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Objective: Osteoarthritis (OA) prevalence and incidence varies between women and men, but it is unknown whether this follows sex-specific differences in systemic factors (e.g. hormones) and/or differences in pre-morbid joint anatomy. We recognize that classifications of sex within humans cannot be reduced to female/male, but given the lack of literature on non-binary individuals, this review is limited to the sexual dimorphism of articular morphotypes., Methods: Based on a Pubmed search using relevant terms, and input from experts, we selected articles based on the authors' judgment of their relevance, interest, originality, and scientific quality; no "hard" bibliometric measures were used to evaluate their quality or importance. Focus was on clinical rather than pre-clinical studies, with most (imaging) data being available for the knee joint., Results: After introducing "sexual dimorphism", the specific literature on articular morphotypes is reviewed, structured by: radiographic joint space width (JSW), meniscus, ligaments, articular cartilage morphology, articular cartilage composition and deformation, and articular tissue response to treatment., Conclusions: Sex-specific differences were clearly observed for JSW, meniscus damage, ligament size, and cartilage morphometry (volume, thickness, and surface areas) but not for cartilage composition. Ligament and cartilage measures were smaller in women even after matching for confounders. Taken together, the findings indicate that female (knee) joints may be structurally more vulnerable and at greater risk of OA. The "one size/sex fits all" approach must be abandoned in OA research, and all observational and interventional studies should report their results for sex-specific strata, at least in pre-specified secondary or post-hoc analyses., Competing Interests: Declaration of Competing Interest Felix Eckstein and Wolfgang Wirth are employees of Chondrometrics GmbH, a company providing professional image analysis service to researchers in academia and to the pharmaceutical industry. Felix Eckstein, Wolfgang Wirth and Reinhard Putz are owners of Chondrometrics GmbH. Felix Eckstein has provided consulting services to Merck KGA, Kolon Tissuegene (KTG), Galapagos, Novartis, 4 P Pharma, and Formation Bio. Felix Eckstein and Wolfgang Wirth have received funding from multiple sources, including public bodies and the pharmaceutical industry (detailed list upon request)., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To explore factors that were associated with meniscus volume in knees free of radiographic osteoarthritis (OA) features and symptoms of OA., Methods: In the third Rotterdam Study cohort, clinical, radiographic, and magnetic resonance data were obtained at baseline (BL) and after 5 years of follow-up. Meniscus volumes and their change over time were calculated after semi-automatic segmentation on Magnetic Resonance Imaging. Knees with radiographic OA features (Kellgren and Lawrence>0) or clinical diagnosis of OA (American College of Rheumatology) at BL were excluded. Ten OA risk factors were adjusted in the multivariable analysis (generalized estimating equations), treating two knees within subjects as repeated measurements., Results: From 1065 knees (570 subjects), the average (standard deviation) age and Body mass index (BMI) of included subjects were 54.3 (3.7) years and 26.5 (4.4) kg/m 2 . At BL, nine factors (varus alignment, higher BMI, meniscus pathologies, meniscus extrusion, cartilage lesions, injury, greater physical activity level, quadriceps muscle strength, and higher age) were significantly associated with greater meniscus volume. Five factors (injury, meniscus pathologies, meniscus extrusion, higher age, and change of BMI) were significantly associated with meniscus volume loss., Conclusions: Modifiable factors (varus alignment, BMI, physical activity level, and quadriceps muscle strength) and non-modifiable factors (higher age, injury, meniscus pathologies, meniscus extrusion, and cartilage lesions) were all associated with meniscus volume or meniscus volume loss over time., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate the role of Piezo1 and Piezo2 in surgically induced osteoarthritis (OA) in mice., Design: Male conditional knockout (cKO) mice missing Piezo1 and Piezo2 in the joint using Gdf5-Cre transgenic mice were induced with post-traumatic OA by destabilization of the medial meniscus (DMM) of the right knee joint at 12 weeks of age. The severity of OA was histologically assessed at 24 weeks of age. OA-associated pain was evaluated by static weight bearing analysis. Additionally, articular chondrocytes isolated from cKO mice were exposed to fluid flow shear stress (FFSS) to evaluate the expression of OA-associated genes., Results: Mice with conditional deletion of Piezo1 and Piezo2 showed normal joint development with no overt histological changes in the knee joint at 12 weeks and 24 weeks. DMM surgery induced moderate to severe OA in both control and cKO mice (median OARSI score: control, 4.67; cKO, 4.23, P = 0.3082), although a few cKO mice showed milder OA. Pain assessment by static weight-bearing analysis suggested Piezo ablation in the joint has no beneficial effects on pain. FFSS increased the expression of OA-related genes both in control and cKO mice to similar extents., Conclusion: Piezo1 and Piezo2 are not essential for normal joint development. Genetic ablation of Piezo channels did not confer evident protective effects on OA progression in mice. In vitro data suggests that different mechanotransducers other than Piezo channels mediate FFSS in mechanical stress-induced gene expression., (Copyright © 2023 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: Meniscal calcifications are associated with the pathogenesis of knee osteoarthritis (OA). We propose a micro-computed tomography (μCT) based 3D analysis of meniscal calcifications ex vivo, including a new grading system., Method: Human medial and lateral menisci were obtained from 10 patients having total knee replacement for medial compartment OA and 10 deceased donors without knee OA (healthy references). The samples were fixed; one subsection was imaged with μCT, and the adjacent tissue was processed for histological evaluation. Calcifications were examined from the reconstructed 3D μCT images, and a new grading system was developed. To validate the grading system, meniscal calcification volumes (CV M ) were quantitatively analyzed and compared between the calcification grades. Furthermore, we estimated the relationship between histopathological degeneration and the calcification severity., Results: 3D μCT images depict calcifications in every sample, including diminutive calcifications that are not visible in histology. In the new grading system, starting from grade 2, each grade results in a CV M that is 20.3 times higher (95% CI 13.3-30.5) than in the previous grade. However, there was no apparent difference in CV M between grades 1 and 2. The calcification grades appear to increase with the increasing histopathological degeneration, although histopathological degeneration is also observed with small calcification grades., Conclusions: 3D μCT grading of meniscal calcifications is feasible. Interestingly, it seems that there are two patterns of degeneration in the menisci of our sample set: 1) with diminutive calcifications (calcification grades 1-2), and 2) with large to widespread calcifications (calcification grades 3-5)., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: We conducted a systematic review in order to understand the relationship between imaging-visualised meniscus pathologies, hyaline cartilage, joint replacement and pain in knee osteoarthritis (OA)., Design: A search of the Medline, Excerpta Medica database (EMBASE) and Cochrane library databases was performed for original publications reporting association between imaging-detected meniscal pathology (extrusion or tear/damage) and longitudinal and cross-sectional assessments of hyaline articular cartilage loss [assessed on magnetic resonance imaging (MRI)], incident joint replacement and pain (longitudinal and cross-sectional) in knee OA. Each association was qualitatively characterised by a synthesis of data from each analysis, based upon study design and quality scoring (including risk of bias assessment and adequacy of covariate adjustment using Cochrane recommended methodology)., Results: In total 4,878 abstracts were screened and 82 publications were included (comprising 72 longitudinal analyses and 49 cross-sectional). Using high quality, well-adjusted data, meniscal extrusion and meniscal tear/damage were associated with longitudinal progression of cartilage loss, cross-sectional cartilage loss severity and joint replacement, independently of age, sex and body mass index (BMI). Medial and lateral meniscal tears were associated with cartilage loss when they occurred in the body and posterior horns, but not the anterior horns. There was a lack of high quality, well-adjusted meniscal pathology and pain publications and no clear independent association between meniscal extrusion or tear/damage with pain severity, progression in pain or incident frequent knee symptoms., Conclusion: Meniscal features have strong associations with cartilage loss and joint replacement in knee OA, but weak associations with knee pain. Systematic review PROSPERO registration number: CRD 42020210910., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: In light of the role of immune cells in OA pathogenesis, the development of sophisticated animal models closely mimicking the immune dysregulation during the disease development and progression could be instrumental for the preclinical evaluation of novel treatments. Among these models, immunologically humanized mice may represent a relevant system, particularly for testing immune-interacting DMOADs or cell therapies before their transfer to the clinic. Our objective, therefore, was to develop an experimental model of OA by destabilization of the medial meniscus (DMM) in humanized mice., Method: Irradiated 5-week-old NOD/LtSz-scid IL2Rγ null (NSG) mice were humanized by intravenous injection of CD34 + human hematopoietic stem cells. The engraftment efficiency was evaluated by flow cytometry 17 weeks after the humanization procedure. Humanized and non-humanized NSG mice underwent DMM or sham surgery and OA development was assessed 1, 6, and 12 weeks after the surgery., Results: 120 days after the humanization, human T and B lymphocytes, macrophages and NK cells, were present in the blood and spleen of the humanized NSG mice. The DMM surgery induced articular cartilage and meniscal alterations associated with an increase in OA and the meniscal score. Moreover, the surgery triggered an inflammatory response that was sustained at a low grade in the DMM group., Conclusions: Our study shows for the first time the feasibility of inducing OA by DMM in humanized mice. This novel OA model could constitute a useful tool to bridge the gap between the preclinical and clinical evaluation of immune interacting DMOADs and cell-based therapies., (Copyright © 2022 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: To delineate the activities of decorin and biglycan in the progression of post-traumatic osteoarthritis (PTOA)., Design: Three-month-old inducible biglycan (Bgn iKO ) and decorin/biglycan compound (Dcn/Bgn iKO ) knockout mice were subjected to the destabilization of the medial meniscus (DMM) surgery to induce PTOA. The OA phenotype was evaluated by assessing joint structure and sulfated glycosaminoglycan (sGAG) staining via histology, surface collagen fibril nanostructure and calcium content via scanning electron microscopy, tissue modulus via atomic force microscopy-nanoindentation, as well as subchondral bone structure and meniscus ossification via micro-computed tomography. Outcomes were compared with previous findings in the inducible decorin (Dcn iKO ) knockout mice., Results: In the DMM model, Bgn iKO mice developed similar degree of OA as the control (0.44 [-0.18 1.05] difference in modified Mankin score), different from the more severe OA phenotype observed in Dcn iKO mice (1.38 [0.91 1.85] difference). Dcn/Bgn iKO mice exhibited similar histological OA phenotype as Dcn iKO mice (1.51 [0.97 2.04] difference vs control), including aggravated loss of sGAGs, salient surface fibrillation and formation of osteophyte. Meanwhile, Dcn/Bgn iKO mice showed further cartilage thinning than Dcn iKO mice, resulting in the exposure of underlying calcified tissues and aberrantly high surface modulus. Bgn iKO and Dcn/Bgn iKO mice developed altered subchondral trabecular bone structure in both Sham and DMM groups, while Dcn iKO and control mice did not., Conclusion: In PTOA, decorin plays a more crucial role than biglycan in regulating cartilage degeneration, while biglycan is more important in regulating subchondral bone structure. The two have distinct activities and modest synergy in the pathogenesis of PTOA., (Copyright © 2021 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

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: Because the literature relating to the influence of degeneration on the viscoelasticity and tissue composition of human lateral menisci remains contradictory or completely lacking, the aim of this study was to fill these gaps by comprehensively characterising the biomechanical properties of menisci with regard to the degree of degeneration., Design: Meniscal tissue from 24 patients undergoing a total knee replacement was collected and the degeneration of each region classified according to Pauli et al. For biomechanical characterisation, compression and tensile tests were performed. Additionally, the water content was determined and infrared (IR) spectroscopy was applied to detect changes in the structural composition, particularly of the proteoglycan and collagen content., Results: With an increasing degree of degeneration, a significant decrease of the equilibrium modulus was detected, while simultaneously the water content and the hydraulic permeability significantly increased. However, the tensile modulus displayed a tendency to decrease with increasing degeneration, which might be due to the significantly decreasing amount of collagen content identified by the IR measurements., Conclusion: The findings of the current study may contribute to the understanding of meniscus degeneration, showing that degenerative processes appear to mainly worsen viscoelastic properties of the inner circumference by disrupting the collagen integrity., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To investigate if cartilage calcification (CC) is a systemic process, the purpose of this study was to determine the prevalence and the amount of meniscal/hyaline CC of the knee joint in the general population by high-resolution imaging (DCR) and to evaluate the association between CC with cartilage degeneration and age., Methods: Cross-sectional DCR-study of 180 knee joints of 90 donors (42 female/48 male, mean age 62.3y). Histological hyaline (OARSI) and meniscal (Krenn) cartilage degeneration was determined of all knees., Results: CC was observed in 100% of the donors (bilaterally in 98%), hyaline cartilage calcification (HCC) in 92% and meniscal calcification (MC) in 100%. CC was detected in more than three out of six distinct cartilage areas in 84.4% of all knees. The mean amount of CC correlated between both sides of donors, the different analyzed areas of the knee joint and between the various types of cartilage structures. There was more calcification in meniscal than in hyaline cartilage (factor 5.3) and in the medial than the lateral compartment (factor 1.2). HCC/MC were already detectable with only mild cartilage lesions and the amount correlated with histological cartilage degeneration, but not with age., Conclusions: The present study provides evidence that meniscal and hyaline CC occurs in a pattern that is compatible with CC being a systemically driven process and that meniscal fibrocartilage is more prone to calcification than hyaline cartilage. Furthermore, the age-independent association between the amount of CC and the grade of degeneration in both hyaline and meniscal cartilage, suggests that CC is an obligatory early event in initiating cartilage degeneration., (Copyright © 2020 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: Weight loss has beneficial effects on clinical outcomes in knee osteoarthritis (OA), but the mechanism is still unclear. Since meniscus extrusion is associated with knee pain, this study assessed whether weight loss by diet and/or exercise is associated with less progression in meniscus extrusion measures over time., Design: The Intensive Diet and Exercise for Arthritis trial (IDEA) was a prospective, single-blind, randomized-controlled trial including overweight and obese older adults with knee pain and radiographic OA. Participants were randomized to 18-month interventions: exercise only, diet only or diet + exercise. In a random subsample of 105 participants, MRIs were obtained at baseline and follow-up. The medial and lateral menisci were segmented and quantitative position and size measures were obtained, along with semiquantitative extrusion measures. Linear and log-binomial regression were used to examine the association between change in weight and change in meniscus measures. Between-group differences were analyzed using an analysis of covariance., Results: Weight loss was associated with less progression over time of medial meniscus extrusion as measured by the maximum (β: -24.59 μm, 95%CI: -41.86, -7.33) and mean (β: -19.08 μm, 95%CI: -36.47, -1.70) extrusion distances. No relationships with weight loss were observed for lateral meniscus position, medial or lateral meniscus size or semiquantitative measures. Change in meniscus position and size did not differ significantly between groups., Conclusions: Weight loss was associated with beneficial modifications of medial meniscus extrusion over 18 months. This may be one of the mechanisms by which weight loss translates into a clinical benefit., Clinical Trial Registration: NCT00381290., (Copyright © 2020 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: To develop and perform ex vivo 3D imaging of meniscus posterior horn microstructure using micro-computed tomography (μCT), and to compare specimens from healthy references against end-stage osteoarthritis (OA) using conventional section-based histology and qualitative μCT., Design: We retrieved human medial and lateral menisci from 10 deceased donors without knee OA (healthy references) and medial and lateral menisci from 10 patients having total knee replacement for medial compartment OA. Meniscal posterior horns were dissected and fixed in formalin. One subsection underwent hexamethyldisilazane (HMDS) treatment and μCT imaging. Pauli's histopathological scoring was performed for 3 other subsections. The differences in histopathological scores were estimated using mixed linear regression, resulting in fixed effects estimates for within-knee comparisons and adjusted for age and body mass index for between-subjects comparisons., Results: 3D visualization with μCT qualitatively revealed similar microstructural changes in the posterior horns as conventional histology. The mean histopathological score was higher for medial menisci from OA knees vs both medial reference menisci (mean difference [95% CI], 3.9 [2.6,5.3]), and lateral menisci from OA knees (3.9 [2.9,5.0]). The scores were similar between lateral menisci from OA knees and lateral reference menisci (0.8 [-0.6,2.2]), and between medial and lateral reference menisci (0.8 [-0.3,1.9])., Conclusions: HMDS-based μCT protocol allows unique 3D visualization of meniscus microstructures. Posterior horns of medial menisci from medial compartment OA knees had higher histopathological scores than both the lateral posterior horns from the same OA knees and medial reference menisci, suggesting a strong association between meniscus degradation and unicompartmental knee OA., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Knee osteoarthritis (KOA) is a heterogeneous condition representing a variety of potentially distinct phenotypes. The purpose of this study was to apply innovative machine learning approaches to KOA phenotyping in order to define progression phenotypes that are potentially more responsive to interventions., Design: We used publicly available data from the Foundation for the National Institutes of Health (FNIH) osteoarthritis (OA) Biomarkers Consortium, where radiographic (medial joint space narrowing of ≥0.7 mm), and pain progression (increase of ≥9 Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] points) were defined at 48 months, as four mutually exclusive outcome groups (none, both, pain only, radiographic only), along with an extensive set of covariates. We applied distance weighted discrimination (DWD), direction-projection-permutation (DiProPerm) testing, and clustering methods to focus on the contrast (z-scores) between those progressing by both criteria ("progressors") and those progressing by neither ("non-progressors")., Results: Using all observations (597 individuals, 59% women, mean age 62 years and BMI 31 kg/m 2 ) and all 73 baseline variables available in the dataset, there was a clear separation among progressors and non-progressors (z = 10.1). Higher z-scores were seen for the magnetic resonance imaging (MRI)-based variables than for demographic/clinical variables or biochemical markers. Baseline variables with the greatest contribution to non-progression at 48 months included WOMAC pain, lateral meniscal extrusion, and serum N-terminal pro-peptide of collagen IIA (PIIANP), while those contributing to progression included bone marrow lesions, osteophytes, medial meniscal extrusion, and urine C-terminal crosslinked telopeptide type II collagen (CTX-II)., Conclusions: Using methods that provide a way to assess numerous variables of different types and scalings simultaneously in relation to an outcome of interest enabled a data-driven approach that identified key variables associated with a progression phenotype., (Copyright © 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

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 determine the contribution of the gut microbiota to the development of injury-induced osteoarthritis (OA)., Design: OA was induced using the destabilized medial meniscus (DMM) model in 20 germ-free (GF) C57BL/6J male mice housed in a gnotobiotic facility and 23 strain-matched specific pathogen free (SPF) mice in 2 age groups -13.5 weeks avg age at DMM (17 SPF and 15 GF) and 43 weeks avg age at DMM (6 SPF and 5 GF). OA severity was measured using scores for articular cartilage structure (ACS), loss of safranin O (SafO) staining, osteophyte size, and synovial hyperplasia. Microbiome analysis by 16S rRNA amplicon sequencing was performed on stool samples and LPS and LPS binding protein (LBP) were measured in plasma., Results: Compared to the SPF DMM mice, the maximum (MAX) ACS score per joint was 28% lower (p = 0.036) in GF DMM mice while the SafO sum score of all sections evaluated per joint was decreased by 31% (p = 0.009). The differences between SPF and GF mice in these scores were greater when only the younger mice were included in the analysis. The younger GF DMM mice also had significant reductions in osteophyte size (36%, P = 0.0119) and LBP (27%, P = 0.007) but not synovial scores or LPS. Differences in relative abundance of a number of Operational Taxonomic Units (OTUs) were noted between SPF mice with high vs low maximum ACS scores., Conclusions: These results suggest factors related to the gut microbiota promote the development of OA after joint injury., (Copyright © 2018 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine the relationship of meniscal damage to magnetic resonance imaging (MRI) features of compartment-specific patellofemoral joint (PFJ) osteoarthritis (OA) at baseline and 2 years later., Method: Individuals from a prospective cohort of individuals aged 50-79 with or at risk of knee OA were included. At the 60-month and 84-month study visit, Whole-Organ MRI Score (WORMS) was used to assess meniscal tears and extrusions as well as cartilage damage and bone marrow lesions (BMLs) in the medial and lateral patella and trochlea. Worsening of structural features was defined as any increase in WORMS score from 60 to 84 months. Logistic regression was used to determine the cross-sectional and longitudinal relation of meniscus damage to features of compartment-specific PFJ OA., Results: Relative to knees without lateral meniscal pathology at baseline, those with grades 3-4 lateral meniscal tear and extrusion had greater risk of worsening of cartilage damage in the lateral PFJ 2 years later (Risk ratio: 1.7 [95% CI: 1.1-2.7) and (1.7 [1.2-2.5]), respectively. Relative to those without medial meniscal pathology at baseline, those with grades 1-2 (0.6 [0.4-0.9]) and 3-4 (0.7 [0.5-1.0]) medial meniscal tears had lower risk of worsening of BMLs in the medial PFJ 2 years later., Conclusion: Meniscal tear and extrusion are associated with increased risk of medial and lateral PFJ OA and more severe meniscal pathology is associated with worsening of PFJ OA 2 years later. Lateral meniscal pathology appears to be more detrimental to the lateral PFJ., (Copyright © 2018 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate the longitudinal changes in meniscal T1ρ/T2 signal post-reconstruction in patients with acute anterior cruciate ligament (ACL) injury and to investigate the association with T1ρ/T2 signal in articular knee cartilage., Method: In this prospective study, knees of 37 patients with ACL-injury and reconstruction in addition to 13 healthy controls were scanned using magnetic resonance imaging (MRI) T1ρ/T2 mapping. Quantitative analysis of the meniscus was performed in the anterior/posterior horns of lateral/medial meniscus fourteen sub-compartments of cartilage spanning the medial/lateral area of the tibia and femoral condyles. Meniscus T1ρ/T2 signals were compared between injured, contralateral and control knees at baseline, 6-months, 1-year and 2-years using t-tests for cross-sectional comparisons and a mixed model for longitudinal comparisons. Pearson-partial correlations between meniscal and cartilage T1ρ/T2 were evaluated., Results: There was a significant decrease of T1ρ/T2 signal in the posterior horn of lateral meniscus (PHLAT) of injured knees during a 2-year period. In the posterior horn of medial meniscus (PHMED), T1ρ/T2 signal of injured knees was significantly elevated at all time points post-reconstruction compared to contralateral and control knees. Within injured knees, PHMED T1ρ/T2 signal showed significant positive correlations with medial tibia (MT) cartilage T1ρ/T2 signal at all time points., Conclusion: A significant decrease in PHLAT T1ρ/T2 signal by 2-years suggests potential tissue recovery after ACL-injury. Elevated T1ρ/T2 signal in the PHMED of injured knees at 2-years correlating with knee cartilage T1ρ/T2 signal elevations suggests involvement of the PHMED in subacute cartilage degeneration after ACL-injury and reconstruction., (Copyright © 2018 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate the ability of magnetic resonance imaging (MRI) adiabatic relaxation times in the rotating frame (adiabatic T 1ρ and T 2ρ ) to detect structural alterations in meniscus tissue of mild OA patients and asymptomatic volunteers., Method: MR images of 24 subjects (age range: 50-67 years, 12 male), including 12 patients with mild osteoarthritis (OA) (Kellgren-Lawrence (KL) = 1, 2) and 12 asymptomatic volunteers, were acquired using a 3 T clinical MRI system. Morphological assessment was performed using semiquantitative MRI OA Knee Score (MOAKS). Adiabatic T 1ρ and T 2ρ (AdT 1ρ , AdT 2ρ ) relaxation time maps were calculated in regions of interest (ROIs) containing medial and lateral horns of menisci. The median relaxation time values of the ROIs were compared between subjects classified based on radiographic findings and MOAKS evaluations., Results: MOAKS assessment of patients and volunteers indicated the presence of meniscal and cartilage lesions in both groups. For the combined cohort group, prolonged AdT 1ρ was observed in the posterior horn of the medial meniscus (PHMED) in subjects with MOAKS meniscal tear (P < 0.05). AdT 2ρ was statistically significantly longer in PHMED of subjects with MOAKS full-thickness cartilage loss (P < 0.05). After adjusting for multiple comparisons, differences in medians of observed AdT 1ρ and AdT 2ρ values between mild OA patients and asymptomatic volunteers did not reach statistical significance., Conclusion: AdT 1ρ and AdT 2ρ measurements have the potential to identify changes in structural composition of meniscus tissue associated with meniscal tear and cartilage loss in a cohort group of mild OA patients and asymptomatic volunteers., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Meniscal pathology is integral to knee osteoarthritis (OA) and its progression; it provides a progression biomarker and a potential treatment target. Magnetic resonance imaging (MRI) demonstrates large heterogeneity in meniscal damage; this structural complexity means measurement is difficult. The aim of this study was to apply novel 3D image analysis to determine which meniscal pathologies demonstrated most change during OA progression., Methods: Knee images were selected from the progression cohort of the Osteoarthritis Initiative choosing participants with risk factors for medial OA progression. Medial and lateral menisci were manually segmented then analysed using a statistical shape model of the tibia as a reference surface. Responsiveness was assessed at 1 year using standardised response means (SRMs) for four constructs: meniscal volume, extrusion volume, thickness and tibial coverage; anatomical sub-regions of these constructs were also explored., Results: Paired images from 86 participants (median age 61.5, 49% female, 56% obese) were included. Reliability of the novel meniscal measurements was very good intraclass correlation coefficients (ICCs all > 0.98). Meniscal volume and extrusion demonstrated no significant change. Moderate responsiveness was observed for medial meniscus thickness (SRM -0.35) and medial tibial coverage (SRM -0.36). No substantial change was seen for the lateral meniscus measures. Sub-region analysis did not improve responsiveness; while greater change was seen in the posterior medial compartment, it was associated with increased variance of the change., Conclusions: The location of meniscal damage was consistently in the posterior medial region, and two measurements (thickness and tibial coverage) were most responsive. Meniscal measures should add to discriminatory power in OA progression assessment., (Copyright © 2017. Published by Elsevier Ltd.)

Objective: Autophagy is a cellular homeostasis mechanism that facilitates normal cell function and survival. Objectives of this study were to determine associations between autophagic responses with meniscus injury, joint aging, and osteoarthritis (OA), and to establish the temporal relationship with structural changes in menisci and cartilage., Methods: Constitutive activation of autophagy during aging was measured in GFP-LC3 transgenic reporter mice between 6 and 30 months. Meniscus injury was created by surgically destabilizing the medial meniscus (DMM) to induce posttraumatic OA in C57BL/6J mice. Levels of autophagy proteins and activation were analyzed by confocal microscopy and immunohistochemistry. Associated histopathological changes, such as cellularity, matrix staining, and structural damage, were graded in the meniscus and compared to changes in articular cartilage., Results: In C57BL/6J mice, basal autophagy was lower in the meniscus than in articular cartilage. With increasing age, expression of the autophagy proteins ATG5 and LC3 was significantly reduced by 24 months. Age-related changes included abnormal Safranin-O staining and reduced cellularity, which preceded structural damage in the meniscus and articular cartilage. In mice with DMM, autophagy was induced in the meniscus while it was suppressed in cartilage. Articular cartilage exhibited the most profound changes in autophagy and structure that preceded meniscus degeneration. Systemic administration of rapamycin to mice with DMM induced autophagy activation in cartilage and reduced degenerative changes in both meniscus and cartilage., Conclusion: Autophagy is significantly affected in the meniscus during aging and injury and precedes structural damage. Maintenance of autophagic activity appears critical for meniscus and cartilage integrity., (Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate the association between baseline meniscal extrusion and the incidence of knee osteoarthritis (KOA) after 30 months in a high-risk population of overweight and obese women, free of clinical and radiological KOA at baseline., Methods: 407 middle-aged overweight women (body mass index - BMI ≥ 27 kg/m 2 ) were evaluated at baseline and after 30 months of follow-up. Meniscal extrusion was defined as grade ≥2 on MRI according to MRI Osteoarthritis Knee Score (MOAKS). The primary outcome measure was KOA after 30 months follow-up, defined using the following criteria: either incidence of radiographic KOA (Kellgren & Lawrence grade 2 or higher), or clinical osteoarthritis (OA) according to the American College of Radiology (ACR) criteria, or medial or lateral joint space narrowing (JSN) of ≥1.0 mm. Using generalized estimating equations (GEE), we determined the association between knees with and without meniscal extrusion and both outcomes, corrected for the baseline differences., Results: 640 knees were available at baseline of which 24% (153) had meniscal extrusion. There was a significantly higher incidence of KOA according to the primary outcome measure in women with meniscal extrusion compared to those without extrusion (28.8%, odds ratio - OR 2.39, 95% CI 1.53, 3.73). A significantly higher incidence was found for the development of radiographic KOA (12.4%, OR 2.61, 95% CI 1.11, 6.13) and medial JSN (11.8%, OR 3.19, 95% CI 1.59, 6.41). Meniscal extrusion was not significantly associated with clinical KOA and lateral JSN., Conclusion: Meniscal extrusion was associated with a significantly higher incidence of KOA, providing an interesting target for early detection of individuals at risk for developing KOA., (Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: Whether meniscal extrusion and bone marrow lesions (BMLs) are independently associated with the risk of knee osteoarthritis (OA) is unknown., Methods: Data was extracted from the Osteoarthritis Initiative (OAI) cohort. Participants were grouped according to the absence (Kellgren-Lawrence (KL) grade ≤ 1, n = 2120) or presence (KL ≥ 2, n = 2249) of radiographic OA (ROA). Baseline meniscal extrusion and tibial BMLs were assessed. Tibial plateau cartilage volume was assessed at baseline and 72 months, while radiographic disease was assessed at baseline and 48 months. Total knee replacement (TKR) was assessed at 72 months., Results: In those with ROA, the presence of a baseline meniscal extrusion (independent of BMLs) was associated with accelerated cartilage volume loss (medial tibia: -2.1%/annum vs -1.5%; lateral: -2.6%/annum vs -1.6%; both P < 0.001), progressive ROA and TKR (Odds ratio (OR) range 1.4-1.8; 95% CI range 1.1-2.9). The presence of a baseline BML was associated with accelerated cartilage volume loss (medial tibia: -2.1%/annum vs -1.6%; lateral: -1.9%/annum vs -1.6%; P ≤ 0.02), progressive ROA and joint replacement (OR range 1.5-2.4; 95% CI range 1.1-3.4). In those with no ROA, a baseline medial meniscal extrusion was associated with accelerated cartilage volume loss (medial tibia: -2.1%/annum vs -1.2%, P < 0.001), and a baseline medial BML with incident ROA (OR 1.7, 95% CI 1.1 to 2.9)., Conclusions: The presence of baseline meniscal extrusion and BMLs are associated with incident and progressive knee of each other (OA) and represent important structural targets for the treatment and prevention of knee OA., (Copyright © 2017. Published by Elsevier Ltd.)

Objective: The aim of this study was to assess cross-sectional and longitudinal effects of meniscal lesions on adjacent cartilage T 1ρ and T 2 relaxation times, patient-reported outcomes and gait biomechanics., Design: Thirty patients with no cartilage morphological defects reported by Whole Organ MRI Score (WORMS) magnetic resonance imaging (MRI) grading and no radiographic osteoarthritis (OA) (Kellgren--Lawrence (KL) ≤ 1) were selected, 15 with posterior meniscus horn lesions and 15 matched controls without meniscal lesions. All were imaged on a 3T MR scanner for three consecutive years, except those who dropped from the study. Sagittal and frontal plane kinematic gait data were acquired at baseline. The Knee Injury and Osteoarthritis Outcome Score (KOOS) survey was taken each time. All images were automatically segmented and registered to an atlas for voxel-by-voxel cross-sectional and longitudinal analyses., Results: Relaxation time comparisons between groups showed elevated T 1ρ of the lateral tibia (LP) and elevated T 2 of the medial tibia (MT) and LT at 1 and 2 years in the lesion group. Longitudinal comparisons within each group revealed greater relaxation time elevations over one and 2 years in the group with lesions. KOOS Quality of Life (QOL) was significantly different between the groups at all time points (P < 0.05), as were other KOOS subcategories. No significant differences in the frontal or sagittal biomechanics were observed between the groups at baseline., Conclusions: Individuals with healthy cartilage and posterior meniscal horn lesions have increased relaxation times when compared to matched controls, increased relaxation time changes over 2 years, and consistently report a lower KOOS QOL, yet show no difference in gait biomechanics., (Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: In rodent osteoarthritis (OA) models, behavioral changes are often subtle and require highly sensitive methods to detect these changes. Gait analysis is one assay that may provide sensitive, quantitative measurement of these behavioral changes. To increase detection sensitivity of gait assessments relative to spatiotemporal gait collection alone, we combined our spatiotemporal and dynamic gait collection systems. Using this combined system, gait was assessed in the rat medial meniscus transection (MMT) model and monoiodoacetate (MIA) injection model of knee OA., Design: 36 male Lewis rats were separated into MMT (n = 8), medial collateral ligament transection (MCLT) (n = 8), skin incision (n = 4), MIA injection (n = 8), and saline injection (n = 8) groups. After initiation of OA, gait data were collected weekly in each group out to 4 weeks., Results: The MMT and MIA injection models produced unique pathologic gait profiles, with MMT animals developing a shuffling gait and MIA injection animals exhibiting antalgic gait. Spatiotemporal changes were also observed in the MMT model at week 1 (P < 0.01), but were not observed in the MIA injection model until week 3 (P < 0.01). Dynamic gait changes were observed in both models as early as 1 week post-surgery (P < 0.01)., Conclusion: Combined analysis of spatiotemporal and dynamic gait data increased detection sensitivity for gait modification in two rat OA models. Analyzing the combined gait data provided a robust characterization of the pathologic gait produced by each model. Furthermore, this characterization revealed different patterns of gait compensations in two common rat models of knee OA., (Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: To determine factors associated with higher degree of meniscal body extrusion in overweight and obese women at high risk of knee osteoarthritis (OA)., Design: We used baseline data of the PRevention of knee Osteoarthritis in Overweight Females (PROOF) study, Netherlands, comprising overweight or obese women aged 50-60 years, free of clinical knee OA. All subjects completed a questionnaire on knee complaints and physical activity, underwent physical examination, radiography, and 1.5 T magnetic resonance imaging (MRI) of both knees. Using the mid-coronal MRI slice, one blinded observer measured tibial plateau width and meniscal body extrusion of both menisci in both knees. The association between baseline factors and meniscal extrusion, were analyzed with a random effects regression model. In addition, we used a fixed effect regression model for evaluation of knee-specific factors., Results: Mean age of the included women (n = 395) was 55.7 years and mean body mass index (BMI) 32.4 kg/m 2 . Of all knees, 23% had an absolute medial meniscus body extrusion ≥3.0 mm and 4% had lateral meniscus body extrusion ≥3.0 mm. In the multivariable model, the medial meniscus extrusion was increased by 0.44 mm (95% confidence interval [CI] 0.11, 0.77) when a medial meniscus tear was present, by 0.20 mm per 5 kg/m 2 (95% CI 0.05, 0.35) increase in BMI and by 0.25 in the presence of mild knee symptoms (95% CI 0.05 to 0.44). Kellgren-Lawrence (KL) grade ≥1 and tibia width were associated with increased both medial and lateral extrusion., Conclusion: In women, ipsilateral meniscus tear and high BMI are factors associated with medial meniscus body extrusion., (Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: Magnetic resonance imaging (MRI) texture analysis is a method of analyzing subchondral bone alterations in osteoarthritis (OA). The objective of this study was to evaluate the association between MR texture analysis and ground-truth subchondral bone histomorphometry at the tibial plateau., Design: The local research ethics committee approved the study. All subjects provided written, informed consent. This was a cross-sectional study carried out at our institution between February and August 2014. Ten participants aged 57-84 with knee OA scheduled for total knee arthroplasty (TKA) underwent pre-operative MRI of the symptomatic knee at 3T using a high spatial-resolution coronal T1 weighted sequence. Tibial plateau explants obtained at the time of TKA underwent histological preparation to allow calculation of bone volume fraction (BV.TV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp) and trabecular number (Tb.N). Texture analysis was performed on the tibial subchondral bone of MRI images matched to the histological sections. Regression models were created to assess the association of texture analysis features with BV.TV, Tb.Th, Tb.Sp and Tb.N., Results: MRI texture features were significantly associated with BV.TV (R 2  = 0.76), Tb.Th (R 2  = 0.47), Tb.Sp (R 2  = 0.75) and Tb.N (R 2  = 0.60, all P < 0.001). Simple gray-value histogram based texture features demonstrated the highest standardized regression coefficients for each model., Conclusion: MRI texture analysis features were significantly associated with ground-truth subchondral bone histomorphometry at the tibial plateau., (Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: Investigation of osteoarthritis (OA) risk alleles suggests that reduced levels of growth and differentiation factor-5 (GDF5) may be a precipitating factor in OA. We hypothesized that intra-articular recombinant human GDF5 (rhGDF5) supplementation to the OA joint may alter disease progression., Methods: A rat medial meniscus transection (MMT) joint instability OA model was used. Animals received either one intra-articular injection, or two or three bi-weekly intra-articular injections of either 30 μg or 100 μg of rhGDF5 beginning on day 21 post surgery after structural pathology had been established. Nine weeks after MMT surgery, joints were processed for histological analysis following staining with toluidine blue. Control groups received intra-articular vehicle injections, comprising a glycine-buffered trehalose solution. OA changes in the joint were evaluated using histopathological end points that were collected by a pathologist who was blinded to treatment., Results: Intra-articular rhGDF5 supplementation reduced cartilage lesions on the medial tibial plateau in a dose-dependent manner when administered therapeutically to intercept OA disease progression. A single 100 μg rhGDF5 injection on day 21 slowed disease progression at day 63. A similar effect was achieved with two bi-weekly injections of 30 μg. Two bi-weekly injections of 100 μg or three bi-weekly injections of 30 μg stopped progression of cartilage lesions. Importantly, three biweekly injections of 100 μg rhGDF5 stimulated significant cartilage repair., Conclusions: Intra-articular rhGDF5 supplementation can prevent and even reverse OA disease progression in the rat MMT OA model. Collectively, these results support rhGDF5 supplementation as an intra-articular disease modifying OA therapy., (Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To determine risk factors associated with increased meniscal body extrusion on knee magnetic resonance (MR) images in subjects free of radiographic osteoarthritis (OA)., Methods: We selected 340 subjects (aged 45-55 years, mean [SD] body mass index 26.7 [4.4], 51% women) with Kellgren-Lawrence grade 0 in both knees and bilateral knee MR images available at the baseline, 24 months, 48 months, and 72 month exam from the Osteoarthritis Initiative (OAI). We assessed mid-coronal 3-T MR images from baseline through the 72-month exam. One observer measured widths of the tibia plateau and medial or lateral meniscal body extrusion for baseline and 72 months follow-up. Another observer assessed meniscal integrity at all four time points. We calculated an extrusion ratio ([meniscal body extrusion]/[tibia width] × 100) to account for knee size. We evaluated risk factors for increased meniscal body extrusion ratio from baseline to 72 months by a multivariable linear regression mixed model for medial and lateral compartment, respectively., Results: In the medial compartment female sex (β = 0.35; 95% confidence interval [CI] 0.16-0.53), incident meniscal tear (β = 0.29; 95% CI 0.22-0.55), and the baseline value of the extrusion ratio (β = 0.63; 95% CI 0.56-0.70) were associated with increased extrusion ratio by 72 months. Results were similar for the lateral compartment., Conclusions: Only female sex, incident meniscal tear, and higher baseline value of extrusion are risk factors for increased meniscal body extrusion in subjects free of radiographic OA. The results suggest that meniscal extrusion may contribute to and mediate the well-known increase in knee OA incidence in middle-aged women., (Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: To establish a standardized protocol for histopathological assessment of murine menisci that can be applied to evaluate transgenic, knock-out/in, and surgically induced OA models., Methods: Knee joints from C57BL/6J mice (6-36 months) as well as from mice with surgically-induced OA were processed and cut into sagittal sections. All sections included the anterior and posterior horns of the menisci and were graded for (1) surface integrity, (2) cellularity, (3) Safranin-O staining distribution and intensity. Articular cartilage in the knee joints was also scored., Results: The new histopathological grading system showed good inter- and intra-class correlation coefficients. The major age-related changes in murine menisci in the absence of OA included decreased Safranin O staining intensity, abnormal cell distribution and the appearance of acellular areas. Menisci from mice with surgically-induced OA showed severe fibrillations, partial/total loss of tissue, and calcifications. Abnormal cell arrangements included both regional hypercellularity and hypocellularity along with hypertrophy and cell clusters. In general, the posterior horns were less affected by age and OA., Conclusion: A new standardized protocol and histopathological grading system has been developed and validated to allow for a comprehensive, systematic evaluation of changes in aging and OA-affected murine menisci. This system was developed to serve as a standardized technique and tool for further studies in murine meniscal pathophysiology models., (Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objectives: The etiology of degenerative meniscus tear is unclear but could be related to a generalized osteoarthritic disease process. We studied whether radiographic hand osteoarthritis (OA) is associated with meniscus damage., Methods: We examined 974 persons aged 50-90 years drawn via census tract data and random-digit dialing from Framingham, Massachusetts, United States. One reader assessed bilateral hand radiographs (30 joints) and another read frontal knee radiographs, all according to the Kellgren-Lawrence (KL) scale. A third reader assessed right knee 1.5-T magnetic resonance imaging (MRI) scans for meniscus damage. We calculated the prevalence of medial and/or lateral meniscus damage in those with one to two and three or more finger joints with radiographic OA (KL grade ≥2) compared to those without radiographic hand OA with adjustment for age, sex, and body mass index. We also evaluated the above association in persons without evidence of radiographic OA (KL grade 0) in their knee (n = 748)., Results: The prevalence of meniscus damage in the knee of subjects with no, one to two, and three or more finger joints with OA was 24.9%, 31.7%, and 47.2%, respectively. The adjusted prevalence ratio (PR) of having meniscus damage was significantly increased in those who had three or more finger joints with OA (1.40 [95% confidence interval (CI) 1.11-1.77]). The estimate remained similar in persons without evidence of radiographic OA in their knee (PR, 1.42 [95% CI 1.03-1.97]). The association was more robust for medial meniscus damage., Conclusion: Results suggest a common non-age related etiologic pathway for both radiographic hand OA and meniscus damage., (Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: To test the hypothesis that quantitative measures of meniscus extrusion predict incident radiographic knee osteoarthritis (KOA), prior to the advent of radiographic disease., Methods: 206 knees with incident radiographic KOA (Kellgren Lawrence Grade (KLG) 0 or 1 at baseline, developing KLG 2 or greater with a definite osteophyte and joint space narrowing (JSN) grade ≥1 by year 4) were matched to 232 control knees not developing incident KOA. Manual segmentation of the central five slices of the medial and lateral meniscus was performed on coronal 3T DESS MRI and quantitative meniscus position was determined. Cases and controls were compared using conditional logistic regression adjusting for age, sex, BMI, race and clinical site. Sensitivity analyses of early (year [Y] 1/2) and late (Y3/4) incidence was performed., Results: Mean medial extrusion distance was significantly greater for incident compared to non-incident knees (1.56 mean ± 1.12 mm SD vs 1.29 ± 0.99 mm; +21%, P < 0.01), so was the percent extrusion area of the medial meniscus (25.8 ± 15.8% vs 22.0 ± 13.5%; +17%, P < 0.05). This finding was consistent for knees restricted to medial incidence. No significant differences were observed for the lateral meniscus in incident medial KOA, or for the tibial plateau coverage between incident and non-incident knees. Restricting the analysis to medial incident KOA at Y1/2 differences were attenuated, but reached significance for extrusion distance, whereas no significant differences were observed at incident KOA in Y3/4., Conclusion: Greater medial meniscus extrusion predicts incident radiographic KOA. Early onset KOA showed greater differences for meniscus position between incident and non-incident knees than late onset KOA., (Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

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: To assess the prevalence of anterior cruciate ligament (ACL) mucoid degeneration in patients referred for routine knee magnetic resonance (MR) imaging, and its association with age and structural joint damage., Method: Four independent radiologists assessed 413 consecutive knee MR examinations for the presence of a normal or ruptured ACL, or ACL mucoid degeneration. Knees with ACL mucoid degeneration were frequency matched by age, sex, and MR field strength with consecutive control knees with a normal ACL (1:2 ratio). Differences in meniscal and cartilage damage of the tibiofemoral compartments, as determined by the Whole-Organ MR Imaging Score (WORMS) system, were compared by Mann-Whitney U tests. Multivariable logistic regression analysis identified the association of ACL mucoid degeneration with severe MTFC cartilage damage (WORMS≥5)., Results: Patients with ACL mucoid degeneration (n = 36; 36% males; median age 55.5 years, range: 26-81) were older than patients with a normal (P < 0.001) or ruptured ACL (P < 0.001), without sex predilection (P = 0.76), and were more frequently diagnosed at 3 T (12%) compared to 1.5 T (2%). Knees with ACL mucoid degeneration had statistically significantly more medial meniscal (P < 0.001) and central and posterior medial tibiofemoral compartment (MTFC) cartilage (P < 0.001) damage compared with control knees (n = 72), but there were no differences in patients ≤50 years (P = 0.09 and 0.32, respectively). In multivariable logistic regression, severe MTFC cartilage damage (WORMS≥5) was significantly associated with ACL mucoid degeneration (odds ratio 4.09, 95% confidence interval 1.29-12.94, P = 0.016)., Conclusion: There is a strong association between ACL mucoid degeneration and cartilage damage in the central and posterior MTFC, especially in patients >50 years., (Copyright © 2015 Osteoarthritis Research Society International. All rights reserved.)

Objective: Identify gene changes in articular cartilage of the medial tibial plateau (MTP) at 2, 4 and 8 weeks after destabilisation of the medial meniscus (DMM) in mice. Compare our data with previously published datasets to ascertain dysregulated pathways and genes in osteoarthritis (OA)., Design: RNA was extracted from the ipsilateral and contralateral MTP cartilage, amplified, labelled and hybridized on Illumina WGv2 microarrays. Results were confirmed by real-time polymerase chain reaction (PCR) for selected genes., Results: Transcriptional analysis and network reconstruction revealed changes in extracellular matrix and cytoskeletal genes induced by DMM. TGFβ signalling pathway and complement and coagulation cascade genes were regulated at 2 weeks. Fibronectin (Fn1) is a hub in a reconstructed network at 2 weeks. Regulated genes decrease over time. By 8 weeks fibromodulin (Fmod) and tenascin N (Tnn) are the only dysregulated genes present in the DMM operated knees. Comparison with human and rodent published gene sets identified genes overlapping between our array and eight other studies., Conclusions: Cartilage contributes a minute percentage to the RNA extracted from the whole joint (<0.2%), yet is sensitive to changes in gene expression post-DMM. The post-DMM transcriptional reprogramming wanes over time dissipating by 8 weeks. Common pathways between published gene sets include focal adhesion, regulation of actin cytoskeleton and TGFβ. Common genes include Jagged 1 (Jag1), Tetraspanin 2 (Tspan2), neuroblastoma, suppression of tumourigenicity 1 (Nbl1) and N-myc downstream regulated gene 2 (Ndrg2). The concomitant genes and pathways we identify may warrant further investigation as biomarkers or modulators of OA., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Vitamin K-dependent (VKD) proteins, including the mineralization inhibitor matrix-gla protein (MGP), are found in joint tissues including cartilage and bone. Previous studies suggest low vitamin K status is associated with higher osteoarthritis (OA) prevalence and incidence., Objective: To clarify what joint tissues vitamin K is relevant to in OA, we investigated the cross-sectional and longitudinal association between vitamin K status and knee OA structural features measured using magnetic resonance imaging (MRI)., Methods: Plasma phylloquinone (PK, vitamin K1) and dephosphorylated-uncarboxylated MGP ((dp)ucMGP) were measured in 791 older community-dwelling adults who had bilateral knee MRIs (mean ± SD age = 74 ± 3 y; 67% female). The adjusted odds ratios (and 95% confidence intervals) [OR (95%CI)] for presence and progression of knee OA features according to vitamin K status were calculated using marginal models with generalized estimating equations (GEEs), adjusted for age, sex, body mass index (BMI), triglycerides and other pertinent confounders., Results: Longitudinally, participants with very low plasma PK (<0.2 nM) were more likely to have articular cartilage and meniscus damage progression after 3 years [OR (95% CIs): 1.7(1.0-3.0), 2.6(1.3-5.2) respectively] compared to sufficient PK (≥ 1.0 nM). Higher plasma (dp)ucMGP (reflective of lower vitamin K status) was associated with higher odds of meniscus damage, osteophytes, bone marrow lesions, and subarticular cysts cross-sectionally [ORs (95% CIs) comparing highest to lowest quartile: 1.6(1.1-2.3); 1.7(1.1-2.5); 1.9(1.3-2.8); 1.5(1.0-2.1), respectively]., Conclusion: Community-dwelling men and women with very low plasma PK were more likely to have progression of articular cartilage and meniscus damage. Plasma (dp)ucMGP was associated with presence of knee OA features but not progression. Future studies are needed to clarify mechanisms underlying vitamin Ks role in OA., (Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate pain behavior and structural damage in mice subjected to either meniscal transection or removal., Methods: Mice (10/group) were subjected to transection of the medial collateral and anterior cruciate ligaments (ACLT/MCLT) followed by either transection (meniscotomy) or removal (meniscectomy) of the medial meniscus. A control group was subjected only to transection of the ligaments. Pain was assessed using the electronic pressure-meter paw test. Cell influx, measured in joint exudates, and joint histopathology were assessed after 49 days. Four other groups subjected to meniscotomy received indomethacin, the inducible nitric oxide synthase (iNOS) inhibitor 1400W, morphine or the vehicles., Results: Both meniscotomy and meniscectomy groups displayed persistent and significant increase in pain behavior as compared to controls, being significantly more severe in the former. Cell influx was more intense in the meniscotomy as compared to the meniscectomy group. Structural damage at the tibia, but not at the femur, was also more severe in the meniscotomy group. Indomethacin and 1400W partially but significantly reduced pain whereas morphine abrogated pain behavior in meniscotomized mice., Conclusion: Meniscal transection rather than resection promotes more severe pain and structural damage in mice. Administration of opioids, cyclooxygenase and nitric oxide (NO) synthase inhibitors provide analgesia in this model. Careful description of the structures damaged is crucial when reporting experimental osteoarthritis (OA)., (Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Joint injury has been recognized as a potent risk factor for the onset of osteoarthritis. The vast majority of studies using imaging technology for longitudinal assessment of patients following joint injury have focused on the injured knee joint, specifically in patients with anterior cruciate ligament injury and meniscus tears where a high risk for rapid onset of post-traumatic osteoarthritis is well known. Although there are many imaging modalities under constant development, magnetic resonance (MR) imaging is the most important instrument for longitudinal monitoring after joint injury. MR imaging is sensitive for detecting early cartilage degeneration and can evaluate other joint structures including the menisci, bone marrow, tendons, and ligaments which can be sources of pain following acute injury. In this review, focusing on imaging following acute knee trauma, several studies were identified with promising short-term results of osseous and soft tissue changes after joint injury. However, studies connecting these promising short-term results to the development of osteoarthritis were limited which is likely due to the long follow-up periods needed to document the radiographic and clinical onset of the disease. Thus, it is recommended that additional high quality longitudinal studies with extended follow-up periods be performed to further investigate the long-term consequences of the early osseous and soft tissue changes identified on MR imaging after acute knee trauma., (Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

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 validate an automatic scheme for the segmentation and quantitative analysis of the medial meniscus (MM) and lateral meniscus (LM) in magnetic resonance (MR) images of the knee., Method: We analysed sagittal water-excited double-echo steady-state MR images of the knee from a subset of the Osteoarthritis Initiative (OAI) cohort. The MM and LM were automatically segmented in the MR images based on a deformable model approach. Quantitative parameters including volume, subluxation and tibial-coverage were automatically calculated for comparison (Wilcoxon tests) between knees with variable radiographic osteoarthritis (rOA), medial and lateral joint space narrowing (mJSN, lJSN) and pain. Automatic segmentations and estimated parameters were evaluated for accuracy using manual delineations of the menisci in 88 pathological knee MR examinations at baseline and 12 months time-points., Results: The median (95% confidence-interval (CI)) Dice similarity index (DSI) (2 ∗|Auto ∩ Manual|/(|Auto|+|Manual|)∗ 100) between manual and automated segmentations for the MM and LM volumes were 78.3% (75.0-78.7), 83.9% (82.1-83.9) at baseline and 75.3% (72.8-76.9), 83.0% (81.6-83.5) at 12 months. Pearson coefficients between automatic and manual segmentation parameters ranged from r = 0.70 to r = 0.92. MM in rOA/mJSN knees had significantly greater subluxation and smaller tibial-coverage than no-rOA/no-mJSN knees. LM in rOA knees had significantly greater volumes and tibial-coverage than no-rOA knees., Conclusion: Our automated method successfully segmented the menisci in normal and osteoarthritic knee MR images and detected meaningful morphological differences with respect to rOA and joint space narrowing (JSN). Our approach will facilitate analyses of the menisci in prospective MR cohorts such as the OAI for investigations into pathophysiological changes occurring in early osteoarthritis (OA) development., (Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: This study aimed to investigate subchondral bone changes using micro-computed tomography (micro-CT) and regional differences in articular cartilage degeneration, focusing on changes of cartilage covered by menisci, in the early phase using a destabilization of the medial meniscus (DMM) model., Method: The DMM model was created as an experimental rat osteoarthritis (OA) model (12 weeks old; n = 24). At 1, 2, and 4 weeks after surgery, the rats were sacrificed, and knee joints were scanned using a Micro-CT system. Histological sections of the medial tibial plateau, which was divided into inner, middle, and outer regions, were prepared and scored using the modified OARSI scoring system. The cartilage thickness was also calculated, and matrix metalloproteinase 13 (MMP13), Col2-3/4c, and vascular endothelial growth factor (VEGF) expression was assessed immunohistochemically., Results: Subchondral bone defects were observed in the middle region, in which the cartilage thickness decreased over time after surgery, and these defects were filled with MMP13- and VEGF-expressing fibrous tissue. The OARSI score increased over time in the middle region, and the score was significantly higher in the middle region than in the inner and outer regions at 1, 2, and 4 weeks after surgery. Col2-3/4c and MMP13 expression was observed primarily in the meniscus-covered outer region, in which the cartilage thickness increased over time., Conclusion: Loss of meniscal function caused cartilage degeneration and subchondral bone defects in the early phase site-specifically in the middle region. Furthermore, our results might indicate cartilage covered by menisci is easily degraded resulting in osmotic swelling of the cartilage in early OA., (Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: To develop a whole joint scoring system, the Anterior Cruciate Ligament OsteoArthritis Score (ACLOAS), for magnetic resonance imaging (MRI)-based assessment of acute anterior cruciate ligament (ACL) injury and follow-up of structural sequelae, and to assess its reliability., Design: Baseline and follow-up 1.5 T MRI examinations from 20 patients of the KANON study, a randomized controlled study comparing a surgical and non-surgical treatment strategy, were assessed for up to six longitudinal visits using a novel MRI scoring system incorporating acute structural tissue damage and longitudinal changes including osteoarthritis (OA) features. Joint features assessed were acute osteochondral injury, traumatic and degenerative bone marrow lesions (BMLs), meniscus morphology and extrusion, osteophytes, collateral and cruciate ligaments including ACL graft, Hoffa-synovitis and effusion-synovitis. Cross-sectional (baseline) and longitudinal (all time points and change) intra- and inter-observer reliability was calculated using weighted (w) kappa statistics and overall percent agreement on a compartmental basis (medial tibio-femoral, lateral tibio-femoral, patello-femoral)., Results: Altogether 87 time points were evaluated. Intra-observer reliability ranged between 0.52 (baseline, Hoffa-synovitis) and 1.00 (several features), percent agreement between 52% (all time points, Hoffa-synovitis) and 100% (several features). Inter-observer reliability ranged between 0.00 and 1.00, which is explained by low frequency of some of the features. Altogether, 73% of all assessed 142 parameters showed w-kappa values between 0.80 and 1.00 and 92% showed agreement above 80%., Conclusions: ACLOAS allows reliable scoring of acute ACL injury and longitudinal changes. This novel scoring system incorporates features that may be relevant for structural outcome not covered by established OA scoring instruments., (Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: The ability of menisci to prevent osteoarthritis (OA) is dependent on the integrity of the complex meniscal entheses, the attachments of the menisci to the underlying subchondral bone (SB). The goal of this study was to determine mechanical and structural changes in meniscal entheses after the onset of OA., Design: Healthy and osteoarthritic meniscal entheses were evaluated for changes in histomorphological characteristics, mineralization, and mechanical properties. Glycosaminoglycans (GAG) and calcium in the insertion were evaluated with histological staining techniques. The extent of calcium deposition was assessed and tidemark (TM) integrity was quantified. Changes in the mineralized zone of the insertion were examined using micro-computed tomography (μCT) to determine bone mineral density, cortical zone thickness, and mineralization gradient. Mechanical properties of the entheses were measured using nano-indentation techniques to obtain material properties based on viscoelastic analysis., Results: GAG thickness in the calcified fibrocartilage (CFC) zone and calcium content were significantly greater in osteoarthritic anterior meniscal entheses. TM integrity was significantly decreased in OA tissue, particularly in the medial anterior (MA) enthesis. The mineralized zone of osteoarthritic meniscal entheses was significantly thicker than in healthy entheses and showed decreased bone mineral density. Fitting of mineralization data to a sigmoidal Gompertz function revealed a lower rate of increase in mineralization in osteoarthritic tissue. Analysis of viscoelastic mechanical properties revealed increased compliance in osteoarthritic tissue., Conclusions: These data suggest that significant changes occur at meniscal enthesis sites with the onset of OA. Mechanical and structural changes in meniscal entheses may contribute to meniscal extrusion, which has been shown to increase the progression of OA., (Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: Meniscus injury increases the risk of osteoarthritis; however, the biologic mechanism remains unknown. We hypothesized that pro-inflammatory stimulation of meniscus would increase production of matrix-degrading enzymes, cytokines and chemokines which cause joint tissue destruction and could contribute to osteoarthritis development., Design: Meniscus and cartilage tissue from healthy tissue donors and total knee arthroplasties (TKAs) was cultured. Primary cell cultures were stimulated with pro-inflammatory factors [IL-1β, IL-6, or fibronectin fragments (FnF)] and cellular responses were analyzed by real-time PCR, protein arrays and immunoblots. To determine if NF-κB was required for MMP production, meniscus cultures were treated with inflammatory factors with and without the NF-κB inhibitor, hypoestoxide., Results: Normal and osteoarthritic meniscus cells increased their MMP secretion in response to stimulation, but specific patterns emerged that were unique to each stimulus with the greatest number of MMPs expressed in response to FnF. Meniscus collagen and connective tissue growth factor (CTGF) gene expression was reduced. Expression of cytokines (IL-1α, IL-1β, IL-6), chemokines (IL-8, CXCL1, CXCL2, CSF1) and components of the NF-κB and tumor necrosis factor (TNF) family were significantly increased. Cytokine and chemokine protein production was also increased by stimulation. When primary cell cultures were treated with hypoestoxide in conjunction with pro-inflammatory stimulation, p65 activation was reduced as were MMP-1 and MMP-3 production., Conclusions: Pro-inflammatory stimulation of meniscus cells increased matrix metalloproteinase production and catabolic gene expression. The meniscus could have an active biologic role in osteoarthritis development following joint injury through increased production of cytokines, chemokines, and matrix-degrading enzymes., (Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: The purpose of this work was to review the current literature on cartilage and meniscal T2 relaxation time., Methods: Electronic searches in PubMed were performed to identify relevant studies about T2 relaxation time measurements as non-invasive biomarker for knee osteoarthritis (OA) and cartilage repair procedures., Results: Initial osteoarthritic changes include proteoglycan loss, deterioration of the collagen network, and increased water content within the articular cartilage and menisci. T2 relaxation time measurements are affected by these pathophysiological processes. It was demonstrated that cartilage and meniscal T2 relaxation time values were significantly increased in subjects with compared to those without radiographic OA and focal knee lesions, respectively. Subjects with OA risk factors such as overweight/obesity showed significantly greater cartilage T2 values than normal controls. Elevated cartilage and meniscal T2 relaxation times were found in subjects with vs without knee pain. Increased cartilage T2 at baseline predicted morphologic degeneration in the cartilage, meniscus, and bone marrow over 3 years. Furthermore, cartilage repair tissue could be non-invasively assessed by using T2 mapping. Reproducibility errors for T2 measurements were reported to be smaller than the T2 differences in healthy and diseased cartilage indicating that T2 relaxation time may be a reliable discriminatory biomarker., Conclusions: Cartilage and meniscal T2 mapping may be suitable as non-invasive biomarker to diagnose early stages of knee OA and to monitor therapy of OA., (Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: Synovitis is associated with pain and other symptoms in patients with knee osteoarthritis (OA), and in patients with meniscal tears even in the absence of radiographic OA. Patients undergoing arthroscopic partial meniscectomy were followed for 2 years to determine whether synovitis predicts post-operative symptoms., Design: Thirty-three patients scheduled for arthroscopy were recruited for this pilot study. Symptoms were assessed using a knee pain scale, the Lysholm score, and the short form-12 (SF-12(®)) pre-operatively and at 16 weeks, 1 year and 2 years post-operatively. Synovial inflammation and hyperplasia were graded on surgical biopsies. Linear mixed effects models were tested to determine whether inflammation or hyperplasia is associated with outcome scores over time., Results: Lysholm scores and SF-12(®) physical component sub-scores were worse pre-operatively in patients with inflammation (Lysholm: 52.42 [95% confidence interval (CI) 42.37, 62.47] vs 72.38 [66.03, 78.72], P < 0.001; SF-12: 36.81 [28.26, 45.37] vs 46.23 [40.14, 52.32], P < 0.05). Up to 2-years post-operatively, patients with inflammation achieved mean scores similar to those without inflammation. As a result, the mean improvement in Lysholm scores was 13.01 [1.48-24.53] points higher than patients without inflammation, P = 0.03. 33% (4/12) of patients with inflammation still had fair to poor Lysholm scores 2 years after surgery compared to 7% (1/15, P=0.14) without inflammation. No association between hyperplasia and symptoms was noted., Conclusions: In this pilot study of patients undergoing partial meniscectomy, synovial inflammation was associated with worse pre-operative symptoms, but not with poorer outcomes in the first 2 years post-arthroscopy. Larger cohorts and longer follow-up should be pursued to confirm this relationship, and determine if the initial response is sustained., (Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: To correlate meniscal T2* relaxation times using ultra-short echo time (UTE) magnetic resonance imaging (MRI) with quantitative microscopic methods, and to determine the effect of meniscal repair on post-operative cartilage T2 values., Design: A medial meniscal tear was created and repaired in the anterior horn of one limb of 28 crossbred mature ewes. MR scans for morphological evaluation, meniscal T2* values, and cartilage T2 values were acquired at 0, 4 and 8 months post-operatively for the Tear and Non-Op limb. Samples of menisci from both limbs were analyzed using multiphoton microscopy (MPM) analysis and biomechanical testing., Results: Significantly prolonged meniscal T2* values were found in repaired limbs than in control limbs, P < 0.0001. No regional differences of T2* were detected for either the repaired or control limbs in the anterior horn. Repaired limbs had prolonged cartilage T2 values, primarily anteriorly, and tended to have lower biomechanical force to failure at 8 months than Non-Op limbs. MPM autofluorescence and second harmonic generation data correlated with T2* values at 8 months (ρ = -0.48, P = 0.06)., Conclusions: T2* mapping is sensitive to detecting temporal and zonal differences of meniscal structure and composition. Meniscal MPM and cartilage T2 values indicate changes in tissue integrity in the presence of meniscal repair., (Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: To describe cartilage matrix and morphology changes, assessed using quantitative magnetic resonance imaging (MRI), after acute anterior cruciate ligament (ACL) injury relative to controls and longitudinally during 2 years following reconstruction., Method: Fifteen patients with acute ACL injuries and 16 healthy volunteers with a similar demographic profile but no history of osteoarthritis or knee injury were studied. The injured knee of each participant was imaged with a 3.0 T MR scanner at baseline (prior to ACL reconstruction); patients' knees were re-imaged 1 and 2 years after ACL reconstruction. Cartilage T1ρ and T2 values in full thickness, superficial layers, and deep layers, and cartilage thickness of the full layer were quantified within subcompartments of the knee joint., Results: In the posterolateral tibial cartilage, T1ρ values were significantly higher in ACL-injured knees than control knees at baseline and were not fully recovered 2 after ACL reconstruction. T1ρ values of medial tibiofemoral cartilage in ACL-injured knees increased over the 2-year study and were significantly elevated compared to that of the control knees. T2 values in cartilage of the central aspect of the medial femoral condyle at the 2-year follow-up were significantly elevated compared with control knees. Cartilage in the posterior regions of the lateral tibia was significantly thinner, while cartilage in the central aspect of the medial femur was significantly thicker than that of controls. Patients with lesions in the posterior horn of the medial meniscus exhibited significantly higher T1ρ values in weight-bearing regions of the tibiofemoral cartilage than that of control subjects over the 2-year period, whereas patients without medial meniscal tears did not., Conclusion: Quantitative MRI provides powerful in vivo tools to quantitatively evaluate early changes of cartilage matrix and morphology after acute ACL injury and reconstruction, which may possibly relate to the development of post-traumatic osteoarthritis in such joints., (Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: Changes in T1ρ and T2 magnetic resonance relaxation times have been associated with articular cartilage degeneration, but similar relationships for meniscal tissue have not been extensively investigated. This work examined relationships between T1ρ and T2 measurements and biochemical and mechanical properties across regions of degenerate human menisci., Design: Average T1ρ and T2 relaxation times were determined for nine regions each of seven medial and 13 lateral menisci from 14 total knee replacement patients. Sulfated glycosaminoglycan (sGAG), collagen and water contents were measured for each region. Biomechanical measurements of equilibrium compressive, dynamic compressive and dynamic shear moduli were made for anterior, central and posterior regions., Results: T1ρ and T2 times showed similar regional patterns, with longer relaxation times in the (radially) middle region compared to the inner and outer regions. Pooled over all regions, T1ρ and T2 times showed strong correlations both with one another and with water content. Correlations with biochemical content varied depending on normalization to wet or dry mass, and both imaging parameters showed stronger correlations with collagen compared to sGAG content. Mechanical properties displayed moderate inverse correlations with increasing T1ρ and T2 times and water content., Conclusion: Both T1ρ and T2 relaxation times correlated strongly with water content and moderately with mechanical properties in osteoarthritic menisci, but not as strongly with sGAG or collagen contents alone. While the ability of magnetic resonance imaging (MRI) to detect early osteoarthritic changes remains the subject of investigation, these results suggest that T1ρ and T2 relaxation times have limited ability to detect compositional variations in degenerate menisci., (Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background: Osteoarthritis (OA) of the knee is characterized by pain and activity limitations. In knee OA, proprioceptive accuracy is reduced and might be associated with pain and activity limitations. Although causes of reduced proprioceptive accuracy are divergent, medial meniscal abnormalities, which are highly prevalent in knee OA, have been suggested to play an important role. No study has focussed on the association between proprioceptive accuracy and meniscal abnormalities in knee OA., Objective: To explore the association between reduced proprioceptive accuracy and medial meniscal abnormalities in a clinical sample of knee OA subjects., Methods: Cross-sectional study in 105 subjects with knee OA. Knee proprioceptive accuracy was assessed by determining the joint motion detection threshold in the knee extension direction. The knee was imaged with a 3.0 T magnetic resonance (MR) scanner. Number of regions with medial meniscal abnormalities and the extent of abnormality in the anterior and posterior horn and body were scored according to the Boston-Leeds Osteoarthritis Knee Score (BLOKS) method. Multiple regression analyzes were used to examine whether reduced proprioceptive accuracy was associated with medial meniscal abnormalities in knee OA subjects., Results: Mean proprioceptive accuracy was 2.9° ± 1.9°. Magnetic resonance imaging (MRI)-detected medial meniscal abnormalities were found in the anterior horn (78%), body (80%) and posterior horn (90%). Reduced proprioceptive accuracy was associated with both the number of regions with meniscal abnormalities (P < 0.01) and the extent of abnormality (P = 0.02). These associations were not confounded by muscle strength, joint laxity, pain, age, gender, body mass index (BMI) and duration of knee complaints., Conclusion: This is the first study showing that reduced proprioceptive accuracy is associated with medial meniscal abnormalities in knee OA. The study highlights the importance of meniscal abnormalities in understanding reduced proprioceptive accuracy in persons with knee OA., (Copyright © 2013 Osteoarthritis Research Society International. All rights reserved.)