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

OBJECTIVE: The study objective was to determine the relationship of magnetic resonance imaging (MRI)-detected features of patellofemoral joint osteoarthritis to pain and functional outcomes.METHODS: We 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.RESULTS: Participants 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).CONCLUSION: MRI-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.

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

Objective To assess whether medial tibiofemoral joint space width (JSW) on 3-dimensional (3-D) standing computed tomography (SCT) correlates more closely with magnetic resonance imaging cartilage morphology (CM) and meniscal scores than does radiographic 2-D JSW. Methods Participants in the Multicenter Osteoarthritis Study, who had standing fixed-flexion posteroanterior knee radiographs, were recruited. Medial tibiofemoral 3-D JSW on SCT and 2-D JSW on fixed-flexion radiographs were compared with medial tibiofemoral cartilage and meniscal morphology using the Whole-Organ Magnetic Resonance Imaging Score (WORMS). Associations between the area of the articular surface with 3-D JSW

This is the accepted version of the following article: Oiestad, B. E., White, D. K., Booton, R., Niu, J., Zhang, Y., Torner, J., ... & Felson, D. T. (2015). The longitudinal course of physical function in people with symptomatic knee osteoarthritis: Data from the MOST study and the OAI. Arthritis care & research., which has been published in final form at http://dx.doi.org/10.1002/acr.22674

Methods177 adults and 86 minors comprising 95 family units were enrolled from two counties in Iowa and followed up for 52 weeks. Random effects logistic regression was used to test the effect of different risk factors on the probability of an individual falling into a differentS. aureuscolonization categories. Additionally, the frequency ofS. aureuscolonization events and familial transmission events were calculated.ResultsThe number of positive environmental sites within a participant’s house was associated with being a persistent carrier compared to being a non-carrier or intermittent carrier. Age, sharing bath towels, and the number of positive environmental sites within a participant’s house were associated with being a persistent or intermittent carrier. Colonization events per year were 3.95 for adults and 3.04 for minors. Duration of colonization was longest for persistent carriers (92.3 days for adults and 97.8 days for minors), and intermittent carriers had the most colonization events.ConclusionsThe average duration of colonization was significantly different when comparing intermittent carriers and non-carriers. We have also established estimates of the duration of colonization and the frequency of transmission events among family units in a non-healthcare population.

Summary 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.

SummaryPurposeTo 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 1.0T 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

s / Osteoarthritis and Cartilage 20 (2012) S54–S296 S154 2005 and April 2009 and were diagnosed by the rheumatologist with primary hand, knee or hip OA. All subjects were followed until 2 November 2011.Mortality was compared between included patients with OA and the general population in the Netherlands, matched for both age and gender. For GARP, the expected numbers of deaths came from age and gender specific mortality data provided in the mortality statistics from 2006 in 5-year age bands and for ‘Zorgpad artrose’ the data came from 2009. Standardized Mortality Ratios (SMR) with 95% confidence intervals (95% CI) were calculated using STATA (version 10.1). Results: The GARP study consisted of 384 participants (82% women) and the mean age at inclusion was 60.1 (range 42-79). The duration of followup was 9.0 (SD 1.2). No excess mortality was observed in OA patients when compared to the general population. 26 patients died, while the expected number of deaths was 48 (SMR 0.54, 95% CI 0.37 0.79). The SMR was 0.47 (0.29 0.76) in women and 0.73 (0.39 1.35) in men. Healthy cohort effect was also tested and not likely present. In our replication cohort we found similar results (11 patients died, SMR 0.45, 95% CI 0.25 0.82). The SMR was also lower in women (0.40, 0.20 0.81) than in men (0.66, 0.21 2.06) Conclusions: In patients consulting health care, OA does not lead to a higher mortality rate in women and a similar trend can be observed in men. These results do not support the hypothesis that metabolic syndrome is an important cause of OA and would influence the mortality of patients consulting primary or secondary health care for their complaints. Whether this is due to selection of patients or reflects a true absence of metabolic syndrome in OA has to be further investigated. 305 THE ASSOCIATION OF STATIN USE AND INCIDENT RADIOGRAPHIC KNEE OSTEOARTHRITIS R.K. Chaganti , I. Tolstykh , N.E. Lane , C.E. McCullough , M.K. Javaid , J.B. Driban , B. Wise , J. Torner , C.E. Lewis , D.T. Felson , M.C. Nevitt . Univ. of California, San Francisco, San Francisco, CA, USA; Univ. of California, Davis, Sacramento, CA, USA; Oxford Univ., Oxford, United Kingdom; 4 Tufts Univ. Med. Ctr., Boston, MA, USA; Univ. of Iowa, Iowa City, IA, USA; Univ. of Alabama, Birmingham, AL, USA; Boston Univ., Boston, MA, USA Purpose: Statin medications are widely used and have been shown to reduce inflammation in cardiovascular disease; animal data suggests a protective role for statins in inflammation associated with cartilage and bone. Based on these findings, we wanted to evaluate the association of statin use with the risk of incident knee radiographic osteoarthritis (ROA). Methods: Subjects were enrolled in MOST, an NIH-funded cohort study of 3026 men and women ages 50-79 years with, or at high risk of knee OA. Subjects had baseline and 30 month follow-up PA and lateral knee x-rays. Tibiofemoral (TF) ROA was defined as the presence of Kellgren/Lawrence (K/L) grade 2. Whole knee (WK) ROA was defined as the presence of either TFROA or patellofemoral (PF) OA, defined as either (1) PF osteophyte grade 2, or 2) as a PF osteophyte grade 1 plus one or more of PF joint space narrowing, sclerosis or cysts . Incident cases were knees without TFROA (or WKROA) at baseline that developed it at 30 months. Statin use Association of Statin Use and Incident TFROA

Objectives: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.Methods: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.Results: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.Conclusions: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.

Summary Objective As cartilage loss and bone marrow lesions (BMLs) are associated with knee joint pain and structural worsening, this study assessed whether non-invasive estimates of articular contact stress may longitudinally predict risk for worsening of knee cartilage morphology and BMLs. Design This was a longitudinal cohort study of adults aged 50–79 years with risk factors for knee osteoarthritis. Baseline and follow-up measures included whole-organ magnetic resonance imaging score (WORMS) classification of knee cartilage morphology and BMLs. Tibiofemoral geometry was manually segmented on baseline magnetic resonance imaging (MRI), and three-dimensional (3D) tibiofemoral point clouds were registered into subject-specific loaded apposition using fixed-flexion knee radiographs. Discrete element analysis (DEA) was used to estimate mean and peak contact stresses for the medial and lateral compartments. The association of baseline contact stress with worsening cartilage and BMLs in the same subregion over 30 months was assessed using conditional logistic regression. Results Subjects ( N = 38, 60.5% female) had a mean ± standard deviation (SD) age and body mass index (BMI) of 63.5 ± 8.4 years and 30.5 ± 3.7 kg/m 2 respectively. Elevated mean articular contact stress at baseline was associated with worsening cartilage morphology and worsening BMLs by 30 months, with odds ratio (OR) [95% confidence interval (CI)] of 4.0 (2.5, 6.4) and 6.6 (2.7, 16.5) respectively. Peak contact stress also was significantly associated with worsening cartilage morphology and BMLs {1.9 (1.5, 2.3) and 2.3 (1.5, 3.6)}(all P Conclusions Detection of higher contact stress 30 months prior to structural worsening suggests an etiological role for mechanical loading. Estimation of articular contact stress with DEA is an efficient and accurate means of predicting subregion-specific knee joint worsening and may be useful in guiding prognosis and treatment.

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

Objective To examine whether obesity increases the risk of progression of knee osteoarthritis (OA). Methods We used data from the Multicenter Osteoarthritis Study, a longitudinal study of persons with or at high risk of knee OA. OA was characterized at baseline and 30 months using posteroanterior fixed-flexion radiographs and Kellgren/Lawrence (K/L) grading, with alignment assessed on full-extremity films. In knees with OA at baseline (K/L grade 2 or 3), progression was defined as tibiofemoral joint space narrowing on the 30-month radiograph. In knees without OA at baseline (K/L grade 0 or 1), incident OA was defined as the development of radiographic OA at 30 months. Body mass index (BMI) at baseline was classified as normal (

Summary Objective Radiographic disease and knee pain are thought to decrease physical activity in people with knee osteoarthritis (OA), but this has not been formally studied. We examined change in objectively measured daily walking over 2 years and evaluated the association of certain risk factors with reduced walking among adults with or at risk of knee OA. Design Steps/day over 7 days were collected at baseline and 2 years later in subjects with or at risk of knee OA from the Multicenter Osteoarthritis Study using a StepWatch. We evaluated the presence of radiographic knee osteoarthritis (ROA), knee pain, worsening of ROA and pain over 2 years, obesity, depressive symptoms, living situation, catastrophizing, fatigue, widespread pain and comorbidities with 2-year change in daily walking using regression models adjusted for potential confounders. Results 1318 met inclusion criteria (age 66.9 ± 7.7, 59% women, BMI 30.6 ± 5.9) and walked 126 ± 1700 steps/day fewer steps at 2 years (95% CI [−218, −35]). People with depressive symptoms at baseline walked 455 fewer steps/day [−872, −68], and there was a trend for people with ROA worsening to walk 183 fewer steps/day [−377.5, 11.7]. No other factors met statistical significance for change in daily walking. Conclusion Adults with or at risk of knee OA experienced only minimal declines in daily walking over 2 years. Nonetheless, depressive symptoms and may be worsening ROA are associated with a decline in steps/day in adults with or at risk of knee OA.

Background: Previous studies suggest that the antioxidants vitamins C and E may protect against development of knee osteoarthritis (OA). We examined the association of circulating levels of vitamin C and E with incident whole knee radiographic OA (WKROA). Methods: We performed a nested case-control study of incident WKROA in MOST, a cohort of 3,026 men and women aged 50-79 years with, or at high risk of, knee OA. Incident cases were knees without either tibiofemoral (TF) or patellofemoral (PF) OA at baseline that developed TF and/or PF OA by 30-month follow-up. Two control knees per case were selected from those eligible for WKROA that did not develop it. Vitamin C and E (alpha-tocopherol) assays were done on baseline supernatant plasma (PCA) and serum samples, respectively. We examined the association of gender-specific tertiles of vitamin C and E with incident WKROA using logistic regression with GEE, adjusting for age, gender, and obesity. Results: Subjects without WKROA at baseline who were in the highest tertile of vitamin C had a higher incidence of WKROA [adjusted OR=2.20 (95% CI: 1.12-4.33); P-value=0.021], with similar results for the highest tertile of vitamin E [adjusted OR=1.89 (1.02-3.50); P-value=0.042], compared to those in the lowest tertiles. P-values for the trend of vitamin C and E tertiles and incident WKROA were 0.019 and 0.030, respectively. Conclusions: Higher levels of circulating vitamin C and E did not provide protection against incident radiographic knee OA, and may be associated with an increased risk of knee OA. © 2013 Osteoarthritis Research Society International.