Improved responsiveness to change in joint space width over 24-month follow-up: comparison of 3D JSW on weight-bearing CT vs 2D JSW on radiographs in the MOST study.

OBJECTIVE: Radiographic joint space width (JSW) has been a standard for measuring knee osteoarthritis (OA) structural change. Limitations in the responsiveness of this approach might be overcome by instead measuring 3D JSW on weight-bearing CT (WBCT). This study compared the responsiveness of 3D JSW measurements using WBCT with the responsiveness of radiographic 2D JSW. DESIGN: Standing, fixed-flexion knee radiographs (XR) and WBCT were acquired ancillary to the 144- and 168-month Multicenter Osteoarthritis Study visits. Tibiofemoral JSW was measured on both XR and WBCT. Responsiveness to change was defined by the standardized response mean (SRM) for change in JSW (1) at predetermined mediolateral locations (JSWx) on both modalities and (2) in the following subregions measured on WBCT images: central medial and lateral femur (CMF/CLF) and tibia (CMT/CLT), and anterior and posterior tibia (AMT/ALT, PMT/MLT). RESULTS: Baseline and 24-month follow-up JSWx measurements were completed for 265 participants (58.1% women). Responsiveness of 3D JSWx for medial tibiofemoral compartment on coronal WBCT (SRM range: -0.18, -0.24) exceeded that for 2D JSWx (-0.10, -0.16). Responsiveness of 3D JSW subregional mean (-0.06, -0.36) and maximal (-1.14, -1.75) CMF and CMT and maximal CLF/CLT 3D JSW changes were statistically significantly greater in comparison with respective medial and lateral 2D JSWx (P ≤ 0.002). CONCLUSIONS: Subregional 3D JSW on WBCT is substantially more responsive to 24-month changes in tibiofemoral joint structure compared to radiographic measurements. Use of subregional 3D JSW on WBCT could enable improved detection of OA structural progression over a 24-month duration in comparison with measurements made on XR.

Prevalence of intra-articular mineralization on knee computed tomography: the multicenter osteoarthritis study.

OBJECTIVE: The aim of this work was to report the prevalence of computed tomography (CT)-detected intra-articular mineralization. DESIGN: We included participants from the Multicenter Osteoarthritis (MOST) Study. At the 12th year visit of the MOST study, bilateral knee CTs were first obtained. All participants also had posteroanterior and lateral radiographs of bilateral knees and completed standard questionnaires. Knee radiographs were assessed for Kellgren & Lawrence grade (KLG) and radiographic evidence of intra-articular mineralization. CT images were scored using the Boston University Calcium Knee Score (BUCKS) for cartilage, menisci, ligaments, capsule, and vasculature. Prevalence of intra-articular mineralization was computed for the total sample, and stratified by age, sex, race, Body Mass Index (BMI), presence of frequent knee pain, and KLG. We also determined distribution of mineralization in the cartilage and meniscus, and co-localization. RESULTS: 4140 bilateral knees from 2070 participants were included (56.7% female, mean age 61.1 years, mean BMI: 28.8 kg/m2). On radiographs 240 knees (5.8%) had intraarticular mineralization, while CT-detected mineralization was present in 9.8% of knees. Prevalence of hyaline articular and meniscus mineralization increased with age and KL grade, and was similar by sex, BMI categories, and comparable in subjects with and without frequent knee pain. Mineralization tended to be ubiquitous in the joint, most commonly involving all three (medial/lateral tibiofemoral and patellofemoral) compartments (3.1%), while the patellofemoral compartment was the most involved compartment in isolation (1.4%). CONCLUSIONS: CT of the knee provides greater visualization of intra-articular mineralization than radiographs and allows better localization of the crystal deposition within the joint. Further studies should focus on the co-localization of intra-articular crystal deposition and corresponding magnetic resonance imaging (MRI)-features of knee osteoarthritis (OA).

Depressive symptoms and multi-joint pain partially mediate the relationship between obesity and opioid use in people with knee osteoarthritis.

OBJECTIVES: To assess the relation of obesity to opioid use in people with or at risk of knee osteoarthritis (OA), and the extent to which this association is mediated by number of painful joints or depressive symptoms. METHODS: We used data from the Multicenter Osteoarthritis Study, a longitudinal cohort of older adults with or at risk of knee OA. Opioid use was identified by prescription medications and self-report. Obesity was defined as BMI ≥ 30 kg/m2. Multi-joint pain was assessed using a standardized body homunculus, and depressive symptoms using the Center for Epidemiological Studies Depression scale. We quantified the direct and indirect effect of obesity on opioid use through the number of painful joints or depressive symptoms using causal mediation analysis by natural-effects models. RESULTS: We studied 2,335 participants (mean age: 68; mean BMI 31 kg/m2; 60% women). Persons with obesity had ∼50% higher odds of opioid use than those without. Estimates of indirect (mediated) effect by the number of painful joints and depressive symptoms suggested an increased odds of opioid use by 34% (odds ratio [OR] = 1.34, 95% CI: 1.04, 1.70) and 35% (OR 1.35, 95% CI: 1.05, 1.71), respectively, in obese vs non-obese individuals. The total effect of obesity on opioid use was higher in women than in men. CONCLUSIONS: Multi-joint pain and depressive symptoms partially explained greater opioid use among obese persons with knee OA, demonstrating that the negative impact of obesity on knee OA extends beyond its influence on knee pain and structural progression.

Association between hamstring coactivation during isokinetic quadriceps strength testing and knee cartilage worsening over 24 months.

OBJECTIVE: This study aimed to determine longitudinal associations, including sex-specific differences, between greater knee flexor antagonist coactivation and worsening cartilage morphology in knees with or at risk for osteoarthritis (OA). DESIGN: Baseline measurements were collected at the 60-month visit of a longitudinal osteoarthritis study following community-dwelling participants (MOST). Knee flexor and extensor muscle activity were measured with surface electromyography during a maximal isokinetic knee extension task. MRI analyzed knee cartilage morphology at baseline and 24-month follow-up. Multivariable adjusted logistic regression models were used to assess associations between coactivation level and cartilage morphology worsening. RESULTS: Analysis of 373 women (mean ± SD age 67.4 ± 7.3 years and BMI 29.7 ± 5.0 kg/m2) and 240 men (66.5 ± 7.8 years and 29.9 ± 4.5 kg/m2) revealed that women had greater medial (P < 0.001), lateral (P < 0.001), and combined (P < 0.001) hamstring coactivation than men. In both sexes, combined hamstring coactivation was associated with patellofemoral cartilage morphology worsening [1.23 (1.02, 1.49)] and to a less significant degree with whole knee cartilage morphology worsening [1.21 (0.98, 1.49)]. In men, greater combined hamstring coactivation was associated with increased risk for whole knee [1.59 (1.06, 2.39)] and patellofemoral [1.38 (1.01, 1.88)] cartilage morphology worsening and point estimates suggested association between medial hamstring coactivation and medial tibiofemoral cartilage morphology worsening. No significant associations were detected between greater hamstring coactivation and cartilage morphology worsening in women. CONCLUSIONS: These findings suggest a longitudinal relationship between antagonist hamstring coactivation during isokinetic knee extensor testing and worsening of cartilage morphology over 24 months in men with or at risk for knee OA.

Heterogeneity of cartilage damage in Kellgren and Lawrence grade 2 and 3 knees: the MOST study.

OBJECTIVE: Eligibility for clinical trials in osteoarthritis (OA) is usually limited to Kellgren-Lawrence (KL) grades 2 and 3 knees. Our aim was to describe the prevalence and severity of cartilage damage in KL 2 and 3 knees by compartment and articular subregion. DESIGN: The Multicenter Osteoarthritis (MOST) study is a cohort study of individuals with or at risk for knee OA. All baseline MRIs with radiographic disease severity KL2 and 3 were included. Knee MRIs were read for cartilage damage in 14 subregions. We determined the frequencies of no, any and widespread full-thickness cartilage damage by knee compartment, and the prevalence of any cartilage damage in 14 articular subregions. RESULTS: 665 knees from 665 participants were included (mean age 63.8 ± 7.9 years, 66.5% women). 372 knees were KL2 and 293 knees were KL3. There was no cartilage damage in 78 (21.0%) medial tibio-femoral joint (TFJ), 157 (42.2%) lateral TFJ and 62 (16.7%) patello-femoral joint (PFJ) compartments of KL2 knees, and 17 (5.8%), 115 (39.3%) and 35 (12.0%) compartments, respectively, of KL3 knees. There was widespread full-thickness damage in 94 (25.3%) medial TFJ, 36 (9.7%) lateral TFJ and 176 (47.3%) PFJ compartments of KL2 knees, and 217 (74.1%), 70 (23.9%) and 104 (35.5%) compartments, respectively, of KL3 knees. The subregions most likely to have any damage were central medial femur (80.5%), medial patella (69.8%) and central medial tibia (69.9). CONCLUSIONS: KL2 and KL3 knees vary greatly in cartilage morphology. Heterogeneity in the prevalence, severity and location of cartilage damage in in KL2 and 3 knees should be considered when planning disease modifying trials for knee OA.

Frontal plane knee alignment mediates the effect of frontal plane rearfoot motion on knee joint load distribution during walking in people with medial knee osteoarthritis.

OBJECTIVE: To examine the nature of differences in the relationship between frontal plane rearfoot kinematics and knee adduction moment (KAM) magnitudes. DESIGN: Cross-sectional study resulting from a combination of overground walking biomechanics data obtained from participants with medial tibiofemoral osteoarthritis at two separate sites. Statistical models were created to examine the relationship between minimum frontal plane rearfoot angle (negative values = eversion) and different measures of the KAM, including examination of confounding, mediation, and effect modification from knee pain, radiographic disease severity, static rearfoot alignment, and frontal plane knee angle. RESULTS: Bivariable relationships between minimum frontal plane rearfoot angle and the KAM showed consistent negative correlations (r = -0.411 to -0.447), indicating higher KAM magnitudes associated with the rearfoot in a more everted position during stance. However, the nature of this relationship appears to be mainly influenced by frontal plane knee kinematics. Specifically, frontal plane knee angle during gait was found to completely mediate the relationship between minimum frontal plane rearfoot angle and the KAM, and was also an effect modifier in this relationship. No other variable significantly altered the relationship. CONCLUSIONS: While there does appear to be a moderate relationship between frontal plane rearfoot angle and the KAM, any differences in the magnitude of this relationship can likely be explained through an examination of frontal plane knee angle during walking. This finding suggests that interventions derived distal to the knee should account for the effect of frontal plane knee angle to have the desired effect on the KAM.

Metabolic osteoarthritis - relation of diabetes and cardiovascular disease with knee osteoarthritis.

OBJECTIVE: There is an interest in identifying a metabolic OA phenotype. We therefore assessed the relation of diabetes and cardiovascular disease to prevalent and incident radiographic (ROA) and symptomatic knee osteoarthritis (SxOA). DESIGN: In two large cohort studies of individuals with or at risk for knee OA, the Multicenter Osteoarthritis Study (MOST) and Osteoarthritis Initiative (OAI), participants self-reported diabetes and cardiovascular disease (CVD) at baseline. We assessed the relation of baseline diabetes and CVD (exposures) to ROA and SxOA cross-sectionally and after 60 (MOST) or 48 (OAI) months of follow-up using logistic regression with GEE to account for 2 knees within an individual, adjusting for potential confounders. RESULTS: In MOST, 6,020 knees of 3,021 participants (60.1% female, mean ± SD age 62.5 ± 8.1, mean BMI 30.7 ± 6.0, 83.3% Caucasian) were included in the analyses. In OAI, 8,645 knees of 4,339 participants (58.2% female, mean ± SD age 61.1 ± 9.2, mean BMI 28.6 ± 4.8, 80.3% Caucasian) were included. We found no significant associations between prevalent diabetes or CVD and prevalent or incident ROA or SxOA. Effect estimates for prevalent ROA and SxOA ranged from 0.80 (95% CI 0.63-1.03) to 1.17 (0.91-1.51). Effect estimates for incident ROA ranged from 0.80 (0.58-1.11) to 0.88 (0.60-1.29) in MOST and from 0.75 (0.50-1.14) to 1.19 (0.81-1.74) in OAI, and for incident SxOA from 0.93 (0.65-1.31) to 1.22 (0.89-1.67) in MOST and from 0.82 (0.59-1.16) to 1.19 (0.85-1.66) in OAI). CONCLUSIONS: Diabetes and CVD were not associated with prevalent or incident knee OA.

Ground reaction force patterns in knees with and without radiographic osteoarthritis and pain: descriptive analyses of a large cohort (the Multicenter Osteoarthritis Study).

OBJECTIVE: To compare ground reaction force patterns (GRF) during walking among legs defined by presence or absence of knee pain and/or radiographic knee osteoarthritis (ROA). METHOD: Principal component analysis extracted major modes of variation (PCs) in GRF data from the Multicenter Osteoarthritis Study during self-paced walking. Legs were categorized as pain + ROA (n = 168), ROA only (n = 303), pain only (n = 476), or control (n = 1877). Relationships between group and GRF PCs were examined using Generalized Estimating Equations, adjusted for age, sex, body mass index, race, and clinic site with and without additional adjustment for gait speed. RESULTS: With or without speed adjustment, pain + ROA had flatter vertical GRF waveforms than control (speed adjusted PC2 difference [95%CI]: -66 [-113,-20]), pain + ROA and ROA only had higher lateral GRF at impact and greater mid-stance medial GRF than control (speed adjusted PC3 difference: 9 [3,16] and 6 [2,10], respectively), and ROA only had higher early vs late medial GRF than control (speed adjusted PC2 difference: 7 [2,13]). Pain only had flatter vertical GRF waveforms and a smaller difference between anterior and posterior GRF than control only without speed adjustment. CONCLUSION: In this large sample, sustained mid-stance loading and higher impact loads were identified in legs with ROA or ROA and pain, even when adjusting for differences in gait speed and other confounders. While it remains to be seen whether these features precede or result from ROA and pain, the presence of these patterns in the speed-adjusted models could have implications on gait interventions aimed to change joint loading.

Fatty acids and osteoarthritis: the MOST study.

OBJECTIVE: Inflammation worsens joint destruction in osteoarthritis (OA) and aggravates pain. Saturated and n-6 fatty acids (FAs) increase, whereas n-3 FAs reduce inflammation. We examined whether FA levels affected the development of OA. DESIGN: We studied participants from the Multicenter Osteoarthritis study (MOST) at risk of developing knee OA. After baseline, repeated knee x-rays and MRIs were obtained and knee symptoms queried through 60 month follow-up. Using baseline fasting samples, serum FAs were analyzed with standard assays. After excluding participants with baseline OA, we defined two sets of cases: those developing radiographic OA and those developing symptomatic OA (knee pain and radiographic OA). Controls did not develop these outcomes. Additionally, we examined worsening of MRI cartilage loss and synovitis and of knee pain using WOMAC and evaluated the number of hand joints affected by nodules. In regression models, we tested the association of each OA outcome with levels of saturated, n-3 and n-6 FAs adjusting for age, sex, BMI, education, race, baseline pain and depressive symptoms. RESULTS: We studied 260 cases with incident symptomatic and 259 with incident radiographic OA. Mean age was 61 years (61% women). We found no signficant nor suggestive associations of FA levels with incident OA (e.g., for incident symptomatic OA, OR per s.d. increase in n-3 FA 1.00 (0.85, 1.18) nor with any OA outcome in knee or hand. CONCLUSION: Despite previously described effects on systemic inflammation, blood levels of FAs were not associated with risk of later knee OA or other OA outcomes.

Statistical shape modeling of the hip and the association with hip osteoarthritis: a systematic review.

OBJECTIVE: To summarize available evidence on the association between hip shape as quantified by statistical shape modeling (SSM) and the incidence or progression of hip osteoarthritis. DESIGN: We conducted a systematic search of five electronic databases, based on a registered protocol (available: PROSPERO CRD42020145411). Articles presenting original data on the longitudinal relationship between radiographic hip shape (quantified by SSM) and hip OA were eligible. Quantitative meta-analysis was precluded because of the use of different SSM models across studies. We used the Newcastle-Ottawa Scale (NOS) for risk of bias assessment. RESULTS: Nine studies (6,483 hips analyzed with SSM) were included in this review. The SSM models used to describe hip shape ranged from 16 points on the femoral head to 85 points on the proximal femur and hemipelvis. Multiple hip shape features and combinations thereof were associated with incident or progressive hip OA. Shape variants that seemed to be consistently associated with hip OA across studies were acetabular dysplasia, cam morphology, and deviations in acetabular version (either excessive anteversion or retroversion). CONCLUSIONS: Various radiographic, SSM-defined hip shape features are associated with hip OA. Some hip shape features only seem to increase the risk for hip OA when combined together. The heterogeneity of the used SSM models across studies precludes the estimation of pooled effect sizes. Further studies using the same SSM model and definition of hip OA are needed to allow for the comparison of outcomes across studies, and to validate the found associations.

Is the association between physical activity and fatigue mediated by physical function or depressive symptoms in symptomatic knee osteoarthritis? The Multicenter Osteoarthritis Study.

Objectives: To examine whether physical activity (PA) was associated with fatigue, and quantify the extent of potential mediation through depressive symptoms or physical function (PF) on the relationship between PA and fatigue in symptomatic knee osteoarthritis (KOA).Method: This longitudinal study used data from the Multicenter Osteoarthritis Study (n = 484), comprising subjects aged ≥ 50 years. Baseline PA was quantified via an ankle-worn accelerometer. The outcome was fatigue, measured using a 0-10 rating scale at 2 year follow-up. Mediators included gait speed as a measure of PF and depressive symptoms at 2 year follow-up. Mediation analysis was carried out after adjustment for baseline confounders. Stratified analysis by baseline fatigue status [no/low (< 4) and high (≥ 4) fatigue] was performed.Results: A significant direct association was found between PA and fatigue at 2 years [unstandardized coefficient (B) = -0.054; 95% confidence interval (CI) -0.107, -0.002, p = 0.041]. The PA-fatigue relationship was not mediated by gait speed (B = -0.006; 95% CI -0.018, 0.001) or depressive symptoms (B = 0.009; 95% CI 0.009, 0.028). In the subgroup with high baseline fatigue, direct associations were found between PA and fatigue (gait speed model:, B = -0.107; 95% CI -0.212, -0.002, p = 0.046; depressive symptoms model: B = -0.110; 95% CI -0.120, -0.020, p = 0.017); but in the no/low baseline fatigue group, no significant association was found between PA and fatigue.Conclusion: In the symptomatic KOA population, higher baseline PA was directly associated with reduced fatigue 2 years later, especially in those with high baseline fatigue. However, this relationship was not mediated by depressive symptoms or PF.

Are contrast-enhanced and non-contrast MRI findings reflecting synovial inflammation in knee osteoarthritis: a meta-analysis of observational studies.

OBJECTIVE: To determine the correlation between knee synovitis assessed on contrast-enhanced (CE) and non-contrast enhanced (NCE) magnetic resonance imaging (MRI) with histology in patients with knee osteoarthritis. METHODS: A comprehensive literature search was performed, and related articles published through July 2018 were extracted. Spearman correlation coefficients of MRI-based scores with histology reports were pooled using random effects model. To evaluate presence of publication bias, Egger test was performed. RESULTS: Of 2377 identified records, eight studies consisting of 246 MRI exams were included. Two studies reported results of dynamic CE (DCE)-MRI examinations (81 knees) and two studies reported results of NCE-MRI. There were moderate positive correlations between CE-MRI scores and macroscopic (r = 0.53 (95% Confidence Interval (CI):0.37-0.66), P < 0.001) as well as microscopic (r = 0.56 (0.39-0.69), P < 0.001) histology. DCE-MRI were strongly correlated (r = 0.71 (0.58-0.80), P-value<0.001), with microscopic histology reports, while the correlation for NCE-MRI was low positive (r = 0.44 (0.20-0.63), P < 0.001). Meta-regression analysis showed that pooled correlation coefficients of DCE-MRI were significantly higher than CE-MRI (Slope = 0.29, SE = 0.13, P-value = 0.02). CE-MRI were also correlated with inflammatory infiltrate (r = 0.42), while the correlations for cell number of synovial lining (r = 0.27) and level of fibrosis (r = 0.29, P < 0.001) were very low. CONCLUSION: Static and dynamic CE-MRI evaluation of knee synovitis were positively correlated with macroscopic and microscopic features of synovial membrane inflammation. Among the features of synovial tissue inflammation, CE-MRI scores correlated best with the inflammatory infiltrates of synovial tissue. Paucity of current evidence warrants further studies to assess performance of NCE-MRI on determining knee synovitis.

Reliability of a new scoring system for intraarticular mineralization of the knee: Boston University Calcium Knee Score (BUCKS).

BACKGROUND: The role of intra-articular mineralization in osteoarthritis (OA) is unclear. Its understanding may potentially advance our knowledge of knee OA pathogenesis. We describe and assess the reliability of a novel computed tomography (CT) scoring system, the Boston University Calcium Knee Score (BUCKS) for evaluating intra-articular mineralization. METHODS: We included subjects from the most recent study visit of the Multicenter Osteoarthritis Study (MOST) Study, a NIH-funded longitudinal cohort of community-dwelling older adults with or at risk of knee OA. All subjects underwent CT of bilateral knees. Each knee was scored at 28 scored locations (14 for cartilage, 6 for menisci, 6 for ligaments, 1 for joint capsule, and 1 popliteal-tibial vessels). A single musculoskeletal radiologist scored cartilage and meniscus subregions, as well as vascular calcifications assigning to each a score ranging from 0 to 3. The joint capsule, medial and lateral posterior meniscal roots, anterior cruciate ligament (ACL)/posterior cruciate ligament (PCL) and 2 collateral ligaments [medial collateral ligament (MCL)/lateral collateral ligament (LCL)] were each scored 0 or 1 for absence or presence of mineralization. To assess reliability, 31 subject CTs were reread 12 weeks later by the same reader and by a second reader and agreement was evaluated using a weighted kappa. RESULTS: The intra-reader reliability ranged from 0.92 for ligaments to 1.0 for joint capsule. The inter-reader reliability ranged from 0.94 for cartilage and ligaments, to 1.0 for joint capsule. CONCLUSION: BUCKS demonstrated excellent reliability and is a potentially useful CT-based tool for studying the role of calcium crystals in knee OA.

Association between Bone marrow lesions & synovitis and symptoms in symptomatic knee osteoarthritis.

OBJECTIVE: Bone marrow lesions (BMLs) on MRI are typically subchondral in location, however, a proportion occur at knee ligament attachments and also include a cyst-like component. Our aim was to determine whether the volume of BML subtypes and synovial tissue volume (STV) was associated with symptoms in symptomatic knee OA. METHOD: Images were acquired in a sub-sample who had taken part in a randomised trial of vitamin D therapy in knee OA (UK-VIDEO). Contrast-enhanced (CE) MRI was performed annually. In those who had ≥1 follow-up and a baseline scan (N = 50), STV and BML volume was assessed. BMLs were categorised by location and by the presence/absence of a cyst-like component. WOMAC was assessed annually. We used fixed-effects panel-regression modelling to examine the association between volume and symptoms. RESULTS: There was no association between knee pain and total subchondral BML volume (b = 0.3 WOMAC units, 95% CI -0.3 to 1.0) or total ligament-based BML volume (b = 1.9, 95% CI -1.6 to 5.3). The volume of subchondral BMLs with a cyst-like component was not associated with pain (b = 0.8, 95% CI -0.5 to 2.1) however, the volume of the cyst-like component itself was associated with pain (b = 51.8, 95% CI 14.2 to 89.3). STV was associated with pain (b = 2.2, 95% CI 0.6 to 3.7). CONCLUSION: The volume of the cyst-like component from subchondral BMLs with a cyst-like component was associated with knee pain. BML location, however, did not influence symptoms. STV was also associated with knee symptoms.

MRI-based screening for structural definition of eligibility in clinical DMOAD trials: Rapid OsteoArthritis MRI Eligibility Score (ROAMES).

PURPOSE: Our aim was to introduce a simplified MRI instrument, Rapid OsteoArthritis MRI Eligibility Score (ROAMES), for defining structural eligibility of patients for inclusion in disease-modifying osteoarthritis drug trials using a tri-compartmental anatomic approach that enables stratification of knees into different structural phenotypes and includes diagnoses of exclusion. We also aimed to define overlap between phenotypes and determine reliability. METHODS: 50 knees from the Foundation for National Institutes of Health Osteoarthritis Biomarkers study, a nested case-control study within the Osteoarthritis Initiative, were selected within pre-defined definitions of phenotypes as either inflammatory, subchondral bone, meniscus/cartilage, atrophic or hypertrophic. A focused scoring instrument was developed covering cartilage, meniscal damage, inflammation and osteophytes. Diagnoses of exclusion were meniscal root tears, osteonecrosis, subchondral insufficiency fracture, tumors, malignant marrow infiltration and acute traumatic changes. Reliability was determined using weighted kappa statistics. Descriptive statistics were used for determining concordance between the a priori phenotypic definition and ROAMES and overlap between phenotypes. RESULTS: ROAMES identified 43 of 50 (86%) pre-defined phenotypes correctly. Of the 50 participants, 27 (54%) had no additional phenotypes other than the pre-defined phenotype. 18 (36%) had one and 5 (10%) had two additional phenotypes. None had three or four additional phenotypes. All features of ROAMES showed almost perfect agreement. One case with osteonecrosis and one with a tumor were detected. CONCLUSIONS: ROAMES is able to screen and stratify potentially eligible knees into different structural phenotypes and record relevant diagnoses of exclusion. Reliability of the instrument showed almost perfect agreement.

Towards prevention of post-traumatic osteoarthritis: report from an international expert working group on considerations for the design and conduct of interventional studies following acute knee injury.

OBJECTIVE: There are few guidelines for clinical trials of interventions for prevention of post-traumatic osteoarthritis (PTOA), reflecting challenges in this area. An international multi-disciplinary expert group including patients was convened to generate points to consider for the design and conduct of interventional studies following acute knee injury. DESIGN: An evidence review on acute knee injury interventional studies to prevent PTOA was presented to the group, alongside overviews of challenges in this area, including potential targets, biomarkers and imaging. Working groups considered pre-identified key areas: eligibility criteria and outcomes, biomarkers, injury definition and intervention timing including multi-modality interventions. Consensus agreement within the group on points to consider was generated and is reported here after iterative review by all contributors. RESULTS: The evidence review identified 37 studies. Study duration and outcomes varied widely and 70% examined surgical interventions. Considerations were grouped into three areas: justification of inclusion criteria including the classification of injury and participant age (as people over 35 may have pre-existing OA); careful consideration in the selection and timing of outcomes or biomarkers; definition of the intervention(s)/comparator(s) and the appropriate time-window for intervention (considerations may be particular to intervention type). Areas for further research included demonstrating the utility of patient-reported outcomes, biomarkers and imaging outcomes from ancillary/cohort studies in this area, and development of surrogate clinical trial endpoints that shorten the duration of clinical trials and are acceptable to regulatory agencies. CONCLUSIONS: These considerations represent the first international consensus on the conduct of interventional studies following acute knee joint trauma.

The association of frontal plane alignment to MRI-defined worsening of patellofemoral osteoarthritis: the MOST study.

OBJECTIVE: To determine the sex-specific relation of frontal plane alignment (FPA) to magnetic resonance imaging (MRI)-defined features of patellofemoral osteoarthritis, and also to tibiofemoral osteoarthritis and knee pain. METHOD: The Multicenter Osteoarthritis Study is cohort study comprised of individuals with or at risk of knee osteoarthritis. We determined the sex-specific dose-response relation of baseline FPA to MRI-defined patellofemoral and tibiofemoral structural worsening, and incident knee pain, over 7 years. RESULTS: In women only, greater varus alignment was associated with medial patellofemoral osteophytes (risk ratio [RR] 1.7 [95% CI 1.2, 2.6]) and valgus with lateral patellofemoral osteophytes (RR 1.9 [1.0, 3.6]). In men, greater varus increased risk for medial tibiofemoral cartilage worsening (RR 1.7 [1.1, 2.6]), and valgus for lateral tibiofemoral cartilage worsening (RR 1.8 [1.6, 2.2]). In women, findings were similar for tibiofemoral cartilage, but varus also increased risk for medial bone marrow lesions [BMLs] (RR 2.2 [1.6, 3.1]) and medial osteophytes (RR 1.8 [1.3, 2.5]), and valgus for lateral BMLs (RR 3.3 [2.2, 4.5]) and osteophytes (RR 2.0 [1.2, 3.2]). Varus increased risk of incident pain in men (RR 1.7 [1.4, 2.2]) and women (RR 1.3 [1.0, 1.6]), valgus did so in men only (RR 1.5 [1.1, 1.9]). CONCLUSION: FPA was associated with patellofemoral osteophyte worsening in women, though overall was more strongly associated with tibiofemoral than patellofemoral osteoarthritis feature worsening. FPA in women was more consistently associated with structural worsening, yet men had higher associations with incident pain.

Scrutinizing the cut-off for "pathological" meniscal body extrusion on knee MRI.

OBJECTIVES: Medial meniscal body extrusion ≥ 3 mm on MRI is often considered "pathologic." The aims of this study were to (1) assess the adequacy of 3 mm as cut-off for "pathological" extrusion and (2) find an optimal cut-off for meniscal extrusion cross-sectionally associated with radiographic knee osteoarthritis, bone marrow lesions (BMLs), and cartilage damage. METHODS: Nine hundred fifty-eight persons, aged 50-90 years from Framingham, MA, USA, had readable 1.5 T MRI scans of the right knee for meniscal body extrusion (measured in mm). BMLs and cartilage damage were read using the whole organ magnetic resonance imaging score (WORMS). Knee X-rays were read according to the Kellgren and Lawrence (KL) scale. We evaluated the performance of the 3-mm cut-off with respect to the three outcomes and estimated a new cut-off maximizing the sum of sensitivity and specificity. RESULTS: The study persons had mean age of 62.2 years, 57.0% were women and the mean body mass index was 28.5 kg/m2. Knees with radiographic osteoarthritis, BMLs, and cartilage damage had overall more meniscal extrusion than knees without. The 3-mm cut-off had moderate sensitivity and low specificity for all three outcomes (sensitivity between 0.68 [95% CI 0.63-0.73] and 0.81 [0.73-0.87], specificity between 0.49 [0.45-0.52] and 0.54 [0.49-0.58]). Using 4 mm maximized the sum of sensitivity and specificity and improved the percentage of correctly classified subjects (from between 54 and 61% to between 64 and 79%). CONCLUSIONS: The 4-mm cut-off may be used as an alternative cut-off for denoting pathological meniscal extrusion. KEY POINTS: • Medial meniscal body extrusion is strongly associated with osteoarthritis. • The 3-mm cut-off for medial meniscal body extrusion has high sensitivity but low specificity with respect to bone marrow lesions, cartilage damage, and radiographic osteoarthritis. • The 4-mm cut-off maximizes the sensitivity and specificity with respect to all three osteoarthritis features.

Is local or central adiposity more strongly associated with incident knee osteoarthritis than the body mass index in men or women?

OBJECTIVE: To determine whether central (abdominal) or peripheral (thigh) adiposity measures are associated with incident radiographic knee osteoarthritis (RKOA) independent of body mass index (BMI) and whether their relation to RKOA was stronger than that of BMI. DESIGN: 161 Osteoarthritis Initiative (OAI) participants (62% female) with incident RKOA (Kellgren/Lawrence grade 0/1 at baseline, developing an osteophyte and joint space narrowing (JSN) grade ≥1 by year-4) were matched to 186 controls (58% female) without incident RKOA. Baseline waist-height-ratio (WHtR), and anatomical cross-sectional areas of thigh subcutaneous (SCF) and intermuscular fat (IMF) were measured, the latter using axial magnetic resonance images. Logistic regression assessed the relationship between each adiposity measure and incident RKOA before and after adjustment for BMI, and area under receiver operating characteristic curves (AUC) for each adiposity measure was compared to that of BMI using chi-squared tests. RESULTS: BMI, WHtR, subcutaneous fat (SCF) and IMF were all significantly associated with incident RKOA when analysed separately, with similar effect sizes (odds ratio range 1.30-1.53). After adjusting for BMI, odds ratios (ORs) for WHtR, SCF and IMF were attenuated and no longer statistically significant. No measure of central or peripheral adiposity was significantly more strongly associated with incident RKOA than BMI. Results were similar for men and women. CONCLUSIONS: Although both central (WHtR) and peripheral (SCF and IMF) adiposity were significantly associated with incident RKOA, neither was more strongly associated with incident RKOA than BMI. The simple measure of BMI appears sufficient to capture the elevated risk of RKOA associated with greater amounts of localised adiposity.