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ObjectiveEligibility for clinical trials in osteoarthritis (OA) is usually limited to Kellgren-Lawrence (KL) grades 2 and 3 knees. Our aim was to describe the prevalence and severity of cartilage damage in KL 2 and 3 knees by compartment and articular subregion.DesignThe Multicenter Osteoarthritis (MOST) study is a cohort study of individuals with or at risk for knee OA. All baseline MRIs with radiographic disease severity KL2 and 3 were included. Knee MRIs were read for cartilage damage in 14 subregions. We determined the frequencies of no, any and widespread full-thickness cartilage damage by knee compartment, and the prevalence of any cartilage damage in 14 articular subregions.Results665 knees from 665 participants were included (mean age 63.8 ± 7.9 years, 66.5% women). 372 knees were KL2 and 293 knees were KL3. There was no cartilage damage in 78 (21.0%) medial tibio-femoral joint (TFJ), 157 (42.2%) lateral TFJ and 62 (16.7%) patello-femoral joint (PFJ) compartments of KL2 knees, and 17 (5.8%), 115 (39.3%) and 35 (12.0%) compartments, respectively, of KL3 knees. There was widespread full-thickness damage in 94 (25.3%) medial TFJ, 36 (9.7%) lateral TFJ and 176 (47.3%) PFJ compartments of KL2 knees, and 217 (74.1%), 70 (23.9%) and 104 (35.5%) compartments, respectively, of KL3 knees. The subregions most likely to have any damage were central medial femur (80.5%), medial patella (69.8%) and central medial tibia (69.9).ConclusionsKL2 and KL3 knees vary greatly in cartilage morphology. Heterogeneity in the prevalence, severity and location of cartilage damage in in KL2 and 3 knees should be considered when planning disease modifying trials for knee OA.

ObjectiveThe study objective was to determine the relationship of magnetic resonance imaging (MRI)-detected features of patellofemoral joint osteoarthritis to pain and functional outcomes.MethodsWe sampled 1,099 participants from the 60-month visit of the Multicenter Osteoarthritis Study (mean ± SD age: 66.8 ± 7.5 years; body mass index: 29.6 ± 4.8; 65% female). We determined the prevalence of MRI-detected features of patellofemoral joint osteoarthritis (eg, cartilage damage, bone marrow lesions, and osteophytes) and assessed the relationship between these features and knee pain severity, knee pain on stairs, chair stand time, and walking less than 6,000 steps per day. We evaluated the relationship of MRI features to each outcome using logistic and linear regression, adjusting for potential covariates.ResultsParticipants with cartilage damage in 3-4 subregions had the highest mean pain severity (22.0/100; 95% confidence interval [CI]: 17.6-26.4 mm). They also showed higher odds of having at least mild pain on stairs (odds ratio [OR]: 3.3; 95% CI: 1.7-6.5) and of walking less than 6,000 steps per day (OR: 2.3; 95% CI: 1.1-4.4) compared with those without cartilage damage. Participants with bone marrow lesions in 3-4 subregions had higher odds of at least mild pain on stairs than those without (OR: 3.3; 95% CI: 2.2-5.2). Participants with osteophytes in 3-4 subregions also had higher odds of walking less than 6,000 steps/day (OR 2.1, 95% CI: 1.3-3.5, respectively).ConclusionMRI-detected features of osteoarthritis of the patellofemoral joint are related to pain and functional performance. This knowledge highlights the need to develop treatments for those with patellofemoral joint osteoarthritis to improve pain and maximize function.

PurposeOur aim was to introduce a simplified MRI instrument, Rapid OsteoArthritis MRI Eligibility Score (ROAMES), for defining structural eligibility of patients for inclusion in disease-modifying osteoarthritis drug trials using a tri-compartmental anatomic approach that enables stratification of knees into different structural phenotypes and includes diagnoses of exclusion. We also aimed to define overlap between phenotypes and determine reliability.Methods50 knees from the Foundation for National Institutes of Health Osteoarthritis Biomarkers study, a nested case-control study within the Osteoarthritis Initiative, were selected within pre-defined definitions of phenotypes as either inflammatory, subchondral bone, meniscus/cartilage, atrophic or hypertrophic. A focused scoring instrument was developed covering cartilage, meniscal damage, inflammation and osteophytes. Diagnoses of exclusion were meniscal root tears, osteonecrosis, subchondral insufficiency fracture, tumors, malignant marrow infiltration and acute traumatic changes. Reliability was determined using weighted kappa statistics. Descriptive statistics were used for determining concordance between the a priori phenotypic definition and ROAMES and overlap between phenotypes.ResultsROAMES identified 43 of 50 (86%) pre-defined phenotypes correctly. Of the 50 participants, 27 (54%) had no additional phenotypes other than the pre-defined phenotype. 18 (36%) had one and 5 (10%) had two additional phenotypes. None had three or four additional phenotypes. All features of ROAMES showed almost perfect agreement. One case with osteonecrosis and one with a tumor were detected.ConclusionsROAMES is able to screen and stratify potentially eligible knees into different structural phenotypes and record relevant diagnoses of exclusion. Reliability of the instrument showed almost perfect agreement.

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

ObjectivesTo determine the relationship between synovitis detected on non-contrast-enhanced (non-CE) magnetic resonance imaging (MRI), biochemical markers of inflammation, and clinical assessment of effusion in people with knee osteoarthritis (OA).MethodWe examined data from the OA Biomarkers Consortium within the Osteoarthritis Initiative (n = 600). Non-CE MRIs were semi-quantitatively scored (grades 0-3) for severity of Hoffa synovitis and effusion synovitis. Serum (s) matrix metalloproteinase-3 (sMMP-3), hyaluronic acid (sHA), and nitrated epitope of the α-helical region of type II collagen (sColl2-1NO2) were quantified. The bulge and patellar tap clinical tests were performed at baseline and performance characteristics were assessed for the detection of effusion synovitis on MRI. Multinomial logistic regression adjusted for covariates was used to assess the association between biochemical and imaging markers at baseline and over 12 and 24 months.ResultsAt baseline, sHA and sMMP-3 were associated with moderate to large (score ≥ 2, n = 117) effusion synovitis, with odds ratio = 1.35 and 1.30 per 1 standard deviation in biochemical markers (95% confidence intervals 1.07, 1.71 and 1.00, 1.69), c-statistics 0.640 and 0.626, respectively. The c-statistics for the presence of Hoffa synovitis (score ≥ 2) were 0.693, 0.694, and 0.694 for sHA, sMMP-3, and sColl2-1NO2, respectively. There was no significant association between biochemical markers (baseline and 12 and 24 month time-integrated concentrations) and changes in MRI markers. The bulge and patellar tap signs were 22.0% and 4.3% sensitive and 88.8% and 94.8% specific, respectively, for detecting effusion synovitis (score ≥ 1) on MRI.ConclusionssHA and sMMP-3 were modestly associated with effusion synovitis at baseline. Clinical signs of effusion are insensitive but highly specific for the presence of any effusion synovitis on non-CE MRI.

ObjectiveTo assess the associations of atrophic tibiofemoral osteoarthritis (OA) with progression of radiographic joint space narrowing (JSN) and magnetic resonance imaging (MRI)-defined progression of cartilage damage.DesignParticipants of the Multicenter Osteoarthritis (MOST) Study with available radiographic and MRI assessments at baseline and 30 months were included. The atrophic OA phenotype was defined as Osteoarthritis Research Society International (OARSI) grades 1 or 2 for JSN and grade 0 for osteophytes. Based on MRI, atrophic OA was defined as tibiofemoral (TF) cartilage damage grades ≥3 in at least 2 of 10 subregions with absent or tiny osteophytes in all TF subregions. Progression of JSN and cartilage loss on MRI, was defined as (1) no, (2) slow, and (3) fast progression. Co-variance and logistic regression with generalized estimated equations were performed to assess the association of atrophic knee OA with any progression, compared to non-atrophic OA knees.ResultsA total of 476 knees from 432 participants were included. There were 50 (10.5%) knees with atrophic OA using the radiographic definition, and 16 (3.4%) knees with atrophic OA using MRI definition. Non-atrophic OA knees more commonly exhibited fast progression of JSN and cartilage damage. Logistic regression showed that the atrophic phenotype of knee OA was associated with a decreased likelihood of progression of JSN and cartilage loss.ConclusionIn this sample, the atrophic phenotype of knee OA was associated with a decreased likelihood of progression of JSN and cartilage loss compared to the non-atrophic knee OA phenotype.

PurposeTo determine the relation of superolateral Hoffa's fat pad (SHFP) hyperintensity to cartilage damage and bone marrow lesions (BMLs) in the patellofemoral joint (PFJ) and tibiofemoral joint (TFJ).MethodsWe used data from the 60 and 84-month study visits from the Multicenter Osteoarthritis (MOST) study. SHFP hyperintensity and Hoffa-synovitis were graded from 0 to 3. Cartilage damage and BMLs were scored in the PFJ and TFJ. Structural damage was defined as: any cartilage damage, full-thickness cartilage damage and any BML. Worsening structural damage was defined as any increase in cartilage and BML scores. Logistic regression was used to determine the relation of SHFP hyperintensity and Hoffa-synovitis (>0) to structural damage, adjusting for age, sex and body mass index (BMI).Results1,094 knees were included in the study. Compared to knees without SHFP hyperintensity, those with SHFP hyperintensity had 1.2 (95% Confidence Interval (CI), 1.1-1.4), 1.7 (1.3-2.3) and 1.6 (1.3-1.9) times the prevalence of any cartilage damage, full-thickness cartilage damage, and BMLs in the lateral PFJ respectively, and 1.1 (1.0-1.2), 1.3 (1.0-1.8), and 1.2 (1.0-1.4) times the prevalence of any cartilage damage, full-thickness cartilage damage, and BMLs in the medial PFJ. SHFP hyperintensity was associated with worsening BMLs in the medial PFJ (RR: 1.4 (1.0-1.9)). In general, there was no relation between SHFP hyperintensity and TFJ outcomes. Hoffa-synovitis was associated both cross-sectionally and longitudinally with structural damage, regardless of definition, in all compartments.ConclusionSHFP hyperintensity may be a local marker of PFJ structural damage.

ObjectivesTo investigate changes in cartilage damage and bone marrow lesions (BMLs) on MRI in the patellofemoral and tibiofemoral joints (TFJs) over 7 years.MethodsThe Multicenter Osteoarthritis (MOST) Study is a cohort study of persons aged 50-79 years at baseline with or at high risk for knee osteoarthritis (OA). Knees were eligible for the current study if they had knee MRI (1.0T) assessed for cartilage damage and BMLs at the baseline and 84-month visits. Knees were categorized as having MRI-detected structural damage (cartilage and BMLs) isolated to the patellofemoral joint (PFJ), isolated to the TFJ, mixed or no damage at baseline and 84-months. We determined the changes in PFJ and TFJ structural damage over 7 years and used logistic regression to assess the relation of baseline compartment distribution to incident isolated PFJ, isolated TFJ and mixed damage.ResultsAmong 339 knees that had full-thickness cartilage loss isolated to the PFJ or TFJ at baseline, only 68 (20.1%) developed full-thickness cartilage loss in the other compartment while 271 (79.9%) continued to only have the initial compartment affected. Compared to knees without full-thickness cartilage damage (n = 582), those with isolated TFJ and PFJ full-thickness cartilage damage had 2.7 (1.5, 4.9) and 5.8 (3.6, 9.6) times the odds of incident mixed full-thickness cartilage damage, respectively. Similar results were seen when using other definitions of MRI-defined structural damage.ConclusionsMost knees with structural damage at baseline do not develop it in the other compartment. Knees that develop mixed structural damage are more likely to start with it isolated to the PFJ.

ObjectivesTo 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.MethodsWe 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.Results196 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.ConclusionBaseline 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.

OBJECTIVE:To investigate the association of cartilage thickness change over 24 months, as determined by magnetic resonance imaging (MRI), with knee osteoarthritis (OA) progression at 24-48 months. METHODS:This nested case-control study included 600 knees with a baseline Kellgren/Lawrence (K/L) grade of 1-3 from 600 Osteoarthritis Initiative (OAI) participants. Case knees (n = 194) had both medial tibiofemoral radiographic joint space loss (≥0.7 mm) and a persistent increase in the Western Ontario and McMaster Universities Osteoarthritis Index pain score (≥9 on a 0-100 scale) 24-48 months from baseline. Control knees (n = 406) included 200 with neither radiographic nor pain progression, 103 with radiographic progression only, and 103 with pain progression only. Medial and lateral femorotibial cartilage was segmented from sagittal 3T MRIs at baseline, 12 months, and 24 months. Logistic regression was used to assess the association of change in cartilage thickness, with a focus on the central medial femorotibial compartment, and OA progression. RESULTS:Central medial femorotibial compartment thickness loss was significantly associated with case status, with an odds ratio (OR) of 1.9 (95% confidence interval [95% CI] 1.6-2.3) (P < 0.0001). Association with case status reached P < 0.05 for both the central femur (OR 1.8 [95% CI 1.5-2.2]) and the central tibia (OR 1.6 [95% CI 1.3-1.9]). Lateral femorotibial compartment cartilage thickness loss, in contrast, was not significantly associated with case status. A reduction in central medial femorotibial compartment cartilage thickness was strongly associated with radiographic progression (OR 4.0 [95% CI 2.9-5.3]; P < 0.0001) and only weakly associated with pain progression (OR 1.3 [95% CI 1.1-1.6]; P < 0.01). CONCLUSION:Our findings indicate that loss of medial femorotibial cartilage thickness over 24 months is associated with the combination of radiographic and pain progression in the knee, with a stronger association for radiographic progression.

Imaging of hip in osteoarthritis (OA) has seen considerable progress in the past decade, with the introduction of new techniques that may be more sensitive to structural disease changes. The purpose of this expert opinion, consensus driven recommendation is to provide detail on how to apply hip imaging in disease modifying clinical trials. It includes information on acquisition methods/techniques (including guidance on positioning for radiography, sequence/protocol recommendations/hardware for magnetic resonance imaging (MRI)); commonly encountered problems (including positioning, hardware and coil failures, artifacts associated with various MRI sequences); quality assurance/control procedures; measurement methods; measurement performance (reliability, responsiveness, and validity); recommendations for trials; and research recommendations.

ObjectiveTo examine the relation of cartilage loss and bone marrow lesions (BMLs) in the medial and lateral patellofemoral joint (PFJ) to knee pain.MethodsWe categorized the location of full-thickness cartilage loss and BMLs in the PFJ on knee magnetic resonance imaging (MRIs) from the Multicenter Osteoarthritis (MOST) and Framingham Osteoarthritis (FOA) Studies as no damage, isolated medial, isolated lateral, or both medial and lateral (mixed). We determined the relation of MRI lesions in each PFJ region to prevalent knee pain. Differences in knee pain severity were compared among categories of PFJ full-thickness cartilage loss and BMLs using quantile regression.ResultsIn MOST (n = 1137 knees), compared with knees without full-thickness cartilage loss, knees with isolated lateral or mixed PFJ full-thickness cartilage loss had 1.9 (1.3, 2.8) and 1.9 (1.2, 2.9) times the odds of knee pain, respectively, while isolated medial cartilage loss had no association with knee pain. BMLs in both the medial and lateral PFJ had 1.5 (1.1, 2.0) times the odds of knee pain compared with knees without BMLs. Knee pain severity was lowest in knees with isolated medial PFJ cartilage loss or BMLs. In FOA (n = 934 knees), neither isolated medial nor lateral cartilage loss was associated with knee pain, whereas isolated BMLs in either region were associated with pain.ConclusionsResults were not completely concordant but suggest that knee pain risk and severity is greatest with cartilage loss isolated to (MOST) or inclusive of (MOST and FOA) the lateral PFJ. While BMLs in either the medial or lateral PFJ are related to pain.

PurposeTo 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 materialsThe 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.ResultsA 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).ConclusionWorsening 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.

ObjectiveTo assess the association of prevalent cartilage damage and cartilage loss over time with incident bone marrow lesions (BMLs) in the same subregion of the tibiofemoral compartments as detected on magnetic resonance imaging (MRI).MethodsThe Multicenter Osteoarthritis Study is an observational study of individuals with or at risk for knee osteoarthritis (OA). Subjects whose baseline and 30-month follow-up MRIs were read for findings of OA were included. MRI was performed with a 1.0 T extremity system. Tibiofemoral compartments were divided into 10 subregions. Cartilage morphology was scored from 0 to 6 and BMLs were scored from 0 to 3. Prevalent cartilage damage and cartilage loss over time were considered predictors of incident BMLs. Associations were assessed using logistic regression, with adjustments for potential confounders.ResultsMedially, incident BMLs were associated with baseline cartilage damage (adjusted odds ratio (OR) 3.9 [95% confidence interval (CI) 3.0, 5.1]), incident cartilage loss (7.3 [95% CI 5.0, 10.7]) and progression of cartilage loss (7.6 [95% CI 5.1, 11.3]) Laterally, incident BMLs were associated with baseline cartilage damage (4.1 [95% CI 2.6, 6.3]), incident cartilage loss (6.0 [95% CI 3.1, 11.8]), and progression of cartilage loss (11.9 [95% CI 6.2, 23.0]).ConclusionPrevalent cartilage damage and cartilage loss over time are strongly associated with incident BMLs in the same subregion, supporting the significance of the close interrelation of the osteochondral unit in the progression of knee OA.

ObjectiveTo examine the relationship of knee malalignment with occurrence of incident and enlarging bone marrow lesions (BMLs) and regression of BMLs.MethodsSubjects from the Multicenter Osteoarthritis Study aged 50-79 years with or at high risk of knee osteoarthritis were studied. Full-limb radiographs were taken at baseline and hip-knee-ankle mechanical axis was measured. Baseline and 30-month magnetic resonance imaging (MRI) of knees (n = 1782) were semiquantitatively assessed for BMLs. Outcome was defined as a change in BML score in femoral/tibial condyle in medial/lateral compartments. Medial compartment in varus alignment and lateral compartment in valgus alignment were combined to form 'more loaded' compartment, while lateral compartment in valgus and medial compartment in varus were combined to form 'less loaded' compartment. Relative risk (RR) of BML score increase or decrease in relation to malalignment was estimated using a log linear regression model with the Poisson assumption, adjusting for age, gender, body mass index, physical activity scale for the elderly, race and clinic site. Further, results were stratified by ipsilateral meniscal and cartilage status at baseline.ResultsBaseline varus alignment was associated with higher risk of BML score increase from baseline to follow-up in the medial compartment [adjusted RRs (95%CI): 1.5 (1.2-1.9)] and valgus alignment in the lateral compartment [1.4 (1.0-2.1)]. Increase in BML score was more likely in the more loaded compartments [1.7 (1.4-2.0)] in malaligned knees. Regardless of ipsilateral cartilage or meniscus status, adjusted RR for BML score increase was higher in the more loaded compartments of malaligned knees than those with neutral alignment. Decrease in BML score was less likely in the more loaded compartments in malaligned knees [0.8 (0.7-1.0)].ConclusionKnee malalignment is associated with increased risk of incident and enlarging BMLs in the more loaded compartments of the tibiofemoral joint.

ObjectiveIn order to increase sensitivity to detect longitudinal change, recording of within-grade changes was introduced for cartilage morphology and bone marrow lesion (BML) assessment in semiquantitative magnetic resonance imaging (MRI) scoring of knee osteoarthritis (OA). The aim of this study was to examine the validity provided by within-grade scoring.DesignThe Multicenter Osteoarthritis (MOST) study is a longitudinal study of subjects with or at risk of knee OA. Baseline and 30 months MRIs were read according to the modified Whole-Organ Magnetic Resonance Imaging Score (WORMS) system including within-grade changes for cartilage and BMLs. We tested the validity of within-grade changes by whether the 30-month changes in cartilage and BML assessment were predicted by baseline ipsi-compartmental meniscal damage and malalignment, factors known to affect cartilage loss and BMLs, using ordinal logistic regression.Results1867 Knees (from 1411 participants) were included. Severe medial meniscal damage predicted partial grade (adjusted odds ratio (aOR) 4.4, 95% confidence interval (95% CI) 2.2, 8.7) but not ≥full grade (aOR 1.3, 95% CI 0.8, 2.2) worsening of cartilage loss and predicted both, partial grade (aOR 9.6, 95% CI 3.6, 25.1) and ≥full grade (aOR 5.1, 95% CI 3.2, 8.2) worsening of BMLs. Severe, but not moderate, malalignment predicted ipsi-compartmental within-grade (medial cartilage damage: aOR 5.5, 95% CI 2.6, 11.6; medial worsening of BMLs: aOR 4.9, 95% CI 2.0, 12.3) but not full grade worsening of BMLs and cartilage damage.ConclusionsWithin-grade changes in semiquantitative MRI assessment of cartilage and BMLs are valid and their use may increase the sensitivity of semiquantitative readings in detecting longitudinal changes in these structures.