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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.)

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.)

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.)

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 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.)

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.)

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.)

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.)

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.