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Objectives: To study bone shape changes as a potential early feature of post-traumatic structural knee OA development, we estimated the association between meniscal status in the anterior cruciate ligament (ACL) injured knee and longitudinal condyle changes in bone surface area., Design: We used data from the KANON trial, including 121 young ACL-injured adults. We obtained baseline and 2-year follow-up knee MRIs. Our outcome was change in the bone surface areas (mean mm2, log-transformed) in 4 locations (femur, tibia, patella, and trochlea femur) in the medial and lateral compartment from baseline to 2 years. Meniscal pathology was defined as both present at baseline and newly developed (i.e., incident or progressed) using ACLOAS. We used multilevel linear regression adjusted for baseline bone area, age, sex, body mass index, treatment arm (i.e., early or optional delayed ACL reconstruction), and location. We analyzed medial and lateral compartment separately. We present results as percentage (%) bone area change difference with 95% confidence intervals (CI)., Results: We analyzed 109 subjects (median 27 (18-36) years, 83% men) due to missing MRI information. The bone surface area increased on average by ∼2% over 2 years. The differences between knees with and without baseline meniscal pathology were 1.1% (95%CI 0.0-2.3%) and 1.4% (95%CI 0.6-2.2%) in the medial and lateral compartment, respectively, and 1.2% (95%CI 0.3-2.0%) and 1.3% (95%CI 0.6-2.0%) for medial and lateral newly developed pathology, respectively., Conclusion: Our finding of ∼1% increase bone area in compartment with meniscal pathology suggests a potentially important association between meniscal integrity and early bone surface area changes after ACL injury. Trial registration number ISRCTN 84752559., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Sprifermin (recombinant human fibroblast growth factor-18), a potential disease-modifying osteoarthritis (OA) drug, demonstrated dose-dependent effects on femorotibial cartilage thickness (by quantitative magnetic resonance imaging [MRI]) in the phase II FORWARD study. This post-hoc analysis evaluated the potential effects of sprifermin on several articular structures in the whole joint over 24 months using semi-quantitative MRI assessment., Design: Patients aged 40-85 years with symptomatic radiographic knee OA, Kellgren-Lawrence grade 2 or 3, and medial minimum joint space width ≥2.5 mm in the target knee were randomized (1:1:1:1:1) to receive three double-blinded, once-weekly, intra-articular injections of sprifermin 30 μg or 100 μg or placebo every 6 (q6mo) or 12 months. 1.5- or 3 T MRIs were read using the Whole-Organ Magnetic Resonance Imaging Score (WORMS) system at baseline and 24 months. Change from baseline at 24 months on compartment and/or whole knee level was assessed for cartilage morphology, bone marrow lesions (BMLs), and osteophytes by delta-subregional and delta-sum (DSM) approaches. Menisci, Hoffa-synovitis, and effusion-synovitis were also evaluated for worsening., Results: 549 patients were included. Dose-dependent treatment effects from baseline to 24 months were observed on cartilage morphology (sprifermin 100 μg q6mo vs placebo; mean DSM (95% confidence interval [CI]) -0.6 (-1.5, 0.2); less cartilage worsening) in the entire knee and BMLs sprifermin 100 μg q6mo vs placebo; mean DSM (95% CI) -0.2 (-0.5, 0.1) in the patellofemoral compartment. No effects over 24 months were observed on osteophytes, menisci, Hoffa-synovitis or effusion-synovitis., Conclusions: Positive effects associated with sprifermin were observed for cartilage morphology changes, and BML improvement. There were no meaningful negative or positive effects associated with sprifermin in the other joint tissues examined., (Copyright © 2020 Osteoarthritis Research Society International. All rights reserved.)

Purpose: Aim was to stratify the knee MRIs of the Foundation for National Institutes of Health Osteoarthritis Biomarkers Consortium (FNIH) cohort into distinct structural phenotypes based on semiquantitative assessment and to determine risk for pain and structural progression over 48 months., Methods: The study sample from the FNIH project was selected as a nested case-control study with knees showing either 1) radiographic and pain progression (i.e., "composite" cases), 2) radiographic progression only ("JSL"), 3) pain progression only, and 4) neither radiographic nor pain progression. MRI was performed on 3T systems. MRIs were read according to the MOAKS scoring system. Knees were stratified into subchondral bone, cartilage/meniscus and inflammatory phenotypes using the baseline visits. The relation of each phenotype to risk of being in the combined JSL plus composite outcome or composite case only group compared to those not having that phenotype was determined using logistic regression. Only KL2 and 3 and those without root tears were included., Results: 485 knees were included. 362 (75%) did not have any phenotype, while 95 (20%) had the bone phenotype, 22 (5%) the cartilage/meniscus phenotype and 19 (4%) the inflammatory phenotype. The bone phenotype was associated with a higher odds of the combined JSL plus composite outcome and composite outcome only (OR 1.81; [95%CI 1.14,2.85] and 1.65; 95%CI [1.04,2.61]) while the inflammatory (OR 0.96 [95%CI 0.38,2.42] and 1.25; 95%CI [0.48,3.25]) and the cartilage/meniscus phenotypes were not significantly associated with outcome (OR 1.30 95%CI [0.55,3.07] and 0.99; 95%CI [0.40,2,49])., Conclusions: The bone phenotype was associated with increased risk of having both radiographic and pain progression. Phenotypic stratification may be useful to consider when selecting patients for inclusion in clinical trials., (Copyright © 2020 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

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/m 2 . 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.

Objectives: To determine meniscal extrusion and cartilage coverage on magnetic resonance (MR) images and factors associated with these parameters in knees of middle-aged and elderly persons free from radiographic tibiofemoral osteoarthritis (OA)., Methods: Seven hundred eighteen persons, free of radiographic tibiofemoral OA, aged 50-90 years from Framingham, MA, USA, were included. We measured meniscal extrusion on 1.5 T MRI of both knees to evaluate both medial and lateral meniscal body extrusion and cartilage coverage. We also determined meniscal morphology and structural integrity. The multivariable association with age, body mass index (BMI), and ipsilateral meniscal damage was also evaluated., Results: The mean meniscal body extrusion medially was 2.7 mm and laterally 1.8 mm. The tibial cartilage coverage was about 30% of ipsilateral cartilage surface (both compartments). The presence of ipsilateral meniscal damage was associated with more extrusion in only the medial compartment, 1.0 mm in men and 0.6 mm in women, and less cartilage coverage proportion, -5.5% in men and -4.6% in women., Conclusions: Mean medial meniscal body extrusion in middle-aged or older persons without radiographic tibiofemoral OA approximates the commonly used cutoff (3 mm) to denote pathological extrusion. Medial meniscal damage is a factor associated with medial meniscal body extrusion and less cartilage coverage., Key Points: • Medial meniscal extrusion in middle-aged/older persons without OA is around 3 mm. • Lateral meniscal extrusion in middle-aged/older persons without OA is around 2 mm. • Meniscal damage is associated with medial meniscal extrusion and less cartilage coverage.

Purpose To investigate the diagnostic performance of three-dimensional (3D) MRI for depicting meniscal injuries of the knee by using surgery as the standard of reference. Materials and Methods A literature search was performed to identify original studies published between 1985 and 2017. Summary receiver operating characteristic curve and sensitivity analyses were performed to compare the diagnostic performance of 3D versus two-dimensional (2D) MRI for the assessment of knee meniscal injuries and to evaluate the impact of relevant covariates on the diagnostic performance for assessment of knee meniscal injuries. Results Of identified records, 31 studies (1743 3D knee MRI examinations) were included (23 studies also reported the results of 2D MRI). All studies before 2008 used gradient-echo (GRE) sequences, whereas all studies after 2011 used fast spin-echo (FSE) sequences. By comparing FSE and GRE sequences with 2D MRI, pooled estimate of sensitivity (90.0%; P = .2 and 90.1%; P = .2 vs 88.5%) and pooled estimate of specificity (91%; P = .3 and 89.8% vs 90.1%; P = .7) were comparable. The 3D FSE sequences demonstrated similar diagnostic performance as 3D GRE sequences, except for slightly improved sensitivity for depicting lateral meniscal injuries (FSE, 84.6%; GRE, 75%; P = .01). The specificity of 3D sequences improved when multiplanar reformatting was performed (P = .02). Conclusion Both three-dimensional (3D) fast spin-echo (FSE) and 3D gradient-echo (GRE) sequences had similar diagnostic performance as two-dimensional sequences, with slight superior sensitivity of 3D FSE sequences compared with 3D GRE sequences for depicting lateral meniscal injuries of the knee. © RSNA, 2018 Online supplemental material is available for this article.

Objective: Magnetic resonance imaging (MRI)-detected structural features are associated with increased risk of radiographic osteoarthritis (ROA). Specific mitochondrial DNA (mtDNA) haplogroups have been associated with incident ROA. Our objective was to compare the presence of MRI-detected structural features across mtDNA haplogroups among knees that developed incident ROA., Design: Knees from the Osteoarthritis Initiative (OAI) that developed incident ROA during 48 months follow-up were identified from Caucasian participants. mtDNA haplogroups were assigned based on a single base extension assay. MRIs were obtained annually between baseline and 4-year follow-up and scored using the MRI Osteoarthritis Knee Score (MOAKS). The association between mtDNA haplogroups and MRI-detected structural features was estimated using log-binomial regression. Participants who carried haplogroup H served as the reference group., Results: The sample included 255 participants contributing 277 knees that developed ROA. Haplogroups included H (116, 45%), J (17, 7%), T (26, 10%), Uk (61, 24%), and the remaining less common haplogroups ("others") (35, 14%). Knees of participants with haplogroup J had significantly lower risk of medium/large bone marrow lesions (BMLs) in the medial compartment [3.2%, relative risks (RR) = 0.17; 95%CI: 0.05, 0.64; P = 0.009] compared to knees of participants who carried haplogroup H [16.3%], as did knees from participants within the "others" group [2.8%, RR = 0.20; 95%CI: 0.08, 0.55; P = 0.002], over the 4 year follow-up period., Conclusions: mtDNA haplogroup J was associated with lower risk of BMLs in the medial compartment among knees that developed ROA. Our results offer a potential hypothesis to explain the mechanism underlying the previously reported protective association between haplogroup J and ROA., (Copyright © 2018. Published by Elsevier Ltd.)

Objective: To give a narrative overview of meniscal tears with a radiologic emphasis on the morphologic type, technical considerations, and on the relevance of the type of meniscal tear in the context of osteoarthritis (OA) research., Design: Total 20 years of the PubMed database were searched for epidemiological, radiological, arthroscopic and biomechanical reports, and review articles focusing on meniscal tears in middle-aged and older individuals, in the setting of OA. Case reports, publications on meniscal tears in young active individuals, and publications not in English were excluded., Results: Meniscal intra-substance signal abnormalities are associated with an increased risk of a degenerative meniscal tear in the same segment. Posterior radial tears of the medial meniscus appear to be a highly relevant event in OA of the knee, with associated cartilage loss and meniscal extrusion. Radial tears are more commonly missed on MRI than other types, and should be carefully looked for on coronal and axial images. While medial meniscus posterior root tears are of "radial" morphology, there is growing interest in looking at them as a separate entity, mainly because they require a different therapeutic approach., Conclusion: There is a lack of data on the relevance of different morphologic types of meniscal tears to the natural history of knee OA, both cross-sectionally and-especially-longitudinally. Further epidemiologic studies should focus on specific meniscal tears based on their morphology to better understand their relevance in the genesis and progression of knee OA., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose To investigate the risk of radiographic joint space narrowing (JSN) progression evaluated in subjects with and those without underlying osteoarthritis at baseline and knee replacement (KR) associated with meniscal surgery in subjects with and those without a reported history of preceding knee trauma. Materials and Methods The HIPAA-compliant protocol was approved by the institutional review boards of the participating centers. Written informed consent was obtained from all participants. Subjects who underwent meniscal surgery with a preceding knee trauma at baseline (n = 564) and those without (n = 147) were drawn from the Osteoarthritis Initiative cohort (n = 4796). Radiographic JSN progression was evaluated by using Osteoarthritis Research Society International grading (progression in 1st-, 2nd-, 3rd-, 4th-, 6th-, or 8th-year radiographic findings compared with baseline). KR was assessed up to the 9th year of study (days passed from inclusion to KR or last follow-up). Cox hazard analysis was used to extract the adjusted hazard ratios (HRs) with adjustments for baseline age, sex, body mass index, physical activity, symptoms, and radiographic osteoarthritis features (Kellgren and Lawrence [KL] grade). Results Meniscal surgery with a history of preceding knee trauma was not associated with radiographic progression of JSN (adjusted HR, 0.91 [95% confidence interval {CI}: 0.78, 1.07]) or KR (adjusted HR, 1.02 [95% CI: 0.79, 1.34]; P = .854). However, meniscal surgery without a history of preceding knee trauma was associated with radiographic progression of JSN (adjusted HR, 1.27 [95% CI: 1.00, 1.63]) and KR (adjusted HR, 2.09 [95% CI: 1.52, 2.89]; P < .001). Additionally, there was a higher risk of KR in subjects with radiographic KL grade of less than 2 (adjusted HR, 6.97 [95% CI: 3.56, 13.64]; P < .001) at baseline in comparison with KL grade of at least 2 (adjusted HR, 1.76 [95% CI: 1.22, 2.54]; P < .05). Conclusion In contrast to subjects without a reported preceding trauma, meniscal surgery is not independently associated with increased risk of radiographic JSN progression and KR in patients with a reported preceding trauma. © RSNA, 2016 Online supplemental material is available for this article.

Osteoarthritis (OA) is a common degenerative musculoskeletal disease highly prevalent in aging societies worldwide. Traditionally, knee OA is diagnosed using conventional radiography. However, structural changes of articular cartilage or menisci cannot be directly evaluated using this method. On the other hand, ultrasound is a promising tool able to provide direct information on soft tissue degeneration. The aim of our study was to systematically determine the site-specific diagnostic performance of semi-quantitative ultrasound grading of knee femoral articular cartilage, osteophytes and meniscal extrusion, and of radiographic assessment of joint space narrowing and osteophytes, using MRI as a reference standard. Eighty asymptomatic and 79 symptomatic subjects with mean age of 57.7 years were included in the study. Ultrasound performed best in the assessment of femoral medial and lateral osteophytes, and medial meniscal extrusion. In comparison to radiography, ultrasound performed better or at least equally well in identification of tibio-femoral osteophytes, medial meniscal extrusion and medial femoral cartilage morphological degeneration. Ultrasound provides relevant additional diagnostic information on tissue-specific morphological changes not depicted by conventional radiography. Consequently, the use of ultrasound as a complementary imaging tool along with radiography may enable more accurate and cost-effective diagnostics of knee osteoarthritis at the primary healthcare level.

Objectives: To provide a comprehensive simultaneous relation of various semiquantitative knee OA MRI features as well as the presence of baseline radiographic osteoarthritis (OA) to quantitative longitudinal cartilage loss., Methods: We studied Multicenter OA Study (MOST) participants from a longitudinal observational study that included quantitative MRI measurement of cartilage thickness. These subjects also had Whole Organ MRI Score (WORMS) scoring of cartilage damage, bone marrow lesions (BMLs), meniscal pathology, and synovitis, as well as baseline radiographic evaluation for Kellgren and Lawrence (KL) grading. Knee compartments were classified as progressors when exceeding thresholds of measurement variability in normal knees. All potential risk factors of cartilage loss were dichotomized into "present" (score ≥2 for cartilage, ≥1 for others) or "absent". Differences in baseline scores of ipsi-compartmental risk factors were compared between progressor and non-progressor knees by multivariable logistic regression, adjusting for age, sex, body mass index, alignment axis (degrees) and baseline KL grade. Odds ratios (OR) and 95% CIs were calculated for medial femorotibial compartment (MFTC) and lateral femorotibial compartment (LFTC) cartilage loss. Cartilage loss across both compartments was studied using Generalized Estimating Equations., Results: 196 knees of 196 participants were included (age 59.8 ± 6.3 years [mean ± SD], BMI 29.5 ± 4.6, 62% women). For combined analyses of MFTC and LFTC, baseline factors related to cartilage loss were radiographic OA (KL grade ≥2: aOR 4.8 [2.4-9.5], cartilage damage (aOR 2.3 [1.2-4.4])), meniscal damage (aOR 3.9 [2.1-7.4]) and extrusion (aOR 2.9 [1.6-5.3]), all in the ipsilateral compartment, but not BMLs or synovitis., Conclusion: Baseline radiographic OA and semiquantitatively (SQ) assessed MRI-detected cartilage damage, meniscal damage and extrusion, but not BMLs or synovitis is related to quantitatively measured ipsi-compartmental cartilage thinning over 30 months., (Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

OBJECTIVE. The purpose of this article is to validate both semiquantitative and quantitative ultrasound assessment of medial meniscal extrusion using MRI assessment as the reference standard. SUBJECTS AND METHODS. Ninety-three consecutive patients with chronic knee pain referred for knee MRI were evaluated by ultrasound and MRI on the same day. Two musculoskeletal radiologists assessed meniscal extrusion on ultrasound and MRI separately and independently and graded it semiquantitatively as follows: 0 (< 2 mm), 1 (≥ 2 mm and < 4 mm), and 2 (≥ 4 mm). Agreement between the ultrasound and MRI evaluations was determined using weighted kappa statistics. Intraclass correlation coefficients were used to evaluate agreement using the absolute values of extrusion (quantitative assessment). We further evaluated the diagnostic performance of ultrasound for the detection of medial meniscal extrusion using MRI as the reference standard. RESULTS. For semiquantitative grading, agreement between ultrasound and MRI was moderate for reader 1 (κ = 0.57) and substantial for reader 2 (κ = 0.64). Substantial agreement was found for both readers (intraclass correlation coefficients, 0.73 and 0.70) when comparing quantitative assessment of meniscal extrusion between ultrasound and MRI. Ultrasound showed excellent sensitivity (95% and 96% for each reader) and good specificity (82% and 70% for each reader) in the detection of meniscal extrusion. CONCLUSION. Ultrasound assessment of meniscal extrusion is reliable and can be used for both quantitative and semiquantitative assessment, exhibiting excellent diagnostic performance for the detection of meniscal extrusion compared with MRI.

Purpose: To determine the association of MRI-assessed worsening of tibiofemoral cartilage damage, meniscal damage, meniscal extrusion, separately and together, with progression of radiographic joint space narrowing (JSN)., Method and Materials: The Multicenter Osteoarthitis Study (MOST) Study is a cohort study of subjects with or at risk for knee osteoarthritis (OA). Knees with radiographic OA Kellgren-Lawrence grade 2 at baseline and with baseline and 30-month 1.0 T MRIs were selected for reading using the WORMS system for cartilage damage, meniscal damage, and meniscal extrusion. The association of worsening of cartilage damage, meniscal damage, and/or meniscal extrusion with increases in the JSN was performed using logistic regression., Results: A total of 276 knees (one per subject) were included (women 68.5%, mean age 62.9 ± 7.8, mean body mass index (BMI) 30.2 ± 5.0). Worsening of each MRI feature was associated with any increase in JSN (P < 0.01). Worsening of cartilage damage was more frequently observed than worsening of meniscal damage and extrusion, and was significantly associated with both slow and fast progression of JSN. An increasing risk of JSN worsening was associated with increasing number of worsening MRI features (P for trend < 0.0001)., Conclusion: Worsening of tibiofemoral cartilage damage, meniscal damage, and meniscal extrusion are independent predictors of JSN progression in the same compartment. Worsening of cartilage damage is more frequently observed in JSN when compared to meniscal worsening. A strong cumulative effect on JSN progression is observed for worsening of more than one MRI feature., (Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: The aim of this review is to describe imaging techniques for evaluation of non-osteochondral structures such as the synovium, menisci in the knee, labrum in the hip, ligaments and muscles and to review the literature from recent clinical and epidemiological studies of OA., Methods: This is a non-systematic narrative review of published literature on imaging of non-osteochondral tissues in OA. PubMed and MEDLINE search for articles published up to 2014, using the keywords osteoarthritis, synovitis, meniscus, labrum, ligaments, plica, muscles, magnetic resonance imaging (MRI), ultrasound, computed tomography (CT), scintigraphy, and positron emission tomography (PET)., Results: Published literature showed imaging of non-osteochondral tissues in OA relies primarily on MRI and ultrasound. The use of semiquantitative and quantitative imaging biomarkers of non-osteochondral tissues in clinical and epidemiological OA studies is reported. We highlight studies that have compared both imaging methodologies directly, and those that have established a relationship between imaging biomarkers and clinical outcomes. We provide recommendations as to which imaging protocols should be used to assess disease-specific changes regarding synovium, meniscus in the knee, labrum in the hip, and ligaments, and highlight potential pitfalls in their usage., Conclusion: MRI and ultrasound are currently the most useful imaging modalities for evaluation of non-osteochondral tissues in OA. MRI evaluation of any tissue needs to be performed using appropriate MR pulse sequences. Ultrasound may be particularly useful for evaluation of small joints of the hand. Nuclear medicine and CT play a limited role in imaging of non-osteochondral tissues in OA., (Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate the relationship between medial meniscal pathology and cartilage matrix status using delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) in medial tibiofemoral cartilage in a sample of middle-aged women., Methods: A total of 148 women ages ≥40 years were included, and 3.0T MRI of the knee was performed at baseline and at 1 year. T2-weighted, fat-suppressed and 3-dimensional inversion recovery-prepared spoiled gradient-recalled echo sequences were acquired 90 minutes after gadolinium injection. Baseline medial meniscal pathology was scored on a scale of 0-3, where 0 = normal, 1 = intrasubstance meniscal signal change, 2 = single tears, and 3 = complex tears/maceration. The central medial femur, the medial tibial plateau, and the posterior medial femur were subjected to dGEMRIC at baseline and at 1 year. Analysis of covariance was used to examine whether baseline and 1-year dGEMRIC indices in the same regions were related to the severity of meniscal damage at baseline, using normal medial menisci (grade 0) as the reference., Results: Medial compartments with grade 3 lesions showed significantly lower dGEMRIC indices (less proteoglycan content) at the central medial femur region compared with compartments with normal menisci. Mean ± SEM differences in dGEMRIC indices between grade 3 and grade 0 menisci at the central medial femur were -119.1 ± 34.2 msec at baseline (P = 0.03) and -120.3 ± 35.2 msec at followup (P = 0.04)., Conclusion: High-grade damage of the medial meniscus showed significant associations with lower dGEMRIC indices. The dGEMRIC technique may be a useful tool in detecting early degenerative changes of cartilage when meniscal function is lost., (Copyright © 2014 by the American College of Rheumatology.)

Objective: Synovitis is thought to be a secondary phenomenon in the osteoarthritis (OA) process and the menisci might be triggers of localized synovitis. The aim was to assess the cross-sectional associations of posterior horn meniscal damage with perimeniscal synovitis, and with synovitis posterior to the posterior cruciate ligament (PCL) using contrast enhanced (CE) MRI., Design: The Multicenter Osteoarthritis (MOST) Study is a longitudinal observational study of subjects with or at risk for knee OA. Subjects are a subset of MOST who were examined with 1.5T CE MRI and had semiquantitative synovitis (scored from 0 to 2 at 11 locations) and meniscal readings (scored with WORMS from 0 to 4) available. Logistic regression was used to assess the association of posterior meniscal damage and perimeniscal synovitis in the same compartment, and between posterior meniscal damage and synovitis posterior to the PCL., Results: Three hundred and seventy seven knees were included (mean age 61.1 years±6.9, mean BMI 29.6±4.9, 44.3% women). The odds for ipsi-compartmental perimeniscal synovitis were increased for knees with medial posterior horn meniscal damage (adjusted odds ratio [aOR] 2.5, 95% confidence intervals [95% CI] 1.3,4.8), but not for lateral damage (aOR 1.7, 95% CI 0.4,6.6). No positive associations were found for meniscal damage and presence of synovitis posterior to the PCL (aOR 0.9, 95% CI 0.6,1.5)., Conclusions: Meniscal damage of the posterior horns is associated with ipsi-compartmental perimensical synovitis. No associations were found for posterior horn meniscal damage with synovitis posterior to the PCL, which suggests that synovitis posterior to the PCL is likely to be triggered by different pathomechanisms., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To assess risk of cartilage loss in the tibiofemoral joint in relation to baseline damage severity, and to analyse the association of nearby pathologic findings on the risk of subsequent cartilage loss., Methods: The Multicenter Osteoarthritis Study is a longitudinal study of individuals with or at high risk for knee osteoarthritis. MRI examinations were assessed according to the Whole Organ MRI Score. Included were all knees with available baseline and 30 months MRIs. Ordinal logistic regression was used to estimate risk of cartilage loss in each subregion in relation to the number of associated articular features including bone marrow lesions, meniscal damage and extrusion and also in regard to baseline damage severity, respectively., Results: 13 524 subregions of 1365 knees were included. 3777 (27.9%) subregions exhibited prevalent cartilage damage at baseline and 1119 (8.3%) subregions showed cartilage loss at 30-month follow-up. Risk of cartilage loss was increased for subregions with associated features (OR 2.53, 95% CI 2.03 to 3.15 for one, 4.32 95% CI 3.42 to 5.47 for two and 5.30 95% CI 3.95 to 7.12 for three associated features; p for trend<0.0001). Subregions with prevalent cartilage damage showed increased risk for further cartilage loss compared to subregions with intact cartilage at baseline with small superficial defects exhibiting highest risk., Conclusions: Risk of cartilage loss is increased for subregions with associated pathology and further increased when more than one type of associated feature is present. In addition, prevalent cartilage damage increases risk for subsequent cartilage loss.

Objective: In order to increase sensitivity to detect longitudinal change, recording of within-grade changes was introduced for cartilage morphology and bone marrow lesion (BML) assessment in semiquantitative magnetic resonance imaging (MRI) scoring of knee osteoarthritis (OA). The aim of this study was to examine the validity provided by within-grade scoring., Design: The Multicenter Osteoarthritis (MOST) study is a longitudinal study of subjects with or at risk of knee OA. Baseline and 30 months MRIs were read according to the modified Whole-Organ Magnetic Resonance Imaging Score (WORMS) system including within-grade changes for cartilage and BMLs. We tested the validity of within-grade changes by whether the 30-month changes in cartilage and BML assessment were predicted by baseline ipsi-compartmental meniscal damage and malalignment, factors known to affect cartilage loss and BMLs, using ordinal logistic regression., Results: 1867 Knees (from 1411 participants) were included. Severe medial meniscal damage predicted partial grade (adjusted odds ratio (aOR) 4.4, 95% confidence interval (95% CI) 2.2, 8.7) but not ≥full grade (aOR 1.3, 95% CI 0.8, 2.2) worsening of cartilage loss and predicted both, partial grade (aOR 9.6, 95% CI 3.6, 25.1) and ≥full grade (aOR 5.1, 95% CI 3.2, 8.2) worsening of BMLs. Severe, but not moderate, malalignment predicted ipsi-compartmental within-grade (medial cartilage damage: aOR 5.5, 95% CI 2.6, 11.6; medial worsening of BMLs: aOR 4.9, 95% CI 2.0, 12.3) but not full grade worsening of BMLs and cartilage damage., Conclusions: Within-grade changes in semiquantitative MRI assessment of cartilage and BMLs are valid and their use may increase the sensitivity of semiquantitative readings in detecting longitudinal changes in these structures., (Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

This paper presents the rationale and design features of the MeTeOR Trial (Meniscal Tear in Osteoarthritis Research; Clinical Trials.gov NCT00597012). MeTeOR is an NIH-funded seven-center prospective randomized controlled trial (RCT) designed to establish the efficacy of arthroscopic partial meniscectomy combined with a standardized physical therapy program as compared with a standardized physical therapy program alone in patients with a symptomatic meniscal tear in the setting of mild to moderate knee osteoarthritic change (OA). The design and execution of a trial that compares surgery with a nonoperative treatment strategy presents distinctive challenges. The goal of this paper is to provide the clinical rationale for MeTeOR and to highlight salient design features, with particular attention to those that present clinical and methodologic challenges., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To assess the associations of meniscal tears, knee mal-alignment, cartilage damage, knee effusion, and body mass index with meniscal extrusion., Materials and Methods: The Multicenter Osteoarthritis study is an observational study of individuals who have or are at risk for knee osteoarthritis (OA). The HIPAA-compliant protocol was approved by the institutional review boards of all participating centers, and written informed consent was obtained from all patients. All subjects with available baseline knee radiographs and magnetic resonance (MR) images were included. MR imaging assessment of meniscal morphologic characteristics, meniscal position, and cartilage morphologic characteristics with use of the Whole-Organ Magnetic Resonance Imaging Score system was performed by two musculoskeletal radiologists. Cross-sectional associations of severity of meniscal tears, knee malalignment, tibiofemoral cartilage damage, knee effusion, and body mass index with meniscal extrusion were assessed by using logistic regression, with multiadjustments when testing each predictor., Results: A total of 1527 subjects (2131 knees; 2116 medial and 2106 lateral menisci) were included. Medially, meniscal tears, varus malalignment, and cartilage damage were associated with meniscal extrusion, with odds ratios (ORs) of 6.3 (95% confidence interval [CI]: 5.0, 8.0), 1.3 (95% CI: 1.1, 1.7), and 1.8 (95% CI: 1.4, 2.2), respectively. Laterally, meniscal tears, valgus malalignment, and cartilage damage were associated with meniscal extrusion, with ORs of 10.3 (95% CI: 7.1, 14.9), 2.2 (95% CI: 1.5, 3.2), and 2.0 (95% CI: 1.3, 2.9), respectively., Conclusion: Meniscal tears are not the only factors associated with meniscal extrusion; other factors include knee malalignment and cartilage damage. Meniscal extrusion is probably an effect of the complex interactions among joint tissues and mechanical stresses involved in the OA process.

The menisci are internal structures that are of central importance for a healthy knee joint; they have a key role in the structural progression of knee osteoarthritis (OA), and the risk of the disease dramatically increases if they are damaged by injury or degenerative processes. Meniscus damage might be considered a signifying feature of incipient OA in middle-aged and elderly people. As approximately every third knee of people in these groups has a damaged meniscus, tears are common incidental findings of knee MRI. However, as most tears do not cause symptoms, careful clinical evaluation is required to determine if a damaged meniscus is likely to directly impact a patient's symptoms. Conservative management of patients with knee pain and a degenerative meniscal tear should be considered as a first-line therapy before surgical treatment is contemplated. Patients with mechanical interference of joint movements, such as painful catching or locking, might need surgical treatment with meniscal repair if possible. In a subset of patients, meniscal resection might relieve pain and other symptoms that potentially originate directly from the torn meniscus. However, the possibility of an increased risk of OA if functional meniscal tissue is removed cannot be overlooked.

Objectives: Meniscal pathology in which the aetiology is often unclear is a frequent finding on knee MRI. This study investigates potential risk factors for medial meniscal lesions or extrusion in middle-aged and elderly persons., Methods: Prospective cohort study using population-based subjects from Birmingham, Alabama and Iowa City, Iowa, USA (the Multicenter Osteoarthritis Study). 644 men and women aged 50-79 years with or at high risk of knee osteoarthritis (Kellgren and Lawrence grade 0-2) but with normal medial meniscal status at baseline were studied. Paired baseline and 30-month 1.0 T knee MRI were scored for meniscal lesions and extrusion (pathology) and the following systemic, knee-specific and compartment-specific potential risk factors were evaluated: age, sex, body mass index, bony enlargement of finger joints, knee trauma, leg-length inequality and knee alignment., Results: Of 791 knees, 77 (9.7%) had medial meniscal pathology at 30 months follow-up. 61 of the 77 (81%) had no report of trauma during follow-up. Including all potential risk factors in the multivariable model, the adjusted OR for medial meniscal pathology was 4.14 (95% CI 2.06 to 8.31) for knee trauma during follow-up, 1.64 (1.00 to 2.70) for five or more bony enlargements of finger joints (vs ≤ 4) and 2.00 (1.18 to 3.40) for varus alignment (vs not varus) at baseline examination. Obesity was a risk factor for the development of meniscal extrusion, OR 3.04 (1.04 to 8.93) but not for meniscal lesions, OR 1.15 (0.52 to 2.54)., Conclusions: Apart from knee trauma, possible generalised osteoarthritis, expressed as multiple bony enlargements of finger joints, varus alignment and obesity are risk factors for medial meniscal pathology.

Objective: Intrasubstance meniscal signal changes not reaching the articular surface on fast spin echo (FSE) sequences are considered to represent mucoid degeneration on MRI. The aim of this study was to evaluate the association of prevalent intrasubstance signal changes with incident tears of the medial meniscus detected on 3.0 T MRI over a 1-year period., Materials and Methods: A total of 161 women aged ≥ 40 years participated in a longitudinal 1-year observational study of knee osteoarthritis. MRI (3.0 T) was performed at baseline and 12-month follow-up. The anterior horn, body, and posterior horn of the medial meniscus were scored by two experienced musculoskeletal radiologists using the Boston-Leeds Osteoarthritis Knee Score (BLOKS) system. Four grades were used to describe the meniscal morphology: grade 0 (normal), grade 1 (intrasubstance signal changes not reaching the articular surface), grade 2 (single tears), and grade 3 (complex tears and maceration). Fisher's exact test and the Cochran-Armitage trend test were performed to evaluate whether baseline intrasubstance signal changes (grade 1) predict incident meniscal tears/maceration (grades 2 and/or 3) in the same subregion of the medial meniscus, when compared to subregions without pathology as the reference group (grade 0)., Results: Medial meniscal intrasubstance signal changes at baseline did not predict tears at follow-up when evaluating the anterior and posterior horns (left-sided p-values 0.06 and 0.59, respectively). No incident tears were detected in the body., Conclusion: We could not demonstrate an association between prevalent medial meniscal intrasubstance signal changes with incident tears over a 1-year period.

Objective: To compare two semiquantitative scoring systems for assessing the prevalence and severity of morphologic cartilage lesions, meniscal damage and bone marrow lesions (BMLs) from Magnetic Resonance Imagings (MRIs) of knees with osteoarthritis (OA)., Methods: From participants in the OA Initiative (OAI), a sample of 115 knees with radiographic OA at high risk of cartilage loss, were selected based on risk factors for progression. Knee MRIs were read separately using both Whole Organ MR Scoring (WORMS) and Boston-Leeds OA Knee Scoring (BLOKS), and a subset was fed back to readers for reliability. Baseline readings were used for comparison of the two methods for inter-reader reliability as well as agreement on presence/absence and severity of MRI features at both the compartment level and finer anatomical subregion levels., Results: Both methods had high inter-reader agreement for all features studied (kappa for WORMS 0.69-1.0 and for BLOKS 0.65-1.0). Although the methods agreed well on presence and severity of morphological cartilage lesions (inter-method kappas from 0.66 to 0.95), BLOKS was more sensitive for full thickness defects. The two methods gave equivalent results for extent (kappa 0.74-0.80) and number (Spearman's Rho=0.85) of BMLs, and little extra information was obtained using the more complex BLOKS BML scoring. Similar results were also obtained for the common types of meniscal damage and extrusion (inter-method kappa 0.85-0.94), but the inclusion in BLOKS of meniscal signal abnormality and uncommon types of tear may be an advantage if these prove clinically meaningful., Conclusion: Both WORMS and BLOKS had high reliability. The two methods gave similar results in this sample for prevalence and severity of cartilage loss, BMLs and meniscal damage. Selecting between, or combining, the two methods should be based on factors such as reader effort, appropriateness for the goals of a study, and longitudinal performance., (Copyright © 2010 Osteoarthritis Research Society International. All rights reserved.)

Objectives: To investigate the association between meniscal pathology and incident or enlarging bone marrow lesions (BML) in knee osteoarthritis., Methods: The authors studied subjects from the Multicenter Osteoarthritis Study aged 50-79 years either with knee osteoarthritis or at high risk of the disease. Baseline and 30-months magnetic resonance images of knees (n=1344) were scored for subchondral BML. Outcome was defined as an increase in BML score in either the tibial or femoral condyle in medial and lateral compartments, respectively. The authors defined meniscal pathology at baseline as the presence of either meniscal lesions or meniscal extrusion. The risk of an increase in BML score in relation to meniscal status in the same compartment was estimated using a log linear regression model adjusted for age, sex, body mass index, physical activity level and mechanical axis. In secondary analyses the investigators stratified by ipsilateral tibiofemoral cartilage status at baseline and compartments with pre-existing BML., Results: The adjusted relative risk of incident or enlarging BML ranged from 1.8; 95% CI 1.3 to 2.3 for mild medial meniscal pathology to 5.0; 95% CI 3.2 to 7.7 for major lateral meniscal pathology (using no meniscal pathology in the same compartment as reference). Stratification by cartilage or BML status at baseline had essentially no effect on these estimates., Conclusions: Knee compartments with meniscal pathology have a substantially increased risk of incident or enlarging subchondral BML over 30 months. Higher relative risks were seen in those with more severe and with lateral meniscal pathology.

Objective: To investigate the association of different types of magnetic resonance imaging (MRI)-detected medial meniscal pathology with subregional cartilage loss in the medial tibiofemoral compartment., Methods: A total of 152 women aged >or=40 years, with and without knee osteoarthritis (OA) were included in a longitudinal 24-month observational study. Spoiled gradient recalled acquisitions at steady state (SPGR) and T2-weighted fat-suppressed MRI sequences were acquired. Medial meniscal status of the anterior horn (AH), body, and posterior horn (PH) was graded at baseline: 0 (normal), 1 (intrasubstance meniscal signal changes), 2 (single tears), and 3 (complex tears/maceration). Cartilage segmentation was performed at baseline and 24-month follow-up in various tibiofemoral subregions using computation software. Multiple linear regression models were applied for the analysis with cartilage loss as the outcome. In a first model, the results were adjusted for age and body mass index (BMI). In a second model, the results were adjusted for age, BMI and medial meniscal extrusion., Results: After adjusting for age, BMI, and medial meniscal extrusion, cartilage loss in the total medial tibia (MT) (0.04 mm, P=0.04) and the external medial tibia (eMT) (0.068 mm, P=0.04) increased significantly for compartments with grade 3 lesions. Cartilage loss in the total central medial femoral condyle (cMF) (0.071 mm, P=0.03) also increased significantly for compartments with grade 2 lesions. Cartilage loss at the eMT was significantly related to tears of the PH (0.074 mm; P=0.03). Cartilage loss was not significantly increased for compartments with grade 1 lesions., Conclusion: The protective function of the meniscus appears to be preserved in the presence of intrasubstance meniscal signal changes. Prevalent single tears and meniscal maceration were found to be associated with increased cartilage loss in the same compartment, especially at the PH., (Copyright 2009 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: To assess the cross-sectional association between meniscal status and joint effusion on magnetic resonance imaging (MRI) in knees without radiographic osteoarthritis (OA)., Design: Knees without OA (Kellgren/Lawrence grade 0) from the Framingham and MOST studies were examined by MRI. Meniscal status was assessed with a score of 0-4 in the anterior horn/body/posterior horn of the medial/lateral meniscus and effusion was assessed using a score of 0-3. The odds ratios (ORs) of joint effusion in those with meniscal damage were estimated using a logistic regression model. A subanalysis was performed for knees without MRI-detected cartilage damage., Results: Of 1368 knees, 296 (21.6%) showed meniscal pathology in at least one subregion. Effusion was present in 133 (44.9%) of knees with meniscal damage vs 328 (30.6%) in those without meniscal damage. The adjusted OR of effusion in a knee with meniscal damage was 1.8, 95% confidence intervals (CI) [1.4, 2.4]. The OR of effusion for the group with meniscal pathology in two compartments was 5.4, 95% CI [2.1, 14.3]. For knees without any cartilage lesions but with meniscal damage in any compartment the OR was 2.3, 95% CI [1.1, 4.5]., Conclusions: Knees without OA but with meniscal pathology exhibit joint effusion to a significantly higher degree than knees without meniscal damage. The association persists for knees without cartilage damage. The prevalence of effusion is further increased when present in two compartments. Concomitant occurrence of synovial activation and meniscal damage contributes to understanding the pathophysiology of early degenerative joint disease.

Objective: Although partial meniscectomy is a risk factor for the development of knee osteoarthritis (OA), there is a lack of evidence that meniscal damage that is not treated with surgery would also lead to OA, suggesting that surgery itself may cause joint damage. Furthermore, meniscal damage is common. The aim of this study was to evaluate the association between meniscal damage in knees without surgery and the development of radiographic tibiofemoral OA., Methods: We conducted a prospective case-control study nested within the observational Multicenter Osteoarthritis Study, which included a sample of men and women ages 50-79 years at high risk of knee OA who were recruited from the community. Patients who had no baseline radiographic knee OA but in whom tibiofemoral OA developed during the 30-month followup period were cases (n = 121). Control subjects (n = 294) were drawn randomly from the same source population as cases but had no knee OA after 30 months of followup. Individuals whose knees had previously undergone surgery were excluded. Meniscal damage was defined as the presence of any medial or lateral meniscal tearing, maceration, or destruction., Results: Meniscal damage at baseline was more common in case knees than in control knees (54% versus 18%; P < 0.001). The model comparing any meniscal damage with no meniscal damage (adjusted for baseline age, sex, body mass index, physical activity, and mechanical knee alignment) yielded an odds ratio of 5.7 (95% confidence interval 3.4-9.4)., Conclusion: In knees without surgery, meniscal damage is a potent risk factor for the development of radiographic OA. These results highlight the need for better understanding, prevention, and treatment of meniscal damage.

Objective: To evaluate the effect of meniscal damage on the development of frequent knee pain, aching, or stiffness in middle-aged and older adults., Methods: The Multicenter Osteoarthritis Study is a prospective study of 3,026 individuals 50 years of age or older who have or are at high risk of developing knee osteoarthritis (OA). We investigated knees at baseline and at 15 months. Case knees (n = 110) were those with no pain, aching, or stiffness on most days at baseline, but that had developed frequent pain, aching, or stiffness at 15 months. Control knees (n = 220) were drawn randomly from knees with no frequent symptoms at baseline that did not become case knees. Using 1.0T magnetic resonance imaging performed at baseline and at followup, 2 musculoskeletal radiologists blinded to the case-control status assessed the meniscal damage using the following scale: 0 = intact, 1 = minor tear, 2 = nondisplaced tear or prior surgical repair, and 3 = displaced tear, resection, maceration, or destruction. The effect of meniscal damage was analyzed by contingency tables and logistic regression., Results: Meniscal damage was common at baseline both in case knees (38%) and in control knees (29%). Although there was a modest association between the meniscal damage score (range 0-3) and the development of frequent knee pain, aching, or stiffness (odds ratio [OR] 1.21, 95% confidence interval [95% CI] 0.96-1.51, adjusted for age, sex, and body mass index), meniscal damage was mostly present in knees with OA. When considering the co-occurrence of OA, we found no independent association between meniscal damage and the development of frequent knee symptoms (OR 1.05, 95% CI 0.80-1.37)., Conclusion: In middle-aged and older adults, any association between meniscal damage and the development of frequent knee pain seems to be present because both pain and meniscal damage are related to OA and not because of a direct link between the two.