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Objective: Intra‐articular (IA) calcium crystal deposition is common in knee osteoarthritis (OA), but of unclear significance. It is possible that low‐grade, crystal‐related inflammation may contribute to knee pain. We examined the longitudinal relation of computed tomography (CT)–detected IA mineralization to the development of knee pain. Methods: We used data from the National Institutes of Health–funded longitudinal Multicenter Osteoarthritis Study. Participants had knee radiographs and bilateral knee CTs at baseline, and pain assessments every 8 months for 2 years. CT images were scored using the Boston University Calcium Knee Score. We longitudinally examined the relation of CT‐detected IA mineralization to the risk of frequent knee pain (FKP), intermittent or constant knee pain worsening, and pain severity worsening using generalized linear mixed‐effects models. Results: We included 2,093 participants (mean age 61 years, 57% women, mean body mass index 28.8 kg/m2). Overall, 10.2% of knees had IA mineralization. The presence of any IA mineralization in the cartilage was associated with 2.0 times higher odds of having FKP (95% confidence interval [CI] 1.38–2.78) and 1.86 times more frequent intermittent or constant pain (95% CI 1.20–2.78), with similar results seen for the presence of any IA mineralization in the meniscus or joint capsule. A higher burden of IA mineralization anywhere within the knee was associated with a higher odds of all pain outcomes (odds ratio ranged from 2.14 to 2.21). Conclusion: CT‐detected IA mineralization was associated with risk of having more frequent, persistent, and worsening knee pain over 2 years. Targeting IA mineralization may have therapeutic potential for pain improvement in knee OA. [ABSTRACT FROM AUTHOR]

Objective: To determine whether intraarticular glucocorticoid (GC) injections are associated with increased knee osteoarthritis (OA) progression compared to hyaluronic acid (HA) injections, which have been reported to delay OA progression and knee replacement. Methods: We identified participants from 2 large cohort studies, the Osteoarthritis Initiative (OAI) and the Multicenter Osteoarthritis Study. Study visits were performed at regular intervals and included questionnaires about intraarticular GC or HA injection use in the previous 6 months and incident total knee replacement (TKR). Knee radiographs were obtained at each study visit and interpreted in a similar manner. Outcome measures were radiographic progression based on Kellgren/Lawrence (K/L) grade and joint space narrowing (JSN) for both cohorts and based on medial joint space width for OAI participants, and incident TKR. We compared preinjection and postinjection radiographs to generate rate ratios of progression comparing GC injection with HA injection. A Cox proportional hazards model was used to estimate the rate of TKR for both groups. Results: We studied 791 participants (980 knees) with knee OA, of whom 629 reported GC injection use and 162 HA injection use. Rate ratios of progression were similar between those receiving GCs and those receiving HA for JSN (1.00 [95% confidence interval (95% CI) 0.83–1.21]), K/L grade (1.03 [95% CI 0.83–1.29]), and medial joint space width (1.03 [95% CI 0.72–1.48]). Hazard of TKR was slightly lower for those receiving intraarticular GC compared to those receiving HA (hazard ratio 0.75 [95% CI 0.51–1.09]). Conclusion: Intraarticular GC injections are not associated with an increased risk of knee OA progression compared to HA. [ABSTRACT FROM AUTHOR]

Objective: To examine whether knee subchondral cysts, measured on magnetic resonance imaging (MRI), are associated with incident knee osteoarthritis (OA) outcomes. Methods: We used longitudinal data from the Multicenter Osteoarthritis Study, a community‐based cohort of subjects with risk factors for knee OA. Participants without a history of knee surgery and/or inflammatory arthritis (i.e., rheumatoid arthritis and gout) were followed up for 84 months for the following incident outcomes: 1) radiographic knee OA (Kellgren/Lawrence grade ≥2), 2) symptomatic radiographic knee OA (radiographic knee OA and frequent knee pain), and 3) frequent knee pain (with or without radiographic knee OA). In a subset of participants, subchondral cysts were scored on baseline MRIs of 1 knee. Multiple logistic regression, with adjustment for participant characteristics and other baseline knee MRI findings, was used to assess whether subchondral cysts were predictive of incident outcomes. Results: Among the participants with knees eligible for analyses of outcomes over 84 months, incident radiographic knee OA occurred in 22.8% of knees with no baseline radiographic knee OA, symptomatic radiographic knee OA occurred in 17.0% of knees with no baseline symptomatic radiographic knee OA, and frequent knee pain (with or without radiographic knee OA) occurred in 28.8% of knees with no baseline radiographic knee OA and 43.7% of knees with baseline radiographic knee OA. With adjustment for age, sex, and body mass index, the presence of subchondral cysts was not associated with incident radiographic knee OA but was associated with increased odds of incident symptomatic radiographic knee OA (odds ratio 1.92 [95% confidence interval 1.16–3.19]) and increased odds of incident frequent knee pain in those who had radiographic knee OA at baseline (odds ratio 2.11 [95% confidence interval 0.87–5.12]). Stronger and significant associations were observed for outcomes based on consistent reports of frequent knee pain within ~1 month of the study visit. Conclusion: Subchondral cysts are likely to be a secondary phenomenon, rather than a primary trigger, of radiographic knee OA, and may predict symptoms in knees with existing disease. [ABSTRACT FROM AUTHOR]

Objective: To develop a bone shape measure that reflects the extent of cartilage loss and bone flattening in knee osteoarthritis (OA) and test it against estimates of disease severity. Methods: A fast region‐based convolutional neural network was trained to crop the knee joints in sagittal dual‐echo steady‐state magnetic resonance imaging sequences obtained from the Osteoarthritis Initiative (OAI). Publicly available annotations of the cartilage and menisci were used as references to annotate the tibia and the femur in 61 knees. Another deep neural network (U‐Net) was developed to learn these annotations. Model predictions were compared to radiologist‐driven annotations on an independent test set (27 knees). The U‐Net was applied to automatically extract the knee joint structures on the larger OAI data set (n = 9,434 knees). We defined subchondral bone length (SBL), a novel shape measure characterizing the extent of overlying cartilage and bone flattening, and examined its relationship with radiographic joint space narrowing (JSN), concurrent pain and disability (according to the Western Ontario and McMaster Universities Osteoarthritis Index), as well as subsequent partial or total knee replacement. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for each outcome were estimated using relative changes in SBL from the OAI data set stratified into quartiles. Results: The mean SBL values for knees with JSN were consistently different from knees without JSN. Greater changes of SBL from baseline were associated with greater pain and disability. For knees with medial or lateral JSN, the ORs for future knee replacement between the lowest and highest quartiles corresponding to SBL changes were 5.68 (95% CI 3.90–8.27) and 7.19 (95% CI 3.71–13.95), respectively. Conclusion: SBL quantified OA status based on JSN severity and shows promise as an imaging marker in predicting clinical and structural OA outcomes. [ABSTRACT FROM AUTHOR]

Purpose To identify baseline characteristics of adults with chronic low back pain (cLBP) that predict response (i.e. a clinically important improvement) and/or modify treatment effect across three nonpharmacologic interventions. Design Secondary analysis of a randomized controlled trial. Setting Academic safety net hospital and seven federally qualified community health centers. Subjects Adults with cLBP (N = 299). Methods We report patient characteristics that were predictors of response and/or modified treatment effect across three 12-week treatments: yoga, physical therapy [PT], and a self-care book. Using preselected characteristics, we used logistic regression to identify predictors of "response," defined as a ≥30% improvement in the Roland Morris Disability Questionnaire. Then, using "response" as our outcome, we identified baseline characteristics that were treatment effect modifiers by testing for statistical interaction (P  < 0.05) across two comparisons: 1) yoga-or-PT vs self-care and 2) yoga vs PT. Results Overall, 39% (116/299) of participants were responders, with more responders in the yoga-or-PT group (42%) than the self-care (23%) group. There was no difference in proportion responding to yoga (48%) vs PT (37%, odds ratio [OR] = 1.5, 95% confidence interval = 0.88 − 2.6). Predictors of response included having more than a high school education, a higher income, employment, few depressive symptoms, lower perceived stress, few work-related fear avoidance beliefs, high pain self-efficacy, and being a nonsmoker. Effect modifiers included use of pain medication and fear avoidance beliefs related to physical activity (both P  = 0.02 for interaction). When comparing yoga or PT with self-care, a greater proportion were responders among those using pain meds (OR = 5.3), which differed from those not taking pain meds (OR = 0.94) at baseline. We also found greater treatment response among those with lower (OR = 7.0), but not high (OR = 1.3), fear avoidance beliefs around physical activity. Conclusions Our findings revealed important subgroups for whom referral to yoga or PT may improve cLBP outcomes. [ABSTRACT FROM AUTHOR]

Objective: Massive weight loss leads to marked knee pain reduction in individuals with knee pain, but the reason for the reduction in pain is unknown. This study was undertaken to quantify the contribution of magnetic resonance imaging (MRI)–evidenced changes in pain‐sensitive structures, bone marrow lesions (BMLs), and synovitis, and changes in pain sensitization or depressive symptoms, to knee pain improvement after substantial weight loss. Methods: Morbidly obese patients with knee pain on most days were evaluated before bariatric surgery or medical weight management and at 1‐year follow‐up for BMLs and synovitis seen on MRI, the pressure pain threshold (PPT) at the patella and the right wrist, depressive symptoms (using the Center for Epidemiologic Studies Depression scale [CES‐D]), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain survey. Natural‐effects models were used to quantify the extent that achieving a minimum clinically important difference (MCID) of ≥18% on the WOMAC pain scale could be mediated by weight loss–induced changes in BMLs, synovitis, PPT, and depressive symptoms. Results: Of 75 participants, 53.3% lost ≥20% of weight by 1 year. Of these, 75% attained the MCID for pain improvement, compared with 34.3% in those who had <20% weight loss. Mediation analyses suggested that, in those with at least 20% weight loss, the odds of pain improvement increased by 62%, 15%, and 22% through changes in patella PPT, wrist PPT, and CES‐D, respectively, but pain improvement was not mediated by MRI changes in BMLs or synovitis. Conclusion: Weight loss–induced knee pain improvement is partially mediated by changes in pain sensitization and depressive symptoms but is independent of MRI changes in BMLs and synovitis. [ABSTRACT FROM AUTHOR]

Objective To examine trends in rheumatoid arthritis (RA) as an underlying cause of death (UCD) in 31 countries across the world from 1987 to 2011. Methods Data on mortality and population were collected from the World Health Organization mortality database and from the United Nations Population Prospects database. Age-standardized mortality rates (ASMRs) were calculated by means of direct standardization. We applied joinpoint regression analysis to identify trends. Between-country disparities were examined using between-country variance and the Gini coefficient. Due to low numbers of deaths, we smoothed the ASMRs using a 3-year moving average. Changes in the number of RA deaths between 1987 and 2011 were decomposed using 2 counterfactual scenarios. Results The absolute number of deaths with RA registered as the UCD decreased from 9,281 (0.12% of all-cause deaths) in 1987 to 8,428 (0.09% of all-cause deaths) in 2011. The mean ASMR decreased from 7.1 million person-years in 1987-1989 to 3.7 million person-years in 2009-2011 (48.2% reduction). A reduction of ≥25% in the ASMR occurred in 21 countries, while a corresponding increase was observed in 3 countries. There was a persistent reduction in RA mortality, and on average, the ASMR declined by 3.0% per year. The absolute and relative between-country disparities decreased during the study period. Conclusion The rates of mortality attributable to RA have declined globally. However, we observed substantial between-country disparities in RA mortality, although these disparities decreased over time. Population aging combined with a decline in RA mortality may lead to an increase in the economic burden of disease that should be taken into consideration in policy-making. [ABSTRACT FROM AUTHOR]

Objective Previous studies have suggested that metabolic syndrome is associated with osteoarthritis (OA). However, analyses have often not included adjustment for body mass index (BMI) and have not addressed whether levels of individual metabolic syndrome components are related to OA. This study was undertaken to examine the relationship of metabolic syndrome and its components with radiographic and symptomatic knee OA. Methods Framingham Study subjects were assessed for OA in 1992-1995 and again in 2002-2005. Near the baseline visit, subjects had components of metabolic syndrome assessed. We defined incident radiographic OA as present when a knee without radiographic OA at baseline had a Kellgren/Lawrence grade of ≥2 at follow-up, and defined incident symptomatic OA as present when a knee developed the new combination of radiographic OA and knee pain. After excluding knees with prevalent OA at baseline, we tested the relationship of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria and its components with the risk of incident radiographic OA and symptomatic OA before and after adjusting for BMI using the risk ratio from a binary regression with generalized estimating equations. Results A total of 991 subjects (55.1% women) with a mean age of 54.2 years were studied, and 26.7% of men and 22.9% of women had metabolic syndrome. Metabolic syndrome and many of its components were associated with both incident radiographic OA and symptomatic OA, but after adjustment for BMI, almost all of these associations became weak and nonsignificant. An association of high blood pressure, especially diastolic pressure, with OA outcomes persisted in both men and women. Conclusion After adjustment for BMI, neither metabolic syndrome nor its components were associated with incident OA. There may be an association between OA and high blood pressure that needs further study. [ABSTRACT FROM AUTHOR]

Objective To determine the risk of incident cartilage damage at follow-up in subregions that are undamaged at baseline, by comparing tibiofemoral joint compartments with a baseline focal partial-thickness or full-thickness cartilage defect against compartments without any baseline cartilage damage, in knees with and those without radiographic osteoarthritis (OA). Methods We included participants in the Multicenter Osteoarthritis Study for whom there were semiquantitative magnetic resonance imaging readings at baseline and at 30 months. We estimated the risk of incident cartilage defects developing in tibiofemoral compartments with prevalent partial-thickness and full-thickness cartilage defects in only one subregion within the compartment, using tibiofemoral compartments with no baseline cartilage defects as a referent. Logistic regression with generalized estimating equations was used for all analyses, with adjustments for confounders. Results A total of 374 compartments (359 knees) were included, and 140 knees (39%) had radiographic OA. Compared to compartments with no baseline cartilage defects, those with partial-thickness (adjusted odds ratio 1.62 [95% confidence interval 1.06-2.47]) and full-thickness (adjusted odds ratio 1.92 [95% confidence interval 1.00-3.66]) cartilage defects in a subregion had a higher risk of incident cartilage defects in other subregions in the same compartment. Conclusion Prevalent focal cartilage defects, regardless of defect depth, in a single subregion within a tibiofemoral joint compartment increase the risk of developing new cartilage damage in other subregions of the same compartment for middle-aged to elderly persons with or at high risk of knee OA. [ABSTRACT FROM AUTHOR]

Objective Many persons with knee pain have joint pain outside the knee, but despite the impact and high frequency of this pain, its distribution and causes have not been studied. We undertook this study to test the hypothesis of those studying gait abnormalities who have suggested that knee pain causes pain in adjacent joints but that pain adaptation strategies are highly individualized. Methods We studied persons ages 50-79 years with or at high risk of knee osteoarthritis who were recruited from 2 community-based cohorts, the Multicenter Osteoarthritis Study and the Osteoarthritis Initiative, and we followed them up for 5-7 years. We excluded those with knee pain at baseline and compared those who had developed knee pain at the first follow-up examination (the index visit) with those who had not. We examined pain on most days at joint regions outside the knee in examinations after the index visit. Logistic regression analyses examined the risk of joint-specific pain adjusted for age, sex, body mass index, and symptoms of depression, and we performed sensitivity analyses excluding those with widespread pain. Results In the combined cohorts, 693 persons had knee pain at the index visit and 2,793 did not. A total of 79.6% of those with bilateral knee pain and 63.8% of those with unilateral knee pain had pain during follow-up in a joint region outside the knee, compared with 49.9% of those without knee pain. There was an increased risk of pain at most extremity joint sites, without a predilection for specific sites. Results were unchanged when those with widespread pain were excluded. Conclusion Persons with chronic knee pain are at increased risk of pain in multiple joints in no specific pattern. [ABSTRACT FROM AUTHOR]

Objective A major barrier to genetic studies of osteoarthritis (OA) is the need to obtain large numbers of individuals with standardized radiographic evaluations for OA. To address this gap, we performed a genome-wide association study (GWAS) of radiographically defined tibiofemoral knee OA in 3,898 cases and 3,168 controls from 4 well-characterized North American cohorts, and we performed replication analysis of previously reported OA loci. Methods We performed meta-analysis using a 2-stage design. Stage 1 (discovery) consisted of a GWAS meta-analysis of radiographic knee OA carried out in the Osteoarthritis Initiative and the Johnston County Osteoarthritis Project. Knee OA was defined as definite osteophytes and possible joint space narrowing or total joint replacement in one or both knees. Stage 2 (validation) was performed in the Multicenter Osteoarthritis Study and the Genetics of Osteoarthritis study. We genotyped lead meta-analysis variants ( P ≤ 1 × 10−4) from stage 1 and tested the association between these variants and knee OA. We then combined results from all cohorts in a meta-analysis. Results Lead variants from stage 1, representing 49 unique loci, were analyzed in stage 2; none met genome-wide significance in the combined analysis of stage 1 and stage 2. We validated 1 locus (rs4867568 near LSP1P3) with nominal significance ( P < 0.05), which was also our top finding in the combined meta-analysis (odds ratio [OR] 0.84 [95% confidence interval (95% CI) 0.79-0.91], P = 3.02 × 10−6). We observed nominally significant associations ( P < 0.05) with 3 previously reported OA loci: rs143383 in GDF5 (OR 1.12 [95% CI 1.04-1.21], P = 2.13 × 10−3), rs835487 in CHST11 (OR 0.93 [95% CI 0.85-0.99], P = 0.03), and rs8044769 in FTO (OR 1.10 [95% CI 1.03-1.19], P = 6.13 × 10−3). Conclusion These findings provide suggestive evidence of a novel knee OA locus and confirm previously reported associations in GDF5, CHST11, and FTO. [ABSTRACT FROM AUTHOR]

Objective To examine neuromuscular factors that predict the incidence and progression of knee instability symptoms in older adults with or at high risk of knee osteoarthritis (OA). Methods At the 60-month clinic visit, participants in the Multicenter Osteoarthritis Study underwent evaluation of quantitative vibratory sense at the knee and isokinetic quadriceps muscle strength. At this 60-month visit, participants were also asked about knee buckling and sensations of knee shifting or slipping without buckling in the past 3 months and then were asked the same questions at the 72- and 84-month follow-up visits. We performed a person-based analysis using Poisson regression analysis with robust error variance to estimate adjusted relative risks (RRs) for the association of vibratory sense and muscle strength with the incidence and worsening of knee slipping/shifting, buckling, and overall knee instability symptoms (either buckling or knee shifting/slipping), with adjustment for relevant confounders. Results A total of 1,803 participants (61% women) were included. Approximately one-third of the participants reported incident or worsening of instability symptoms over the study period. After adjustment for relevant confounders, better vibratory acuity (adjusted RR 0.78, 95% confidence interval [95% CI] 0.56-1.09), P = 0.020 for trend) and greater quadriceps strength (adjusted RR 0.53, 95% CI 0.38-0.75, P < 0.001) protected against incident knee instability symptoms. Greater quadriceps strength (adjusted RR 0.73, 95% CI 0.58-0.92, P = 0.008) also protected against worsening of knee instability symptoms. Conclusion Vibratory acuity and quadriceps muscle strength are important predictors of the incidence and worsening of knee instability over 2 years. These neuromuscular factors are potentially modifiable and should be considered in interventional studies of instability in persons with or at risk of knee OA. [ABSTRACT FROM AUTHOR]

Objective Osteoarthritis (OA) is a disease with a significant inflammatory component. The aim of this analysis was to determine the relationship between synovial fluid (SF) white blood cell (WBC) count and 2 parameters: disease severity and the reduction in knee pain after intraarticular (IA) steroid injection. Methods Subjects with painful knee OA were recruited for participation in an open-label study of IA steroid therapy. Information was obtained about knee pain using the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire, and a proportion of subjects underwent magnetic resonance imaging (MRI). Prior to injection with 80 mg methylprednisolone acetate, the index knee joint was aspirated and the fluid obtained was forwarded for assessment of SF WBC count. Results Information on SF WBC count was available for 55 subjects. An increase in WBC count category (≤100, 101-250, and 251-1,000 cells/mm3) was associated with an increase in synovial tissue volume ( P = 0.028) and with other MRI-based measures of disease severity. Also, with each increase in SF WBC count category, there was a greater reduction in KOOS score after steroid injection (for WBC count of ≤100 cells/mm3 [referent], mean ± SD 12.5 ± 15.2; for WBC count of 101-250 cells/mm3, mean ± SD 21.3 ± 20.6 [β coefficient 0.279, P = 0.049]; for WBC count of 251-1,000 cells/mm3, mean ± SD 29.3 ± 15.2 [β coefficient 0.320, P = 0.024]). Conclusion Although all participants in the analysis had SF WBC counts within the 'normal' range, total SF WBC count appears to be a biomarker for synovitis on MRI and may also predict response to antiinflammatory treatment. [ABSTRACT FROM AUTHOR]

Objective. We aimed to examine whether the current users of specific NSAIDs have an increased risk of venous thromboembolism (VTE) among knee OA patients. Methods. We conducted a population-based case-control study using The Health Improvement Network, a database of patient records from general practices in the UK. For every VTE case, we identified five controls matched on age, sex and calendar year of study enrolment. We used conditional logistic regression to assess the association between current use of specific NSAIDs and risk of VTE relative to remote NSAID users. Results. Among knee OA patients with at least one NSAID prescription, we identified 4020 incident cases of VTE and 20 059 matched controls. Adjusted odd ratios (ORs) relative to the remote users were 1.38 (95% CI: 1.32, 1.44) for recent users and 1.43 (95% CI: 1.36, 1.49) for current users. Among the current NSAID users, the risk of VTE was increased with diclofenac [OR 1.63 (95% CI: 1.53, 1.74)], ibuprofen [OR = 1.49 (95% CI: 1.38, 1.62)], meloxicam [OR = 1.29 (95% CI: 1.11, 1.50)] and coxibs [celecoxib, OR =1.30 (95% CI: 1.11, 1.51); rofecoxib, OR = 1.44 (95% CI: 1.18, 1.76)]; naproxen did not increase VTE risk [OR =1.00 (95% CI: 0.89, 1.12)]. Conclusion. Compared with the remote users of NSAIDs, the risk of VTE increased for current users of diclofenac, ibuprofen, meloxicam, and coxibs, but not for naproxen, in the knee OA population. Clinicians should consider the risk profile for specific NSAIDs when recommending their use. [ABSTRACT FROM AUTHOR]

STUDY DESIGN: Secondary analysis of a randomized controlled trial. BACKGROUND: The use of external supports has been questioned because they may lead to weakness in the surrounding muscles. To our knowledge, there is no investigation into the effect of knee supports or braces on quadriceps muscle strength and quadriceps inhibition in individuals with patellofemoral joint (PFJ) osteoarthritis (OA). OBJECTIVES: To investigate the effects of a flexible knee support on quadriceps maximum voluntary contraction (MVC) and arthrogenous muscle inhibition (AMI) in patients with PFJ OA. METHODS: The study included 108 participants who had at least 3 months of patellofemoral pain and a Kellgren-Lawrence score of 2 or 3 for PFJ OA. The participants were randomized to a group that wore a flexible knee support (brace) or a group that did not wear a support (no brace) in a 6-week randomized controlled trial, followed by an openlabel trial, in which all participants wore the brace for a total of 12 weeks. Quadriceps MVC, measured isometrically, and quadriceps AMI, measured by twitch interpolation, were assessed ahe 6-week and 12-week time points. RESULTS: After 6 weeks, MVC did not differ between the brace and no-brace groups (9.09 Nm; 95% confidence interval [CI]: -4.89, 23.07; P = .20). Arthrogenous muscle inhibition significantly decreased in the brace group (-8.62%; 95% CI: -13.90%, -3.33%; P = .002). After 12 weeks, in all of the participants who wore a flexible knee support, MVC increased by 7.98 Nm (95% CI: 2.52, 13.45; P = .004) and AMI decreased (-8.42%; 95% CI: -11.48%, -5.36%; P<.001). Although statistically significant, these results have doubtful clinical significance. CONCLUSION: A patellofemoral flexible knee support in participants with PFJ OA does not have an adverse effect on quadriceps MVC or AMI. Using a knee support should not be discouraged because of concerns about deleterious effects on quadriceps strength and inhibition. LEVEL OF EVIDENCE: Therapy, level 1b. . [ABSTRACT FROM AUTHOR]

Objective To identify patterns of coexisting lesions seen on magnetic resonance imaging (MRI) in knees that are free of radiographic osteoarthritis (OA) and to examine the relationship of these MRI-detected lesions to incident OA. Methods Study subjects were individuals enrolled in the Multicenter Osteoarthritis Study, a prospective cohort study. In each subject, 1 knee in which radiographic OA was absent in both the tibiofemoral and patellofemoral joints at baseline was selected for study, with followup for 84 months. We used a novel approach, latent class analysis, to group the constellation of MRI lesions in each joint, i.e., cartilage damage, bone marrow lesion, meniscal tear, meniscal extrusion, synovitis, and effusion, into a manageable number of subgroups. The association of these subgroups with incident radiographic OA in the same joint was assessed using logistic regression. Results Among 885 eligible knees (203 with incident disease in the tibiofemoral joint, 64 with incident disease in the patellofemoral joint), 4 latent subgroups in the tibiofemoral joint were identified (described briefly as minimal lesions, mild lesions, moderate lesions [but limited meniscal lesions], and severe lesions). The odds ratios of incident tibiofemoral joint OA in the latter 3 subgroups (compared to the knees with minimal lesions as the referent) were 5.6, 1.8, and 5.0, respectively. A similar set of 4 subgroups in the patellofemoral joint was identified, except that the fourth subgroup had limited meniscal lesions. The odds ratios of incident disease in the patellofemoral joint were 3.8, 5.1, and 13.7 in the subgroups with mild lesions, moderate lesions, and severe lesions, respectively. Conclusion Different patterns of coexisting MRI lesions, which have different implications with regard to risk of knee OA, were identified. Meniscal damage seemed to play a different role in the development of incident disease in tibiofemoral versus patellofemoral joints. [ABSTRACT FROM AUTHOR]

Objective To examine whether magnetic resonance imaging (MRI)-based 3-dimensional (3-D) bone shape predicts the onset of radiographic knee osteoarthritis (OA). Methods We conducted a case-control study using data from the Osteoarthritis Initiative by identifying knees that developed incident tibiofemoral radiographic knee OA (case knees) during followup, and matching them each to 2 random control knees. Using knee MRIs, we performed active appearance modeling of the femur, tibia, and patella and linear discriminant analysis to identify vectors that best classified knees with OA versus those without OA. Vectors were scaled such that −1 and +1 represented the mean non-OA and mean OA shapes, respectively. We examined the relation of 3-D bone shape to incident OA (new-onset Kellgren and Lawrence [K/L] grade ≥2) occurring 12 months later using conditional logistic regression. Results A total of 178 case knees (incident OA) were matched to 353 control knees. The whole joint (i.e., tibia, femur, and patella) 3-D bone shape vector had the strongest magnitude of effect, with knees in the highest tertile having a 3.0 times higher likelihood of developing incident radiographic knee OA 12 months later compared with those in the lowest tertile (95% confidence interval [95% CI] 1.8-5.0, P < 0.0001). The associations were even stronger among knees that had completely normal radiographs before incidence (K/L grade of 0) (odds ratio 12.5 [95% CI 4.0-39.3]). Bone shape at baseline, often several years before incidence, predicted later OA. Conclusion MRI-based 3-D bone shape predicted the later onset of radiographic OA. Further study is warranted to determine whether such methods can detect treatment effects in trials and provide insight into the pathophysiology of OA development. [ABSTRACT FROM AUTHOR]

Objective To study the effect of valgus malalignment on knee osteoarthritis (OA) incidence and progression. Methods We measured the mechanical axis from long limb radiographs from the Multicenter Osteoarthritis Study (MOST) and the Osteoarthritis Initiative (OAI) to define limbs with valgus malalignment (mechanical axis of ≥1.1° valgus) and examined the effect of valgus alignment versus neutral alignment (neither varus nor valgus) on OA structural outcomes. Posteroanterior radiographs and knee magnetic resonance (MR) images were obtained at the time of the long limb radiograph and at followup examinations. Lateral progression was defined as an increase in joint space narrowing (on a semiquantitative scale) in knees with OA, and incidence was defined as new lateral narrowing in knees without radiographic OA. We defined lateral cartilage damage and progressive meniscal damage as increases in cartilage or meniscus scores at followup on the Whole-Organ Magnetic Resonance Imaging Score scale (for the MOST) or the Boston Leeds Osteoarthritis Knee Score scale (for the OAI). We used logistic regression with adjustment for age, sex, body mass index, and Kellgren/Lawrence grade, as well as generalized estimating equations, to evaluate the effect of valgus alignment versus neutral alignment on disease outcomes. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs). Results We studied 5,053 knees (881 valgus) of subjects in the MOST cohort and 5,953 knees (1,358 valgus) of subjects in the OAI cohort. In both studies, all strata of valgus malalignment, including 1.1° to 3° valgus, were associated with an increased risk of lateral disease progression. In knees without radiographic OA, valgus alignment >3° was associated with incidence (e.g., in the MOST, adjusted OR 2.5 [95% CI 1.0-5.9]). Valgus alignment >3° was also associated with cartilage damage on MR imaging in knees without OA (e.g., in the OAI, adjusted OR 5.9 [95% CI 1.1-30.3]).We found a strong relationship of valgus malalignment with progressive lateral meniscal damage. Conclusion Valgus malalignment increases the risk of knee OA radiographic progression and incidence as well as the risk of lateral cartilage damage. It may cause these effects, in part, by increasing the risk of meniscal damage. [ABSTRACT FROM AUTHOR]

Objective Knee osteoarthritis (OA) and pain are assumed to be barriers to meeting physical activity guidelines, but this has not been formally evaluated. The purpose of this study was to determine the proportions of people with and those without knee OA and knee pain who meet recommended physical activity levels through walking. Methods We performed a cross-sectional analysis of community-dwelling adults from the Multicenter Osteoarthritis Study who had or who were at high risk of knee OA. Participants wore a StepWatch activity monitor to record steps per day for 7 days. The proportion of participants who met the recommended physical activity levels was defined as those accumulating ≥150 minutes per week at ≥100 steps per minute in bouts lasting ≥10 minutes. These proportions were also determined for those with and those without knee OA, as classified by radiography and by severity of knee pain. Results Of the 1,788 study participants (mean ± SD age 67.2 ± 7.7 years, mean ± SD body mass index 30.7 ± 6.0 kg/m2, 60% women), lower overall percentages of participants with radiographic knee OA and knee pain met recommended physical activity levels. However, these differences were not statistically significant between those with and those without knee OA; 7.3% and 10.1% of men ( P = 0.34) and 6.3% and 7.8% of women ( P = 0.51), respectively, met recommended physical activity levels. Similarly, for those with moderate/severe knee pain and those with no knee pain, 12.9% and 10.9% of men ( P = 0.74) and 6.7% and 11.0% of women ( P = 0.40), respectively, met recommended physical activity levels. Conclusion Disease and pain have little impact on achieving recommended physical activity levels among people with or at high risk of knee OA. [ABSTRACT FROM AUTHOR]

Objective To describe the association of osteophytes with concomitant cartilage damage, assessed using semiquantitative magnetic resonance imaging (MRI), and to describe the prevalence of atrophic and hypertrophic phenotypes of tibiofemoral knee osteoarthritis (OA) in a population-based cohort. Methods Participants of the Framingham Knee Osteoarthritis Study were examined with a 1.5T MRI system using triplanar intermediate-weighted fat-suppressed sequences. Cartilage and osteophytes were assessed using the Whole-Organ Magnetic Resonance Imaging Score (WORMS). Overall prevalence of knees with severe cartilage damage and concomitant osteophyte status were described. Odds ratios for the likelihood of having severe cartilage damage according to osteophyte size were estimated using a logistic regression model. An additional analysis assessed knees according to phenotype in relation to radiographic OA status, with the atrophic phenotype being defined as knees with absent or only tiny osteophytes (WORMS grade ≤2 on a 0-7 scale) in all 10 tibiofemoral subregions but exhibiting severe cartilage damage, and the hypertrophic phenotype being defined as knees with large osteophytes (WORMS grade ≥5 on a 0-7 scale) but lacking substantial cartilage damage. Results In this study, 1,597 knees of 1,248 subjects were included. Of the 67 knees with large osteophytes, 54 (80.6%) exhibited severe cartilage damage. The risk of severe cartilage damage increased markedly with increasing osteophyte size. Twenty-one knees (1.3%) showed an atrophic phenotype. Only 3 knees (0.2%) exhibited a hypertrophic phenotype. Conclusion The majority of knees with severe tibiofemoral cartilage damage exhibited moderate to large osteophytes. The larger the osteophyte, the more likely was the presence of severe cartilage damage. A minority of knees exhibited the atrophic phenotype, which also included knees without radiographic OA. The hypertrophic phenotype was extremely rare. [ABSTRACT FROM AUTHOR]

As the population ages, there is a growing burden owing to musculoskeletal diseases, such as knee osteoarthritis, and subsequent functional decline. In the absence of a cure, there is a need to identify factors amenable to intervention to prevent or slow this process. The Multicenter Osteoarthritis Study cohort was developed for this purpose. In this study, associations between variability in peak knee flexor and extensor torque at baseline and worsening of pain and physical function over the subsequent 60 mos were assessed in a cohort of 2680 participants. The highest quartile of baseline knee flexor torque variability was found to be associated longitudinally with worsening pain (fourth quartile β estimate, mean ± SE, 0.49 ± 0.19; P = 0.0115; with R² = 0.28 and P for trend across quartiles = 0.0370) and physical function scores (fourth quartile β estimate, mean ± SE, 1.39 ± 0.64; P = 0.0296; with R² = 0.25 and P for trend across quartiles = 0.0371), after adjusting for baseline knee osteoarthritis and maximum knee flexor torque. There were no associations between baseline knee extensor torque and worsening pain or physical function by 60 mos. The presence of greater variability in maximum knee flexor strength may identify patients who may benefit from therapies aimed at preventing worsening knee pain and physical function. [ABSTRACT FROM AUTHOR]