusted for age and body mass index (BMI) using analysis of covariance (ANCOVA). Serum TNFα concentrations were compared between groups using bootstrap t-test., Results: The Pre-OA group had less extended knees (P = 0.021) and decreased maximum external knee extension moment (P = 0.0062) in terminal stance during gait, as well as increased resting serum TNFα concentration (P = 0.040) as compared to Control subjects. There were no group differences in heel strike flexion angle (P = 0.14), in maximum knee flexion moment (P = 0.91), nor in first peak knee adduction moment (KAM) (post-hoc analysis, P = 0.39)., Conclusions: The finding that asymptomatic subjects with cartilage loss had gait and inflammatory characteristics similar to those previously reported in symptomatic OA patients supports the idea that there are specific mechanical and biological factors that precede the onset of knee pain in the pathogenesis of OA., (Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate the effect of a neuro-muscular exercise (NEMEX) therapy program compared with instructions in optimized analgesics and anti-inflammatory drug use (PHARMA), on measures of knee-joint load in people with mild to moderate knee osteoarthritis (OA). We hypothesized that knee joint loading during walking would be reduced by NEMEX and potentially increased by PHARMA., Design: Single-blind, randomized controlled trial (RCT) comparing NEMEX therapy twice a week with PHARMA. Participants with mild-to-moderate medial tibiofemoral knee OA were randomly allocated (1:1) to one of two 8-week treatments. Primary outcome was change in knee load during walking (Knee Index, a composite score from all three planes based on 3D movement analysis) after 8 weeks of intervention. Secondary outcomes were frontal plane peak knee adduction moment (KAM), Knee Injury and Osteoarthritis Outcome Scores (KOOS) and functional performance tests., Results: Ninety three participants (57% women, 58 ± 8 years with a body mass index [BMI] of 27 ± 4 kg/m 2 (mean ± standard deviation [SD])) were randomized to NEMEX group (n = 47) or PHARMA (n = 46); data from 44 (94%) and 41 (89%) participants respectively, were available at follow-up. 49% of the participants in NEMEX and only 7% in PHARMA demonstrated good compliance. We found no difference in the primary outcome as evaluated by the Knee Index -0.07 [-0.17; 0.04] Nm/%BW HT. Secondary outcomes largely supported this finding., Conclusions: We found no difference in the primary outcome; knee joint load change during walking from a NEMEX program vs information on the recommended use of analgesics and anti-inflammatory drugs. ClinicalTrials.gov Identifier: NCT01638962 (July 3, 2012). Ethical Committee: S-20110153., (Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background: Altered knee kinematics after anterior cruciate ligament injury and reconstruction (ACLR) have been implicated in the development of posttraumatic osteoarthritis (PTOA), leading to poor long-term clinical outcomes., Purpose: This study was conducted to determine (1) whether the average knee center of rotation (KCOR), a multidimensional metric of knee kinematics, of the ACL-reconstructed knee during walking differs from that of the uninjured contralateral knee; (2) whether KCOR changes between 2 and 4 years after surgery; and (3) whether early KCOR changes predict patient-reported outcomes 8 years after ACLR., Study Design: Descriptive laboratory study., Methods: Twenty-six human participants underwent gait analysis with calculation of bilateral KCOR during walking at 2 and 4 years after unilateral ACLR. Knee injury and Osteoarthritis Outcome Score (KOOS) and Lysholm score results were collected at 2, 4, and 8 years after ACLR in 13 of these participants., Results: The ACL-reconstructed knee showed greater medial compartment motion because of pivoting about a more lateral KCOR ( P = .03) than the contralateral knee at 2 years. KCOR became less lateral over time ( P = .047), with values approaching those of the uninjured knee by 4 years ( P = .55). KCOR was also more anterior in the ACL-reconstructed knee at 2 years ( P = .02). Between 2 and 4 years, KCOR moved posteriorly in 16 (62%) and anteriorly in 10 (38%) participants. Increasing the anterior position of KCOR in the ACL-reconstructed knee from 2 to 4 years correlated with worsening clinical outcomes at 4 years (KOOS-Quality of Life, R 2 = 0.172) and more strongly at 8 years (Lysholm score, R 2 = 0.41; KOOS-Pain, R 2 = 0.37; KOOS-Symptoms, R 2 = 0.58; and KOOS-Quality of Life, R 2 = 0.50)., Conclusion: The observed changes to KCOR during walking between 2 and 4 years after ACLR show progressive improvement toward kinematic symmetry over the 2-year follow-up. The correlation between increasingly abnormal kinematics and worsening clinical outcomes years later in a subset of participants provides a potential explanation for the incidence of PTOA after ACLR.

This study tested the hypothesis that side-to-side differences in knee gait mechanics 2 years after anterior cruciate ligament (ACL) reconstruction are associated with long-term (∼8 years post-reconstruction) changes in patient-reported outcome scores. Sixteen subjects (5 males; age: 29.1 ± 7.1 years) with primary unilateral ACL reconstruction were gait tested at baseline (2.2 ± 0.3 years post-ACL reconstruction) and filled out KOOS and Lysholm surveys. At long-term follow-up (7.7 ± 0.7 years post-ACL reconstruction), the same subjects completed KOOS and Lysholm surveys. Pearson correlation coefficients assessed relationships between side-to-side differences in kinematics and kinetics at baseline and changes in Lysholm and KOOS Pain/QOL scores from 2 to 8 years post-ACL reconstruction. Significant associations were seen between greater average varus rotation (Lysholm: R = -0.654, p = 0.006) and less anterior femoral displacement (Lysholm: R = 0.578, p = 0.019) during stance of the ACL reconstructed knee versus the contralateral knee at baseline and worse follow-up outcome scores. Significant associations were seen between greater peak knee flexion moment (KOOS Pain: R = -0.572, p = 0.026; KOOS QOL: R = -0.636, p = 0.011), peak knee adduction moment (Lysholm: R = -0.582, p = 0.018; KOOS Pain: R = -0.742, p = 0.002; KOOS QOL: R = -0.551, p = 0.033), and peak internal rotation moment (Lysholm: R = 0.525, p = 0.037; KOOS Pain: R = 0.815, p < 0.001; KOOS QOL: R = 0.777, p = 0.001) in the ACL reconstructed knee at baseline with worse follow-up outcomes. The results of this study support the hypotheses that early changes in gait mechanics following ACL reconstruction are associated with longer-term clinical changes in patient-reported outcomes, suggesting that biomechanical markers obtained as early as 2 years after ACL reconstruction may be useful to understand clinical outcomes in this population. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:634-640, 2017., (© 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Background: Changes in knee kinematics have been identified in the early stages of osteoarthritis (OA). However, there is a paucity of information on the nature of kinematic change that occur with aging prior to the development of OA, This study applied a robust statistical method (Principal Component Analysis) to test the hypothesis that coupling between primary (flexion) and secondary (anterior-posterior translation, internal-external rotation) joint motions in walking would differ for age groupings of healthy subjects., Methods: Seventy-four healthy participants divided into three groups with mean ages of 24 ± 2.3 years (younger), 48 ± 4.7years (middle-age) and 64 ± 2.4 years (older) were examined. Principal Component Analysis was used to characterize and statistically compare the patterns of knee joint movement and their relationships in walking., Results: There were significant differences between the younger group and both the middle-age and older groups in the knee frontal plane angle and the coupling between knee flexion (PC1, p≤0.04) and the relative magnitudes of secondary plane motions in early and late stance (PC3, p<0.01). Two additional principal components (PC2, p = 0.03 and PC5, p<0.01) described differences in early stance knee flexion and relationship with secondary plane motion through-out stance for the older compared with middle-age group., Conclusions: It appears there are changes in knee kinematics that occur with aging. The kinematic differences were identified for middle-aged as well as older adults suggesting midlife changes in neuromuscular physiology or behavior may have important consequences. These kinematic measures offer the potential to identify early markers for the risk of developing knee OA with aging., Competing Interests: The authors have declared that no competing interests exist.

Reducing the knee adduction moment (KAM) is a promising treatment for medial compartment knee osteoarthritis (OA). Although several gait modifications to lower the KAM have been identified, the potential to combine modifications and individual dose-responses remain unknown. This study hypothesized that: (i) there is a general scheme consisting of modifications in trunk sway, step width, walking speed, and foot progression angle that reduces the KAM; (ii) gait modifications can be combined; and (iii) dose-responses differ among individuals. Walking trials with simultaneous modifications in step width, walking speed, progression angle, and trunk sway were analyzed for 10 healthy subjects. Wider step width, slower speed, toeing-in, and increased trunk sway resulted in reduced first KAM peak, whereas wider step width, faster speed, and increased trunk sway reduced the KAM angular impulse. Individual regressions accurately modeled the amplitude of the KAM variables relative to the amplitude of the gait modification variables, while the dose-responses varied strongly among participants. In conclusion, increasing trunk sway, increasing step width, and toeing-in are three gait modifications that could be combined to reduce KAM variables related to knee OA. Results also indicated that some gait modifications reducing the KAM induced changes in the knee flexion moment possibly indicative of an increase in knee loading. Taken together with the different dose-responses among subjects, this study suggested that gait retraining programs should consider this general scheme of modifications with individualization of the modification amplitudes. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1547-1556, 2016., (© 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Although kinematic alterations during walking have been reported with knee osteoarthritis (OA), there is a paucity of longitudinal data, therefore limiting our understanding of the role of kinematics in OA development. This study tested the hypothesis that less knee extension angle and less posterior displacement of the femur relative to the tibia during the heel-strike portion of the gait cycle are associated with greater loss of medial cartilage thickness during a follow-up period of five years. This study also tested for associations between flexion-extension angle and anterior-posterior displacement during other periods of the gait cycle and 5-year cartilage thinning. 16 subjects with moderate medial knee OA were tested with gait analysis and MRI at baseline and had a follow-up MRI after 5 years. Linear regressions were used to assess the relationship between changes in cartilage thickness and baseline kinematics using Pearson correlation coefficients. Multivariate regressions were also performed to adjust for gender, baseline age, BMI, walking speed, Kellgren/Lawrence grade, and baseline knee pain score. As hypothesized, baseline knee flexion angle and femoral displacement during heel-strike and other gait cycle periods were significantly associated with medial femoral and tibial cartilage thinning at the 5 year follow-up; these associations were strengthened after adjustment for covariates. This study provided new insight into the pathogenesis of knee OA where baseline knee kinematics were associated with longitudinal disease progression. These results could serve as a basis for developing newer gait modification interventions to reduce the risk for developing knee OA., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The incidence of anterior cruciate ligament (ACL) injuries may be decreased through the use of intervention programs that focus on increasing the knee flexion angle during jump landing, which decreases strain on the ACL., Purpose: To investigate whether intervention training designed to change the knee flexion angle during landing causes secondary changes in other known measures associated with the risk of ACL injuries and to examine the time points when these secondary measures change., Study Design: Controlled laboratory study., Methods: A total of 39 healthy recreational athletes performed a volleyball block jump task in an instrumented gait laboratory. The participants first completed the jumps without any modification to their normal landing technique. They were then given oral instruction to land softly and to increase their knee flexion angle during landing. Lower body kinematics and kinetics were measured before and after the modification using an optoelectronic motion capture system., Results: The knee flexion angle after the modification significantly increased from 11.2° to 15.2° at initial contact and from 67.8° to 100.7° at maximum flexion, and the time between initial contact and maximum flexion increased from 177.4 to 399.4 milliseconds. The flexion modification produced a substantial reduction in vertical ground-reaction force (243.1 to 187.8 %BW) with a concomitant reduction in the maximum flexion moment. Interestingly, the flexion modification only affected the abduction angle and abduction moment for the group of participants that landed in an initial adducted position before the modification and had no significant effect on the group that landed in an abducted position., Conclusion: Increasing the knee flexion angle during jump landing may be an effective intervention to improve knee biomechanical risk factors associated with an ACL injury. However, the fact that the flexion modification only influenced critical risk factors (the abduction angle and abduction moment) in participants who initially landed in an adducted position suggests that the selection of interventions to prevent ACL injuries should account for patient-specific characteristics., Clinical Relevance: The study helps elucidate how increasing the knee flexion angle affects lower body biomechanics and provided evidence for the need to introduce patient-specific strategies for preventing ACL injuries., (© 2016 The Author(s).)