Effects of neuromuscular control and strengthening exercises on MRI-measured thigh tissue composition and muscle properties in people with knee osteoarthritis - an exploratory secondary analysis from a randomized controlled trial.

OBJECTIVE: To investigate the effects of adding strength training to neuromuscular control exercises on thigh tissue composition and muscle properties in people with radiographic-symptomatic knee osteoarthritis (KOA). METHODS: In this exploratory secondary analysis of a randomized controlled trial, using a complete-case approach, participants performed 12 weeks of twice-weekly neuromuscular control exercise and patient education (NEMEX, n = 34) or NEMEX plus quadriceps strength training (NEMEX+ST, n = 29). Outcomes were MRI-measured inter- and intramuscular adipose tissue (InterMAT, IntraMAT), quadriceps muscle cross-sectional area (CSA), knee-extensor strength, specific strength (strength/lean CSA) and 30 s chair-stands. Between-group effects were compared using a mixed model analysis of variance. RESULTS: At 12 weeks, responses to NEMEX+ST overlapped with NEMEX for all outcomes. Both groups reduced InterMAT (NEMEX+ST=25 %, NEMEX=21 %); between-group difference: 0.8cm2 (95 % CI: -0.1, 1.7). NEMEX+ST decreased IntraMAT (2 %) and NEMEX increased IntraMAT (4 %); between-group difference 0.1 %-points (-0.3, 0.5). Both groups increased quadriceps CSA and lean CSA (CSA minus IntraMAT), improved knee-extensor strength and specific strength, and improved chair-stand performance with a trend towards greater effects in NEMEX+ST. CONCLUSION: Adding strength training to 12 weeks of neuromuscular control exercises provided largely similar effects to neuromuscular control exercises alone in decreasing InterMAT and IntraMAT, in improving knee-extensor strength, CSA and in improving performance-based function in KOA persons, with a trend towards greater effects with additional strength training. Notably, both groups substantially reduced InterMAT and improved specific strength (an index of muscle quality). Our hypothesis-generating work warrants exploration of the roles played by InterMAT and IntraMAT in exercise effects in KOA.

30 Years of MRI-based cartilage & bone morphometry in knee osteoarthritis: From correlation to clinical trials.

OBJECTIVE: The first publication on morphometric analysis of articular cartilage using magnetic resonance imaging (MRI) in 1994 set the scene for a game change in osteoarthritis (OA) research. The current review highlights milestones in cartilage and bone morphometry, summarizing the rapid progress made in imaging, its application to understanding joint (patho-)physiology, and its use in interventional clinical trials. METHODS: Based on a Pubmed search of articles from 1994 to 2023, the authors subjectively selected representative work illustrating important steps in the development or application of magnetic resonance-based cartilage and bone morphometry, with a focus on studies in humans, and on the knee. Research on OA-pathophysiology is addressed only briefly, given length constraints. Compositional and semi-quantitative assessment are not covered here. RESULTS: The selected articles are presented in historical order as well as by content. We review progress in the technical aspects of image acquisition, segmentation and analysis, advances in understanding tissue growth, physiology, function, and adaptation, and a selection of clinical trials examining the efficacy of interventions on knee cartilage and bone. A perspective is provided of how lessons learned may be applied to future research and clinical management. CONCLUSIONS: Over the past 30 years, MRI-based morphometry of cartilage and bone has contributed to a paradigm shift in understanding articular tissue physiology and OA pathophysiology, and to the development of new treatment strategies. It is likely that these technologies will continue to play a key role in the development and (accelerated) approval of therapy, potentially targeted to different OA phenotypes.

Imaging Biomarkers of Osteoarthritis.

Currently no disease-modifying osteoarthritis drug has been approved for the treatment of osteoarthritis (OA) that can reverse, hold, or slow the progression of structural damage of OA-affected joints. The reasons for failure are manifold and include the heterogeneity of structural disease of the OA joint at trial inclusion, and the sensitivity of biomarkers used to measure a potential treatment effect.This article discusses the role and potential of different imaging biomarkers in OA research. We review the current role of radiography, as well as advances in quantitative three-dimensional morphological cartilage assessment and semiquantitative whole-organ assessment of OA. Although magnetic resonance imaging has evolved as the leading imaging method in OA research, recent developments in computed tomography are also discussed briefly. Finally, we address the experience from the Foundation for the National Institutes of Health Biomarker Consortium biomarker qualification study and the future role of artificial intelligence.

Association between knee magnetic resonance imaging markers and knee symptoms over 6-9 years in young adults.

OBJECTIVES: To describe associations between MRI markers with knee symptoms in young adults. METHODS: Knee symptoms were assessed using the WOMAC scale during the Childhood Determinants of Adult Health Knee Cartilage study (CDAH-knee; 2008-2010) and at the 6- to 9-year follow-up (CDAH-3; 2014-2019). Knee MRI scans obtained at baseline were assessed for morphological markers (cartilage volume, cartilage thickness, subchondral bone area) and structural abnormalities [cartilage defects and bone marrow lesions (BMLs)]. Univariable and multivariable (age, sex, BMI adjusted) zero-inflated Poisson (ZIP) regression models were used for analysis. RESULTS: The participants' mean age in CDAH-knee and CDAH-3 were 34.95 (s.d. 2.72) and 43.27 (s.d. 3.28) years, with 49% and 48% females, respectively. Cross-sectionally, there was a weak but significant negative association between medial femorotibial compartment (MFTC) [ratio of the mean (RoM) 0.99971084 (95% CI 0.9995525, 0.99986921), P < 0.001], lateral femorotibial compartment (LFTC) [RoM 0.99982602 (95% CI 0.99969915, 0.9999529), P = 0.007] and patellar cartilage volume [RoM 0.99981722 (95% CI 0.99965326, 0.9999811), P = 0.029] with knee symptoms. Similarly, there was a negative association between patellar cartilage volume [RoM 0.99975523 (95% CI 0.99961427, 0.99989621), P = 0.014], MFTC cartilage thickness [RoM 0.72090775 (95% CI 0.59481806, 0.87372596), P = 0.001] and knee symptoms assessed after 6-9 years. The total bone area was negatively associated with knee symptoms at baseline [RoM 0.9210485 (95% CI 0.8939677, 0.9489496), P < 0.001] and 6-9 years [RoM 0.9588811 (95% CI 0.9313379, 0.9872388), P = 0.005]. The cartilage defects and BMLs were associated with greater knee symptoms at baseline and 6-9 years. CONCLUSION: BMLs and cartilage defects were positively associated with knee symptoms, whereas cartilage volume and thickness at MFTC and total bone area were weakly and negatively associated with knee symptoms. These results suggest that the quantitative and semiquantitative MRI markers can be explored as a marker of clinical progression of OA in young adults.

The Impact of Exercise Training and Supplemental Oxygen on Peripheral Muscles in Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial.

OBJECTIVE: Exercise training is a cornerstone of the treatment of chronic obstructive pulmonary disease, whereas the related interindividual heterogeneity in skeletal muscle dysfunction and adaptations are not yet fully understood. We set out to investigate the effects of exercise training and supplemental oxygen on functional and structural peripheral muscle adaptation. METHODS: In this prospective, randomized, controlled, double-blind study, 28 patients with nonhypoxemic chronic obstructive pulmonary disease (forced expiratory volume in 1 second, 45.92% ± 9.06%) performed 6 wk of combined endurance and strength training, three times a week while breathing either supplemental oxygen or medical air. The impact on exercise capacity, muscle strength, and quadriceps femoris muscle cross-sectional area (CSA) was assessed by maximal cardiopulmonary exercise testing, 10-repetition maximum strength test of knee extension, and magnetic resonance imaging, respectively. RESULTS: After exercise training, patients demonstrated a significant increase in functional capacity, aerobic capacity, exercise tolerance, quadriceps muscle strength, and bilateral CSA. Supplemental oxygen affected significantly the training impact on peak work rate when compared with medical air (+0.20 ± 0.03 vs +0.12 ± 0.03 W·kg -1 , P = 0.047); a significant increase in CSA (+3.9 ± 1.3 cm 2 , P = 0.013) was only observed in the training group using oxygen. Supplemental oxygen and exercise-induced peripheral desaturation were identified as significant opposing determinants of muscle gain during this exercise training intervention, which led to different adaptations of CSA between the respective subgroups. CONCLUSIONS: The heterogenous functional and structural muscle adaptations seem determined by supplemental oxygen and exercise-induced hypoxia. Indeed, supplemental oxygen may facilitate muscular training adaptations, particularly in limb muscle dysfunction, thereby contributing to the enhanced training responses on maximal aerobic and functional capacity.

Association of quantitative measures of medial meniscal extrusion with structural and symptomatic knee osteoarthritis progression - Data from the OAI FNIH biomarker study.

OBJECTIVE: To study the association of quantitative medial meniscal position measures with radiographic and symptomatic knee osteoarthritis (OA) progression over 2-4 years. METHODS: The FNIH OAI Biomarkers study comprised 600 participants in four subgroups: 194 case knees with combined structural (medial minimum joint space width (minJSW) loss ≥0.7 mm) and symptomatic (persistent Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale increase ≥9 [0-100 scale]) progression; 200 knees with neither structural nor symptomatic progression; 103 knees with isolated structural and 103 with isolated symptomatic progression. Coronal double echo at steady state (DESS) MRIs were used for segmenting five central slices of the medial meniscus. Associations with progression were examined using logistic regression (adjusted for demographic and clinical data). RESULTS: Greater baseline medial meniscal extrusion was associated with combined structural/symptomatic progression (OR 1.59; 95%CI: [1.25,2.04]). No relationship was observed for tibial plateau coverage or meniscal overlap distance. The two-year increase in meniscal extrusion (OR 1.48 [1.21, 1.83]), and reduction in tibial plateau coverage (OR 0.70 [0.58,0.86]) and overlap distance (OR 0.73 [0.60,0.89]) were associated with combined progression. Greater baseline extrusion was associated with isolated structural and less extrusion with isolated symptomatic progression. The longitudinal increase in meniscal extrusion, and reduction in tibial plateau coverage and overlap distance were associated with structural, but not with symptomatic progression. CONCLUSION: Baseline measures of medial meniscal extrusion were consistently positively associated with combined radiographic/symptomatic progression and with isolated structural, but not with isolated symptomatic progression. These measures may therefore allow one to assess the risk of structural knee OA progression and to monitor interventions restoring meniscal position and function.

Comparison of evaluation metrics of deep learning for imbalanced imaging data in osteoarthritis studies.

PURPOSE: To compare the evaluation metrics for deep learning methods that were developed using imbalanced imaging data in osteoarthritis studies. MATERIALS AND METHODS: This retrospective study utilized 2996 sagittal intermediate-weighted fat-suppressed knee MRIs with MRI Osteoarthritis Knee Score readings from 2467 participants in the Osteoarthritis Initiative study. We obtained probabilities of the presence of bone marrow lesions (BMLs) from MRIs in the testing dataset at the sub-region (15 sub-regions), compartment, and whole-knee levels based on the trained deep learning models. We compared different evaluation metrics (e.g., receiver operating characteristic (ROC) and precision-recall (PR) curves) in the testing dataset with various class ratios (presence of BMLs vs. absence of BMLs) at these three data levels to assess the model's performance. RESULTS: In a subregion with an extremely high imbalance ratio, the model achieved a ROC-AUC of 0.84, a PR-AUC of 0.10, a sensitivity of 0, and a specificity of 1. CONCLUSION: The commonly used ROC curve is not sufficiently informative, especially in the case of imbalanced data. We provide the following practical suggestions based on our data analysis: 1) ROC-AUC is recommended for balanced data, 2) PR-AUC should be used for moderately imbalanced data (i.e., when the proportion of the minor class is above 5% and less than 50%), and 3) for severely imbalanced data (i.e., when the proportion of the minor class is below 5%), it is not practical to apply a deep learning model, even with the application of techniques addressing imbalanced data issues.

Machine-learning predicted and actual 2-year structural progression in the IMI-APPROACH cohort.

In the Innovative Medicine's Initiative Applied Public-Private Research enabling OsteoArthritis Clinical Headway (IMI-APPROACH) knee osteoarthritis (OA) study, machine learning models were trained to predict the probability of structural progression (s-score), predefined as >0.3 mm/year joint space width (JSW) decrease and used as inclusion criterion. The current objective was to evaluate predicted and observed structural progression over 2 years according to different radiographic and magnetic resonance imaging (MRI)-based structural parameters. Radiographs and MRI scans were acquired at baseline and 2-year follow-up. Radiographic (JSW, subchondral bone density, osteophytes), MRI quantitative (cartilage thickness), and MRI semiquantitative [SQ; cartilage damage, bone marrow lesions (BMLs), osteophytes] measurements were obtained. The number of progressors was calculated based on a change exceeding the smallest detectable change (SDC) for quantitative measures or a full SQ-score increase in any feature. Prediction of structural progression based on baseline s-scores and Kellgren-Lawrence (KL) grades was analyzed using logistic regression. Among 237 participants, around 1 in 6 participants was a structural progressor based on the predefined JSW-threshold. The highest progression rate was seen for radiographic bone density (39%), MRI cartilage thickness (38%), and radiographic osteophyte size (35%). Baseline s-scores could only predict JSW progression parameters (most P>0.05), while KL grades could predict progression of most MRI-based and radiographic parameters (P<0.05). In conclusion, between 1/6 and 1/3 of participants showed structural progression during 2-year follow-up. KL scores were observed to outperform the machine-learning-based s-scores as progression predictor. The large amount of data collected, and the wide range of disease stage, can be used for further development of more sensitive and successful (whole joint) prediction models. Trial Registration: Clinicaltrials.gov number NCT03883568.

Exploring the differences between radiographic joint space width and MRI cartilage thickness changes using data from the IMI-APPROACH cohort.

OBJECTIVE: Longitudinal weight-bearing radiographic joint space width (JSW) and non-weight-bearing MRI-based cartilage thickness changes often show weak correlations. The current objective was to investigate these correlations, and to explore the influence of different factors that could contribute to longitudinal differences between the two methods. METHODS: The current study included 178 participants with medial osteoarthritis (OA) out of the 297 knee OA participants enrolled in the IMI-APPROACH cohort. Changes over 2 years in medial JSW (ΔJSWmed), minimum JSW (ΔJSWmin), and medial femorotibial cartilage thickness (ΔMFTC) were assessed using linear regression, using measurements from radiographs and MRI acquired at baseline, 6 months, and 1 and 2 years. Pearson R correlations were calculated. The influence of cartilage quality (T2 mapping), meniscal extrusion (MOAKS scoring), potential pain-induced unloading (difference in knee-specific pain scores), and increased loading (BMI) on the correlations was analyzed by dividing participants in groups based on each factor separately, and comparing correlations (slope and strength) between groups using linear regression models. RESULT: Correlations between ΔMFTC and ΔJSWmed and ΔJSWmin were statistically significant (p < 0.004) but weak (R < 0.35). Correlations were significantly different between groups based on cartilage quality and on meniscal extrusion: only patients with the lowest T2 values and with meniscal extrusion showed significant moderate correlations. Pain-induced unloading or BMI-induced loading did not influence correlations. CONCLUSIONS: While the amount of loading does not seem to make a difference, weight-bearing radiographic JSW changes are a better reflection of non-weight-bearing MRI cartilage thickness changes in knees with higher quality cartilage and with meniscal extrusion.

Quantitative CT of the knee in the IMI-APPROACH osteoarthritis cohort: Association of bone mineral density with radiographic disease severity, meniscal coverage and meniscal extrusion.

OBJECTIVE: Osteoarthritis (OA) is a highly prevalent chronic condition. The subchondral bone plays an important role in onset and progression of OA making it a potential treatment target for disease-modifying therapeutic approaches. However, little is known about changes of periarticular bone mineral density (BMD) in OA and its relation to meniscal coverage and meniscal extrusion at the knee. Thus, the aim of this study was to describe periarticular BMD in the Applied Public-Private Research enabling OsteoArthritis Clinical Headway (APPROACH) cohort at the knee and to analyze the association with structural disease severity, meniscal coverage and meniscal extrusion. DESIGN: Quantitative CT (QCT), MRI and radiographic examinations were acquired in 275 patients with knee osteoarthritis (OA). QCT was used to assess BMD at the femur and tibia, at the cortical bone plate (Cort) and at the epiphysis at three locations: subchondral (Sub), mid-epiphysis (Mid) and adjacent to the physis (Juxta). BMD was evaluated for the medial and lateral compartment separately and for subregions covered and not covered by the meniscus. Radiographs were used to determine the femorotibial angle and were evaluated according to the Kellgren and Lawrence (KL) system. Meniscal extrusion was assessed from 0 to 3. RESULTS: Mean BMD differed significantly between each anatomic location at both the femur and tibia (p < 0.001) in patients with KL0. Tibial regions assumed to be covered with meniscus in patients with KL0 showed lower BMD at Sub (p < 0.001), equivalent BMD at Mid (p = 0.07) and higher BMD at Juxta (p < 0.001) subregions compared to regions not covered with meniscus. Knees with KL2-4 showed lower Sub (p = 0.03), Mid (p = 0.01) and Juxta (p < 0.05) BMD at the medial femur compared to KL0/1. Meniscal extrusion grade 2 and 3 was associated with greater BMD at the tibial Cort (p < 0.001, p = 0.007). Varus malalignment is associated with significant greater BMD at the medial femur and at the medial tibia at all anatomic locations. CONCLUSION: BMD within the epiphyses of the tibia and femur decreases with increasing distance from the articular surface. Knees with structural OA (KL2-4) exhibit greater cortical BMD values at the tibia and lower BMD at the femur at the subchondral level and levels beneath compared to KL0/1. BMD at the tibial cortical bone plate is greater in patients with meniscal extrusion grade 2/3.

Worsening of Articular Tissue Damage as Defined by Semi-Quantitative MRI Is Associated With Concurrent Quantitative Cartilage Loss Over 24 Months.

OBJECTIVE: To assess the association of worsening of magnetic resonance imaging (MRI) semi-quantitative (SQ) tissue features with concurrent change in quantitative (Q) cartilage thickness measurements over 24 months within the Foundation for the National Institutes of Health (FNIH) Biomarker Consortium study. METHODS: In all, 599 participants were included. SQ assessment included cartilage damage, meniscal extrusion and damage, osteophytes, bone marrow lesions (BMLs), and effusion- and Hoffa-synovitis. Change in medial compartment Q cartilage thickness was stratified by concurrent ipsicompartmental SQ changes. Between-group comparisons were performed using analysis of covariance (ANCOVA) with adjustment for age, sex, and body mass index (BMI). Results were presented as adjusted mean difference. RESULTS: Knees with any increase in SQ cartilage scores in the medial compartment (n = 268) showed more Q cartilage loss compared to knees that remained stable (mean adjusted difference [MAD] = -0.16 mm, 95% confidence interval [CI]: [-0.19, -0.13] mm). Knees with any increase in meniscal extrusion in the medial compartment (n = 98) showed more Q cartilage loss than knees without (MAD = -0.18 mm, 95% CI: [-0.22, -0.14] mm. Comparable findings were seen for meniscal damage worsening. Regarding BMLs, an increase by one subregion resulted in a MAD of Q cartilage loss of -0.10 mm, 95% CI: [-0.14, -0.06] mm, while this effect almost tripled for change in two or more subregions. Increase in either effusion- and/or Hoffa-synovitis by one grade resulted in a MAD of -0.07 mm, 95% CI: [-0.10, -0.03] mm. CONCLUSION: Worsening of SQ cartilage damage, meniscal extrusion and damage, number of subregions affected by BML, maximum size of BMLs and worsening of effusion- and/or Hoffa synovitis is associated with increased Q cartilage loss.

Quantitative measurement of cartilage morphology in osteoarthritis: current knowledge and future directions.

Quantitative measures of cartilage morphology ("cartilage morphometry") extracted from high resolution 3D magnetic resonance imaging (MRI) sequences have been shown to be sensitive to osteoarthritis (OA)-related change and also to treatment interventions. Cartilage morphometry is therefore nowadays widely used as outcome measure for observational studies and randomized interventional clinical trials. The objective of this narrative review is to summarize the current status of cartilage morphometry in OA research, to provide insights into aspects relevant for the design of future studies and clinical trials, and to give an outlook on future developments. It covers the aspects related to the acquisition of MRIs suitable for cartilage morphometry, the analysis techniques needed for deriving quantitative measures from the MRIs, the quality assurance required for providing reliable cartilage measures, and the appropriate participant recruitment criteria for the enrichment of study cohorts with knees likely to show structural progression. Finally, it provides an overview over recent clinical trials that relied on cartilage morphometry as a structural outcome measure for evaluating the efficacy of disease-modifying OA drugs (DMOAD).

Selection of Knees With Subsequent Cartilage Thickness Loss Based on Magnetic Resonance Imaging Semiquantitative Grading: Data From the Osteoarthritis Initiative Foundation for the National Institutes of Health Biomarker Cohort.

OBJECTIVE: To investigate which magnetic resonance imaging (MRI)-based articular pathologies are predictive of subsequent medial femorotibial compartment quantitative cartilage thickness loss and therefore suitable for enrichment of clinical trials with participants showing a high likelihood for structural progression. METHODS: Semiquantitative MRI Osteoarthritis Knee Score (MOAKS) assessments at baseline and quantitative cartilage thickness measurements at baseline and year-2 follow-up were performed in 599 participants (age 62 years; body mass index 31 kg/m2 ; 59% female) from the Osteoarthritis Initiative-based Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium. Knees were classified as medial femorotibial compartment (MFTC) progressors or nonprogressors based on MFTC cartilage thickness change (smallest detectable change threshold -111 µm). Logistic regression was used to investigate the association between baseline presence and severity of MFTC MOAKS pathologies with subsequent MFTC progression. The standardized response mean (SRM) was computed to estimate the sensitivity to change that can be achieved when selecting knees based on MOAKS pathologies. RESULTS: Presence of MFTC MOAKS cartilage damage (odds ratio [OR] 2.77 [95% confidence interval (95% CI) 1.76, 4.36]), MFTC bone marrow lesions (OR 2.69 [95% CI 1.89, 3.83]), medial meniscus extrusion or damage (OR 2.21 [95% CI 1.37, 3.55]), as well as MOAKS severity subscales for cartilage and meniscus damage were associated with subsequent progression. The SRM was greater in knees with than in knees without the presence of these pathologies and was associated with the severity of those pathologies. CONCLUSION: MRI-based grading of articular pathologies makes it possible to specifically select progressor knees suitable for inclusion in clinical trials but also to identify knees in which treatment is not indicated (e.g., knees without cartilage damage despite presence of radiographic osteoarthritis).

Structural tissue damage and 24-month progression of semi-quantitative MRI biomarkers of knee osteoarthritis in the IMI-APPROACH cohort.

BACKGROUND: The IMI-APPROACH cohort is an exploratory, 5-centre, 2-year prospective follow-up study of knee osteoarthritis (OA). Aim was to describe baseline multi-tissue semiquantitative MRI evaluation of index knees and to describe change for different MRI features based on number of subregion-approaches and change in maximum grades over a 24-month period. METHODS: MRIs were acquired using 1.5 T or 3 T MRI systems and assessed using the semi-quantitative MRI OA Knee Scoring (MOAKS) system. MRIs were read at baseline and 24-months for cartilage damage, bone marrow lesions (BML), osteophytes, meniscal damage and extrusion, and Hoffa- and effusion-synovitis. In descriptive fashion, the frequencies of MRI features at baseline and change in these imaging biomarkers over time are presented for the entire sample in a subregional and maximum score approach for most features. Differences between knees without and with structural radiographic (R) OA are analyzed in addition. RESULTS: Two hundred eighty-nine participants had readable baseline MRI examinations. Mean age was 66.6 ± 7.1 years and participants had a mean BMI of 28.1 ± 5.3 kg/m2. The majority (55.3%) of included knees had radiographic OA. Any change in total cartilage MOAKS score was observed in 53.1% considering full-grade changes only, and in 73.9% including full-grade and within-grade changes. Any medial cartilage progression was seen in 23.9% and any lateral progression on 22.1%. While for the medial and lateral compartments numbers of subregions with improvement and worsening of BMLs were very similar, for the PFJ more improvement was observed compared to worsening (15.5% vs. 9.0%). Including within grade changes, the number of knees showing BML worsening increased from 42.2% to 55.6%. While for some features 24-months change was rare, frequency of change was much more common in knees with vs. without ROA (e.g. worsening of total MOAKS score cartilage in 68.4% of ROA knees vs. 36.7% of no-ROA knees, and 60.7% vs. 21.8% for an increase in maximum BML score per knee). CONCLUSIONS: A wide range of MRI-detected structural pathologies was present in the IMI-APPROACH cohort. Baseline prevalence and change of features was substantially more common in the ROA subgroup compared to the knees without ROA. TRIAL REGISTRATION: Clinicaltrials.gov identification: NCT03883568.

Muscle weakness is associated with non-contractile muscle tissue of the vastus medialis muscle in knee osteoarthritis.

BACKGROUND: Quadriceps weakness is assumed to be associated with compositional properties of the vastus medialis muscle in patients with knee osteoarthritis (OA). METHODS: The aim was to determine the association of non-contractile muscle tissue in the vastus medialis muscle, measured with routine MRI, with muscle extensor strength in patients with knee OA. Sagittal T1-weighted 3T MRI of 94 patients with knee OA, routinely acquired in clinical practice were used for analysis. Using the MRI's, the amount of non-contractile muscle tissue in the vastus medialis muscle was measured, expressed as a percentage of (non)-contractile tissue, dichotomized into a low and a high non-contractile percentage group. Muscle strength was assessed by isokinetic measurement of knee extensors and by conduction of the Get-Up and Go (GUG) test. In regression analyses, associations of percentage of non-contractile muscle tissue with muscle strength and GUG time were determined and controlled for sex, age, BMI and radiographic severity. RESULTS: A high percentage of non-contractile muscle tissue (> 11.2%) was associated with lower muscle strength (B = -0.25, P = 0.006) and with longer GUG time (B = 1.09, P = 0.021). These associations were specifically confounded by sex and BMI, because these two variables decreased the regression coefficient (B) with > 10%. CONCLUSIONS: A high percentage of non-contractile muscle tissue in the vastus medialis muscle measured by clinical T1-weighted 3T MRI is associated with muscle weakness. The association is confounded by sex and BMI. Non-contractile muscle tissue seems to be an important compositional property of the vastus medialis muscle underlying quadriceps weakness.

Association of Superficial Cartilage Transverse Relaxation Time With Osteoarthritis Disease Progression: Data From the Foundation for the National Institutes of Health Biomarker Study of the Osteoarthritis Initiative.

OBJECTIVE: To study whether layer-specific cartilage transverse relaxation time (T2) and/or longitudinal change is associated with clinically relevant knee osteoarthritis (OA) disease progression. METHODS: The Foundation for the National Institutes of Health Biomarker Consortium was a nested case-control study on 600 knees from 600 Osteoarthritis Initiative participants. Progressor knees had both medial tibiofemoral radiographic joint space width (JSW) loss (≥0.7 mm) and a persistent increase in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score (≥9 on a 0-100 scale) at 24-48 months from baseline (n = 194). Multiecho spin-echo (MESE) magnetic resonance images (MRIs) for cartilage T2 analysis had been acquired in the right knees only (97 progressor knees). These were compared to 104 control knees without JSW or pain progression. Fifty-three knees had JSW progression, and 57 pain progression only. Cartilage thickness segmentations obtained from double-echo steady-state MRI were matched to MESE MRI to extract superficial and deep femorotibial cartilage T2. Superficial medial femorotibial compartment (MFTC) T2 at baseline was the primary, and change in deep MFTC T2 between baseline and 12 months was the secondary analytic outcome of this post hoc exploratory study. RESULTS: Baseline superficial MFTC T2 was significantly elevated in progressor knees (adjusted mean 47.2 msec [95% confidence interval (95% CI) 46.5, 48.0]) and JSW progression only knees (adjusted mean 47.3 msec [95% CI 46.3, 48.3]), respectively, versus non-progressor knees (45.8 msec [95% CI 45.0, 46.5]) after adjustment for age, sex, body mass index, WOMAC pain score, and medial joint space narrowing grade (analysis of covariance). Change in T2 was not significantly associated with case status. CONCLUSION: Baseline superficial, but not deep, medial cartilage T2 is associated with clinically relevant disease progression in knee OA.

Meniscus position and size in knees with versus without structural knee osteoarthritis progression: data from the osteoarthritis initiative.

OBJECTIVE: To explore whether and which quantitative 3D measures of medial and/or lateral meniscus position and size are associated with subsequent medial femorotibial structural progression of knee osteoarthritis and to determine the correlation between central slice and total meniscus measures. MATERIALS AND METHODS: Knees with radiographic osteoarthritis from Osteoarthritis Initiative participants with longitudinal medial MRI-based cartilage thickness and radiographic joint space width (JSW) loss over 12 months were selected. These 37 structural progressor knees (64.7 ± 8.0y, 30.2 ± 4.6 kg/m2, 35% men) were matched 1:1 to 37 non-progressor knees (64.6 ± 9.8y, 30.2 ± 4.4 kg/m2, 35% men) without cartilage thickness or JSW loss. Quantitative measures of meniscus position and size were computed from manual segmentations of coronal baseline MRIs. Cohen's D was used as measure of effect size. RESULTS: Maximum extrusion distance of the total medial meniscus and mean extrusion in the central 5 and in the central slice were greater for progressor than non-progressor knees (Cohen's D 0.58-0.66). No significant differences were observed for medial tibial coverage or mean extrusion (entire meniscus). Among medial meniscus morphology measures, only mean height differed between progressor vs non-progressor knees (Cohen's D 0.40). Among lateral meniscus measures, height and volume were greater in progressor vs. non-progressor knees (Cohen's D 0.46-0.83). Mean extrusion measures were highly correlated between the entire meniscus and the central (r = 0.88) or the central 5 (r = 0.93) slices. CONCLUSIONS: 3D maximum and central medial meniscus extrusion may serve as predictors for subsequent structural progression. Central meniscus extrusion measures could substitute 3D extrusion measurement across the entire meniscus.

Responsiveness of Subcutaneous Fat, Intermuscular Fat, and Muscle Anatomical Cross-Sectional Area of the Thigh to Longitudinal Body Weight Loss and Gain: Data from the Osteoarthritis Initiative (OAI).

Thigh subcutaneous (SCF) and intermuscular (IMF) fat have been associated with joint health and function. Here, we explore the (sex-specific) responsiveness of SCF, IMF, and muscle during longitudinal weight loss and gain, as well as the change in questionnaire-based and physical performance-based knee function measures. This exploratory study included 103 Osteoarthritis Initiative (OAI) participants, who displayed a ≥10% weight loss or gain between baseline (BL) and 2-year (Y2) follow-up (and maintained half of that weight loss until year 4) and had axial 3T magnetic resonance images (MRI) for measuring SCF, IMF, and muscle cross sectional areas (CSAs). The standardized response mean (SRM = mean divided by the standard deviation of the change) was used as a measure of responsiveness. A total of 52 OAI participants (73% women) displayed ≥10% weight loss, and 51 (67% women) ≥10% weight gain. Both SCF and IMF CSAs showed a significant decrease (mean change) with weight loss (SCF: -22%, SRM = -1.2; IMF: -15%, SRM = -0.7) and a significant increase with weight gain (SCF: +27%, SRM = 1.1; IMF: +21%, SRM = 0.6). Muscle CSAs showed significant changes during weight loss (extensor: -8.3%, SRM = -1.1; flexor: -7.2%, SRM = -1.0), but not during weight gain. Knee function measures were not relevantly associated with bidirectional changes in body weight. SCF and IMF CSAs are highly responsive to bidirectional weight change, whereas muscle CSAs were only responsive to weight loss. These findings highlight that MRI represents a sensitive tool for monitoring changes in thigh adipose tissue composition that may be applied during specific diet and/or exercise interventions.

Longitudinal Relationship Between Tibiofemoral Contact Stress at Baseline and Worsening of Knee Pain Over 84 Months in the Multicenter Osteoarthritis Study.

OBJECTIVE: The aim of the study was to determine whether tibiofemoral contact stress predicts risk for worsening knee pain over 84 ms in adults aged 50-79 yrs with or at elevated risk for knee osteoarthritis. DESIGN: Baseline tibiofemoral contact stress was estimated using discrete element analysis. Other baseline measures included weight, height, hip-knee-ankle alignment, Kellgren-Lawrence grade, and Western Ontario and McMaster Universities Osteoarthritis Index pain subscale. Logistic regression models assessed the association between baseline contact stress and 84-mo worsening of Western Ontario and McMaster Universities Osteoarthritis Index pain subscale. RESULTS: Data from the dominant knee (72.6% Kellgren-Lawrence grade 0/1 and 27.4% Kellgren-Lawrence grade ≥ 2) of 208 participants (64.4% female, mean ± SD body mass index = 29.6 ± 5.1 kg/m 2 ) were analyzed. Baseline mean and peak contact stress were 3.3 ± 0.9 and 9.4 ± 4.3 MPa, respectively. Forty-seven knees met the criterion for worsening pain. The highest tertiles in comparison with the lowest tertiles of mean (odds ratio [95% confidence interval] = 2.47 [1.03-5.95], P = 0.04) and peak (2.49 [1.03-5.98], P = 0.04) contact stress were associated with worsening pain at 84 mos, after adjustment for age, sex, race, clinic site, and baseline pain. Post hoc sensitivity analyses including adjustment for body mass index and hip-knee-ankle alignment attenuated the effect. CONCLUSIONS: These findings suggest that elevated tibiofemoral contact stress can predict the development of worsening of knee pain.