Longitudinal changes in tibial and femoral cartilage thickness are associated with baseline ambulatory kinetics and cartilage oligomeric matrix protein (COMP) measures in an asymptomatic aging population.

OBJECTIVE: To address the need for early knee osteoarthritis (OA) markers by testing if longitudinal cartilage thickness changes are associated with specific biomechanical and biological measures acquired at a baseline test in asymptomatic aging subjects. DESIGN: Thirty-eight asymptomatic subjects over age 45 years were studied at baseline and at an average of 7-9 year follow-up. Gait mechanics and knee MRI were measured at baseline and MRI was obtained at follow-up to assess cartilage thickness changes. A subset of the subjects (n = 12) also had serum cartilage oligomeric matrix protein measured at baseline in response to a mechanical stimulus (30-min walk) (mCOMP). Baseline measures, including the knee extension (KEM), flexion (KFM), adduction (KAM) moments and mCOMP, were tested for associations with cartilage thickness changes in specific regions of the knee. RESULTS: Cartilage change in the full medial femoral condyle (p = 0.005) and external medial femoral region (p = 0.041) was negatively associated with larger early stance peak KEM. Similarly, cartilage change in the full medial femoral region (p = 0.009) and medial femoral external region (p = 0.043) was negatively associated with larger first peak KAM, while cartilage change in the anterior medial tibia was positively associated with larger first peak KAM (p = 0.003). Cartilage change in the anterior medial tibia was also significantly associated (p = 0.011) with mCOMP levels 5.5-h post-activity (percentage of pre-activity levels). CONCLUSIONS: Interactions found between gait, mechanically-stimulated serum biomarkers, and cartilage thickness in an at-risk aging asymptomatic population suggest the opportunity for early detection of OA with new approaches that bridge across disciplines and scales.

Modeling knee osteoarthritis pathophysiology using an integrated joint system (IJS): a systematic review of relationships among cartilage thickness, gait mechanics, and subchondral bone mineral density.

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

MRI UTE-T2* profile characteristics correlate to walking mechanics and patient reported outcomes 2 years after ACL reconstruction.

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

One year effectiveness of neuromuscular exercise compared with instruction in analgesic use on knee function in patients with early knee osteoarthritis: the EXERPHARMA randomized trial.

OBJECTIVE: To test long-term effectiveness of neuromuscular exercise (NEMEX) with instructions in optimized pharmacological treatment (PHARMA) on activities of daily living (ADL) in patients with early knee osteoarthritis. DESIGN: 12-months follow-up from a randomized controlled trial. Participants with mild-to-moderate medial tibiofemoral knee osteoarthritis were randomly allocated to 8 weeks NEMEX or PHARMA. The primary outcome measure was the ADL-subscale of the Knee Injury and Osteoarthritis Outcome Score (KOOS). Secondary outcome measures included the other four KOOS-subscales, the University of California Activity Score (UCLA) and the European Quality of Life-5 Dimensions. RESULTS: Ninety-three patients (57% women, 58 ± 8 years, body mass index 27 ± 4 kg/m2) were randomized to NEMEX (n = 47) or PHARMA group (n = 46) with data from 85% being available at 12-months follow-up. Good compliance was achieved for 49% of the participants in NEMEX (≥12 sessions) and 7% in PHARMA (half the daily dose of acetaminophen/NSAIDs ≥ 28 days). Within-group improvements in NEMEX were considered to be clinically relevant (≥10 points) for all KOOS-subscales, except Sport/Rec whereas, no between-groups difference in the primary outcome KOOS ADL (3.6 [-2.1 to 9.2]; P = 0.216) was observed. For KOOS Symptoms, a statistically significant difference of 7.6 points (2.6-12.7; P = 0.004) was observed in favor of NEMEX with 47% improving ≥10 points. CONCLUSIONS: No difference in improvement in difficulty with ADL was observed. NEMEX improved knee symptoms to a greater extent with half of patients reporting clinically relevant improvements. CLINICALTRIALS. GOV IDENTIFIER: NCT01638962 (July 3, 2012). ETHICAL COMMITTEE: S-20110153.

Speed, age, sex, and body mass index provide a rigorous basis for comparing the kinematic and kinetic profiles of the lower extremity during walking.

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

Altered gait mechanics and elevated serum pro-inflammatory cytokines in asymptomatic patients with MRI evidence of knee cartilage loss.

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

The effect of instruction in analgesic use compared with neuromuscular exercise on knee-joint load in patients with knee osteoarthritis: a randomized, single-blind, controlled trial.

OBJECTIVE: To investigate the effect of a neuro-muscular exercise (NEMEX) therapy program compared with instructions in optimized analgesics and anti-inflammatory drug use (PHARMA), on measures of knee-joint load in people with mild to moderate knee osteoarthritis (OA). We hypothesized that knee joint loading during walking would be reduced by NEMEX and potentially increased by PHARMA. DESIGN: Single-blind, randomized controlled trial (RCT) comparing NEMEX therapy twice a week with PHARMA. Participants with mild-to-moderate medial tibiofemoral knee OA were randomly allocated (1:1) to one of two 8-week treatments. Primary outcome was change in knee load during walking (Knee Index, a composite score from all three planes based on 3D movement analysis) after 8 weeks of intervention. Secondary outcomes were frontal plane peak knee adduction moment (KAM), Knee Injury and Osteoarthritis Outcome Scores (KOOS) and functional performance tests. RESULTS: Ninety three participants (57% women, 58 ± 8 years with a body mass index [BMI] of 27 ± 4 kg/m2 (mean ± standard deviation [SD])) were randomized to NEMEX group (n = 47) or PHARMA (n = 46); data from 44 (94%) and 41 (89%) participants respectively, were available at follow-up. 49% of the participants in NEMEX and only 7% in PHARMA demonstrated good compliance. We found no difference in the primary outcome as evaluated by the Knee Index -0.07 [-0.17; 0.04] Nm/%BW HT. Secondary outcomes largely supported this finding. CONCLUSIONS: We found no difference in the primary outcome; knee joint load change during walking from a NEMEX program vs information on the recommended use of analgesics and anti-inflammatory drugs. ClinicalTrials.gov Identifier: NCT01638962 (July 3, 2012). Ethical Committee: S-20110153.

Baseline knee adduction and flexion moments during walking are both associated with 5 year cartilage changes in patients with medial knee osteoarthritis.

OBJECTIVE: To test the hypothesis that knee cartilage changes over 5 years are associated with baseline peak knee adduction moment (KAM) and peak knee flexion moment (KFM) during early stance. DESIGN: Baseline KAM and KFM were measured in sixteen subjects with medial knee osteoarthritis (OA). Regional changes in cartilage thickness and changes in medial-to-lateral thickness ratio were quantified using magnetic resonance imaging (MRI) at baseline and again after 5 years. Multiple regression was used to determine whether baseline measures of KAM and KFM were associated with cartilage changes over 5 years. Associations with baseline pain score, Kellgren-Lawrence (KL) grade, walking speed, age, gender, and body mass index (BMI) were tested one-by-one in the presence of KAM and KFM. RESULTS: Changes over 5 years in femoral medial-to-lateral thickness ratio were associated with baseline KAM, KFM, and pain score (R(2) = 0.60, P = 0.010), and most significantly with KAM (R(2) = 0.33, P = 0.019). Changes in tibial medial-to-lateral thickness ratio were associated with baseline KAM, KFM, and walking speed (R(2) = 0.49, P = 0.039), with KFM driving this association (R(2) = 0.40, P = 0.009). Changes in medial tibial thickness were associated with baseline KAM, KFM, and walking speed (R(2) = 0.49, P = 0.041); KFM also drove this association (R(2) = 0.42, P = 0.006). CONCLUSIONS: The findings that the KAM has a greater influence on femoral cartilage change and the KFM has a greater influence on tibial cartilage change provide new insight into the tibiofemoral variations in cartilage changes associated with walking kinetics. These results suggest that both KAM and KFM should be considered when designing disease interventions as well as when assessing the risk for OA progression.

The regional sensitivity of chondrocyte gene expression to coactive mechanical load and exogenous TNF-α stimuli.

Both mechanical load and elevated levels of proinflammatory cytokines have been associated with the risk for developing osteoarthritis (OA), yet the potential interaction of these mechanical and biological factors is not well understood. The purpose of this study was to evaluate the response of chondrocytes to the effects of dynamic unconfined compression, TNF-α, and the simultaneous effects of dynamic unconfined compression and TNF-α. The response to these three treatments was markedly different and, taken together, the response in the gene expression of chondrocytes to the different treatment conditions suggest a complex interaction between structure, biology, and mechanical loading.

Age-related differences in sagittal-plane knee function at heel-strike of walking are increased in osteoarthritic patients.

OBJECTIVE: To compare age-related patterns of gait with patterns associated with knee osteoarthritis (OA), the following hypotheses were tested: (H1) The sagittal-plane knee function during walking is different between younger and older asymptomatic subjects; (H2) The age-related differences in H1 are increased in patients with knee OA. DESIGN: Walking trials were collected for 110 participants (1.70 ± 0.09 m, 80 ± 14 kg). There were 29 younger asymptomatic subjects (29 ± 4 years) and 81 older participants (59 ± 9 years), that included 27 asymptomatic subjects and 28 and 26 patients with moderate and severe medial knee OA. Discrete variables characterizing sagittal-plane knee function were compared among the four groups using ANOVAs. RESULTS: During the heel-strike portion of the gait cycle at preferred walking speed, the knee was less extended and the shank less inclined in the three older groups compared to the younger asymptomatic group. There were similar differences between the severe OA group and the older asymptomatic and moderate OA groups. Both OA groups also had the femur less posterior relative to the tibia and smaller extension moment than the younger group. During terminal stance, the severe OA group had the knee less extended and smaller knee extension moment than the younger asymptomatic and older moderate OA groups. CONCLUSIONS: The differences in knee function, particularly those during heel-strike which were associated with both age and disease severity, could form a basis for looking at mechanical risk factors for initiation and progression of knee OA on a prospective basis.

Is increased joint loading detrimental to obese patients with knee osteoarthritis? A secondary data analysis from a randomized trial.

OBJECTIVE: To investigate whether increased knee joint loading due to improved ambulatory function and walking speed following weight loss achieved over 16 weeks accelerates symptomatic and structural disease progression over a subsequent 1 year weight maintenance period in an obese population with knee osteoarthritis (OA). METHODS: Data from a prospective study of weight loss in obese patients with knee OA (the CARtilage in obese knee OsteoarThritis (CAROT) study) were used to determine changes in knee joint compressive loadings (model estimated) during walking after a successful 16 week weight loss intervention. The participants were divided into 'Unloaders' (participants that reduced joint loads) and 'Loaders' (participants that increased joint loads). The primary symptomatic outcome was changes in knee symptoms, measured with the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire, during a subsequent 52 weeks weight maintenance period. The primary structural outcome was changes in tibiofemoral cartilage loss assessed semi-quantitatively (Boston Leeds Knee Osteoarthritis Score (BLOKS) from MRI after the 52 weight maintenance period. RESULTS: 157 participants (82% of the CAROT cohort) with medial and/or lateral knee OA were classified as Unloaders (n = 100) or Loaders (n = 57). The groups showed similar significant changes in symptoms (group difference: -2.4 KOOS points [95% CI -6.8:1.9]) and cartilage loss (group difference: -0.06 BLOKS points [95% CI -0.22:0.11) after 1 year, with no statistically significant differences between Loaders and Unloaders. CONCLUSION: For obese patients undergoing a significant weight loss, increased knee joint loading for 1 year was not associated with accelerated symptomatic and structural disease progression compared to a similar weight loss group that had reduced ambulatory compressive knee joint loads. CLINICALTRIALSGOV: NCT00655941.

Application of principal component analysis in clinical gait research: identification of systematic differences between healthy and medial knee-osteoarthritic gait.

For a successful completion of a movement task the motor control system has to observe a multitude of internal constraints that govern the coordination of its segments. The purpose of this study was to apply principal component (PC) analysis to detect differences in the segmental coordination between healthy subjects and patients with medial knee osteoarthritis (OA). It was hypothesized that (1) systematic differences in patterns of whole body movement would be identifiable with this method even in small sample sized groups and that (2) these differences will include compensatory movements in the OA patients in both the lower and upper body segments. Marker positions and ground reaction forces of three gait trials of 5 healthy and 5 OA participants with full body marker sets were analyzed using a principal component analysis. Group differences in the PC-scores were determined for the first 10 PC-vectors and a linear combination of those PC-vectors where differences were found defined a discriminant vector. Projecting the original trials onto this discriminant vector yielded significant group differences (t(d=8)=3.011; p=0.017) with greater upper body movement in patients with knee OA that was correlated with the medial-lateral ground reaction force. These results help to characterize the adaptation of whole-body gait patterns to knee OA in a relatively small population and may provide an improved basis for the development of interventions to modify knee load. The PC-based motion analysis offered a highly sensitive approach to identify characteristic whole body patterns of movement associated with pathological gait.

A relationship between mechanically-induced changes in serum cartilage oligomeric matrix protein (COMP) and changes in cartilage thickness after 5 years.

OBJECTIVE: To evaluate the hypothesis that a mechanical stimulus (30-min walk) will produce a change in serum concentrations of cartilage oligomeric matrix protein (COMP) that is associated with cartilage thickness changes on magnetic resonance imaging (MRI). METHODS: Serum COMP concentrations were measured by enzyme-linked immunosorbent assay in 17 patients (11 females, age: 59.0±9.2 years) with medial compartment knee osteoarthritis (OA) at study entry immediately before, immediately after, 3.5 h, and 5.5 h after a 30-min walking activity. Cartilage thickness changes in the medial femur and medial tibia were determined from MR images taken at study entry and at 5-year follow-up. Relationships between changes in cartilage thickness and COMP levels, with post-activity concentrations expressed as a percentage of pre-activity levels, were assessed by the calculation of Pearson correlation coefficients and by multiple linear regression analysis, with adjustments for age, sex, and body mass index (BMI). RESULTS: Changes in COMP levels 3.5 h and 5.5 h post-activity were correlated with changes in cartilage thickness in the medial femur and tibia at the 5-year follow-up. The results were strengthened after analyses were adjusted for age, sex, and BMI. Neither baseline pre-activity COMP levels nor changes in COMP levels immediately post-activity were correlated with cartilage thickness changes. CONCLUSIONS: The results of this study support the hypothesis that a change in COMP concentration induced by a mechanical stimulus is associated with cartilage thinning at 5 years. Mechanically-induced changes in mechano-sensitive biomarkers should be further explored in the context of stimulus-response models to improve the ability to assess OA progression.

Kinematic adaptations to a variable stiffness shoe: mechanisms for reducing joint loading.

A recently described variable-stiffness shoe has been shown to reduce the adduction moment and pain in patients with medial-compartment knee osteoarthritis. The mechanism associated with how this device modifies overall gait patterns to reduce the adduction moment is not well understood. Yet this information is important for applying load modifying intervention for the treatment of knee osteoarthritis. A principal component analysis (PCA) was used to test the hypothesis that there are differences in the frontal plane kinematics that are correlated with differences in the ground reaction forces (GRFs) and center of pressure (COP) for a variable-stiffness compared to a constant-stiffness control shoe. Eleven healthy adults were tested in a constant-stiffness control shoe and a variable-stiffness shoe while walking at self-selected speeds. The PCA was performed on trial vectors consisting of all kinematic, GRF and COP data. The projection of trial vectors onto the linear combination of four PCs showed there were significant differences between shoes. The interpretation of the PCs indicated an increase in the ankle eversion, knee abduction and adduction, decreases in the hip adduction and pelvic obliquity angles and reduced excursion of both the COP and peak medial-lateral GRFs for the variable-stiffness compared to the control shoe. The variable-stiffness shoe produced a unique dynamic change in the frontal plane motion of the ankle, hip and pelvis that contributed to changes in the GRF and COP and thus reduced the adduction moment at a critical instant during gait suggesting a different mechanism that was seen with fixed interventions (e.g. wedges).

Vibration training intervention to maintain cartilage thickness and serum concentrations of cartilage oligometric matrix protein (COMP) during immobilization.

OBJECTIVE: To test the hypotheses that 1) 14-days of immobilization of young healthy subjects using a 6 degrees -"head-down-tilt-bed-rest"-model (6 degrees -HDT) would reduce cartilage thickness in the knee and serum Cartilage oligometric matrix protein (COMP) concentration and 2) isolated whole body vibration training would counteract the bed rest effects. METHOD: The study was performed and designed in compliance with the Declaration of Helsinki and is registered as trial DRKS00000140 in the German Clinical Trial Register (register.germanctr.de). Eight male healthy subjects (78.0+/-9.5kg; 179+/-0.96cm, 26+/-5 years) performed 14 days of 6 degrees -HDT. The study was designed as a cross-over-design with two study phases: a training and a control intervention. During the training intervention, subjects underwent 2x5-min whole body vibration training/day (Frequency: 20Hz; amplitude: 2-4mm). Magnetic resonance (MR) images (slice thickness: 2mm; in-plane resolution: 0.35x0.35mm; pixels: 448x512) were taken before and after the 6 degrees -HDT periods. Average cartilage thicknesses were calculated for the load bearing regions on the medial and lateral articulating surfaces in the femur and tibia. RESULTS: While the control intervention resulted in an overall loss in average cartilage thickness of -8% (pre: 3.08mm+/-0.6mm post: 2.82mm+/-0.6mm) in the weight-bearing regions of the tibia, average cartilage thickness increased by 21.9% (pre: 2.66mm+/-0.45mm post: 3.24mm+/-0.63mm) with the vibration intervention. No significant differences were found in the weight-bearing regions of the femur. During both interventions, reduced serum COMP concentrations were observed (control intervention: -13.6+/-8.4%; vibration intervention: -9.9+/-3.3%). CONCLUSION: The results of this study suggest that articular cartilage thickness is sensitive to unloading and that vibration training may be a potent countermeasure against these effects. The sensitivity of cartilage to physical training is of high relevance for training methods in space flight, elite and sport and rehabilitation after illness or injury.

Central and peripheral region tibial plateau chondrocytes respond differently to in vitro dynamic compression.

OBJECTIVE: The objective of this study was to test the hypotheses that chondrocytes from distinct regions of the porcine tibial plateau: (1) display region-specific baseline gene expression, and (2) respond differently to in vitro mechanical loading. METHODS: Articular cartilage explants were obtained from central (not covered by meniscus) and peripheral (covered by meniscus) regions of porcine tibial plateaus. For baseline gene expression analysis, samples were snap frozen. To determine the effect of mechanical loading, central and peripheral region explants were exposed to equivalent dynamic compression (0-100 kPa) and compared to site-matched free-swelling controls (FSCs). mRNA levels for type II collagen (CII), aggrecan (AGGR), matrix metalloproteinase 1 (MMP-1), MMP-3, MMP-13, A disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAM-TS4), ADAM-TS5, tissue inhibitor of metalloproteinases 1 (TIMP-1), TIMP-2, and tumor necrosis factor alpha (TNFalpha) were quantified using real time polymerase chain reaction (RT-PCR). RESULTS: At baseline, mRNA levels for the structural proteins CII and AGGR were approximately twofold greater in the central region compared with peripheral region explants. In vitro dynamic compression strongly affected expression levels for CII, AGGR, MMP-3, and TIMP-2 relative to FSCs. Response differed significantly by region, with greater upregulation of CII, AGGR, and MMP-3 in central region explants. CONCLUSIONS: Chondrocytes from different regions of the porcine tibial plateau express mRNA for structural proteins at different levels and respond to equivalent in vitro mechanical loading with distinctive changes in gene expression. These regional biological variations appear to be related to the local mechanical environment in the normal joint, and thus may indicate a sensitivity of the joint to conditions that alter joint loading such as anterior cruciate ligament (ACL) injury, meniscectomy, or joint instability.

A markerless motion capture system to study musculoskeletal biomechanics: visual hull and simulated annealing approach.

Human motion capture is frequently used to study musculoskeletal biomechanics and clinical problems, as well as to provide realistic animation for the entertainment industry. The most popular technique for human motion capture uses markers placed on the skin, despite some important drawbacks including the impediment to the motion by the presence of skin markers and relative movement between the skin where the markers are placed and the underlying bone. The latter makes it difficult to estimate the motion of the underlying bone, which is the variable of interest for biomechanical and clinical applications. A model-based markerless motion capture system is presented in this study, which does not require the placement of any markers on the subject's body. The described method is based on visual hull reconstruction and an a priori model of the subject. A custom version of adapted fast simulated annealing has been developed to match the model to the visual hull. The tracking capability and a quantitative validation of the method were evaluated in a virtual environment for a complete gait cycle. The obtained mean errors, for an entire gait cycle, for knee and hip flexion are respectively 1.5 degrees (+/-3.9 degrees ) and 2.0 degrees (+/-3.0 degrees ), while for knee and hip adduction they are respectively 2.0 degrees (+/-2.3 degrees ) and 1.1 degrees (+/-1.7 degrees ). Results for the ankle and shoulder joints are also presented. Experimental results captured in a gait laboratory with a real subject are also shown to demonstrate the effectiveness and potential of the presented method in a clinical environment.

Considerations in measuring cartilage thickness using MRI: factors influencing reproducibility and accuracy.

OBJECTIVE: The primary goal of this study was to describe and evaluate conditions that could influence the precision and accuracy of measuring in vivo cartilage thickness in the weight bearing regions of the knee from magnetic resonance imaging (MRI). DESIGN: Three-dimensional (3D) models of the femoral cartilage were created from segmented MR images. The weight bearing regions on femoral cartilage were selected for the portion of the tibiofemoral joint that sustains contact during walking. Six regions of interest (three on each condyle) were located on the femur. Average cartilage thickness was calculated over each region. The sensitivity of the precision of the measurements to observer variability was evaluated using intra- and inter-observer reproducibility tests of cartilage thickness measurements from the MRI-derived 3D models. In addition, the quantitative influence of a rule-based protocol for segmentation was evaluated using the inter-observer reproducibility protocol. Accuracy tests were conducted on porcine knees by comparing 3D models from MR images and laser scans across weight bearing and non-weight bearing regions. RESULTS: The precision was substantially better for the intra-observer tests (Coefficient of variation (CV) = 1-3%) than the inter-observer tests. Adding a rule-based protocol reduced variability in inter-observer tests substantially (CV = 6.6% vs 8.3%). Accuracy tests showed that the central and weight bearing regions on each condyle were more accurate than boundary and non-weight bearing regions. In addition, these results indicate that care should be taken when determining cartilage thickness of weight bearing regions with cartilage degenerations, since the thickness of thinner cartilage can be systematically overestimated in MR images. CONCLUSIONS: A rule-based approach can substantially increase inter-observer reproducibility when measuring cartilage thickness from multiple observers. This improvement in inter-observer reproducibility could be an important consideration for longitudinal studies of disease progression. In quantifying cartilage thickness, central and weight bearing regions on each condyle can provide more accurate measurement than boundary and non-weight bearing regions with average accuracy of +/-0.2-0.3 mm. An important finding of this study was that the weight bearing regions, which are usually of the greatest clinical interest, were measured most accurately by sagittal plane imaging.

MR imaging of articular cartilage at 1.5T and 3.0T: comparison of SPGR and SSFP sequences.

OBJECTIVE: To compare articular cartilage signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and thickness measurements on a 1.5 T and a 3.0 T magnetic resonance (MR) scanner using three-dimensional spoiled gradient recalled echo (3D-SPGR) and two 3D steady-state free precession (SSFP) sequences. METHODS: Both knees of five volunteers were scanned at 1.5 T and at 3.0 T using a transmit-receive quadrature extremity coil. Each examination consisted of a sagittal 3D-SPGR sequence, a sagittal fat suppressed 3D-SSFP (FS-SSFP) sequence, and a sagittal Dixon 3D-SSFP sequence. For quantitative analysis, we compared cartilage SNR and CNR efficiencies, as well as average cartilage thickness measurements. RESULTS: For 3D-SPGR, cartilage SNR efficiencies at 3.0 T increased compared to those at 1.5 T by a factor of 1.83 (range: 1.40-2.09). In comparison to 3D-SPGR, the SNR efficiency of FS-SSFP increased by a factor of 2.13 (range: 1.81-2.39) and for Dixon SSFP by a factor of 2.39 (range: 1.95-2.99). For 3D-SPGR, CNR efficiencies between cartilage and its surrounding tissue increased compared to those at 1.5 T by a factor of 2.12 (range: 1.75-2.47), for FS-SSFP by a factor 2.11 (range: 1.58-2.80) and for Dixon SSFP by a factor 2.39 (range 2.09-2.83). Average cartilage thicknesses of load bearing regions were not different at both field strengths or between sequences (P>0.05). Mean average cartilage thickness measured in all knees was 2.28 mm. CONCLUSION: Articular cartilage imaging of the knee on a 3.0 T MR scanner shows increased SNR and CNR efficiencies compared to a 1.5 T scanner, where SSFP-based techniques show the highest increase in SNR and CNR efficiency. There was no difference between average cartilage thickness measurements performed at the 1.5 T and 3.0 T scanners or between the three different sequences.

Sensitivity of finite helical axis parameters to temporally varying realistic motion utilizing an idealized knee model.

Various uses of the screw or helical axis have previously been reported in the literature in an attempt to quantify the complex displacements and coupled rotations of in vivo human knee kinematics. Multiple methods have been used by previous authors to calculate the axis parameters, and it has been theorized that the mathematical stability and accuracy of the finite helical axis (FHA) is highly dependent on experimental variability and rotation increment spacing between axis calculations. Previous research has not addressed the sensitivity of the FHA for true in vivo data collection, as required for gait laboratory analysis. This research presents a controlled series of experiments simulating continuous data collection as utilized in gait analysis to investigate the sensitivity of the three-dimensional finite screw axis parameters of rotation, displacement, orientation and location with regard to time step increment spacing, utilizing two different methods for spatial location. Six-degree-of-freedom motion parameters are measured for an idealized rigid body knee model that is constrained to a planar motion profile for the purposes of error analysis. The kinematic data are collected using a multicamera optoelectronic system combined with an error minimization algorithm known as the point cluster method. Rotation about the screw axis is seen to be repeatable, accurate and time step increment insensitive. Displacement along the axis is highly dependent on time step increment sizing, with smaller rotation angles between calculations producing more accuracy. Orientation of the axis in space is accurate with only a slight filtering effect noticed during motion reversal. Locating the screw axis by a projected point onto the screw axis from the mid-point of the finite displacement is found to be less sensitive to motion reversal than finding the intersection of the axis with a reference plane. A filtering effect of the spatial location parameters was noted for larger time step increments during periods of little or no rotation.