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Background: Knee osteoarthritis (OA) is more common in females than in males; however, the biological mechanisms for the difference in sex in patients with knee OA are not well understood. Knee shape is associated with OA and with sex, but the patterns of change in the bone's shape over time and their relation to sex and OA are unknown and may help inform how sex is associated with shape and OA and whether the effect is exerted early or later in life.Questions/purposes (1) Does knee shape segregate stably into different groups of trajectories of change (groups of knees that share similar patterns of changes in bone shape over time)? (2) Do females and males have different trajectories of bone shape changes? (3) Is radiographic OA at baseline associated with trajectories of bone shape changes?, Methods: We used data collected from the NIH-funded Osteoarthritis Initiative (OAI) to evaluate a cohort of people aged 45 to 79 years at baseline who had either symptomatic knee OA or were at high risk of having it. The OAI cohort included 4796 participants (58% females; n = 2804) at baseline who either had symptomatic knee OA (defined as having radiographic tibiofemoral knee OA and answering positively to the question "have you had pain, aching or stiffness around the knee on most days for at least one month during the past 12 months") or were at high risk of symptomatic knee OA (defined as having knee symptoms during the prior 12 months along with any of the following: overweight; knee injury; knee surgery other than replacement; family history of total knee replacement for OA; presence of Heberden's nodes; daily knee bending activity) or were part of a small nonexposed subcohort. From these participants, we limited the eligible group to those with radiographs available and read at baseline, 2 years, and 4 years, and randomly selected participants from each OAI subcohort in a manner to enrich representation in the study of the progression and nonexposed subcohorts, which were smaller in number than the OA incidence subcohort. From these patients, we randomly sampled 473 knees with radiographs available at baseline, 2 years, and 4 years. We outlined the shape of the distal femur and proximal tibia on radiographs at all three timepoints using statistical shape modelling. Five modes (each mode represents a particular type of knee bone shape variation) were derived for the proximal tibia and distal femur's shape, accounting for 78% of the total variance in shape. Group-based trajectory modelling (a statistical approach to identify the clusters of participants following a similar progression of change of bone shape over time, that is, trajectory group) was used to identify distinctive patterns of change in the bone shape for each mode. We examined the association of sex and radiographic OA at baseline with the trajectories of each bone shape mode using a multivariable polytomous regression model while adjusting for age, BMI, and race., Results: Knee bone shape change trajectories segregated stably into different groups. In all modes, three distinct trajectory groups were derived, with the mean posterior probabilities (a measure of an individual's probability of being in a particular group and often used to characterize how well the trajectory model is working to describe the population) ranging from 84% to 99%, indicating excellent model fitting. For most of the modes of both the femur and tibia, the intercepts for the three trajectory groups were different; however, the rates of change were generally similar in each mode. Females and males had different trajectories of bone shape change. For Mode 1 in the femur, females were more likely to be in trajectory Groups 3 (odds ratio 30.2 [95% CI 12.2 to 75.0]; p < 0.001) and 2 than males (OR 4.1 [95% CI 2.3 to 7.1]; p < 0.001); thus, females had increased depth of the intercondylar fossa and broader shaft width relative to epicondylar width compared with males. For Mode 1 in the tibia, females were less likely to be in trajectory Group 2 (OR 0.5 [95% CI 0.3 to 0.9]; p = 0.01) than males (that is, knees of females were less likely to display superior elevation of tibial plateau or decreased shaft width relative to head width). Radiographic OA at baseline was associated with specific shape-change trajectory groups. For Mode 1 in the femur, knees with OA were less likely to be in trajectory Groups 3 (OR 0.4 [95% CI 0.2 to 0.8]; p = 0.008) and 2 (OR 0.6 [95% CI 0.3 to 1.0]; p = 0.03) than knees without OA; thus, knees with OA had decreased depth of the intercondylar fossa and narrower shaft width relative to epicondylar width compared with knees without OA. For Mode 1 in the tibia, knees with OA were not associated with trajectory., Conclusions: The shapes of the distal femur and proximal tibia did not change much over time. Sex and baseline knee radiographic OA status are associated with the trajectory of change in the bone's shape, suggesting that both may contribute earlier in life to the associations among trajectories observed in older individuals. Future studies might explore sex-related bone shape change earlier in life to help determine when the sex-specific shapes arise and also the degree to which these sex-related shapes are alterable by injury or other events., Level of Evidence: Level III, prognostic study.

Objectives: To determine meniscal extrusion and cartilage coverage on magnetic resonance (MR) images and factors associated with these parameters in knees of middle-aged and elderly persons free from radiographic tibiofemoral osteoarthritis (OA)., Methods: Seven hundred eighteen persons, free of radiographic tibiofemoral OA, aged 50-90 years from Framingham, MA, USA, were included. We measured meniscal extrusion on 1.5 T MRI of both knees to evaluate both medial and lateral meniscal body extrusion and cartilage coverage. We also determined meniscal morphology and structural integrity. The multivariable association with age, body mass index (BMI), and ipsilateral meniscal damage was also evaluated., Results: The mean meniscal body extrusion medially was 2.7 mm and laterally 1.8 mm. The tibial cartilage coverage was about 30% of ipsilateral cartilage surface (both compartments). The presence of ipsilateral meniscal damage was associated with more extrusion in only the medial compartment, 1.0 mm in men and 0.6 mm in women, and less cartilage coverage proportion, -5.5% in men and -4.6% in women., Conclusions: Mean medial meniscal body extrusion in middle-aged or older persons without radiographic tibiofemoral OA approximates the commonly used cutoff (3 mm) to denote pathological extrusion. Medial meniscal damage is a factor associated with medial meniscal body extrusion and less cartilage coverage., Key Points: • Medial meniscal extrusion in middle-aged/older persons without OA is around 3 mm. • Lateral meniscal extrusion in middle-aged/older persons without OA is around 2 mm. • Meniscal damage is associated with medial meniscal extrusion and less cartilage coverage.

Background: Knee bone shape differs between men and women and the incidence of knee osteoarthritis (OA) is higher in women than in men. Therefore, the purpose of the present study was to determine whether the observed difference in the incidence of knee radiographic OA (ROA) between men and women is mediated by bone shape., Methods: We randomly sampled 304 knees from the OAI with incident ROA (i.e., development of Kellgren/Lawrence grade ≥ 2 by month 48) and 304 knees without incident ROA. We characterized distal femur and proximal tibia shape on baseline radiographs using Statistical Shape Modeling. If a specific bone shape was associated with the risk of incident ROA, marginal structural models were generated to assess the mediation effect of that bone shape on the relation of sex and risk of incident knee ROA adjusting for baseline covariates., Results: Case and control participants were similar by age, sex and race, but case knees were from higher body mass index (BMI) participants (29.4 vs. 27.0; p < 0.001). Women had 49% increased odds of incident knee ROA compared with men (adjusted odds ratio (OR) = 1.49, 95% Confidence Interval (C.I.): 1.04, 2.12). There was an inconsistent mediation effect for tibial mode 2 between sex and incident knee ROA, with an indirect effect OR of 0.96 (95% C.I.: 0.91-1.00) and a direct effect OR of 1.56 (95% C.I.: 1.08-2.27), suggesting a protective effect for this mode. Similar findings were also observed for the mediation effect of tibia mode 10 and femur mode 4. These shape modes primarily involved differences in the angular relation of the heads to the shafts of the femur and tibia., Conclusions: Distal femur and proximal tibia bone shapes partially and inconsistently mediated the relationship between sex and incident knee OA. Women had a higher risk of incident ROA, and specific bone shapes modestly protected them from even higher risk of ROA. The clinical significance of these findings warrant further investigation.

Objective: Participation restriction, common among people with knee osteoarthritis (OA), may be influenced by affect. We examined the risk of incident participation restriction over 84 months conferred by positive and negative affect among people with knee OA., Methods: Participants were from the Multicenter Osteoarthritis Study and had or were at high risk of knee OA. Participation restriction was measured using the Instrumental Role Limitation subscale of the Late-Life Disability Index, and affect was measured using the positive affect and depressed mood subscales of the Center for Epidemiologic Studies Depression Scale. Robust Poisson regression was used to calculate the risk of incident participation restriction over 84 months conferred by combinations of low and high positive and negative affect, adjusting for covariates., Results: Of 1,810 baseline participants (mean age 62.1 years, 56% female), 470 (26%) had incident participation restriction over 84 months. Participants with low positive affect had 20% greater risk of incident participation restriction than those with high positive affect; participants with high negative affect had 50% greater risk of incident participation restriction compared to those with low negative affect. Participants with both low positive and high negative affect had 80% greater risk of incident participation restriction compared to other combinations of positive and negative affect., Conclusion: Low positive and high negative affect, both alone and in combination, increase the risk of participation restriction among adults with knee OA. Efforts aimed at preventing participation restriction in this population should consider these mood states., (© 2017, American College of Rheumatology.)

Objective: To evaluate the relationship between chondrocalcinosis and pain or synovitis in knee joints by examining data from the Osteoarthritis Initiative (OAI)., Methods: Data were obtained from the OAI public-use data sets. The relationship between chondrocalcinosis on baseline knee radiograph and pain at baseline and at 4 years was examined. Analyses were adjusted for age, sex, body mass index, and Kellgren-Lawrence (K/L) grade and the correlation between 2 knees in a subject was controlled using generalized estimating equations. The relationship between chondrocalcinosis and synovitis on magnetic resonance imaging (MRI) was examined by comparing knees with chondrocalcinosis at baseline and age, sex, and K/L grade-matched knees with no chondrocalcinosis. We read MRIs of a subset of knees for synovitis using the MRI Osteoarthritis Knee Score (MOAKS) on baseline and 4-year MRI., Results: Knees with chondrocalcinosis (n = 162) more often had pain compared to knees without chondrocalcinosis (n = 2,030) at baseline and had higher Western Ontario and McMaster Universities Osteoarthritis Index pain scores, both at baseline (mean 2.4 [95% confidence interval (95% CI) 1.9, 2.9]) versus mean 1.8 [95% CI 1.7, 1.9]) and at 4 years (mean 2.5 [95% CI 1.9, 3.1] versus mean 1.6 [95% CI 1.5, 1.8]), as well as higher Intermittent and Constant Osteoarthritis Pain intermittent pain scores at 4 years. There was no difference in MOAKS synovitis scores at baseline and at 4 years between the chondrocalcinosis group (n = 102) and the control group (n = 99)., Conclusion: Knees with chondrocalcinosis had increased pain and did not have higher synovitis scores on MRI compared to knees without chondrocalcinosis. The mechanisms by which chondrocalcinosis is associated with increased pain remain to be determined., (© 2017, American College of Rheumatology.)

Objective: Dietary fiber may reduce knee pain, in part by lowering body weight and reducing inflammation. In this study, we assessed whether fiber intake was associated with patterns of knee pain development., Methods: In a prospective, multicenter cohort of 4,796 men and women ages 45-79 years with or at risk of knee osteoarthritis, participants underwent annual followups for 8 years. Dietary fiber intake was estimated using a validated food frequency questionnaire at baseline. Group-based trajectory modeling was used to identify Western Ontario and McMaster Universities Osteoarthritis Index pain trajectories, which were assessed for associations with dietary fiber intake using polytomous regression models., Results: Of the eligible participants (4,470 persons and 8,940 knees, mean ± SD age 61.3 ± 9.1 years, 58% women), 4.9% underwent knee replacement and were censored at the time of surgery. Four distinct knee pain patterns were identified: no pain (34.5%), mild pain (38.1%), moderate pain (21.2%), and severe pain (6.2%). Dietary total fiber was inversely related to membership in the moderate or severe pain groups (P ≤ 0.006 for trend for both). Subjects in the highest versus those in the lowest quartile of total fiber intake had a lower risk of belonging to the moderate pain pattern group (odds ratio [OR] 0.76 [95% confidence interval (95% CI) 0.61-0.93]) and severe pain pattern group (OR 0.56 [95% CI 0.41-0.78]). Similar results were found with grain fiber and these 2 pain pattern groups., Conclusion: Our findings suggest that a high intake of dietary total or grain fiber, particularly the recommended daily fiber average intake of 25 gm per day, is associated with a lower risk of developing moderate or severe knee pain over time., (© 2016, American College of Rheumatology.)

The objective of this project was to determine the relationship between medial tibiofemoral joint space width measured on fixed-flexion radiographs and the three-dimensional joint space width distribution on low-dose, standing CT (SCT) imaging. At the 84-month visit of the Multicenter Osteoarthritis Study, 20 participants were recruited. A commercial SCT scanner for the foot and ankle was modified to image knees while standing. Medial tibiofemoral joint space width was assessed on radiographs at fixed locations from 15% to 30% of compartment width using validated software and on SCT by mapping the distances between three-dimensional subchondral bone surfaces. Individual joint space width values from radiographs were compared with three-dimensional joint space width values from corresponding sagittal plane locations using paired t-tests and correlation coefficients. For the four medial-most tibiofemoral locations, radiographic joint space width values exceeded the minimal joint space width on SCT by a mean of 2.0 mm and were approximately equal to the 61st percentile value of the joint space width distribution at each respective sagittal-plane location. Correlation coefficients at these locations were 0.91-0.97 and the offsets between joint space width values from radiographs and SCT measurements were consistent. There were greater offsets and variability in the offsets between modalities closer to the tibial spine. Joint space width measurements on fixed-flexion radiographs are highly correlated with three-dimensional joint space width from SCT. In addition to avoiding bony overlap obscuring the joint, a limitation of radiographs, the current study supports a role for SCT in the evaluation of tibiofemoral OA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1388-1395, 2017., (© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

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., (© 2016, American College of Rheumatology.)

Objective: High knee extensor strength may be important to protect against the development of knee osteoarthritis (OA) in populations at elevated risk, such as individuals with meniscal pathology. We investigated the extent to which high knee extensor muscle strength was associated with a decreased risk of developing radiographic or symptomatic knee OA in individuals with medial meniscal pathology., Methods: We studied knees that at the baseline visit of the Multicenter Osteoarthritis Study had medial meniscal pathology but did not have radiographic knee OA (373 knees in 373 participants) or symptomatic knee OA (combination of radiographic knee OA and frequent knee symptoms; 531 knees in 531 participants). Isokinetic knee extensor strength was measured at baseline, and participants were followed for development of incident radiographic knee OA or incident symptomatic knee OA at 84 months. Separate binomial regression analyses with robust SEs adjusted for age, history of knee surgery, physical activity level, and clinic site were conducted for men and women., Results: High knee extensor strength (normalized by allometric scaling) was associated with a reduced risk of radiographic knee OA in women (relative risk [RR] 0.52, 95% confidence interval [95% CI] 0.29-0.94) but not in men (RR 0.56, 95% CI 0.27-1.16). High knee extensor strength did not protect against the development of symptomatic knee OA, either in women or men., Conclusion: The results only partly confirm the hypothesis that high knee extensor muscle strength protects against later development of knee OA in individuals with medial meniscal pathology., Competing Interests: Ali Guermazi is President of Boston Imaging Core Lab (BICL), LLC and Consultant to MerckSerono, Genzyme, OrthoTrophix and TissueGene. Frank Roemer: CMO, Shareholder BICL, LLC., (© 2016, American College of Rheumatology.)

Objective: Pain and functional decline are hallmarks of knee osteoarthritis (OA). Nevertheless, longitudinal studies unexpectedly reveal stable or improved physical function. The aim of this study was to impute missing and pre-total knee replacement (TKR) values to describe physical function over time among people with symptomatic knee OA., Methods: We included participants from the Multicenter Osteoarthritis Study (MOST) and the Osteoarthritis Initiative (OAI) with incident symptomatic knee OA, observed during the first 30 months in MOST and 36 months in OAI. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical function (WOMAC-PF), the 5-times sit-to-stand test, and the 20-meter-walk test were assessed at 4 and 5 years in MOST and at 6 years in OAI. We used a multiple imputation method for missing visits, and estimated pre-TKR values close to the time of TKR, using a fitted local regression smoothing curve. In mixed-effect models, we investigated the physical function change over time, using data before and after imputation and calculation of pre-TKR values., Results: In MOST, 225 (8%) had incident knee OA, with corresponding 577 (12.7%) in OAI. After adjusting for pre-TKR values and imputing missing values, we found that WOMAC-PF values remained stable or slightly declined over time, and the 20-meter-walk test results changed from stable in nonimputed analyses to worsening using imputed data., Conclusion: Data from MOST and OAI showed stable to worsening physical function over time in people with incident symptomatic knee OA after imputing missing values and adjusting pre-TKR values., (© 2016, American College of Rheumatology.)

Background: Debilitating pain associated with knee osteoarthritis (OA) often leads patients to seek and complete total knee arthroplasty (TKA). To date, few studies have evaluated the relation of functional impairment to the risk of TKA, despite the fact that OA is associated with functional impairment., Questions/purposes: The purpose of our study was to (1) evaluate whether function as measured by WOMAC physical function subscale was associated with undergoing TKA; and (2) whether any such association varied by sex., Methods: The National Institutes of Health-funded Multicenter Osteoarthritis Study (MOST) is an observational cohort study of persons aged 50 to 79 years with or at high risk of symptomatic knee OA who were recruited from the community. All eligible subjects with complete data were included in this analysis. Our study population sample consisted of 2946 patients with 5796 knees; 1776 (60%) of patients were women. We performed a repeated-measures analysis using baseline WOMAC physical function score to predict the risk of TKA from baseline to 30 months and WOMAC score at 30 months to predict risk of incident TKA from 30 months to 60 months. We used generalized estimating equations to account for the correlation between two knees within an individual and across the two periods. We calculated relative risk (RR) of TKA over 30 months by WOMAC function using a score of 0 to 5 as the referent in multiple binomial regressions with log link., Results: Those with the greatest functional impairment (WOMAC scores 40-68; 62 TKAs in 462 knee periods) had 15.5 times (95% confidence interval [CI], 7.6-31.8; p<0.001) the risk of undergoing TKA over 30 months compared with the referent group (12 TKAs in 3604 knee periods), adjusting for basic covariates, and 5.9 times (95% CI, 2.8-12.5; p<0.001) the risk after further adjusting for knee pain severity. At every level of functional limitation, the RR for TKA for women was higher than for men, but interaction with sex did not reach significance after adjustment for covariates including ipsilateral pain (p=0.138)., Conclusions: Baseline physical function appears to be an important element in patients considering TKA. Future studies should examine whether interventions to improve function can reduce the need for TKA., Level of Evidence: Level III, observational cohort study.

Objective: To determine the diagnostic performance of standing computerized tomography (SCT) of the knee for osteophytes and subchondral cysts compared with fixed-flexion radiography, using MRI as the reference standard., Methods: Twenty participants were recruited from the Multicenter Osteoarthritis Study. Participants' knees were imaged with SCT while standing in a knee-positioning frame, and with postero-anterior fixed-flexion radiography and 1T MRI. Medial and lateral marginal osteophytes and subchondral cysts were scored on bilateral radiographs and coronal SCT images using the OARSI grading system and on coronal MRI using Whole Organ MRI Scoring. Imaging modalities were read separately with images in random order. Sensitivity, specificity and accuracy for the detection of lesions were calculated and differences between modalities were tested using McNemar's test., Results: Participants' mean age was 66.8 years, body mass index was 29.6 kg/m(2) and 50% were women. Of the 160 surfaces (medial and lateral femur and tibia for 40 knees), MRI revealed 84 osteophytes and 10 subchondral cysts. In comparison with osteophytes and subchondral cysts detected by MRI, SCT was significantly more sensitive (93 and 100%; p < 0.004) and accurate (95 and 99%; p < 0.001 for osteophytes) than plain radiographs (sensitivity 60 and 10% and accuracy 79 and 94%, respectively). For osteophytes, differences in sensitivity and accuracy were greatest at the medial femur (p = 0.002)., Conclusions: In comparison with MRI, SCT imaging was more sensitive and accurate for detection of osteophytes and subchondral cysts than conventional fixed-flexion radiography. Additional study is warranted to assess diagnostic performance of SCT measures of joint space width, progression of OA features and the patellofemoral joint.

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.

Objective: To examine the cross-sectional association of whole-knee synovitis assessed by contrast-enhanced magnetic resonance imaging (CEMRI) with radiographic tibiofemoral osteoarthritis (OA), non-CEMRI-assessed cartilage damage, and meniscal status., Methods: Multicenter Osteoarthritis Study (MOST) is a cohort study of people with or at high risk of knee OA. Subjects are a subset of MOST who volunteered for both CEMRI and non-CEMRI. Using CEMRI, synovitis was assessed at 11 sites and graded 0-2 at each site. Presence of "whole-knee synovitis" was defined as the synovitis score of ≥ 1 at any site from each knee. Cartilage and meniscal damage was evaluated using non-CEMRI based on the Whole Organ MRI Score. Logistic regression was used to assess associations of synovitis with radiographic OA (Kellgren-Lawrence grade ≥ 2), widespread cartilage damage, and meniscal damage, adjusting for age, sex, and body mass index (BMI). Additional analyses were performed excluding subjects who had chondrocalcinosis on radiography and those taking antiinflammatory medications., Results: Four hundred four subjects were included (mean age 58.8 ± 7.0 yrs, BMI 29.6 ± 4.9 kg/m(2), 45.5% women). On CEMRI, the maximum synovitis score across 11 sites in each knee was 0 in 106 knees (26.2%), 1 in 135 (33.4%), and 2 in 163 (40.4%). Synovitis was associated with radiographic OA [adjusted OR (aOR) 3.25, 95% CI 1.98-5.35] and widespread cartilage damage (aOR 1.91, 95% CI 1.24-2.92). Severe meniscal damage showed a borderline significant association with synovitis (aOR 1.74, 95% CI 0.99-3.04). Additional analyses as described did not notably change the results., Conclusion: CEMRI-detected synovitis is strongly associated with tibiofemoral radiographic OA and MRI-detected widespread cartilage damage.

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., (Copyright © 2013 by the American College of Rheumatology.)

Background: Some of the poor functional outcomes of knee arthroplasty may be due to pain in the contralateral, unreplaced knee. We investigated the relationship between the preoperative pain status of the contralateral knee and the risk of a poor postoperative functional outcome in patients who underwent knee arthroplasty., Methods: We analyzed data on 271 patients in the Multicenter Osteoarthritis Study who had undergone knee arthroplasty since the time of enrollment. Eighty-six percent of these patients were white, 72% were female, and the mean age was sixty-seven years. The severity of pain in the knee contralateral to the one that was replaced was measured before the knee arthroplasty with use of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scale, with the scores being grouped into four categories (0, 1 to 4, 5 to 9, and 10 to 20). Poor post-arthroplasty function six months or more after surgery was determined with use of the Patient Acceptable Symptom State (PASS) outcome tool and a clinical performance measure of walking speed. We evaluated the relationship between contralateral pain severity and the functional outcomes with use of Poisson regression., Results: Seventy-two (27%) of 264 patients demonstrated poor post-arthroplasty function by failing to attain the threshold PASS score, and seventy-six (30%) of 250 subjects had a slow walking speed. As the pre-arthroplasty pain in the contralateral knee increased, there was a steady increase in the proportion with poor post-arthroplasty function (p &lt; 0.0001 for PASS and p = 0.04 for slow walking speed). Compared with patients who had no pre-arthroplasty pain in the contralateral knee, those in the highest category of contralateral pain severity had 4.1 times the risk (95% confidence interval, 1.5 to 11.5) of having poor self-reported post-arthroplasty function. Patients in whom both knees had been replaced at the time of outcome collection were less likely to have poor self-reported function than those in whom only one knee had been replaced., Conclusions: Preoperative pain in the contralateral knee is strongly associated with self-reported post-arthroplasty functional outcome and may therefore be a useful indicator of prognosis or a potential target of perioperative intervention., Level of Evidence: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

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 1.5T CE MRI and had semiquantitative synovitis (scored from 0 to 2 at 11 locations) and meniscal readings (scored with WORMS from 0 to 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., (Copyright © 2013 Elsevier Inc. All rights reserved.)

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., (Copyright © 2013 by the American College of Rheumatology.)

Objective: Gait speed is an important marker of health in adults and slows with aging. While knee osteoarthritis (OA) can result in difficulty walking, it is not known if radiographic knee OA (ROA) and/or knee pain are associated with a fast decline trajectory of gait speed over time., Methods: Gait speed trajectories were constructed using a multinomial modeling strategy from repeated 20-meter walk tests measured annually over 4 years among participants from the Osteoarthritis Initiative, a prospective cohort study of adults ages 45-79 years at baseline with or at high risk of knee OA. We grouped participants into 4 knee OA categories (having neither ROA nor knee pain, ROA only, knee pain only, or symptomatic knee OA [ROA and pain]) and examined their association with trajectories of gait speed using a multivariable polytomous regression model adjusting for age and other potential confounders., Results: Of the 4,179 participants (mean ± SD age 61.1 ± 9.1 years, 57.6% women, mean ± SD body mass index 28.5 ± 4.8 kg/m(2) ), 5% (n = 205) were in a fast decline trajectory, slowing at a rate of 2.75%/year. People with symptomatic knee OA had an almost 9-fold risk (odds ratio 8.9; 95% confidence interval [95% CI] 3.1, 25.5) of being in a fast decline trajectory compared with those with neither pain nor ROA. Participants with knee pain had 4.5 times the odds of a fast decline (95% CI 1.4, 14.6), and those with ROA only had a slight but non-statistically significant increased risk., Conclusion: People with symptomatic knee OA have the highest risk of a fast decline trajectory of gait speed compared with people with ROA or pain alone., (Copyright © 2013 by the American College of Rheumatology.)

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., (Copyright © 2013 by the American College of Rheumatology.)

Objective: While depressive symptoms and knee pain are independently known to impede daily walking in older adults, it is unknown whether positive affect promotes daily walking. This study investigated this association among adults with knee osteoarthritis (OA) and examined whether knee pain modified this association., Methods: This study is a cross-sectional analysis of the Multicenter Osteoarthritis Study. We included 1,018 participants (mean ± SD age 63.1 ± 7.8 years, 60% women) who had radiographic knee OA and had worn a StepWatch monitor to record their number of steps per day. High and low positive affect and depressive symptoms were based on the Center for Epidemiologic Studies Depression Scale. Knee pain was categorized as present in respondents who reported pain on most days at both a clinic visit and a telephone screening., Results: Compared to respondents with low positive affect (27% of all respondents), those with high positive affect (63%) walked a similar number of steps per day, while those with depressive symptoms (10%) walked less (adjusted β -32.6 [95% confidence interval (95% CI) -458.9, 393.8] and -579.1 [95% CI -1,274.9, 116.7], respectively). There was a statistically significant interaction of positive affect by knee pain (P = 0.0045). Among the respondents with knee pain (39%), those with high positive affect walked significantly more steps per day (adjusted β 711.0 [95% CI 55.1, 1,366.9]) than those with low positive affect., Conclusion: High positive affect was associated with more daily walking among adults with painful knee OA. Positive affect may be an important psychological factor to consider for promoting physical activity among people with painful knee OA., (Copyright © 2012 by the American College of Rheumatology.)

Objective: We conducted a cross-sectional study to describe the prevalence of tibiofemoral joint space narrowing (JSN) in medial and lateral compartments and assess whether it differs by sex and ethnic groups, and, if it does, to what extent such a difference is accounted for by knee malalignment., Methods: The Multicenter Osteoarthritis Study is an observational study of persons ages 50-79 years with either symptomatic knee osteoarthritis or high risk of disease. Knee radiographs were assessed for JSN in each tibiofemoral compartment. Mechanical axis angle was measured using full-extremity films. We compared the proportion of knees with medial compartment JSN and with lateral JSN between men and women, as well as between whites and African Americans, using a logistic regression model adjusting for covariates (race or sex and body mass index, age, education, and clinic site). We used generalized estimating equations to account for correlation between 2 knees within a person., Results: Of 5,202 knees (2,652 subjects), 1,532 (29.5%) had medial JSN and 427 (8.2%) had lateral JSN. Lateral JSN was more prevalent in the knees of women than in men (odds ratio [OR] 1.9, 95% confidence interval [95% CI] 1.5-2.4) and was also higher in the knees of African Americans than in whites (OR 2.4, 95% CI 1.7-3.3). Further adjustment for malalignment attenuated the OR for sex but not the OR for race., Conclusion: Women and African Americans are more likely to have lateral JSN than men and whites, respectively. Valgus malalignment may contribute to the higher prevalence in women., (Copyright © 2012 by the American College of Rheumatology.)

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., (Copyright © 2012 by the American College of Rheumatology.)

Objective: To evaluate if two different measures of synovial activation, baseline Hoffa synovitis and effusion synovitis, assessed by MRI, predict cartilage loss in the tibiofemoral joint at 30 months follow-up in subjects with neither cartilage damage nor tibiofemoral radiographic osteoarthritis of the knee., Methods: Non-contrast-enhanced MRI was performed using proton density-weighted fat-suppressed sequences in the axial and sagittal planes and a short tau inversion recovery sequence in the coronal plane. Hoffa synovitis, effusion synovitis and cartilage status were assessed semiquantitatively according to the WORMS scoring system. Included were knees that had neither radiographic osteoarthritis nor MRI-detected tibiofemoral cartilage damage at the baseline visit. The presence of Hoffa synovitis was defined as any grade ≥ 2 (range 0-3) and effusion synovitis as any grade ≥ 2 (range 0-3). Logistic regression was performed to examine the relation of the presence of either measure to the risk of cartilage loss at 30 months adjusting for other potential confounders., Results: Of 514 knees included in the analysis, the prevalence of Hoffa synovitis and effusion synovitis at the baseline visit was 8.4% and 10.3%, respectively. In the multivariable analysis, baseline effusion synovitis was associated with an increased risk of cartilage loss. No such association was observed for baseline Hoffa synovitis., Conclusions: Baseline effusion synovitis, but not Hoffa synovitis, predicted cartilage loss. The findings suggest that effusion synovitis, a reflection of inflammatory activity including joint effusion and synovitic thickening, may play a role in the future development of cartilage lesions in knees without osteoarthritis.

Objective: To assess the cross-sectional relation of planus foot morphology to ipsilateral knee pain and compartment-specific knee cartilage damage in older adults., Methods: In the Framingham Studies, we adapted the Staheli Arch Index (SAI) to quantify standing foot morphology from pedobarographic recordings. We inquired about knee pain and read 1.5 T magnetic resonance image (MRI) scans using the Whole-Organ MRI Score. Logistic regression compared the odds of knee pain among the most planus feet to the odds among all other feet, and estimated odds within categories of increasing SAI. Similar methods estimated the odds of cartilage damage in each knee compartment. Generalized estimating equations adjusted for age, sex, body mass index, and nonindependent observations., Results: Among 1,903 participants (56% women, mean ± SD age 65 ± 9 years), 22% of knees were painful most days. Cartilage damage was identified in 45% of medial tibiofemoral (TF), 27% of lateral TF, 58% of medial patellofemoral (PF), and 42% of lateral PF compartments. Compared with other feet, the most planus feet had 1.3 times (95% confidence interval [95% CI] 1.1-1.6) the odds of knee pain (P = 0.009), and 1.4 times (95% CI 1.1-1.8) the odds of medial TF cartilage damage (P = 0.002). Odds of pain (P for linear trend = 0.05) and medial TF cartilage damage (P for linear trend = 0.001) increased linearly across categories of increasing SAI. There was no association between foot morphology and cartilage damage in other knee compartments., Conclusion: Planus foot morphology is associated with frequent knee pain and medial TF cartilage damage in older adults., (Copyright © 2011 by the American College of Rheumatology.)

Objective: To examine whether the consistency or persistence of knee pain, in addition to its severity, predicts incident total knee replacement (TKR)., Methods: The Multicenter Osteoarthritis Study (MOST) is a longitudinal study of persons aged 50 to 79 years with symptomatic knee osteoarthritis or at high risk of disease. Subjects were queried about the presence of knee pain on most days of the previous 30 days (i.e., frequent knee pain; FKP) at 2 timepoints: a telephone screen followed by a clinic visit (median separation 4 weeks). We defined a knee as having "consistent pain" if the subject answered positively to the FKP question at both timepoints, "inconsistent pain" if FKP was positive at only one timepoint, or as "no FKP" if negative at both. We examined the association between consistent FKP and risk of TKR using multiple binomial regression with generalized estimating equations., Results: In 3026 persons (mean age 63 yrs, mean body mass index 30.4), 2979 knees (50%) had no FKP at baseline, 1279 knees (21.5%) had inconsistent FKP, and 1696 knees (28.5%) had consistent FKP. Risk of TKR over 30 months was 0.8%, 2.6%, and 8.8% for knees with no, inconsistent, and consistent FKP, respectively. Relative risks of TKR over 30 months were 1.2 (95% CI 0.6-2.3) and 2.3 (95% CI 1.2-4.4) for knees with inconsistent and consistent FKP, compared with those without FKP. This association was consistent across each level of pain severity on the Western Ontario and McMaster Universities Osteoarthritis Index., Conclusion: Consistency of frequent knee pain is associated with an increased risk of TKR independently of knee pain severity.

Purpose: To assess the association of prevalent bone marrow edema-like lesions (BMLs) and full-thickness cartilage loss with incident subchondral cyst-like lesions (SCs) in the knee to evaluate the bone contusion versus synovial fluid intrusion theories of SC formation., Materials and Methods: The Multicenter Osteoarthritis study is a longitudinal study of individuals who have or are at risk for knee osteoarthritis. The HIPAA-compliant protocol was approved by the institutional review boards of all participating centers, and written informed consent was obtained from all participants. Magnetic resonance images were acquired at baseline and 30-month follow-up and read semiquantitatively by using the Whole-Organ Magnetic Resonance Imaging Score system. The tibiofemoral and patellofemoral joints were subdivided into 14 subregions. BMLs and SCs were scored from 0 to 3. Cartilage morphology was scored from 0 to 6. The association of prevalent BMLs and full-thickness cartilage loss with incident SCs in the same subregion was assessed by using logistic regression with mutual adjustment for both predictors., Results: A total of 1283 knees were included. After adjustment for full-thickness cartilage loss, prevalent BMLs showed a strong and significant association with incident SCs in the same subregion, with an odds ratio of 12.9 (95% confidence interval [CI]: 8.9, 18.6). After adjustment for BMLs, prevalent full-thickness cartilage loss showed a significant but much less important association with incident SCs in the same subregion (odds ratio, 1.4; 95% CI: 1.0, 2.0). There was no apparent relationship between severity of full-thickness cartilage loss at baseline and incident SCs., Conclusion: Prevalent BMLs strongly predict incident SCs in the same subregion, even after adjustment for full-thickness cartilage loss, which supports the bone contusion theory of SC formation., ((c) RSNA, 2010.)

Introduction: Subchondral bone attrition (SBA), a feature of osteoarthritis, may be caused by excess focal load to bone, and/or inadequate bone quality to withstand loads through the joint. This study evaluated the effects of malalignment, which can cause focal excessive load, and systemic bone density on the presence and incidence of SBA., Methods: The Multicenter Osteoarthritis Study is a cohort of individuals who have or are at high risk of knee osteoarthritis. Baseline alignment and bone mineral density (BMD) measures were assessed. Baseline and 30-month knee magnetic resonance images were graded for SBA (grade 0-3) using the whole-organ magnetic resonance imaging score. The study evaluated the association of alignment in medial and lateral compartments, respectively, and systemic BMD with baseline presence of SBA and incident SBA using logistic regression and adjusting for age, sex and body mass index., Results: Of 1253 participants (mean age 62 years, mean BMI 30, 61% women), 33% had baseline SBA and 44% had knee osteoarthritis. Associations between the presence and incidence of SBA with malalignment in both compartments were noted (odds ratios (95% CI) 2.9 (2.1 to 4.0) and 1.9 (1.2 to 2.9), respectively, for varus knees in the medial compartment; 4.5 (2.8 to 7.1) and 2.1 (1.1 to 4.1), respectively, for valgus knees in the lateral compartment). Low BMD was not associated with SBA., Conclusions: The presence and incidence of SBA are associated with malalignment in a compartment-specific manner, but not with low BMD. SBA may be a marker of increased load experienced by overlying cartilage, which may contribute to increased forces transmitted to the cartilage due to alteration in subchondral bone.

Objective: Progression of knee osteoarthritis (OA) has typically been assessed in the medial tibiofemoral (TF) compartment on the anteroposterior (AP) or posteroanterior (PA) view. We propose a new approach using multiple views and compartments that is likely to be more sensitive to change and reveals progression throughout the knee., Methods: We tested our approach in the Multicenter Osteoarthritis Study, a study of persons with OA or at high risk of disease. At baseline and 30 months, subjects provided PA (fixed flexion without fluoro) and lateral weight-bearing knee radiographs. Paired radiographs were read by 2 readers who scored joint space (JS) using a 0-3 atlas-based scale. When JS narrowed but narrowing did not reach a full grade on the scale, readers used half-grades. Change was scored in medial and lateral TF compartments on both PA and lateral views and in the patellofemoral (PF) joint on lateral view. A knee showed progression when there was at least a half-grade worsening in JS width in any compartment at followup. Disagreements were adjudicated by a panel of 3 readers. To validate progression, we tested definitions for TF progression to see if malalignment on long-limb radiographs at baseline (>or=3 degrees malaligned in any direction with nonmalaligned knees being reference) increased risk of progression. A valid definition of progression would show that malalignment strongly predicted progression., Results: We studied 842 knees with either Kellgren-Lawrence grade>or=2 or PF OA at baseline in 606 subjects (age range 50-79 yrs, mean 63.9 yrs; 66.6% women). Mean body mass index was 31.9, and 32.8% of knees had frequent knee pain at baseline. Of these, 500 knees (59.4%) showed progression. Of the 500, 75 (15%) had progression only in the PF joint, while the remainder had progression in the TF joint. Malalignment increased the risk of overall progression in TF joint and increased the risk of half-grade progression, suggesting that half-grade progression had validity., Conclusion: PA and lateral views obtained in persons at high risk of OA progression can produce a cumulative incidence of progression above 50% at 30 months. Keys to increasing the yield include imaging PF and lateral compartments, using semiquantitative scales designed to detect change, and examining more than one radiographic view.

Objective: We examined the relation between occupational exposures to frequent squatting/kneeling and/or heavy lifting with cartilage morphology, based on magnetic resonance imaging (MRI), at the tibiofemoral and patellofemoral joints in men and determined which compartments are most affected., Methods: We evaluated 192 men with symptomatic knee osteoarthritis (OA). The more symptomatic knee was imaged using MRI. Cartilage was scored using the Whole Organ MRI Score semiquantitative method at the medial and lateral tibiofemoral joint and patellofemoral joint. Occupational exposures to frequent squatting, kneeling, and/or heavy lifting were assessed using a validated questionnaire., Results: Among the 192 men [mean (+/- standard deviation) age 69 +/- 9 yrs, body mass index (BMI) 30.8 +/- 4.7 kg/m(2)], those reporting occupational exposure to squatting/kneeling alone, heavy lifting alone, both squatting/kneeling and heavy lifting, or none of these activities numbered 7, 40, 47, and 98, respectively. Compared with men with no occupational exposure to these activities, and following adjustment for age, BMI, and history of knee injury or surgery, we found that men reporting occupational exposures to both squatting/kneeling and heavy lifting had a modest increased risk for worse cartilage morphology scores at the patellofemoral joint [odds ratio (OR) 1.8, 95% confidence interval (CI) 1.1 to 3.2] and medial tibiofemoral joint (OR 1.6, 95% CI 0.9, 3.0), although the latter did not reach statistical significance., Conclusion: Men with frequent occupational squatting/kneeling and heavy lifting have a greater likelihood for worse cartilage morphology scores at the patellofemoral joint. These findings add support to the important role of biomechanical loading on the pathogenesis of knee OA, particularly patellofemoral OA.

Objective: To examine the relationship between longitudinal fluctuations in synovitis with change in pain and cartilage in knee osteoarthritis., Methods: Study subjects were patients 45 years of age and older with symptomatic knee osteoarthritis from the Boston Osteoarthritis of the Knee Study. Baseline and follow-up assessments at 15 and 30 months included knee magnetic resonance imaging (MRI), BMI and pain assessment (VAS) over the last week. Synovitis was scored at 3 locations (infrapatellar fat pad, suprapatellar and intercondylar regions) using a semiquantitative scale (0-3) at all 3 time points on MRI. Scores at each site were added to give a summary synovitis score (0-9)., Results: We assessed 270 subjects whose mean (SD) age was 66.7 (9.2) years, BMI 31.5 (5.7) kg/m(2); 42% were female. There was no correlation of baseline synovitis with baseline pain score (r = 0.09, p = 0.17). The change in summary synovitis score was correlated with the change in pain (r = 0.21, p = 0.0003). An increase of one unit in summary synovitis score resulted in a 3.15-mm increase in VAS pain score (0-100 scale). Effusion change was not associated with pain change. Of the 3 locations for synovitis, changes in the infrapatellar fat pad were most strongly related to pain change. Despite cartilage loss occurring in over 50% of knees, synovitis was not associated with cartilage loss in either tibiofemoral or patellofemoral compartment., Conclusions: Change in synovitis was correlated with change in knee pain, but not loss of cartilage. Treatment of pain in knee osteoarthritis (OA) needs to consider treatment of synovitis.

Background: Knee buckling is common in persons with advanced knee osteoarthritis and after orthopedic procedures. Its prevalence in the community is unknown., Objective: To examine the prevalence of knee buckling in the community, its associated risk factors, and its relation to functional limitation., Design: Cross-sectional, population-based study., Setting: The Framingham Osteoarthritis Study., Participants: 2351 men and women age 36 to 94 years (median, 63.5 years)., Measurements: Participants were asked whether they had experienced knee buckling or "giving way" and whether it led to falling. They were also asked about knee pain and limitations in function by using the Short Form-12 and Western Ontario and McMaster Universities Osteoarthritis Index, had isometric tests of quadriceps strength, and underwent weight-bearing radiography and magnetic resonance imaging of the knee. Radiographs were scored for osteoarthritis by using the Kellgren-Lawrence scale, and magnetic resonance images were read for anterior cruciate ligament tears. The relationship of buckling to functional limitation was examined by using logistic regression that adjusted for age, sex, body mass index, and knee pain severity., Results: Two hundred seventy-eight participants (11.8%) experienced at least 1 episode of knee buckling within the past 3 months; of these persons, 217 (78.1%) experienced more than 1 episode and 35 (12.6%) fell during an episode. Buckling was independently associated with the presence of knee pain and with quadriceps weakness. Over half of those with buckling had no osteoarthritis on radiography. Persons with knee buckling had worse physical function than those without buckling, even after adjustment for severity of knee pain and weakness. For example, 46.9% of participants with buckling and 21.7% of those without buckling reported limitations in their work (adjusted odds ratio, 2.0 [95% CI, 1.5 to 2.7])., Limitation: Causal inferences are limited because of the study's cross-sectional design., Conclusion: In adults, knee buckling is common and is associated with functional loss.

Objective: Results of cross-sectional studies have suggested that bone marrow lesions (BMLs) visualized on magnetic resonance imaging (MRI) are related to knee pain, but no longitudinal studies have been done. This study was undertaken to determine whether enlarging BMLs are associated with new knee pain., Methods: Subjects ages 50-79 years with knee osteoarthritis (OA) or at high risk of knee OA were asked twice at baseline about the presence of knee pain, aching, or stiffness (classified as frequent knee pain) on most days; absence of knee pain was the baseline eligibility criterion. At 15 months' followup, subjects were again queried twice about frequent knee pain. A case knee was defined as absence of knee pain at baseline but presence of knee pain both times at followup. Controls were selected randomly from among knees with absence of pain at baseline. All MR images were scored for volume of BMLs in the medial, lateral, and patellofemoral compartments. We focused on the maximal change in BML score among the knee compartments from baseline to 15 months. Multiple logistic regression, with adjustments for demographic and clinical variables, was used to assess whether an increased BML score is predictive of the development of knee pain., Results: Among case knees, 54 of 110 (49.1%) showed an increase in BML score within a compartment, whereas only 59 of 220 control knees (26.8%) showed an increase (P < 0.001 by chi-square test). A BML score increase of at least 2 units was much more common in case knees than in control knees (27.5% versus 8.6%; adjusted odds ratio 3.2, 95% confidence interval 1.5-6.8). Among case knees with increased BMLs, most already had BMLs at baseline, with enlarging BMLs at followup, but among the subset of knees with no BMLs at baseline, new BMLs were more common in case knees (11 [32.4%] of 34) than in control knees (9 [10.8%] of 83)., Conclusion: Development of knee pain is associated with an increase in BMLs as revealed on MRI.

Objective: To examine the relationship of knee malalignment to the occurrence of knee osteoarthritis (OA) among subjects without radiographic OA at baseline to determine whether malalignment is a risk factor for incident disease or simply a marker of increasing disease severity., Methods: We selected 110 incident tibiofemoral (TF) OA case knees (76 subjects) and 356 random control knees (178 subjects) from among participants in the Framingham Osteoarthritis Study. Case knees did not have OA at baseline (1992-1994 examination) but had developed OA (Kellgren/Lawrence grade>or=2) at followup (2002-2005 examination) (mean of 8.75 years between examinations). Control knees did not have OA at baseline. Standardized digital radiographs of the fully extended knee with weight-bearing were read using a standard protocol and eFilm viewing software. We measured the anatomic axis, the condylar angle, the tibial plateau angle, and the condylar tibial plateau angle. The interobserver intraclass correlation coefficient (ICC) ranged from 0.93 to 0.96 and the intraobserver ICC from 0.94 to 0.97. In a knee-specific analysis, we examined the relationship of each alignment measurement to the risk of TF OA using generalized estimating equations, adjusting for age, sex, and body mass index (BMI). We used the same approach to assess the association between each alignment measurement and the risk of medial TF OA., Results: Subjects in the case population were older and had a higher BMI than the controls. The alignment values were normally distributed and were not different between the cases and the controls. After adjustment for age, sex and BMI, there was no significant increase in incident OA in the highest quartile compared with the lowest quartile category for any of the alignment measures (P for trend for anatomic axis and condylar tibial plateau angle was 0.83 and 0.80, respectively). Similar results were also observed for medial compartment OA., Conclusion: We found that baseline knee alignment is not associated with either incident radiographic TF OA or medial TF OA. These results suggest that malalignment is not a risk factor for OA, but rather is a marker of disease severity and/or its progression.

Objective: Few risk factors for knee osteoarthritis (OA) are appreciated, and the discordance between symptoms and the severity of structural disease has not been explained. Knee height contributes to moments around the knee. The longer the leg, the more torque is present. Although this would suggest that having long legs would be related to the occurrence of knee OA and pain, this issue has not been studied. Our aim was to explore the association between knee height, knee pain, and knee OA., Methods: We recruited a random sample of Beijing residents ages 60 years and older. Subjects answered questions about joint symptoms, and radiographs of their knees were obtained. A knee joint with a Kellgren/Lawrence grade of >/=2 was defined as having radiographic OA. Patellofemoral OA was defined as being present when grade >/=1 osteophytes or grade >/=1 joint space narrowing was observed on skyline views of the patella or anterior femur. Subjects were considered to have symptomatic OA when both radiographic OA and self-reported pain were present in the same joint. Knee height was measured on the right leg using a sliding broad-blade caliper; the subject was seated, and the subject's feet were bare. We used logistic regression analyses to assess whether knee height was associated with prevalent radiographic and symptomatic OA. We then assessed whether knee height was associated with knee symptoms independently of structural change., Results: A total of 1,006 men (mean +/- SD age 68.4 +/- 6.4 years) and 1,500 women (mean +/- SD age 67.5 +/- 6.1 years) participated in this study. Higher knee height was associated with an increasing prevalence of both radiographic and symptomatic OA, especially among women. For radiographic OA, the magnitude of association was similar for the patellofemoral and tibiofemoral compartments. Among women with knee pain, higher knee height was associated with more severe knee pain (P = 0.0004 for the highest quartile versus the lowest quartile of knee height) independently of the severity of radiographic OA., Conclusion: Knee height is associated with prevalent radiographic and symptomatic knee OA. It may also play an important role in knee symptoms. This study highlights the importance of mechanical forces in the determination of OA and knee symptoms.

Objective: Whereas obesity increases overall loading of the knee, limb malalignment concentrates that loading on a focal area, to the level at which cartilage damage may occur. This study evaluated whether the effect of body weight on progression of knee osteoarthritis (OA) differs depending on the degree of limb malalignment., Methods: The study population comprised 228 veterans and community recruits with symptomatic knee OA (pain on most days and radiographic disease) who volunteered to participate in a natural history study and from whom baseline radiographs were obtained to assess alignment; 227 (99.6%) completed a 30-month followup. Of 403 knees assessed at baseline, 394 (97.8%) were followed up. Participants' body mass index (BMI) was assessed at each examination. The main outcome measure was progression of knee OA, defined as narrowing of the tibiofemoral joint space by 1 grade (semiquantitative scale 0-3) on radiographs of the fluoroscopically positioned knee. The association between BMI and the risk of knee OA progression was assessed after adjusting for age, sex, and limb alignment, using logistic regression and generalized estimating equations., Results: Of 394 knees, 90 (22.8%) showed disease progression, and limb alignment was strongly associated with progression risk. The risk of progression increased with increasing weight (for each 2-unit increase in BMI, odds ratio [OR] for progression 1.08, 95% confidence interval [95% CI] 1.00-1.16). However, among those knees with neutral alignment (0-2 degrees ), increases in BMI had no effect on risk of progression (OR 1.00), and in those with severe malalignment (> or =7 degrees ), the effect was similarly null (OR 0.93). The effect of BMI on progression was limited to knees in which there was moderate malalignment (OR per 2-unit increase in BMI 1.23, 95% CI 1.05-1.45)., Conclusion: Although elevated BMI increases the risk of knee OA progression, the effect of BMI is limited to knees in which moderate malalignment exists, presumably because of the combined focus of load from malalignment and the excess load from increased weight. This has implications for clinical recommendations and for trials testing weight loss in those with knee OA.

ObjectiveWhether widespread pain (WSP) affects the risk of developing knee pain or knee osteoarthritis (OA) is unknown and could enhance understanding of pain mechanisms in OA.MethodsSubjects from the Multicenter OA (MOST) study, a US National Institutes of Health-funded prospective cohort of older adults with or at risk of knee OA, were characterized regarding WSP, defined as pain above and below the waist on both sides of the body and axially using a standard homunculus, excluding knee pain at 60 months (baseline). Followup occurred 2 years later. We assessed the relation of WSP to odds of knee pain worsening (≥ 2-point increase in the Western Ontario and McMaster Universities Arthritis Index pain subscale) using logistic regression, and to odds of incident radiographic knee OA (ROA; Kellgren-Lawrence arthritis scale ≥ grade 2 of either knee among those free of ROA at baseline) and incident consistent frequent knee pain (CFKP; knee pain on most days during the past month among participants free of knee pain at baseline) in 1 or both knees using multinomial regression adjusting for potential confounders.ResultsThere were 1752 participants available for analysis [mean age (SD) 67.0 yrs (7.7), body mass index 30.5 kg/m2 (5.9), 59% women]. Baseline presence of WSP was not associated with worsened knee pain (adjusted OR 1.15, 95% CI 0.89-1.48, p = 0.30), ROA (adjusted OR 0.86, 95% CI 0.46-1.63, p = 0.65), or incident CFKP (adjusted OR 1.69, 95% CI 0.96-2.96, p = 0.07).ConclusionWSP was not significantly associated with worsening knee pain, incident ROA, or CFKP. Development of knee pain and ROA does not appear to be influenced by underlying WSP.

ObjectiveTo 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.MethodsStudy 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.ResultsAmong 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.ConclusionDifferent 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.

BackgroundParticipation is an important, yet seldom studied, outcome after total knee replacement (TKR).ObjectiveThe purpose of this study was to investigate the extent and predictors of participation and participation restriction among people after TKR.Materials and methodsThis study investigated the changes in pain, function, and participation scores (measured using a subscale of the Late-Life Function and Disability Instrument) from pre-TKR to ≥1 year post-TKR among a subsample of participants from the Multicenter Osteoarthritis Study (MOST) longitudinal cohort (MOST is funded by the National Institutes of Health). The proportions of individuals with participation restriction pre-TKR and ≥1 and ≥2 years post-TKR were calculated for all participants and for important demographic subgroups. The association between demographic and clinical factors and participation was estimated using linear regression. The association between demographic and clinical factors and participation restriction was estimated using logistic regression.ResultsThere were 292 individuals with outcome data ≥1 year post-TKR. Of these, 218 (75%) had data pre-TKR and ≥1 year post-TKR and 160 (55%) had data ≥2 years post-TKR. There were mean improvements in pain, function, and participation at ≥1 and 2 years. However, approximately 30% of the study sample had participation restriction pre-TKR and post-TKR, and the proportion decreased significantly only for those