Eligibility for clinical trials in osteoarthritis (OA) is usually limited to Kellgren–Lawrence (KL) grades 2 and 3 knees. Our aim was to describe the prevalence and severity of cartilage damage in KL ...2 and 3 knees by compartment and articular subregion.
The Multicenter Osteoarthritis (MOST) study is a cohort study of individuals with or at risk for knee OA. All baseline MRIs with radiographic disease severity KL2 and 3 were included. Knee MRIs were read for cartilage damage in 14 subregions. We determined the frequencies of no, any and widespread full-thickness cartilage damage by knee compartment, and the prevalence of any cartilage damage in 14 articular subregions.
665 knees from 665 participants were included (mean age 63.8 ± 7.9 years, 66.5% women). 372 knees were KL2 and 293 knees were KL3. There was no cartilage damage in 78 (21.0%) medial tibio-femoral joint (TFJ), 157 (42.2%) lateral TFJ and 62 (16.7%) patello-femoral joint (PFJ) compartments of KL2 knees, and 17 (5.8%), 115 (39.3%) and 35 (12.0%) compartments, respectively, of KL3 knees. There was widespread full-thickness damage in 94 (25.3%) medial TFJ, 36 (9.7%) lateral TFJ and 176 (47.3%) PFJ compartments of KL2 knees, and 217 (74.1%), 70 (23.9%) and 104 (35.5%) compartments, respectively, of KL3 knees. The subregions most likely to have any damage were central medial femur (80.5%), medial patella (69.8%) and central medial tibia (69.9).
KL2 and KL3 knees vary greatly in cartilage morphology. Heterogeneity in the prevalence, severity and location of cartilage damage in in KL2 and 3 knees should be considered when planning disease modifying trials for knee OA.
Summary Objective In order to increase sensitivity to detect longitudinal change, recording of within-grade changes was introduced for cartilage morphology and bone marrow lesion (BML) assessment in ...semiquantitative magnetic resonance imaging (MRI) scoring of knee osteoarthritis (OA). The aim of this study was to examine the validity provided by within-grade scoring. Design The Multicenter Osteoarthritis (MOST) study is a longitudinal study of subjects with or at risk of knee OA. Baseline and 30 months MRIs were read according to the modified Whole-Organ Magnetic Resonance Imaging Score (WORMS) system including within-grade changes for cartilage and BMLs. We tested the validity of within-grade changes by whether the 30-month changes in cartilage and BML assessment were predicted by baseline ipsi-compartmental meniscal damage and malalignment, factors known to affect cartilage loss and BMLs, using ordinal logistic regression. Results 1867 Knees (from 1411 participants) were included. Severe medial meniscal damage predicted partial grade (adjusted odds ratio (aOR) 4.4, 95% confidence interval (95% CI) 2.2, 8.7) but not ≥full grade (aOR 1.3, 95% CI 0.8, 2.2) worsening of cartilage loss and predicted both, partial grade (aOR 9.6, 95% CI 3.6, 25.1) and ≥full grade (aOR 5.1, 95% CI 3.2, 8.2) worsening of BMLs. Severe, but not moderate, malalignment predicted ipsi-compartmental within-grade (medial cartilage damage: aOR 5.5, 95% CI 2.6, 11.6; medial worsening of BMLs: aOR 4.9, 95% CI 2.0, 12.3) but not full grade worsening of BMLs and cartilage damage. Conclusions Within-grade changes in semiquantitative MRI assessment of cartilage and BMLs are valid and their use may increase the sensitivity of semiquantitative readings in detecting longitudinal changes in these structures.
Summary In osteoarthritis (OA) the synovium is often inflamed and inflammatory cytokines contribute to cartilage damage. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have anti-inflammatory effects ...whereas omega-6 polyunsaturated fatty acids (n-6 PUFAs) have, on balance, proinflammatory effects. The goal of our study was to assess the association of fasting plasma phospholipid n-6 and n-3 PUFAs with synovitis as measured by synovial thickening on contrast enhanced (CE) knee MRI and cartilage damage among subjects in the Multicenter Osteoarthritis Study (MOST). MOST is a cohort study of individuals who have or are at high risk of knee OA. An unselected subset of participants who volunteered obtained CE 1.5 T MRI of one knee. Synovitis was scored in six compartments and a summary score was created. This subset also had fasting plasma, analyzed by gas chromatography for phospholipid fatty acid content, and non-CE MRI, read for cartilage morphology according to the Whole-Organ Magnetic Resonance Imaging Score (WORMS) method. The association between synovitis and cartilage morphology and plasma PUFAs was assessed using logistic regression after controlling for the effects of age, sex, and BMI. 472 out of 535 subjects with CE MRI had complete data on synovitis, cartilage morphology and plasma phospholipids. Mean age was 60 years, mean BMI 30, and 50% were women. We found an inverse relation between total n-3 PUFAs and the specific n-3, docosahexaenoic acid with patellofemoral cartilage loss, but not tibiofemoral cartilage loss or synovitis. A positive association was observed between the n-6 PUFA, arachidonic acid, and synovitis. In conclusion, systemic levels of n-3 and n-6 PUFAs which are influenced by diet, may be related to selected structural findings in knees with or at risk of OA. Future studies manipulating the systemic levels of these fatty acids may be warranted to determine the effects on structural damage in knee OA.
Summary Objective Greater quadriceps strength has been found to reduce risk for symptomatic knee osteoarthritis (SxKOA) and knee joint space narrowing (JSN). However, this finding could relate to ...muscle mass or activation pattern. The purpose of this study was to assess whether greater thigh muscle mass protects against (1) incident radiographic (RKOA), (2) incident SxKOA or (3) worsening of knee JSN by 30-month follow-up. Design Multicenter Osteoarthritis (MOST) study participants, who underwent dual-energy X-ray absorptiometry (DXA) at the Iowa site were included. Thigh muscle mass was calculated from DXA image sub-regions. Sex-stratified, knee-based analyses controlled for incomplete independence between limbs within subjects. The effect of thigh lean mass and specific strength as predictors of ipsilateral RKOA, SxKOA and worsening of JSN were assessed, while controlling for age, body mass index (BMI), and history of knee surgery. Results A total of 519 men (948 knees) and 784 women (1453 knees) were included. Mean age and BMI were 62 years and 30 kg/m2 . Thigh muscle mass was not associated with risk for RKOA, SxKOA or knee JSN. However, in comparison with the lowest tertile, those in the highest and middle tertiles of knee extensor specific strength had a lower risk for SxKOA and JSN odds ratio (OR) 0.29–0.68. Conclusions Thigh muscle mass does not appear to confer protection against incident or worsening knee OA. These findings suggest that future studies of risk for knee OA should focus on the roles of knee extensor neuromuscular activation and muscle physiology, rather than the muscle mass.
The aim of this work was to report the prevalence of computed tomography (CT)-detected intra-articular mineralization.
We included participants from the Multicenter Osteoarthritis (MOST) Study. At ...the 12th year visit of the MOST study, bilateral knee CTs were first obtained. All participants also had posteroanterior and lateral radiographs of bilateral knees and completed standard questionnaires. Knee radiographs were assessed for Kellgren & Lawrence grade (KLG) and radiographic evidence of intra-articular mineralization. CT images were scored using the Boston University Calcium Knee Score (BUCKS) for cartilage, menisci, ligaments, capsule, and vasculature. Prevalence of intra-articular mineralization was computed for the total sample, and stratified by age, sex, race, Body Mass Index (BMI), presence of frequent knee pain, and KLG. We also determined distribution of mineralization in the cartilage and meniscus, and co-localization.
4140 bilateral knees from 2070 participants were included (56.7% female, mean age 61.1 years, mean BMI: 28.8 kg/m2). On radiographs 240 knees (5.8%) had intraarticular mineralization, while CT-detected mineralization was present in 9.8% of knees. Prevalence of hyaline articular and meniscus mineralization increased with age and KL grade, and was similar by sex, BMI categories, and comparable in subjects with and without frequent knee pain. Mineralization tended to be ubiquitous in the joint, most commonly involving all three (medial/lateral tibiofemoral and patellofemoral) compartments (3.1%), while the patellofemoral compartment was the most involved compartment in isolation (1.4%).
CT of the knee provides greater visualization of intra-articular mineralization than radiographs and allows better localization of the crystal deposition within the joint. Further studies should focus on the co-localization of intra-articular crystal deposition and corresponding magnetic resonance imaging (MRI)-features of knee osteoarthritis (OA).
Anterior knee pain (AKP) is associated with patellofemoral osteoarthritis (PFOA), but longitudinal studies are lacking. If AKP precedes PFOA, it may create an opportunity to identify and intervene ...earlier in the disease process. The purpose of this study was to examine the longitudinal relation of AKP to worsening patellofemoral (PF) cartilage over two years.
Participants were recruited from the Multicenter Osteoarthritis Study, a longitudinal study of individuals with or at risk for knee osteoarthritis (OA). Exclusion criteria included bilateral knee replacements, arthritis other than OA, and radiographic PFOA. At baseline, participants completed a knee pain map questionnaire and underwent knee magnetic resonance imaging (MRI). Imaging was repeated at 2-year follow-up. Exposure was presence of frequent AKP. Outcome was worsening cartilage damage in the PF joint defined as increase in MRI Osteoarthritis Knee Score from baseline to 2 years. Log-binomial models were used to calculate risk ratios (RR).
One knee from 1083 participants (age 56.7 ± 6.6 years; body mass index 28.0 ± 4.9 kg/m
) was included. Frequent AKP and frequent isolated AKP were present at baseline in 14.5% and 3.6%, respectively. Frequent AKP was associated with an increased risk (RR: 1.78, 95% confidence interval: 1.21, 2.62) of 2-year worsening cartilage damage in the lateral PF compartment. No association was found between frequent AKP and worsening in the medial PF joint.
Frequent AKP at baseline was associated with worsening cartilage damage in the lateral PF joint over 2 years.
Summary Objective To determine the effect of physical activity on knee osteoarthritis (OA) development in persons without knee injury and according to knee alignment. Design We combined data from ...Multicenter Osteoarthritis (MOST) and Osteoarthritis Initiative (OAI), studies of persons with or at high risk of OA. Subjects had long limb and repeated posteroanterior knee radiographs and completed the physical activity survey for the elderly (PASE). We studied persons without radiographic OA and excluded knees with major injury and without long limb films. We followed subjects 30 months (in MOST) and 48 months (in OAI) for one of two incident outcomes: (1) symptomatic tibiofemoral OA (radiographic OA and knee pain), or (2) tibiofemoral narrowing. ‘Active’ persons were those with PASE score in the highest quartile by gender. We examined risk of OA in active group using logistic regression adjusting for age, gender, body mass index (BMI), Western Ontario and McMaster Arthritis Index (WOMAC) pain score, Kellgren and Lawrence (KL) grade (0 or 1), and study of origin. We also analyzed knees from malaligned and neutrally aligned limbs. Results The combined sample comprised 2,073 subjects (3,542 knees) with mean age 61 years. The cumulative incidence of symptomatic tibiofemoral OA was 1.12% in the active group vs 1.82% in the others (odds ratio (OR) among active group 0.6, 95% confidence interval (CI) 0.3, 1.3). Joint space narrowing occurred in 3.41% of knees in the active group vs 4.04% in the others (OR among active group 0.9 (95% CI 0.5, 1.5)). Results did not differ by alignment status. Conclusions Physical activity in the highest quartile did not affect the risk of developing OA.
Inflammation worsens joint destruction in osteoarthritis (OA) and aggravates pain. Saturated and n-6 fatty acids (FAs) increase, whereas n-3 FAs reduce inflammation. We examined whether FA levels ...affected the development of OA.
We studied participants from the Multicenter Osteoarthritis study (MOST) at risk of developing knee OA. After baseline, repeated knee x-rays and MRIs were obtained and knee symptoms queried through 60 month follow-up. Using baseline fasting samples, serum FAs were analyzed with standard assays. After excluding participants with baseline OA, we defined two sets of cases: those developing radiographic OA and those developing symptomatic OA (knee pain and radiographic OA). Controls did not develop these outcomes. Additionally, we examined worsening of MRI cartilage loss and synovitis and of knee pain using WOMAC and evaluated the number of hand joints affected by nodules. In regression models, we tested the association of each OA outcome with levels of saturated, n-3 and n-6 FAs adjusting for age, sex, BMI, education, race, baseline pain and depressive symptoms.
We studied 260 cases with incident symptomatic and 259 with incident radiographic OA. Mean age was 61 years (61% women). We found no signficant nor suggestive associations of FA levels with incident OA (e.g., for incident symptomatic OA, OR per s.d. increase in n-3 FA 1.00 (0.85, 1.18) nor with any OA outcome in knee or hand.
Despite previously described effects on systemic inflammation, blood levels of FAs were not associated with risk of later knee OA or other OA outcomes.
Higher intake of fiber has been associated with lower risk of incident symptomatic osteoarthritis (OA). We examined whether levels of alkylresorcinol (AR), a marker of whole grain intake, were ...associated with OA in subjects in The Multicenter Osteoarthritis (MOST) Study.
Knee x-rays and knee pain were assessed at baseline and through 60-months. Stored baseline fasting plasma samples were analyzed for AR homologues (C17:0, C19:0, C21:0, C23:0, C25:0) and total AR levels (AR sum). Two nested case–control studies, one for incident radiographic OA and one for incident symptomatic OA were performed with participants re-assessed at 15, 30 and 60 months. Multivariable conditional logistic regression with baseline covariates including age, sex, BMI, physical activity, quadriceps strength, race, smoking, depressive symptoms, diabetes and knee injury tested the association of log transformed AR levels with OA outcomes.
Seven hundred seventy-seven subjects were, on average, in their 60's, and most were women. For 60-month cumulative incidence, there was no significant association between quartiles of AR concentration and incident radiographic (e.g., for incident radiographic OA, highest vs lowest quartile of AR sum showed RR = 0.93 (95% CI 0.59, 1.47), and for symptomatic OA RR was 1.22 (95% CI 0.76, 1.94). In secondary analyses examining 30-month incidence, high AR levels were associated with a reduced risk of X-ray OA (RR = 0.31 (95% CI 0.15, 0.64).
In primary analyses, AR levels were not associated with risk of OA, but secondary analyses left open the possibility that high AR levels may protect against OA.
To describe the natural history of subchondral bone marrow lesions (BMLs) in a sample of subjects with knee osteoarthritis (OA) or at risk of developing it. Additionally, to examine the association ...of change in BMLs from baseline to 30-month follow-up with the risk of cartilage loss in the same subregion at follow-up.
1.0 T MRI was performed using proton density-weighted, fat-suppressed sequences. BML size and cartilage status were scored in the same subregions according to the WORMS system. Subregions were categorised based on comparison of baseline and follow-up BML status. A logistic regression model was used to assess the association of change in BML status with cartilage loss over 30 months using stable BMLs as the reference group.
395 knees were included. 66% of prevalent BMLs changed in size; 50% showed either regression or resolution at follow-up. The adjusted odds ratios (95% confidence intervals) of cartilage loss in the same subregion at follow-up for the different groups were 1.2 (0.5 to 1.6) for regressing BMLs, 0.9 (0.5 to 1.6) for resolving BMLs, 2.8 (1.5 to 5.2) for progressing BMLs, 0.2 (0.1 to 0.3) for subregions with no BMLs at baseline and follow-up and 3.5 (2.1 to 5.9) for newly developing BMLs. BML size at baseline was associated with risk of subsequent cartilage loss.
The majority of pre-existing BMLs decreased in size at follow-up. Absence of BMLs was associated with a decreased risk of cartilage loss, while progressing and new BMLs showed a high risk of cartilage loss in the same subregion.
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