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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., (© 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.)

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.)

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.)

The purpose of this study was to compare gait biomechanics between limbs and to matched uninjured controls (i.e., sex, age, and body mass index) preoperatively and at 2, 4, 6, and 12 months following primary unilateral anterior cruciate ligament reconstruction (ACLR). Functional mixed effects models were used to identify differences in gait biomechanics throughout the stance phase between the a) ACLR limb and uninvolved limb, b) ACLR limb and controls, and c) uninvolved limb and controls. Compared with the uninvolved limb, the ACLR limb demonstrated lesser knee extension moment (KEM; within 8-37% range of stance) during early stance as well as lesser knee flexion moment (KFM; 45-84%) and greater knee flexion angle (KFA; 43-90%) during mid- to late stance at all timepoints. Compared with controls, the ACLR limb demonstrated lesser vertical ground reaction force (vGRF; 5-26%), lesser KEM (7-47%), and lesser knee adduction moment (KAM; 12-35%) during early stance as well as greater vGRF (39-63%) and greater KFA (34-95%) during mid- to late stance at all timepoints. Compared with controls, the uninvolved limb demonstrated lesser KFA (1-56%) and lesser KEM (12-54%) during early to mid-stance at all timepoints. While gait becomes more symmetrical over the first 12 months post-ACLR, the ACLR and uninvolved limbs both demonstrate persistent aberrant gait biomechanics compared to controls. Biomechanical waveforms throughout stance can be generally described as less dynamic following ACL injury and ACLR compared with uninjured controls., (Journal of Orthopaedic Research© 2024 The Author(s). Journal of Orthopaedic Research ® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Lesser peak vertical ground reaction force (vGRF) has been widely reported among individuals with anterior cruciate ligament reconstruction (ACLR). Peak vGRF remains less than uninjured controls and relatively stable during the first year following ACLR. However, it is unknown whether there are subgroups of individuals exhibiting consistently greater peak vGRF in the first 6-months following ACLR and if individuals with consistently greater peak vGRF exhibit kinematic and kinetic gait differences compared to individuals with low vGRF. The purpose of this study was to determine if distinct clusters exist based upon magnitude of peak vGRF 2- and 6-months post-ACLR. Subsequently, we explored between cluster differences in vGRF, knee flexion angle, and sagittal and frontal plane knee kinetics throughout stance between clusters. Forty-three individuals (58.1%female, 21.4 ± 4.4 years-old, 95.3% patellar-tendon autograft) completed five gait trials at their habitual walking speed 2- and 6-months post-ACLR. A single K-means cluster analysis was used to identify clusters of individuals based on peak vGRF at 2- and 6-months post-ACLR. Functional waveform analyses were used to compare gait outcomes between clusters with and without controlling for gait speed and age. We identified two clusters that included a subgroup with high vGRF (n = 16) and low vGRF (n = 27). The cluster with high vGRF demonstrated greater vGRFs, knee flexion angles, and knee extension moments during early stance as compared to the low vGRF cluster 2- and 6-months post-ACLR. Individuals with peak vGRF ≥1.02 times body-weight 2-months post-ACLR had 35.4 times greater odds of being assigned to the high vGRF cluster., (© 2024 Orthopaedic Research Society.)

Background: Despite quadriceps weakness in individuals after quadriceps tendon anterior cruciate ligament reconstruction (QT-ACLR), and its association with knee joint mechanics, no studies have addressed gait mechanics in both partial-thickness (PT-Q) and full-thickness (FT-Q) options for QT-ACLR., Objective: To assess gait mechanics across a QT-ACLR cohort. We hypothesized that QT-ACLR would show changes in knee joint mechanics compared to control participants (CON) and nonoperated limbs. Additionally, we hypothesized that FT-Q operated limbs would show greater changes compared to PT-Q and CON., Design: Retrospective cohort study., Setting: University-affiliated sports medicine institute., Participants: Sixteen patients who underwent QT-ACLR (7 FT-Q: Age (years) = 28.6 ± 7.3, post-op (months) = 23.5 ± 10.7, 9 PT-Q: Age = 25.2 ± 4.3, post-op = 24.4 ± 11.7) were recruited and compared to 11 CON (age = 23.4 ± 4.8)., Intervention: Participants underwent gait testing with force plate integrated motion capture., Main Outcome Measures: Mixed repeated-measures analyses of covariance, adjusted for gait speed, were used to determine significant main effects or interactions in peak knee flexion angle, sagittal knee range of motion, peak internal knee extension moment (KEM), and peak internal knee flexion moment., Results: When measured an average of 2 years after surgery, no main effect for limb or limb by depth interaction were detected. A significant effect by group was observed for peak KEM (p = .03, η 2  = .27) and peak knee flexion angle (p = .04, η 2  = .24) in the loading response phase. FT-Q (p = .02) and PT-Q (p = .03) showed lower KEM compared to the CON group in both limbs. The FT-Q group showed lower peak knee flexion angle compared to the CON group (p = .01)., Conclusions: Knee joint symmetry may be recovered 2 years following QT-ACLR, but lower KEM compared to CON for both graft options and lower peak knee flexion angle than CON for the FT-Q group may indicate a need for further investigation in QT-ACLR., (© 2024 The Author(s). PM&R published by Wiley Periodicals LLC on behalf of American Academy of Physical Medicine and Rehabilitation.)

Anatomical knee joint features and osteoarthritis (OA) severity are associated, however confirming causals link to altered knee loading is challenging. This study leverages statistical shape models (SSM) to investigate the relationship between joint shape/alignment and knee loading during gait in knee OA (KOA) patients to understand their contribution to elevated medial knee loading in OA. Musculoskeletal (MSK) models were created for the mean as well as the first eight SSM principal modes of variation (-3,-2,-1, +1, +2, +3 standard deviations for each mode) and used as input to a MSK modeling framework. Using an identical KOA gait pattern (i.e., joint kinematics and ground reaction forces), we ran simulations for each MSK model and evaluated medial compartment loading magnitude and contact distribution at the instant of first and second peak of knee joint loading. An increase in external rotation, posterior tibia translation and a decrease in medial joint space and medial femoral condylar size predisposed the medial compartment knee joint to overloading during gait. This was coupled with an anterior and medial shift in contact location with increasing external rotated tibial position and increasing posterior tibial translation with respect to the femur. Next, results also highlighted a posterior shift of the medial compartment loading location with decreasing medial joint space. This study provides important population-based insights on how knee shape and alignment predispose individuals with KOA to elevated medial compartmental knee loading. This information can be crucial in assessing the risk for medial KOA development and progression., (© 2024 Orthopaedic Research Society.)

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.)

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.)

Individuals who have undergone anterior cruciate ligament reconstruction (ACLR) are at greater risk of developing knee osteoarthritis (OA). This elevated risk of knee OA is associated with high tibiofemoral (TF) compressive force, due to a combination of low knee flexion angles and increased co-contraction of the hamstrings and quadriceps during limb loading. Prolonged vibration of the hamstrings fatigues the intrafusal muscle fibers, which reduces autonomic reflexive excitation of the hamstrings and alleviates reciprocal inhibition to the quadriceps. The aim of this study was to examine the effect of prolonged hamstrings vibration on TF compressive force in individuals who have undergone ACL reconstruction. Fourteen participants with unilateral ACLR and 14 participants without knee injury performed a single-leg drop-land task before and after prolonged (20 min) vibration of the hamstrings. Peak TF compressive force, knee flexion angle, and hamstrings/quadriceps co-contraction were calculated during the deceleration phase of the drop-land task before and after vibration. The ACLR group experienced an 18% decrease in TF compressive force, a 32% increase in knee flexion angle, and a 38% decrease in hamstrings/quadriceps co-contraction after hamstrings vibration. There was no difference in any of the parameters in the noninjured group after vibration. These data suggest that acute prolonged hamstrings vibration has the potential to mitigate TF compressive force, which may protect the knee joint in the long term. Clinical significance: The results of this research are expected to lead to improved clinical care for ACLR patients because it holds promise for mitigating altered joint mechanics and perhaps slowing down the onset of posttraumatic knee osteoarthritis., (© 2023 Orthopaedic Research Society.)

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.)

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.)

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.)

Osteoarthritis (OA) is a leading cause of human suffering and disability for which disease-modifying treatments are lacking. OA occurs through complex and dynamic interplays between diverse factors over long periods of time. The traditional research and clinical focus on OA, the end stage disease, obscured understanding pathogenesis prior to reaching a common pathway defined by pain and functional deficits, joint deformity, and radiographic changes. To emphasize disease modification and prevention, we describe a multi-disciplinary systems-based approach encompassing biology, mechanics, and structure to define pre-osteoarthritic disease processes. Central to application of this model is the concept of "pre-osteoarthritis," conditions where clinical OA has not yet developed. Rather, joint homeostasis has been compromised and there are potentially reversible markers for heightened OA risk. Key messages from this perspective are (i) to focus research onto defining pre-OA through identifying and validating biological, mechanical, and imaging markers of OA risk, (ii) to emphasize multi-disciplinary approaches, and (iii) to propose that developing personalized interventions to address reversible markers of OA risk in healthy joints may be the key to prevention. Ultimately, a systems-based analysis of OA pathogenesis shows potential to transform clinical practice by facilitating development and testing of new strategies to prevent or delay the onset of osteoarthritis., (© 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Knee osteoarthritis (OA), a leading cause of disability, is more prevalent in women than men. Wearing high heeled shoes has been implicated as a potential contributing factor for the higher lifetime risk of osteoarthritis in women. This study tests the hypotheses that changes to knee kinematics and kinetics observed during high heeled walking increase in magnitude with increasing heel height and are accentuated by a 20% increase in weight. Fourteen healthy females were tested using marker-based gait analysis in combinations of footwear (flat athletic shoe, 3.8 cm and 8.3 cm heeled shoes) and weight (with and without 20% bodyweight vest). At preferred walking speed, knee flexion angle at heel-strike and midstance increased with increasing heel height and weight. Maximum knee extension moment during loading response decreased with added weight; maximum knee extension moment during terminal stance decreased with heel height; maximum adduction moments increased with heel height. Many of the changes observed with increasing heel height and weight were similar to those seen with aging and OA progression. This suggests that high heel use, especially in combination with additional weight, may contribute to increased OA risk in women., (© 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Gait measures are receiving increased attention in the evaluation of patients with knee osteoarthritis (OA). Yet, there remains a need to assess variability of gait analysis in patients with knee osteoarthritis over time and how pain affects variation in these gait parameters. The purpose of this study was to determine if important gait parameters, such as the knee adduction moment, knee flexion moment, peak vertical ground reaction force, and speed, were repeatable in patients with mild-to-moderate knee OA over a trial period of 12 weeks. Six patients were enrolled in this cross-over study design after meeting strict inclusion criteria. Gait tests were conducted three times at 4 week intervals and once after the placebo arm of a randomized treatment sequence; each gait test followed a 2-week period of receiving a placebo for a pain modifying drug. Repeatability for each gait variable was found using intraclass correlation coefficients (ICC) with a two-way random model. This study found that the knee adduction moment was repeatable throughout the four gait tests. However, normalized peak vertical ground reaction force and knee flexion moment were not as repeatable, varying with pain. This suggests that these gait outcomes could offer a more objective way to measure a patient's level of pain., (Copyright © 2012 Orthopaedic Research Society.)

The study aim was to address the need for objective markers of pain-modifying interventions by testing the hypothesis that selective gait measures of knee joint loading can distinguish differences between non-steroidal anti-inflammatory (NSAID), analgesic treatment (opioid-receptor agonist), and placebo in patients medial knee osteoarthritis (OA). A randomized, single-blind washout, double-blind treatment, double-dummy cross-over trial using three treatment arms placebo, opioid (Oxycodone), and NSAID (Celecoxib) in medial compartment knee OA patients. Six patients with Kellgren-Lawrence radiographic severity grades of 2 or 3 completed six testing sessions (gait and pain assessment) at 2-week intervals. A significant increase was found in the knee total reaction moment and vertical ground reaction force (GRF) for Celecoxib compared to placebo (p=0.005, p=0.003), but not for Oxycodone compared to placebo (p=0.20, p=0.27) treatments. Walking speed was significantly higher for the Celecoxib and Oxycodone compared to placebo treatment (p=0.041 and p=0.031, respectively). Self-reported function (WOMAC scores) was not different among treatments (p>0.05). The changes in total reaction moments and GRFs for only the NSAID suggest that greater increases in joint loading occurs when joint inflammation is treated in addition to pain. The total knee reaction moment, representing the magnitude of the extrinsic moment, appears to be a sensitive marker, more so than self-reported metrics, for evaluating knee OA treatment effects., (Copyright © 2011 Orthopaedic Research Society.)

Recent reports have indicated that anatomical placement of the anterior cruciate ligament (ACL) graft is an important factor for restoration of joint function following ACL reconstruction. The objective of this study was to address a need for a better understanding of anatomical variations in ACL position and orientation within the joint. Specifically, variations in the ACL anatomy were assessed by testing for side-to-side ACL footprint location symmetry in a healthy population relative to the operative and contralateral knee in a patient population after traditional transtibial single-bundle ACL reconstruction. MRI and three-dimensional modeling techniques were used to determine the in vivo tibiofemoral ACL footprint centers and the resulting ACL orientations in both knees of 30 healthy subjects and 30 subjects after transtibial ACL reconstruction. While there were substantial inter-subject variations in ACL anatomy, the side-to-side RMS differences in the ACL footprint center were 1.20 and 1.34 mm for the femur and tibia, respectively, for the healthy subjects and no clinically meaningful intra-subject differences were measured. However, there were large intra-subject side-to-side differences after transtibial ACL reconstruction, with ACL grafts placed 5.63 and 7.64 mm from the center of the contralateral femoral and tibial ACL footprint centers, respectively. Grafts were placed more medial, anterior, and superior on the femur and more posterior on the tibia; producing grafts that were more vertical in the sagittal and coronal planes. Given the large variation among subjects, these findings advocate the use of the contralateral ACL morphology for retrospectively evaluating patient-specific anatomic graft placement., (Copyright © 2011 Orthopaedic Research Society.)

This study investigated the load-modifying and clinical efficacy of variable-stiffness shoes after 12 months in subjects with medial compartment knee osteoarthritis. Subjects who completed a prior 6-month study were asked to wear their assigned constant-stiffness control or variable-stiffness intervention shoes during the remainder of the study. Changes in peak knee adduction moment, total Western Ontario and McMaster Universities (WOMAC), and WOMAC pain scores were assessed. Seventy-nine subjects were enrolled, and 55 completed the trial. Using an intention-to-treat analysis, the variable-stiffness shoes reduced the within-day peak knee adduction moment (-5.5%, p < 0.001) in the intervention subjects, while the constant-stiffness shoes increased the peak knee adduction moment in the control subjects (+3.1%, p = 0.015) at the 12-month visit. WOMAC pain and total scores for the intervention group were significantly reduced from baseline to 12 months (-32%, p = 0.002 and -35%, p = 0.007, respectively). The control group had a reduction of 27% in WOMAC pain score (p = 0.04) and no significant reduction in total WOMAC score. Reductions in WOMAC pain and total scores were similar between groups (p = 0.8 and p = 0.47, respectively). In the intervention group, reductions in adduction moment were related to improvements in pain and function (R(2)  = 0.11, p = 0.04). Analysis by disease severity revealed greater efficacy in adduction moment reduction in the less severe intervention group. While the long-term effects of the intervention shoes on pain and function did not differ from control, the data suggest wearing the intervention shoe reduces the within-day adduction moment after long-term wear, and thus should reduce loading on the affected medial compartment of the knee., (Copyright © 2011 Orthopaedic Research Society.)

External knee adduction moment can be reduced using footwear interventions, but the exact changes in in vivo medial joint loading remain unknown. An instrumented knee replacement was used to assess changes in in vivo medial joint loading in a single patient walking with a variable-stiffness intervention shoe. We hypothesized that during walking with a load modifying variable-stiffness shoe intervention: (1) the first peak knee adduction moment will be reduced compared to a subject's personal shoes; (2) the first peak in vivo medial contact force will be reduced compared to personal shoes; and (3) the reduction in knee adduction moment will be correlated with the reduction in medial contact force. The instrumentation included a motion capture system, force plate, and the instrumented knee prosthesis. The intervention shoe reduced the first peak knee adduction moment (13.3%, p = 0.011) and medial compartment joint contact force (12.3%; p = 0.008) compared to the personal shoe. The change in first peak knee adduction moment was significantly correlated with the change in first peak medial contact force (R(2) = 0.67, p = 0.007). Thus, for a single subject with a total knee prosthesis the variable-stiffness shoe reduces loading on the affected compartment of the joint. The reductions in the external knee adduction moment are indicative of reductions in in vivo medial compressive force with this intervention., (© 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

This study tested the effects of variable-stiffness shoes on knee adduction moment, pain, and function in subjects with symptoms of medial compartment knee osteoarthritis over 6 months. Patients were randomly and blindly assigned to a variable-stiffness intervention or constant-stiffness control shoe. The Western Ontario and McMaster Universities (WOMAC) score served as the primary outcome measure. Joint loading, the secondary outcome measure, was assessed using the external knee adduction moment. Peak external knee adduction moment, total WOMAC, and WOMAC pain scores were assessed at baseline and after 6 months. The total WOMAC and WOMAC pain scores for the intervention group were reduced from baseline to 6 months (p = 0.017 and p = 0.002, respectively), with no significant reductions for the control group. There was no difference between groups in magnitude of the reduction in total WOMAC (p = 0.50) or WOMAC pain scores (p = 0.31). The proportion of patients achieving a clinically important improvement in pain was greater in the intervention group than in the control group (p = 0.012). The variable-stiffness shoes reduced the peak knee adduction moment (-6.6% vs. control, p < 0.001) in the 34 intervention subjects at 6 months. The adduction moment reduction significantly improved (p = 0.03) from the baseline reduction. The constant-stiffness control shoe increased the peak knee adduction moment (+6.3% vs. personal, p = 0.004) in the 26 control subjects at 6 months. The results of this study showed that wearing the variable-stiffness shoe lowered the adduction moment, reduced pain, and improved functionality after 6 months of wear. The lower adduction moment associated with wearing this shoe may slow the rate of progression of osteoarthritis after long-term use., ((c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

The aim of this study was to test the hypothesis that a change in serum cartilage oligomeric matrix protein (COMP) concentration is related to joint load during a 30-min walking exercise in patients with medial compartment knee osteoarthritis (OA) and in age-matched control subjects. Blood samples were drawn from 42 patients with medial compartment knee OA and from 41 healthy age-matched control subjects immediately before, immediately after, and 0.5, 1.5, 3.5, and 5.5 h after a 30-min walking exercise on a level outdoor walking track at self-selected normal speed. Serum COMP concentrations were determined using a commercial ELISA. Basic time-distance gait variables were recorded using an activity monitor. Joint loads were measured using gait analysis. Serum COMP concentrations increased immediately after the walking exercise (+6.3% and +5.6%; p < 0.001) and decreased over 5.5 h after the exercise (-11.1% and -14.6%; p < 0.040 and p = 0.001) in patients and control subjects, respectively. The magnitude of increase in COMP concentration did not differ between groups (p = 0.902) and did not correlate with any variables describing ambulatory loads at the joints of the lower extremity. These results, taken together with a previous study of a younger healthy population, suggest the possibility that the influence of ambulatory loads on cartilage turnover is dependent on age., ((c) 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

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 degrees) knees was not significantly smaller (p = 0.09, power = 0.99) than the PLIA of contralateral (24.1 +/- 4.8 degrees) 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., (Copyright 2008 Orthopaedic Research Society)

The purpose of this study was to determine if there is a distinctive characteristic in the pattern of movement (forward trunk lean to reduce demand on the quadriceps muscle) during stair climbing in patients with knee osteoarthritis (OA) that is associated with the severity of the disease. Twenty-three patients with radiographically diagnosed knee OA and 20 physically active adults performed stair ascending trials without support at their self-selected speed. Standard gait analysis was used to calculate three-dimensional lower extremity joint kinematics and kinetics. Forward trunk lean, or trunk flexion, was defined as the sagittal plane projection of the angle between a line connecting the midpoint of the trans-acromion line and the midpoint of the trans-iliac crest line and the global vertical axis. Patients with more severe knee OA (KL >or= 3) had greater forward trunk lean (+6.3 degrees , p = 0.045) and lower knee net quadriceps moments (-35.2%, p = 0.001) than controls. In more severe patients, the forward trunk lean was correlated with a reduction in the net quadriceps moment during stair climbing (R(2) = 0.590, p = 0.006). The results of this study identified a distinctive compensatory pattern of movement to reduce the quadriceps demand during stair climbing in patients with more severe knee OA by increasing forward trunk lean. Assessing forward trunk lean during stair climbing may be a useful functional marker for evaluating osteoarthritis status and quadriceps function that appears to be a more sensitive indicator of disease severity than perceived pain., ((c) 2008 Orthopaedic Research Society.)

The levitation tricompartment offloader (TCO) brace is designed to unload all three knee compartments by reducing compressive forces caused by muscle contraction. This study aimed to determine the effect of the TCO on knee contact forces and quadriceps muscle activity in individuals with knee osteoarthritis. Lower limb kinematics, kinetics, and electromyography data were collected during a chair rise-and-lower task. A three-dimensional inverse dynamics model of the lower leg and foot was used with a sagittal plane knee model to compute knee joint forces. TCO brace use significantly decreased forces in the tibiofemoral [p = 0.001; mean difference, MD (97.5% confidence interval, CI) -0.62 (-0.91, -0.33) body weight (BW)] and patellofemoral [p = 0.001; MD (97.5% CI) -0.88 (-1.36, -0.39) BW] compartments in high-power mode. Significant reductions in quadriceps tendon force [p = 0.002; MD (97.5% CI) -0.53 (-0.83, -0.23) BW] and electromyography intensity of the vastus medialis [p = 0.018, MD (97.5% CI) -30.7 (-59.1, -2.3)] and vastus lateralis [p = 0.012, MD (97.5% CI) -26.2 (-48.5, -3.9)] were also observed. The TCO significantly reduced tibiofemoral and patellofemoral contact forces throughout chair lower, and when knee flexion was greater than 50° during chair rise in high power. These results demonstrate that the TCO reduces contact forces in the tibiofemoral and patellofemoral joint compartments and confirms that the TCO unloads the joint by reducing compressive forces caused by the quadriceps. Clinical significance: The magnitude of knee joint unloading provided by the TCO is similar to that achieved by clinically recommended levels of bodyweight loss and is therefore expected to result in clinical benefits for knee osteoarthritis patients., (© 2023 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Although an anterior cruciate ligament (ACL) deficiency induces knee osteoarthritis, particularly in the medial compartment, the kinematics remains partially unclear. This study investigated the in vivo knee kinematics of ACL-deficient and normal knees by comparing them during squatting. This prospective comparative study included 17 ACL-deficient knees and 20 normal knees. The kinematics was investigated under fluoroscopy using a two- to three-dimensional registration technique. The anteroposterior (AP) translation of the medial and lateral sides of the femur, axial rotation of the femur relative to the tibia, and kinematic pathways were evaluated and compared. At first, the medial AP position of the femur translated anteriorly from 0° to midflexion, afterward it translated posteriorly in both ACL-deficient and normal knees. However, the medial AP position of the femur in the ACL-deficient knees was located significantly posteriorly compared with normal knees at 0-110° flexion. The lateral AP position of the femur translated posteriorly from 0° to 150° flexion in both ACL-deficient and normal knees. The lateral AP position of the femur in the ACL-deficient knees was located significantly posteriorly compared with that in normal knees at 0-10° flexion. The femur showed external rotation from 0° to 150° flexion in both ACL-deficient and normal knees. A medial pivot motion and subsequent bicondylar rollback were observed in both knees in the kinematic pathway. In conclusion, the AP position of the femur relative to the tibia was altered due to ACL deficiency, particularly in the medial compartment., (© 2022 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

We examined the relationship between activity, peak load, medial to lateral load distribution, and flexion angle at peak load for activities of daily living. An instrumented knee prosthesis was used to measure knee joint force simultaneously with motion capture during walking, chair sit to stand and stand to sit, stair ascending and descending, squatting from a standing position, and golf swings. The maximum total compressive load at the knee was highest during stair ascending and descending and lowest during rising from a chair. Maximum total compressive load occurred at substantially different flexion angles ranging from 8.5 degrees during walking to 91.8 degrees during squatting. For all activities, total compressive load exceeded 2 times body weight, and for most activities 2.5 times body weight. Most activities placed a greater load on the medial compartment than the lateral compartment. Activities were grouped into three categories: high cycle loading (walk), high load (stair ascent, descent, and golf), and high flexion angle (chair sit to stand/stand to sit, and squat). The results demonstrate that the forces and motion sustained by the knee are highly activity-dependent and that the unique loading characteristics for specific activities should be considered for the design of functional and robust total knee replacements, as well as for rehabilitation programs for patients with knee osteoarthritis or following total knee arthroplasty., ((c) 2008 Orthopaedic Research Society)

Following ACL injury a reduction in the peak knee flexion moment during walking (thought to be created by a decrease of quadriceps contraction) has been described as an adaptation to reduce anterior tibial translation (ATT) relative to the femur. However, the amount of ATT caused by quadriceps contraction is influenced by the patellar ligament insertion angle (PLIA). The purpose of this study was to test the hypothesis that quadriceps usage during walking correlates to individual anatomical variations in the extensor mechanism as defined by PLIA. PLIA and gait were measured for ACL-deficient knees, using subjects' contralateral knees as controls. In ACL-deficient knees, PLIA was negatively correlated (R2 = 0.59) to peak knee flexion moment (balanced by net quadriceps moment), while no correlation was found in contralateral knees. Reduction in peak flexion moment in ACL-deficient knees compared to their contralateral knees was distinctive in subjects with large PLIA, possibly to avoid excessive ATT. These results suggest that subject-specific anatomic variability of knee extensor mechanism may account for the individual variability previously observed in adaptation to a quadriceps reduction strategy following ACL injury. The average (+/-1 SD) PLIA of ACL-deficient knees (21.1 +/- 3.4 degrees) was less than the average PLIA of contralateral knees (23.9 +/- 3.1 degrees). This altered equilibrium position of the tibiofemoral joint associated with reduced PLIA and adaptations of gait patterns following ACL injury may be associated with degenerative changes in the articular cartilage. In the future, individually tailored treatment and rehabilitation considering individuals' specific extensor anatomy may improve clinical outcomes., (Copyright 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

The purpose of this study was to evaluate shoe sole material stiffness changes and angle changes that are intended to reduce the peak knee adduction moment during walking. Fourteen physically active adults were tested wearing their personal shoes (control) and five intervention pairs, two with stiffness variations, two with angle variations, and a placebo shoe. The intervention shoes were evaluated based on how much they reduced the peak knee adduction moment compared to the control shoe. An ANOVA test was used to detect differences between interventions. Linear regression analysis was used to determine a relationship between the magnitude of the knee adduction moment prior to intervention and the effectiveness of the intervention in reducing the peak knee adduction moment. Peak knee adduction moments were reduced for the altered stiffness and altered angle shoes (p < 0.010), but not for the placebo shoe (p = 0.363). Additionally, linear regression analysis showed that subjects with higher knee adduction moments prior to intervention had larger reductions in the peak knee adduction moment (p < 0.010). These results demonstrate that shoe sole stiffness and angle interventions can be used to reduce the peak knee adduction moment and that subjects with initially higher peak knee adduction moments have higher reductions in their peak knee adduction moments.

The objective of this study was to test the hypothesis that during a weight bearing activity such as walking, a dynamic range (envelope of motion) exists in the relationship between the secondary knee motions (anterior-posterior (AP) translation, internal-external (IE) rotation, and abduction-adduction (Ab-Adduction)) and knee flexion angle. In addition differences in the envelope of motion between a weight bearing and non-weight bearing activity were tested. The hypothesis was evaluated by testing for differences (offsets) in secondary displacements at specific knee flexion angles during the walking cycle and seated leg extension (non-weight bearing). Kinematic measurements were obtained using a previously developed point cluster technique to analyze the six-degrees of freedom movement of the knee. During walking, phase plots of the IE rotation and AP translation versus knee flexion demonstrated significant offsets from one phase of the gait cycle to another at the same flexion angle. During the non-weight bearing activity, no significant offset in the secondary movement was found; the knee followed the same pathway of motion during the flexion and extension phase of this activity. The characteristics of the secondary motions during walking indicated that secondary knee movements are caused by the external forces (muscle, inertial and gravitational) that act on the knee during the various phases of the walking cycle. The boundaries of the envelope appear to reflect the characteristics of the passive restraints. The weight bearing secondary motion AP and IE rotation seen during a walking activity demonstrated an envelope of dynamic laxity that could potentially be used to evaluate functional instabilities at the knee.

There is a lack of fundamental information on the knee biomechanics in deep flexion beyond 90 degrees. In this study, mechanical loads during activities requiring deep flexion were quantified on normal knees from 19 subjects, and compared with those in walking and stair climbing. The deep flexion activities generate larger net quadriceps moments (6.9-13.5% body weight into height) and net posterior forces (58.3-67.8% body weight) than routine ambulatory activities. Moreover, the peak net moments and the net posterior forces were generated between 90 degrees and 150 degrees of flexion. The large moments and forces will result in high stress at high angles of flexion. These loads can influence pathological changes to the joint and are important considerations for reconstructive procedures of the knee. The posterior cruciate ligament should have a substantial role during deep flexion, since there was a large posterior load that must be sustained at the knee. The mechanics of the knee in deep flexion are likely a factor causing problems of posterior instability in current total knee arthroplasty. Thus, it is important to consider the magnitude of the loads at the knee in the treatment of patients that commonly perform deep flexion during activities of daily living.

This study tested whether the peak external knee adduction moments during walking in subjects with knee osteoarthritis (OA) were correlated with the mechanical axis of the leg, radiographic measures of OA severity, toe out angle or clinical assessments of pain, stiffness or function. Gait analysis was performed on 62 subjects with knee OA and 49 asymptomatic control subjects (normal subjects). The subjects with OA walked with a greater than normal peak adduction moment during early stance (p = 0.027). In the OA group, the mechanical axis was the best single predictor of the peak adduction moment during both early and late stance (R = 0.74, p < 0.001). The radiographic measures of OA severity in the medial compartment were also predictive of both peak adduction moments (R = 0.43 to 0.48, p < 0.001) along with the sum of the WOMAC subscales (R = -0.33 to -0.31, p < 0.017). The toe out angle was predictive of the peak adduction moment only during late stance (R = -0.45, p < 0.001). Once mechanical axis was accounted for, other factors only increased the ability to predict the peak knee adduction moments by 10 18%. While the mechanical axis was indicative of the peak adduction moments, it only accounted for about 50% of its variation, emphasizing the need for a dynamic evaluation of the knee joint loading environment. Understanding which clinical measures of OA are most closely associated with the dynamic knee joint loads may ultimately result in a better understanding of the disease process and the development of therapeutic interventions.

Objective: To define the association between change in body mass index (BMI) and the incidence and progression of the structural defects of knee osteoarthritis as assessed by radiography., Methods: Radiographic analyses of knees at baseline and at 4-5 years of follow-up were obtained from the following 3 independent cohort studies: the Osteoarthritis Initiative (OAI) study, the Multicenter Osteoarthritis Study (MOST), and the Cohort Hip and Cohort Knee (CHECK) study. Logistic regression analyses using generalized estimating equations, with clustering of both knees within individuals, were used to investigate the association between change in BMI from baseline to 4-5 years of follow-up and the incidence and progression of knee osteoarthritis., Results: A total of 9,683 knees (from 5,774 participants) in an "incidence cohort" and 6,075 knees (from 3,988 participants) in a "progression cohort" were investigated. Change in BMI was positively associated with both the incidence and progression of the structural defects of knee osteoarthritis. The adjusted odds ratio (OR) for osteoarthritis incidence was 1.05 (95% confidence interval [95% CI] 1.02-1.09), and the adjusted OR for osteoarthritis progression was 1.05 (95% CI 1.01-1.09). Change in BMI was also positively associated with degeneration (i.e., narrowing) of the joint space and with degeneration of the femoral and tibial surfaces (as indicated by osteophytes) on the medial but not on the lateral side of the knee., Conclusion: A decrease in BMI was independently associated with lower odds of incidence and progression of the structural defects of knee osteoarthritis and could be a component in preventing the onset or worsening of knee osteoarthritis., (© 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Although treatments for osteoarthritis of the knee are often directed at relieving pain, pain may cause patients to alter how they perform activities to decrease the loads on the joints. The knee-adduction moment is a major determinant of the load distribution between the medial and lateral plateaus. Therefore, the interrelationship between pain and the external knee-adduction moment during walking may be especially important for understanding mechanical factors related to the progression of medial tibiofemoral osteoarthritis. Fifty-three subjects with symptomatic radiographic evidence of osteoarthritis of the knee were studied. These subjects were a subset of those enrolled in a double-blind study in which gait analysis and radiographic and clinical evaluations were performed after a 2-week washout of anti-inflammatory and analgesic treatment. The subjects then took a nonsteroidal anti-inflammatory drug, acetaminophen, or placebo for 2 weeks, and the gait and clinical evaluations were repeated. The change in the peak external adduction moment between the two evaluations was inversely correlated with the change in pain (R = 0.48, p < 0.001) and was significantly different between those whose pain increased (n = 7), decreased (n = 18), or remained unchanged (n = 28) (p = 0.009). Those with increased pain had a significant decrease in the peak external adduction (p = 0.005) and flexion moments (p = 0.023). In contrast, the subjects with decreased pain tended to have an increase in the peak external adduction moment (p = 0.095) and had a significant increase in the peak external extension moment (p = 0.017). The subjects whose pain was unchanged had no significant change in the peak external adduction (p = 0.757), flexion (p = 0.234), or extension (p = 0.465) moments. Thus, decreases in pain among patients with medial tibiofemoral osteoarthritis were related to increased loading of the degenerative portion of the joints. Additional long-term prospective studies are needed to determine whether increased loading during walking actually results in accelerated progression of the disease.

This study related mechanisms of gait compensations to the level of pain and to limitations in passive motion in patients with osteoarthritis of the hip. Joint motion, moments, and intersegmental forces were calculated for 19 patients with unilateral osteoarthritis of the hip (12 men and seven women) and for a group of normal subjects (12 men and seven women) with a similar age distribution. The patients who had osteoarthritis walked with a decreased dynamic range of motion (17 +/- 4 degrees) of the hip and with a hesitation or reversal in the direction of the sagittal plane motion as they extended the hip. The patients with a hesitation or reversal in motion had a greater loss in the range of motion of the hip during gait (p < 0.004) and a greater passive flexion contracture (p < 0.022) than those with a smooth pattern of hip motion. This alteration in the pattern of motion was interpreted as a mechanism to increase effective extension of the hip during stance through increased anterior pelvic tilt and lumbar lordosis. The patients who had osteoarthritis of the hip walked with significantly decreased external extension, adduction, and internal and external rotation moments (p < 0.008). The decreased extension moment was significantly correlated with an increased level of pain (R = 0.78; p < 0.001). This finding suggests that decreasing muscle forces (hip flexors) may be one mechanism used to adapt to pain.

Dual energy x-ray absorptiometry was used to measure periprosthetic, distal femoral, and proximal tibial bone mass in the affected and contralateral limbs of eight patients 10 years after unilateral total hip arthroplasty with a cementless, porous-coated titanium alloy femoral stem. Gait analyses to assess the presence of asymmetries in loading of the lower extremities were also performed 10 years postoperatively. The patients had excellent clinical results and no other significant lower extremity pathology. On the basis of comparison of the affected and unaffected proximal femora, bone loss adjacent to the proximal medial aspect of the femoral stem was determined to be 34% (p < 0.001). However, the patients also had 16% less bone in the ipsilateral proximal tibia (p = 0.003) and 15% less bone in the ipsilateral femur 3 cm distal to the prosthesis (p = 0.007) compared with the contralateral limb. When normalized to the asymmetry in tibial bone mineral content, the estimated proximal medial periprosthetic bone loss was still statistically significant, but the magnitude was reduced from 34 to 17% (p = 0.009). The gait analyses indicated that several measures that influence the loads at the hip and knee joints were reduced in the involved limb compared with the contralateral limb. Furthermore, the bilateral difference in the vertical component of the external force acting on the proximal tibia was correlated with the bilateral difference in tibial bone mineral content (r = 0.80, p = 0.02). These data suggest that two mechanical factors, the local stress-shielding effect of the prosthesis and the global effect of decreased loading of the limb, can both make significant contributions to periprosthetic bone loss. It is apparent that the magnitude of the periprosthetic bone loss related to stress-shielding has been overestimated by as much as 50% in retrospective studies.

Anatomic and mechanical factors that affect loading in the knee joint can contribute to pathologic changes seen at the knee in degenerative joint disease and should be considered in treatment planning. The objectives of this study were to quantify the relationships between the alignment of the bones of the lower extremity, foot progression angle, and knee adduction moment, and to determine the reliability of our gait measurements. Gait analysis and complete radiographic evaluation of the lower extremity were performed on 11 healthy subjects. The gait measurements were recorded with an optoelectronic digitizer and a multi-component force plate. The subjects who had radiographic measurements indicative of varus alignment of the lower extremity had statistically higher peaks in knee adduction moment in early stance. Conversely, those with valgus alignment of the lower extremity had statistically lower peaks in knee adduction moment in early stance. The subjects who had a large toe-out angle and low ankle inversion moment peaks in late stance had significantly lower peaks in knee adduction moment in late stance. These significant (low to moderate) correlations suggest that the limbs with more valgus alignment and those with a toe-out gait exhibited a reduced peak adduction moment at the knee. To verify the reproducibility of the data, gait analysis testing was performed on each lower limb on 2 separate days for each subject. Analysis of variance showed that there was no significant difference between test limbs or test days for each subject. Our results suggest that the alignment of the lower limb and the foot progression angle, which can be readily measured in a clinical setting, can serve as predictors of knee joint loading in healthy individuals. These findings may have important implications for both surgical and nonsurgical treatment of abnormalities of the knee joint.

Many studies have illustrated the effect of mechanical loading on articular cartilage and the corresponding changes in chondrocyte metabolism, yet the mechanism through which the cells respond to loading still is unclear. The purpose of this study was to evaluate the change in shape of chondrocytes under a statically applied uniaxial compressive load. Isolated chondrocytes from rat chondrosarcoma were embedded in 2% agarose gel. Strains of 5, 10, and 15% were applied, and images of the cell were recorded from initial loading to equilibrium (15 minutes). A finite-element model was used to model the experimental setup and to estimate the mechanical properties of the chondrocyte at equilibrium. The transient behavior of the composite in the experiment was analyzed with use of a standard linear viscoelastic model. We found that all cells decreased in cross-sectional area under each of the applied compressive strains. In the finite-element model, the elasticity of the chondrocyte was similar to that of the surrounding agarose gel (4.0 kPa) and had a Poisson's ratio of 0.4. Viscoelastic analysis showed that the chondrocytes contributed a significant viscoelastic component to the behavior of the composite in comparison with the agarose gel alone. If a decrease in cell volume proportional to the decrease in cross-sectional area is assumed, the decrease observed was greater than would be predicted by a passive cellular response due to an equivalent osmotic pressure. This indicates that the chondrocyte may be altering its intracellular composition by cellular processes in response to mechanical loading.

A 6 df measurement system was used to investigate the initial relative bone-implant motion of two types of cementless total hip replacement femoral components-a straight stem and a curved stem. Five pairs of fresh frozen femurs from human cadavers were tested with loads applied to the femoral head at angles characteristic of level walking, stair-climbing, and rising from a chair. The most important findings were that (a) the resultant proximal translations were twice as high with the straight stem as with the curved stem at load angles encountered in stair-climbing and rising from a chair, (b) both stem types had more motion at load angles encountered in stair-climbing and rising from a chair than in level walking, with the increases ranging from 3 to 14-fold, (c) there was as much as 66-fold more motion distally than proximally, and (d) the amount of interface motion varied by 5-fold between the medial and lateral surfaces of the distal part of the implant because of the combined effects of translation and rotation. The amount of initial bone-implant motion of the femoral component was found to be particularly sensitive to off-axis loading; this suggests that stair-climbing and rising from a chair should be avoided in the early postoperative period when a cementless porous-coated femoral stem has been used.

The objectives of this study were to estimate pre- and postoperative lower limb kinematics and kinetics and knee intra-articular forces during gait using musculoskeletal modeling in a cohort of patients with knee osteoarthritis (OA) undergoing high tibial osteotomy (HTO), compare these to controls, and determine correlations between changes in these parameters and Knee Injury and Osteoarthritis Outcome Score (KOOS) subscores after HTO. Sixteen patients with isolated, symptomatic medial compartment knee OA completed pre- and postoperative gait analysis (mean follow-up time: 8.6 months). Sixteen age- and sex-matched asymptomatic volunteers participated as controls. Musculoskeletal modeling was used to evaluate lower limb joint moments and knee contact forces during gait. While HTO had limited influence on sagittal plane kinematics and moments, significant changes in the load distribution at the knee after HTO were observed with a lower postoperative compressive load on the medial compartment during midstance and a higher compressive load on the lateral compartment during early and late stance. Moreover, the lateral shear force in midstance was significantly lower after HTO. Changes in the external knee adduction moment (KAM) did not always coincide with reductions in the knee compressive force in the medial compartment. Biomechanical changes did not correlate with improvements in KOOS subscores. Hence, HTO effectively unloaded the medial compartment by redistributing part of the overall compressive force to the lateral compartment during gait with limited influence on gait function. The KAM may not adequately describe compartmental load magnitude or changes induced by interventions at the compartment level. Clinical trial registration: ClinicalTrials. gov Identifier-NCT02622204. Clinical significance: This study provides important evidence for changes in joint level loads after corrective osteotomy as joint preserving surgery and emphasizes the need for additional biomechanical outcomes of such interventions., (© 2022 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Knee osteoarthritis patient phenotyping is relevant to developing targeted treatments and assessing the treatment efficacy of total knee arthroplasty (TKA). This study aimed to identify clusters among TKA candidates based on demographic and knee mechanic features during gait, and compare gait changes between clusters postoperatively. TKA patients underwent 3D gait analysis 1-week pre (n = 134) and 1-year post-TKA (n = 105). Principal component analysis was applied to frontal and sagittal knee angle and moment waveforms, extracting major patterns of variability. Age, sex, body mass index, gait speed, and frontal and sagittal pre-TKA angle and moment PC scores previously identified as relevant to TKA outcomes were standardized (mean = 0, SD = 1, [134 × 15]). Multidimensional scaling and machine learning-based hierarchical clustering were applied. Final clusters were validated by examining intercluster differences pre-TKA and gait feature changes (Post PCscore  - Pre PCscore ) by k-way Χ 2 and ANOVA tests. Four TKA candidate phenotypes yielded optimum clustering metrics, interpreted as higher and lower functioning clusters that were predominantly male and female. Higher functioning clusters pre-TKA (clusters 1 and 4) had more dynamic sagittal flexion moment (p < 0.001) and frontal plane adduction moment (p < 0.001) loading/un-loading patterns during stance. Post-TKA, higher functioning clusters demonstrated less knee mechanic improvements during gait (flexion angle p < 0.001; flexion moment p < 0.001). TKA candidates can be characterized by four clusters, predominately separated by sex and knee joint biomechanics. Post-TKA knee kinematics and kinetics improvements were cluster-specific; lower functioning clusters experienced more improvement. Cluster-based patient profiling may aid in triaging and developing OA management and surgical strategies meeting group-level function needs., (© 2022 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

The gait of normal subjects and patients with varus deformities at the knee was studied by analyzing the interaction between the dynamic (muscular) and passive (ligamentous) restraints affecting lateral stability of the knee. A statistically determinant model predicted that the midstance-phase adducting moment during normal gait would cause lateral knee joint opening if either antagonistic muscle force and/or pretension in the lateral soft tissues were not present at the knee. The patient group tended to compensate for a high midstance-phase adducting moment by walking with a style of gait that demanded more muscle force (greater flexion-extension moments). This walking style reduced the chance of lateral joint opening. It can be speculated that this style of gait would help to maintain equilibrium at the knee. The higher muscle force would aid in resisting the adducting moment, keeping the joint closed laterally and thus increasing the stability of the knee.

About a third of knee joint disorders originate from the patellofemoral (PF) site that makes stair ascent a difficult activity for patients. A detailed finite element model of the knee joint is coupled to a lower extremity musculoskeletal model to simulate the stance phase of stair ascent. It is driven by the mean of measurements on the hip-knee-ankle moments-angles as well as ground reaction forces reported in healthy individuals. Predicted muscle activities compare well to the recorded electromyography data. Peak forces in quadriceps (3.87 BW, body weight, at 20% instance in our 607 N subject), medial hamstrings (0.77 BW at 20%), and gastrocnemii (1.21 BW at 80%) are estimated. Due to much greater flexion angles-moments in the first half of stance, large PF contact forces (peak of 3.1 BW at 20% stance) and stresses (peak of 4.83 MPa at 20% stance) are estimated that exceed their peaks in level walking by fourfold and twofold, respectively. Compared with level walking, ACL forces diminish in the first half of stance but substantially increase later in the second half (peak of 0.76 BW at 75% stance). Under nearly similar contact forces at 20% of stance, the contact stress on the tibiofemoral (TF) medial plateau reaches a peak (9.68 MPa) twice that on the PF joint suggesting the vulnerability of both joints. Compared with walking, stair ascent increases peak ACL force and both peak TF and PF contact stresses. Reductions in the knee flexion moment and/or angle appear as a viable strategy to mitigate internal loads and pain., (© 2022 John Wiley & Sons Ltd.)

Obesity increases the risk of knee osteoarthritis (OA). Knee joint contact characteristics have been thought to provide insights into the pathogenesis of knee OA; however, the cartilage contact characteristics in individuals with obesity have not been fully described. We conducted cartilage-to-cartilage contact analyses through high-precision fluoroscopy imaging with subject-specific magnetic resonance cartilage models. Twenty-five individuals with obesity were recruited for this study, and previously published data consisted of eight nonobese individuals who were used as the comparator group. In both groups, knees were imaged by a dual fluoroscopic imaging system during treadmill walking, and the tibiofemoral cartilage contact locations were analyzed and described on the tibial plateau in the medial-lateral (ML) and anterior-posterior (AP) directions and on femoral condyle surfaces using contact angles in the sagittal plane and deviation angles in a plane perpendicular to the sagittal plane. On the medial tibial plateau, the ML contact locations in the individuals with obesity were located more medially than in the nonobese group throughout the stance phase. The medial plateau AP contact locations in individuals with obesity showed a different pattern compared with the nonobese group. The ML contact excursions on the medial plateau in the individuals with obesity were larger than in the nonobese group. These findings suggest that obesity affects the contact location mainly in the medial compartment, which explains, in part, the high prevalence of medial knee OA in the obese population., (© 2022 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Aberrant joint loading contributes to the development of posttraumatic knee osteoarthritis (PTOA) following anterior cruciate ligament reconstruction (ACLR); yet little is known about the association between joint loading due to daily walking and cartilage health post-ACLR. Accelerometer-based measures of daily steps and cadence (i.e., rate of steps/min) provide information regarding daily walking in a real-world setting. The purpose of this study was to determine the association between changes in serum cartilage oligomeric matrix protein (COMP; %∆COMP), a mechanosensitive biomarker that is associated with osteoarthritis progression, following a standardized walking protocol and daily walking in individuals with ACLR and uninjured controls. Daily walking was assessed over 7 days using an accelerometer worn on the right hip in 31 individuals with ACLR and 21 controls and quantified as mean steps/day and time spent in ≥100 steps/min. Serum COMP was measured before and following a 3000-step walking protocol at a preferred speed. %∆COMP was calculated as a change in COMP relative to the prewalking value. Linear regressions were used to examine associations between daily walking and %∆COMP after adjusting for preferred speed. Fewer daily steps (ΔR 2  = 0.18, p = 0.02) and fewer minutes spent in ≥100 steps/min (ΔR 2  = 0.16, p = 0.03) were associated with greater %∆COMP following walking in individuals with ACLR; no statistically significant associations existed in controls (daily steps: ΔR 2  = 0.03, p = 0.47; time ≥100 steps/min: ΔR 2  < 0.01, p = 0.81). Clinical significance: Individuals with ACLR who engage in less daily walking undergo greater %ΔCOMP, which may represent greater cartilage degradation or turnover in response to walking., (© 2022 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

We combined mobile biplane X-ray imaging and magnetic resonance imaging to measure the regions of articular cartilage contact and cartilage thickness at the tibiofemoral and patellofemoral joints during six functional activities: standing, level walking, downhill walking, stair ascent, stair descent, and open-chain (non-weight-bearing) knee flexion. The contact centers traced similar paths on the medial and lateral femoral condyles, femoral trochlea, and patellar facet in all activities while their locations on the tibial plateau were more varied. The translations of the contact centers on the femur and patella were tightly coupled to the tibiofemoral flexion angle in all activities (r 2  > 0.95) whereas those on the tibia were only moderately related to the flexion angle (r 2  > 0.62). The regions of contacting cartilage were significantly thicker than the regions of non-contacting cartilage on the patella, femoral trochlea, and the medial and lateral tibial plateaus in all activities (p < 0.001). There were no significant differences in thickness between contacting and non-contacting cartilage on the medial and lateral femoral condyles in all activities, except open-chain knee flexion. Our results provide partial support for the proposition that cartilage thickness is adapted to joint load and do not exclude the possibility that other factors, such as joint congruence, also play a role in regulating the structure and organization of healthy cartilage. The data obtained in this study may serve as a guide when evaluating articular contact motion in osteoarthritic and reconstructed knees., (© 2021 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)