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1.  Hand osteoarthritis in relation to mortality and incidence of cardiovascular disease: data from the Framingham Heart Study 
Objectives
To study whether hand osteoarthritis (OA) is associated with increased mortality and cardiovascular events in a large community based cohort (Framingham Heart Study) in which OA, mortality and cardiovascular events have been carefully assessed.
Methods
We examined whether symptomatic (≥1 joint (s) with radiographic OA and pain in the same joint) and radiographic hand OA (≥1 joint(s) with radiographic OA without pain) were associated with mortality and incident cardiovascular events (coronary heart disease, congestive heart failure and/or atherothrombotic brain infarction) using Cox proportional hazards models. In the adjusted models, we included possible confounding factors from baseline (eg, metabolic factors, medication use, smoking/alcohol). We also adjusted for the number of painful joints in the lower limb and physical inactivity.
Results
We evaluated 1348 participants (53.8% women) with mean (SD) age of 62.2 (8.2) years, of whom 540 (40.1%) and 186 (13.8%) had radiographic and symptomatic hand OA, respectively. There was no association between hand OA and mortality. Although there was no significant relation to incident cardiovascular events overall or a relation of radiographic hand OA with events, we found a significant association between symptomatic hand OA and incident coronary heart disease (myocardial infarction/coronary insufficiency syndrome) (HR 2.26, 95% CI 1.22 to 4.18). The association remained after additional adjustment for pain in the lower limb or physical inactivity.
Conclusions
Symptomatic hand OA, but not radiographic hand OA, was associated with an increased risk of coronary heart disease events. The results suggest an effect of pain, which may be a possible marker of inflammation.
doi:10.1136/annrheumdis-2013-203789
PMCID: PMC3959628  PMID: 24047870
2.  Assessment of Osteoarthritis Candidate Genes in a Meta-Analysis of Nine Genome-Wide Association Studies 
Objective
To assess candidate genes for association with osteoarthritis (OA) and identify promising genetic factors and, secondarily, to assess the candidate gene approach in OA.
Methods
A total of 199 candidate genes for association with OA were identified using Human Genome Epidemiology (HuGE) Navigator. All of their single-nucleotide polymorphisms (SNPs) with an allele frequency of >5% were assessed by fixed-effects meta-analysis of 9 genome-wide association studies (GWAS) that included 5,636 patients with knee OA and 16,972 control subjects and 4,349 patients with hip OA and 17,836 control subjects of European ancestry. An additional 5,921 individuals were genotyped for significantly associated SNPs in the meta-analysis. After correction for the number of independent tests, P values less than 1.58 × 10−5 were considered significant.
Results
SNPs at only 2 of the 199 candidate genes (COL11A1 and VEGF) were associated with OA in the meta-analysis. Two SNPs in COL11A1 showed association with hip OA in the combined analysis: rs4907986 (P = 1.29 × 10−5, odds ratio [OR] 1.12, 95% confidence interval [95% CI] 1.06−1.17) and rs1241164 (P = 1.47 × 10−5, OR 0.82, 95% CI 0.74−0.89). The sex-stratified analysis also showed association of COL11A1 SNP rs4908291 in women (P = 1.29 × 10−5, OR 0.87, 95% CI 0.82−0.92); this SNP showed linkage disequilibrium with rs4907986. A single SNP of VEGF, rs833058, showed association with hip OA in men (P = 1.35 × 10−5, OR 0.85, 95% CI 0.79−0.91). After additional samples were genotyped, association at one of the COL11A1 signals was reinforced, whereas association at VEGF was slightly weakened.
Conclusion
Two candidate genes, COL11A1 and VEGF, were significantly associated with OA in this focused meta-analysis. The remaining candidate genes were not associated.
doi:10.1002/art.38300
PMCID: PMC4660891  PMID: 24757145
4.  Identifying and Treating Pre-Clinical and Early Osteoarthritis 
Synopsis
Osteoarthritis is the most common form of arthritis and nonsurgical treatments of disease have limited efficacy. Studies suggest, at least for disease in the knee, that most persons with painful OA already have extensive structural disease including malalignment, which may preclude successful stabilization or reversal of disease. This provides a strong rationale for developing strategies to prevent disease or to identify and treat it early. A variety of approaches, reviewed here, are likely to capture those at high risk of or with early disease; imaging techniques offer great promise of characterizing structural changes before they are irreversible. However, given the absence of effective treatments, it is unclear whether structural disease could be successfully slowed or prevented in those with early symptoms or those at high risk of disease.
doi:10.1016/j.rdc.2014.07.012
PMCID: PMC4251520  PMID: 25437286
osteoarthritis; knee pain; magnetic resonance imaging; biomarkers
5.  No association between daily walking and structural changes in people at risk of or with mild knee osteoarthritis. Prospective data from the Multicenter Osteoarthritis Study 
The Journal of rheumatology  2015;42(9):1685-1693.
Objective
We investigated the association between objectively measured daily walking and knee structural change, defined either as radiographic worsening or as cartilage loss, in people at risk of or with knee osteoarthritis (OA).
Methods
Participants from the Multicenter Osteoarthritis (MOST) study with Kellgren and Lawrence (KL) grades 0–2 and daily walking (measured with the StepWatch) at the 60-month visit, were included. Participants had fixed flexion weight bearing radiographs and knee magnetic resonance images (MRIs) at 60 and 84 months. Radiographic worsening was read in both knees using the OARSI grading, and MRIs were read for one knee using WORMS semiquantitative scoring. Odds ratios (OR) and 95% confidence intervals (CI) were calculated comparing those in the middle tertile against the lowest and highest tertiles of daily walking using logistic regression models and generalized estimating equations. Data on walking with moderate to vigorous intensity (minutes with >100 steps/min/day) was associated to structural change using multivariate and logistic regression models.
Results
The 1179 study participants (59% females) were 67.0 (±7.6) years, with a mean (±SD) body mass index of 29.8 (±5.3) kg/m2 who walked 6981 (±2630) steps/day. After adjusting for confounders, we found no significant associations between daily walking and radiographic worsening or cartilage loss. More time spent walking at a moderate to vigorous intensity was not associated with either radiographic worsening or cartilage loss.
Conclusion
Results from the MOST study indicated no association between daily walking and structural changes over two years in people at risk of or with mild knee OA.
doi:10.3899/jrheum.150071
PMCID: PMC4558377  PMID: 26077404
physical activity; osteoarthritis; structural changes; MRI
6.  Lateral Wedge Insoles as a Conservative Treatment for Pain in Patients With Medial Knee Osteoarthritis 
JAMA  2013;310(7):722-730.
IMPORTANCE
There is no consensus regarding the efficacy of lateral wedge insoles as a treatment for pain in medial knee osteoarthritis.
OBJECTIVE
To evaluate whether lateral wedge insoles reduce pain in patients with medial knee osteoarthritis compared with an appropriate control.
DATA SOURCES
Databases searched include the Cochrane Central Register of Controlled Trials, EMBASE, AMED, MEDLINE, CINAHL Plus, ScienceDirect, SCOPUS, Web of Science, and BIOSIS from inception to May 2013, with no limits on study date or language. The metaRegister of Controlled Trials and the NHS Evidence website were also searched.
STUDY SELECTION
Included were randomized trials comparing shoe-based treatments (lateral heel wedge insoles or shoes with variable stiffness soles) aimed at reducing medial knee load, with a neutral or no wedge control condition in patients with painful medial knee osteoarthritis. Studies must have included patient-reported pain as an outcome.
DATA EXTRACTION AND SYNTHESIS
Trial data were extracted independently by 2 researchers using a standardized form. Risk of bias was assessed using the Cochrane Risk of Bias tool by 2 observers. Eligible studies were pooled using a random-effects approach.
MAIN OUTCOME AND MEASURES
Change in self-reported knee pain at follow-up.
RESULTS
Twelve trials met inclusion criteria with a total of 885 participants of whom 502 received lateral wedge treatment. The pooled standardized mean difference (SMD) suggested a favorable association with lateral wedges compared with control (SMD, −0.47; 95% CI, −0.80 to −0.14); however, substantial heterogeneity was present (I2 = 82.7%). This effect size represents an effect of −2.12 points on the 20-point Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain scale. Larger trials with a lower risk of bias suggested a null association. Meta-regression analyses showed that higher effect sizes (unstandardized β, 1.07 [95% CI, 0.28 to 1.87] for trials using a no treatment control) were seen in trials using a no wedge treatment control group (n = 4 trials; SMD, −1.20 [95% CI, −2.09 to −0.30]) and lower effect sizes (unstandardized β, 0.26 [95% CI, 0.002 to 0.52] for each bias category deemed low risk) when the study method was deemed at low risk of bias. Among trials in which the control treatment was a neutral insole (n = 7), lateral wedges showed no association (SMD, −0.03 [95% CI, −0.18 to 0.12] on WOMAC; this represents an effect of −0.12 points), and results showed little heterogeneity (I2 = 7.1%).
CONCLUSIONS AND RELEVANCE
Although meta-analytic pooling of all studies showed a statistically significant association between use of lateral wedges and lower pain in medial knee osteoarthritis, restriction of studies to those using a neutral insole comparator did not show a significant or clinically important association. These findings do not support the use of lateral wedges for this indication.
doi:10.1001/jama.2013.243229
PMCID: PMC4458141  PMID: 23989797
7.  The Current and Future Status of Biomarkers in Osteoarthritis 
The Journal of rheumatology  2014;41(5):834-836.
doi:10.3899/jrheum.140094
PMCID: PMC4438757  PMID: 24788463
8.  Genome-wide association study meta-analysis of chronic widespread pain: evidence for involvement of the 5p15.2 region 
Annals of the Rheumatic Diseases  2012;72(3):427-436.
Background and objectives
Chronic widespread pain (CWP) is a common disorder affecting ∼10% of the general population and has an estimated heritability of 48–52%. In the first large-scale genome-wide association study (GWAS) meta-analysis, we aimed to identify common genetic variants associated with CWP.
Methods
We conducted a GWAS meta-analysis in 1308 female CWP cases and 5791 controls of European descent, and replicated the effects of the genetic variants with suggestive evidence for association in 1480 CWP cases and 7989 controls. Subsequently, we studied gene expression levels of the nearest genes in two chronic inflammatory pain mouse models, and examined 92 genetic variants previously described associated with pain.
Results
The minor C-allele of rs13361160 on chromosome 5p15.2, located upstream of chaperonin-containing-TCP1-complex-5 gene (CCT5) and downstream of FAM173B, was found to be associated with a 30% higher risk of CWP (minor allele frequency=43%; OR=1.30, 95% CI 1.19 to 1.42, p=1.2×10−8). Combined with the replication, we observed a slightly attenuated OR of 1.17 (95% CI 1.10 to 1.24, p=4.7×10−7) with moderate heterogeneity (I2=28.4%). However, in a sensitivity analysis that only allowed studies with joint-specific pain, the combined association was genome-wide significant (OR=1.23, 95% CI 1.14 to 1.32, p=3.4×10−8, I2=0%). Expression levels of Cct5 and Fam173b in mice with inflammatory pain were higher in the lumbar spinal cord, not in the lumbar dorsal root ganglions, compared to mice without pain. None of the 92 genetic variants previously described were significantly associated with pain (p>7.7×10−4).
Conclusions
We identified a common genetic variant on chromosome 5p15.2 associated with joint-specific CWP in humans. This work suggests that CCT5 and FAM173B are promising targets in the regulation of pain.
doi:10.1136/annrheumdis-2012-201742
PMCID: PMC3691951  PMID: 22956598
Gene Polymorphism; Fibromyalgis/Pain Syndromes; Epidemiology
9.  The Relationship Between Reductions in Knee Loading and Immediate Pain Response Whilst Wearing Lateral Wedged Insoles in Knee Osteoarthritis 
Studies of lateral wedge insoles (LWIs) in medial knee osteoarthritis (OA) have shown reductions in the average external knee adduction moment (EKAM) but no lessening of knee pain. Some treated patients actually experience increases in the EKAM which could explain the overall absence of pain response. We examined whether, in patients with painful medial OA, reductions in the EKAM were associated with lessening of knee pain. Each patient underwent gait analysis whilst walking in a control shoe and two LWI’s. We evaluated the relationship between change in EKAM and change in knee pain using Spearman Rank Correlation coefficients and tested whether dichotomizing patients into biomechanical responders (decreased EKAM) and non-responders (increased EKAM) would identify those with reductions in knee pain. In 70 patients studied, the EKAM was reduced in both LWIs versus control shoe (−5.21% and −6.29% for typical and supported wedges, respectively). The change in EKAM using LWIs was not significantly associated with the direction of knee pain change. Further, 54% were biomechanical responders, but these persons did not have more knee pain reduction than non-responders. Whilst LWIs reduce EKAM, there is no clearcut relationship between change in medial load when wearing LWIs and corresponding change in knee pain.
doi:10.1002/jor.22666
PMCID: PMC4372252  PMID: 24903067
osteoarthritis; knee; pain; adduction moment; lateral wedge
10.  Measures of Knee Function 
Arthritis care & research  2011;63(0 11):S208-S228.
doi:10.1002/acr.20632
PMCID: PMC4336550  PMID: 22588746
11.  Does Clinically Important Change in Function After Knee Replacement Guarantee Good Absolute Function? The Multicenter Osteoarthritis Study 
The Journal of rheumatology  2013;41(1):60-64.
Objective
Poor functional outcomes post knee replacement are common, but estimates of its prevalence vary, likely in part because of differences in methods used to assess function. The agreement between improvement in function and absolute good levels of function after knee replacement has not been evaluated. We evaluated the attainment of improvement in function and absolute good function after total knee replacement (TKR) and the agreement between these measures.
Methods
Using data from The Multicenter Osteoarthritis (MOST) Study, we determined the prevalence of achieving a minimal clinically important improvement (MCII, ≥ 14.2/68 point improvement) and Patient Acceptable Symptom State (PASS, ≤ 22/68 post-TKR score) on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function subscale at least 6 months after knee replacement. We also assessed the frequency of co-occurrence of the 2 outcomes, and the prevalence according to pre-knee replacement functional status.
Results
We included 228 subjects who had a knee replacement during followup (mean age 65 yrs, mean body mass index 33.4,73% female). Seventy-one percent attained the PASS for function after knee replacement, while only 44% attained the MCII. Of the subjects who met the MCII, 93% also attained the PASS; however, of subjects who did not meet the MCII, 54% still achieved a PASS. Baseline functional status was associated with attainment of each MCII and PASS.
Conclusion
There was only partial overlap between attainment of a good level of function and actually improving by an acceptable amount. Subjects were more likely to attain an acceptable level of function than to achieve a clinically important amount of improvement post knee replacement.
doi:10.3899/jrheum.130313
PMCID: PMC3914207  PMID: 24293582
12.  The association of parity with osteoarthritis and knee replacement in the Multicenter Osteoarthritis Study 
Objective
We evaluated the association of parity to both risk of knee replacement (KR) and knee osteoarthritis (OA).
Design
The NIH-funded Multicenter Osteoarthritis Study (MOST) is a longitudinal observational study of persons age 50 to 79 years with either symptomatic knee OA or at elevated risk of disease. Baseline and 30-month knee radiographic OA (ROA) was defined as Kellgren/Lawrence (K/L) grade≥2 or KR. Women were grouped based by number of births: 0; 1 (reference group); 2; 3; 4; and 5 or more. We examined the relation of parity to the incidence over 30 months of ROA and KR using a Poisson regression model. Generalized estimating equations were used to control for correlation between two knees within a subject. We adjusted for age, BMI, race, education, occupation, baseline estrogen use, clinical site, injury, and for KR analyses WOMAC pain and use of pain medication.
Results
Among 1618 women who reported parity information, mean age was 62.6 years, mean BMI 30.7 kg/m2, mean WOMAC pain subscale score 3.7 at baseline. There were 115 KRs and 134 cases of incident knee ROA over 30 months. The relative risk of incident KR was 2.7 times as high (95% CI: 1.0, 7.3) and relative risk of incident knee ROA was 2.6 times as high (95% CI: 1.2, 5.3) among women with 5–12 children compared with those with one birth.
Conclusion
Parity in women at risk for OA is associated with both incident ROA and KR, particularly for those with more than 4 children.
doi:10.1016/j.joca.2013.08.025
PMCID: PMC3855897  PMID: 24029601
parity; knee; osteoarthritis; joint replacement
14.  Assessment of synovitis with contrast-enhanced MRI using a whole-joint semiquantitative scoring system in people with, or at high risk of, knee osteoarthritis: the MOST study 
Annals of the rheumatic diseases  2010;70(5):805-811.
Objectives
To introduce a comprehensive and reliable scoring system for the assessment of whole-knee joint synovitis based on contrast-enhanced (CE) MRI.
Methods
Multicenter Osteoarthritis Study (MOST) is a cohort study of people with, or at high risk of, knee osteoarthritis (OA). Subjects are an unselected subset of MOST who volunteered for CE-MRI. Synovitis was assessed at 11 sites of the joint. Synovial thickness was scored semiquantitatively: grade 0 (<2 mm), grade 1 (2–4 mm) and grade 2 (>4 mm) at each site. Two musculoskeletal radiologists performed the readings and inter- and intrareader reliability was evaluated. Whole-knee synovitis was assessed by summing the scores from all sites. The association of Western Ontario and McMaster Osteoarthritis Index pain score with this summed score and with the maximum synovitis grade for each site was assessed.
Results
400 subjects were included (mean age 58.8±7.0 years, body mass index 29.5±4.9 kg/m2, 46% women). For individual sites, intrareader reliability (weighted κ) was 0.67–1.00 for reader 1 and 0.60–1.00 for reader 2. Inter-reader agreement (κ) was 0.67–0.92. For the summed synovitis scores, intrareader reliability (intraclass correlation coefficient (ICC)) was 0.98 and 0.96 for each reader and inter-reader agreement (ICC) was 0.94. Moderate to severe synovitis in the parapatellar subregion was associated with the higher maximum pain score (adjusted OR (95% CI), 2.8 (1.4 to 5.4) and 3.1 (1.2 to 7.9), respectively).
Conclusions
A comprehensive semiquantitative scoring system for the assessment of whole-knee synovitis is proposed. It is reliable and identifies knees with pain, and thus is a potentially powerful tool for synovitis assessment in epidemiological OA studies.
doi:10.1136/ard.2010.139618
PMCID: PMC4180232  PMID: 21187293
15.  The Diagnostic Performance of Anterior Knee Pain and Activity-related Pain in Identifying Knees with Structural Damage in the Patellofemoral Joint: The Multicenter Osteoarthritis Study 
The Journal of rheumatology  2014;41(8):1695-1702.
Objective
To determine the diagnostic test performance of location of pain and activity-related pain in identifying knees with patellofemoral joint (PFJ) structural damage.
Methods
The Multicenter Osteoarthritis Study is a US National Institutes of Health-funded cohort study of older adults with or at risk of knee osteoarthritis. Subjects identified painful areas around the knee on a knee pain map and the Western Ontario and McMaster Universities Osteoarthritis Index was used to assess pain with stairs and walking on level ground. Cartilage damage and bone marrow lesions were assessed from knee magnetic resonance imaging. We determined the sensitivity, specificity, positive and negative predictive values for presence of anterior knee pain (AKP), pain with stairs, absence of pain while walking on level ground, and combinations of tests in discriminating knees with isolated PFJ structural damage from those with isolated tibiofemoral joint (TFJ) or no structural damage. Knees with mixed PFJ/TFJ damage were removed from our analyses because of the inability to determine which compartment was causing pain.
Results
There were 407 knees that met our inclusion criteria. “Any” AKP had a sensitivity of 60% and specificity of 53%; and if AKP was the only area of pain, the sensitivity dropped to 27% but specificity rose to 81%. Absence of moderate pain with walking on level ground had the greatest sensitivity (93%) but poor specificity (13%). The combination of “isolated” AKP and moderate pain with stairs had poor sensitivity (9%) but the greatest specificity (97%) of strategies tested.
Conclusion
Commonly used questions purported to identify knees with PFJ structural damage do not identify this condition with great accuracy.
doi:10.3899/jrheum.131555
PMCID: PMC4182011  PMID: 24931959
OSTEOARTHRITIS; PAIN; MAGNETIC RESONANCE IMAGING
16.  MRI-based three-dimensional bone shape of the knee predicts onset of knee osteoarthritis: Data from the Osteoarthritis Initiative 
Arthritis and rheumatism  2013;65(8):2048-2058.
Objective
To examine whether MRI-based 3D bone shape predicts the onset of radiographic knee osteoarthritis (OA).
Methods
We conducted a case-control study within the Osteoarthritis Initiative by identifying knees that developed incident tibiofemoral radiographic knee OA (case knees) over follow-up, and matching them to two random control knees. Using knee MRI's, we used active appearance modeling of the femur, tibia and patella and linear discriminant analysis to identify vectors that best classified knees having OA vs. not. Vectors were scaled such that -1 and +1 represented the mean non-OA and mean OA shapes, respectively. We examined the relation of 3D bone shape to incident OA (new onset Kellgren and Lawrence (KL) grade ≥2) occurring 12 months later using conditional logistic regression.
Results
178 case knees (incident OA) were matched to 353 control knees. The whole joint (i.e., tibia, femur, and patella) 3D bone shape vector had the strongest magnitude of effect, with knees in the highest tertile having 3.0 times higher likelihood of developing incident radiographic knee OA 12 months later compared with those in the lowest tertile (95% CI 1.8-5.0, p<0.0001). The associations were even stronger among knees that showed completely normal radiographs before incidence (KL grade 0) (OR 12.5, 95% CI 4.0-39.3). Bone shape at baseline, often several years before incidence, predicted later OA.
Conclusions
MRI-based 3D 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 pathophysiologic insight into OA development.
doi:10.1002/art.37987
PMCID: PMC3729737  PMID: 23650083
17.  The ACR20 and defining a threshold for response in rheumatic diseases: too much of a good thing 
In the past 20 years great progress has been made in the development of multidimensional outcome measures (such as the Disease Activity Score and ACR20) to evaluate treatments in rheumatoid arthritis, a process disseminated throughout rheumatic diseases. These outcome measures have standardized the assessment of outcomes in trials, making it possible to evaluate and compare the efficacy of treatments. The methodologic advances have included the selection of pre-existing outcome measures that detected change in a sensitive fashion (in rheumatoid arthritis, this was the Core Set Measures). These measures were then combined into a single multidimensional outcome measure and such outcome measures have been widely adopted in trials and endorsed by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) and regulatory agencies. The secular improvement in treatment for patients with rheumatoid arthritis has been facilitated in part by these major methodologic advancements. The one element of this effort that has not optimized measurement of outcomes nor made it easier to detect the effect of treatments is the dichotomization of continuous measures of response, creating responders and non-responder definitions (for example, ACR20 responders; EULAR good responders). Dichotomizing response sacrifices statistical power and eliminates variability in response. Future methodologic work will need to focus on improving multidimensional outcome measurement without arbitrarily characterizing some patients as responders while labeling others as non-responders.
doi:10.1186/ar4428
PMCID: PMC3978644  PMID: 24387346
18.  The association between meniscal damage of the posterior horns and localized posterior synovitis detected on T1-weighted contrast-enhanced MRI—the MOST study 
Objective
Synovitis is thought to be a secondary phenomenon in the osteoarthritis (OA) process and the menisci might be triggers of localized synovitis. The aim was to assess the cross-sectional associations of posterior horn meniscal damage with perimeniscal synovitis, and with synovitis posterior to the posterior cruciate ligament (PCL) using contrast enhanced (CE) MRI.
Design
The Multicenter Osteoarthritis (MOST) Study is a longitudinal observational study of subjects with or at risk for knee OA. Subjects are a subset of MOST who were examined with 1.5 T CE MRI and had semiquantitative synovitis (scored from 0–2 at 11 locations) and meniscal readings (scored with WORMS from 0–4 ) available. Logistic regression was used to assess the association of posterior meniscal damage and perimeniscal synovitis in the same compartment, and between posterior meniscal damage and synovitis posterior to the PCL.
Results
Three hundred and seventy seven knees were included (mean age 61.1 years ± 6.9, mean BMI 29.6 ± 4.9, 44.3% women). The odds for ipsi-compartmental perimeniscal synovitis were increased for knees with medial posterior horn meniscal damage (adjusted odds ratio [aOR] 2.5, 95% confidence intervals [95% CI] 1.3,4.8), but not for lateral damage (aOR 1.7, 95% CI 0.4,6.6). No positive associations were found for meniscal damage and presence of synovitis posterior to the PCL (aOR 0.9, 95% CI 0.6,1.5).
Conclusions
Meniscal damage of the posterior horns is associated with ipsi-compartmental perimensical synovitis. No associations were found for posterior horn meniscal damage with synovitis posterior to the PCL, which suggests that synovitis posterior to the PCL is likely to be triggered by different pathomechanisms.
doi:10.1016/j.semarthrit.2012.10.005
PMCID: PMC3640766  PMID: 23270763
Osteoarthritis; Magnetic resonance imaging; Synovitis; Meniscal damage
19.  Physical activity, alignment and knee osteoarthritis: Data from MOST and the OAI 
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 MOST and 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, BMI, WOMAC pain score, Kellgren and Lawrence grade (0 or 1), and study of origin. We also analyzed knees from malaligned and neutrally aligned limbs.
Results
The combined sample comprised 2073 subjects (3542 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 (OR among active group 0.6, 95% 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.
doi:10.1016/j.joca.2013.03.001
PMCID: PMC3648587  PMID: 23523851
physical activity; knee osteoarthritis; alignment; radiography
20.  Breaking the Law of Valgus: the surprising and unexplained prevalence of medial patellofemoral cartilage damage 
Annals of the rheumatic diseases  2012;71(11):1827-1832.
Objectives
To compare the prevalence of medial and lateral patellofemoral (PF) cartilage damage in three large osteoarthritis (OA) studies and determine the relationship of this damage to varus, neutral, and valgus knee alignment.
Methods
In the Boston OA of the Knee (BOKS), Framingham OA (FOA), and Multicenter OA (MOST) studies, MRIs were read for cartilage morphology at the medial and lateral patella and trochlea femoris using Whole-Organ MRI Scores (WORMS). WORMS scores ≥ 2 (any cartilage defect), ≥ 3 (areas of partial thickness loss), ≥ 4 (diffuse partial thickness loss), and ≥ 5 (extensive full thickness loss) were all variously considered as thresholds to identify damage that may indicate OA. Full-limb radiographs were measured for mechanical alignment, and varus (< −2°), neutral (−2° to 2°), and valgus (> 2°) knees were identified.
Results
The prevalence of medial PF cartilage damage exceeded that of lateral damage in all three OA studies and according to nearly every threshold. Only among severely involved knees (WORMS ≥ 4 or ≥ 5) did the prevalence of lateral PF cartilage damage approximate that of medial damage. The high prevalence of medial PF damage persisted in all strata of knee alignment. Even among knees with valgus malalignment, the prevalence of lateral PF cartilage damage equaled or surpassed that of medial PF damage only when the threshold was specific to severely involved knees.
Conclusions
Medial PF cartilage damage is at least as prevalent among older adults as lateral PF cartilage damage.
doi:10.1136/annrheumdis-2011-200606
PMCID: PMC4011177  PMID: 22534825
Osteoarthritis; Knee; Patellofemoral Joint; Prevalence; Articular Cartilage
21.  Comparing the functional impact of knee replacements in two cohorts 
Background
To examine if different rates of total knee replacement (TKR) in two similar cohorts with symptomatic knee osteoarthritis (OA) were associated with different functional impact of disease.
Methods
Subjects from the Multicenter Osteoarthritis Study (MOST) and the Osteoarthritis Initiative (OAI), persons with or at high risk of OA, had knee radiographs, completed Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) surveys and had TKRs confirmed at each visit. At each visit, subjects were defined as having symptomatic OA (SxOA) if ≥ one knee had pain and radiographic OA or if they had a TKR. WOMAC function scores at each visit were compared by analysis of covariance adjusting for age, sex, body mass index, race, site, depression, comorbidity, painful leg joints and knees affected. Post-TKR function scores were imputed to estimate scores that would have been present without TKR.
Results
Subjects with SxOA (n > 750 in MOST and in OAI) had a mean age 66 to 67 years; most were women and were White. Subjects were followed 4–5 years. Among those with SxOA, more TKRs were done in MOST (35%) than OAI (19%). Adjusted mean WOMAC function (0–68, 68 = worst) improved from 26.9 to 21.9 in MOST and from 24.5 to 22.0 in OAI (difference between MOST and OAI in change in WOMAC function, p = .01). Estimates of function without TKRs showed function would not have changed in MOST (23.2 at baseline to 22.4).
Conclusions
Functional status of subjects with knee OA in MOST improved more than in OAI, probably because of higher rates of TKRs. The decline suggests that TKR diminishes the functional impact of OA in the community.
doi:10.1186/1471-2474-15-145
PMCID: PMC4016673  PMID: 24885404
Total knee replacement; Function; Epidemiology
22.  Using magnetic resonance imaging to determine the compartmental prevalence of knee joint structural damage 
Objective
To describe the prevalence of magnetic resonance imaging (MRI) detected structural damage in the patellofemoral joint (PFJ) and tibiofemoral (TFJ) in a population-based cohort. A secondary aim was to evaluate the patterns of compartmental involvement in knees with pain, between men and women, and in different age and body mass index (BMI) categories.
Methods
We studied 970 knees, one knee per subject, from the Framingham Osteoarthritis Study, a population-based cohort study of persons 51–92 years old. Cartilage damage and bone marrow lesions (BMLs) were assessed using the Whole Organ Magnetic Resonance Imaging Score (WORMS). The prevalence of isolated PFJ, isolated TFJ, and mixed structural damage was determined using the following definitions: any cartilage damage, full thickness cartilage loss, any BML, and the combination of full thickness cartilage loss with any BML.
Results
The mean age and body mass index was 63.4 years and 28.6 m/kg2, respectively; 57% were female. Isolated PFJ damage occurred in 15–20% of knees and isolated TFJ damage occurred in 8–17% of knees depending on the definition used. The prevalence of isolated PFJ damage was greater than isolated TFJ damage using all definitions except the any BML definition. This pattern was similar between genders and among age and BMI categories. In those with knee pain, isolated PFJ was at least as common as TFJ damage depending on the definition used.
Conclusion
Using MRI to assess knee joint structural damage, isolated PFJ damage was at least as common as, if not more common than, isolated TFJ damage.
doi:10.1016/j.joca.2013.02.003
PMCID: PMC3638815  PMID: 23428598
osteoarthritis; patellofemoral; magnetic resonance imaging
24.  Walking to meet physical activity guidelines in knee osteoarthritis: Is 10,000 steps enough? 
Objective
To study if step goals (e.g. walking 10,000 steps/day) approximate meeting 2008 Physical Activity Guidelines for Americans among adults with or at high risk of knee OA.
Design
Cross-sectional observational cohort
Setting
Community
Participants
People with or at high risk of knee OA
Interventions
None
Main Outcome Measures
Objective physical activity data were collected over 7 consecutive days from people with or at high risk of knee (OA) participating in the Multicenter Osteoarthritis Study. Using activity monitor data, we determined the proportion that 1) walked ≥10,000 steps/day, 2) met the 2008 Physical Activity Guidelines, and 3) achieved both recommendations.
Results
Of 1788 subjects studied (age 67 ± 8 yrs, BMI 31 ± 6 kg/m2, 60% women), 16.7% of men and 12.6% of women walked ≥10,000 steps/day, while 6% of men and 5% of women met the 2008 Physical Activity Guidelines for Americans. Of those walking ≥10,000 steps/day, 16.7% and 26.7% of men and women also met the 2008 Physical Activity Guidelines.
Conclusions
Among this sample of older adults with or at high risk of knee OA, walking ≥10,000 steps/day did not translate into meeting public health guidelines. These findings highlight the disparity between number of steps/day believed to be needed and recommended time-intensity guidelines to achieve positive health benefits.
doi:10.1016/j.apmr.2012.11.038
PMCID: PMC3608824  PMID: 23228625
Physical Activity; knee osteoarthritis; pedometer; Public Health Guidelines; Walking
25.  PERIPATELLAR SYNOVITIS: COMPARISON BETWEEN NON-CONTRAST-ENHANCED AND CONTRAST-ENHANCED MRI AND ASSOCIATION WITH PAIN. THE MOST STUDY 
Purpose
To assess the diagnostic performance of signal changes in Hoffa's fat pad (HFP) assessed on non-contrast-enhanced (CE) MRI in detecting synovitis, and the association of pain with signal changes in Hoffa’s fat pad on non-CE MRI and peripatellar synovial thickness on CE MRI.
Methods
The Multicenter Osteoarthritis (MOST) Study is an observational study of individuals who have or are at high risk for knee OA. All subjects with available non-CE and CE MRIs were included. Signal changes in HFP were scored from 0 to 3 in 2 regions using non-CE MRI. Synovial thickness was scored from 0 to 2 on CE MRI in 5 peripatellar regions. Sensitivity, specificity and accuracy of HFP signal changes were calculated considering synovial thickness on CE MRI as the reference standard. We used logistic regression to assess the associations of HFP changes (non-CE MRI) and synovial thickness (CE MRI) with pain from walking up or down stairs, after adjusting for potential confounders.
Results
A total of 393 subjects were included. Sensitivity of infrapatellar and intercondylar signal changes in HFP was high (71% and 88%), but specificity was low (55% and 30%). No significant associations were found between HFP changes on non-CE MRI and pain. Grade 2 synovial thickness assessed on CE MRI was significantly associated with pain after adjustments for potential confounders.
Conclusion
Signal changes in HFP detected on non-CE MRI are a sensitive but non-specific surrogate for the assessment of synovitis. CE MRI identifies associations with pain better than non-CE MRI.
doi:10.1016/j.joca.2012.12.006
PMCID: PMC3578385  PMID: 23277189
Knee osteoarthritis; synovitis; magnetic resonance imaging; knee pain

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