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The aim of the study was to determine whether tibiofemoral contact stress predicts risk for worsening knee pain over 84 ms in adults aged 50-79 yrs with or at elevated risk for knee osteoarthritis.Baseline tibiofemoral contact stress was estimated using discrete element analysis. Other baseline measures included weight, height, hip-knee-ankle alignment, Kellgren-Lawrence grade, and Western Ontario and McMaster Universities Osteoarthritis Index pain subscale. Logistic regression models assessed the association between baseline contact stress and 84-mo worsening of Western Ontario and McMaster Universities Osteoarthritis Index pain subscale.Data from the dominant knee (72.6% Kellgren-Lawrence grade 0/1 and 27.4% Kellgren-Lawrence grade ≥ 2) of 208 participants (64.4% female, mean ± SD body mass index = 29.6 ± 5.1 kg/m 2 ) were analyzed. Baseline mean and peak contact stress were 3.3 ± 0.9 and 9.4 ± 4.3 MPa, respectively. Forty-seven knees met the criterion for worsening pain. The highest tertiles in comparison with the lowest tertiles of mean (odds ratio [95% confidence interval] = 2.47 [1.03-5.95], P = 0.04) and peak (2.49 [1.03-5.98], P = 0.04) contact stress were associated with worsening pain at 84 mos, after adjustment for age, sex, race, clinic site, and baseline pain. Post hoc sensitivity analyses including adjustment for body mass index and hip-knee-ankle alignment attenuated the effect.These findings suggest that elevated tibiofemoral contact stress can predict the development of worsening of knee pain.

Key Clinical Points Osteoarthritis of the Knee Potential long-term consequences of knee osteoarthritis include reduced physical activity, deconditioning, impaired sleep, fatigue, depression, functi...

Summary Objective To develop a model of early osteoarthritis, by examining whether radiographically normal knees with contralateral joint space narrowing (JSN), but without contralateral trauma history, display greater longitudinal cartilage composition change (transverse relaxation time; T2) than subjects with bilaterally normal knees. Methods 120 radiographically normal knees (Kellgren Lawrence grade [KLG] 0) from the Osteoarthritis Initiative were studied. 60 case knees displayed definite contralateral radiographic knee osteoarthritis (KLG ≥ 2) whereas 60 reference subjects were bilaterally KLG0, and were matched 1:1 to cases based on age, sex, and BMI. All had multi-echo spin-echo MRI acquired at year (Y) 1 and 4 follow-up, with cartilage T2 being determined in superficial and deep cartilage layers across 16 femorotibial subregions. T2 across all regions was considered the primary analytic focus. Results Of 60 KLG0 case knees (30 female, age: 65.0 ± 8.8 y, BMI: 27.6 ± 4.4 kg/m2), 21/22/13/4 displayed contralateral JSN 0/1/2/3, respectively. The longitudinal increase in the deep layer cartilage T2 between Y1 and Y4 was significantly greater (P = 0.03; Cohen's D 0.50) in the 39 KLG0 case knees with contralateral JSN (1.2 ms; 95% confidence interval [CI] [0.4, 2.0]) than in matched KLG0 reference knees (0.1 ms; 95% CI [−0.5, 0.7]). No significant differences were identified in superficial T2 change. T2 at Y1 was significantly greater in case than in reference knees, particularly in the superficial layer of the medial compartment. Conclusions Radiographically normal knees with contralateral, non-traumatic JSN represent an applicable model of early osteoarthritis, with deep layer cartilage composition (T2) changing more rapidly than in bilaterally normal knees. Clinicaltrials.gov identification NCT00080171 .

Objective To investigate the 2-year association of varus knee thrust observed during walking to the odds of worsening Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee pain in older adults with or at risk of osteoarthritis (OA). Methods Video recordings of self-paced walking trials of Multicenter Osteoarthritis Study participants were assessed for the presence of varus thrust at baseline. Knee pain was assessed using the WOMAC questionnaire at baseline and at 2 years. Logistic regression was used to estimate the odds of worsening knee pain (defined as either any increase in WOMAC score or as clinically important worsening), adjusting for age, sex, race, body mass index, clinic site, gait speed, and static knee alignment. Analyses were repeated, stratified by baseline radiographic OA status and among the subset of knees without baseline WOMAC pain. Results A total of 1,623 participants contributed 3,204 knees. Varus thrust was observed in 31.5% of knees. Knees with varus thrust had 1.44 times (95% confidence interval [95% CI] 1.19-1.73) the odds of any worsening and 1.37 times (95% CI 1.11-1.69) the odds of clinically important worsening WOMAC pain compared to knees without thrust. Knees with thrust without baseline WOMAC pain had 2.01 times (95% CI 1.47-2.74) the odds of incident total pain. Conclusion Results indicate that varus thrust is a risk factor for worsening and incident knee pain. Targeting varus thrust through noninvasive therapies could prevent development or worsening of knee pain in older adults with or at risk for knee OA.

Objectives Disability prevention strategies are more achievable before osteoarthritis disease drives impairment. It is critical to identify high-risk groups, for strategy implementation and trial eligibility. An established measure, gait speed is associated with disability and mortality. We sought to develop and validate risk stratification trees for incident slow gait in persons at high risk for knee osteoarthritis, feasible in community and clinical settings. Methods Osteoarthritis Initiative (derivation cohort) and Multicenter Osteoarthritis Study (validation cohort) participants at high risk for knee osteoarthritis were included. Outcome was incident slow gait over up to 10-year follow-up. Derivation cohort classification and regression tree analysis identified predictors from easily assessed variables and developed risk stratification models, then applied to the validation cohort. Logistic regression compared risk group predictive values; area under the receiver operating characteristic curves (AUCs) summarised discrimination ability. Results 1870 (derivation) and 1279 (validation) persons were included. The most parsimonious tree identified three risk groups, from stratification based on age and WOMAC Function. A 7-risk-group tree also included education, strenuous sport/recreational activity, obesity and depressive symptoms; outcome occurred in 11%, varying 0%–29 % (derivation) and 2%–23 % (validation) depending on risk group. AUCs were comparable in the two cohorts (7-risk-group tree, 0.75, 95% CI 0.72 to 0.78 (derivation); 0.72, 95% CI 0.68 to 0.76 (validation)). Conclusions In persons at high risk for knee osteoarthritis, easily acquired data can be used to identify those at high risk of incident functional impairment. Outcome risk varied greatly depending on tree-based risk group membership. These trees can inform individual awareness of risk for impaired function and define eligibility for prevention trials.

Summary Objective Examine associations of hip abductor strength with (1) cartilage damage worsening in the tibiofemoral and patellofemoral compartments 2 years later, and (2) poor function and disability outcomes 5 years later. Methods Participants had knee osteoarthritis (K/L ≥ 2) in at least one knee. Hip abductor strength was measured using Biodex Dynamometry. Participants underwent 3.0T MRI of both knees at baseline and 2 years later. Baseline-to-2-year cartilage damage progression, defined as any worsening of WORMS cartilage damage score, was assessed at each tibiofemoral and patellofemoral surface. LLFDI (Late-Life Function and Disability Instrument) and Chair-Stand-Rate were recorded at baseline and 5-year follow-up; outcomes analyzed using quintiles. Poor outcomes were defined as remaining in the same low-function quintiles or being in a worse quintile at 5-year follow-up. We analyzed associations of baseline hip abductor strength with cartilage damage worsening and function and disability outcomes using multivariable log-binomial models. Results 275 knees from 164 persons [age = 63.7 (SD = 9.8) years, 79.3% women] comprised the structural outcome sample, and 187 persons [age = 64.2 (9.7), 78.6% women] the function and disability outcomes sample. Greater baseline hip abductor strength was associated with reduced risks of baseline-to-2-year medial patellofemoral and lateral tibiofemoral cartilage damage worsening [adjusted relative risks (RRs) range: 0.80–0.83) and with reduced risks of baseline-to-5-year poor outcomes for Chair-Stand-Rate and LLFDI Basic Lower-Extremity Function and Disability Limitation (adjusted RRs range: 0.91–0.94). Conclusion Findings support a beneficial role of hip abductor strength for disease modification and for function and disability outcomes, and as a potential therapeutic target in managing knee osteoarthritis.

Summary Objective To investigate individual preferences for physical activity (PA) attributes in adults with chronic knee pain, to identify clusters of individuals with similar preferences, and to identify whether individuals in these clusters differ by their demographic and health characteristics. Design An adaptive conjoint analysis (ACA) was conducted using the Potentially All Pairwise RanKings of all possible Alternatives (PAPRIKA) method to determine preference weights representing the relative importance of six PA attributes. Cluster analysis was performed to identify clusters of participants with similar weights. Chi-square and ANOVA were used to assess differences in individual characteristics by cluster. Multinomial logistic regression was used to assess associations between individual characteristics and cluster assignment. Results The study sample included 146 participants; mean age 65, 72% female, 47% white, non-Hispanic. The six attributes (mean weights in parentheses) are: health benefit (0.26), enjoyment (0.24), convenience (0.16), financial cost (0.13), effort (0.11) and time cost (0.10). Three clusters were identified: Cluster 1 (n = 33): for whom enjoyment (0.35) is twice as important as health benefit; Cluster 2 (n = 63): for whom health benefit (0.38) is most important; and Cluster 3 (n = 50): for whom cost (0.18), effort (0.18), health benefit (0.17) and enjoyment (0.18) are equally important. Cluster 1 was healthiest, Cluster 2 most self-efficacious, and Cluster 3 was in poorest health. Conclusions Patients with chronic knee pain have preferences for PA that can be distinguished effectively using ACA methods. Adults with chronic knee pain, clustered by PA preferences, share distinguishing characteristics. Understanding preferences may help clinicians and researchers to better tailor PA interventions.

Objective The benefits of physical activity among persons with or at higher risk for knee osteoarthritis are well established. However, activity levels in this population are low, in part due to concern that activity will damage the knee joint. We hypothesized that sedentary and moderate-vigorous physical activity are each associated with greater risk of radiographic worsening of knee OA. Methods In Osteoarthritis Initiative participants with or at higher risk for knee OA enrolled in an accelerometer substudy at 48 months (study baseline), physical activity was measured by a uniaxial accelerometer (ActiGraph GT1M). Radiographic progression was defined as any 48 month to 96 month worsening of Kellgren/Lawrence (K/L) grade scores. All analyses were knee-level; we used multivariable logistic regression with generalized estimating equations, adjusting for key covariates. Results Of the 1,206 participants, 631 (52%) were female, the mean ± SD age was 64 ± 9 years, and mean ± SD body mass index (BMI) was 28 ± 5. The mean ± SD average daily sedentary activity was 602 ± 86 minutes, average daily light activity was 284 ± 75 minutes, and average daily moderate-vigorous activity was 20 ± 20 minutes. In 1,978 knees, 267 (14%) had worsening of K/L grade scores. In the multivariable model, age, sex, BMI, and pain, were associated with K/L grade worsening, but neither sedentary activity (adjusted odds ratio [OR] 0.99 [95% confidence interval (95% CI) 0.97-1.01]) nor moderate-vigorous activity (adjusted OR 1.00 [95% CI 0.91-1.09]) were associated with K/L grade worsening. Conclusion In persons with or at higher risk for knee OA, age, sex, BMI, and pain, but not objectively measured average daily minutes of sedentary or moderate-vigorous activity, were associated with subsequent worsening of K/L grade. Whether findings differ in persons with more severe knee OA and/or engaged more frequently in moderate-vigorous activity should be examined in future studies.

Objective Identify distinct trajectories of lack of knee confidence over an 8-year follow-up period and examine baseline factors associated with poor trajectories in persons with or at risk for knee osteoarthritis (OA). Methods The Osteoarthritis Initiative is a prospective cohort study of persons with or at high risk for knee OA. Confidence in the knees was assessed within the Knee Injury and Osteoarthritis Outcome Score instrument querying how much the individual is troubled by lack of confidence in his/her knee(s), rated as not-at-all (0), mildly (1), moderately (2), severely (3), and extremely (4) troubled, reported annually from baseline to 96 months. Lack of knee confidence was defined as a score ≥ 2. We used latent class models to identify subgroups that share similar underlying knee confidence trajectories over an 8-year period, and multivariable multinomial logistic regression models to examine baseline factors associated with poor trajectories. Results Among 4515 participants [mean age 61.2 years (SD 9.2), BMI 28.6 kg/m2 (4.8); 2640 (58.5%) women], four distinct knee confidence trajectories were identified: persistently good (65.6%); declining (9.1%); poor, improving (13.9%); and persistently poor (11.4%). Baseline predictors associated with persistently poor confidence (reference: persistently good) were younger age, male sex, higher BMI, depressive symptoms, more advanced radiographic disease, worse knee pain, weaker knee extensors, history of knee injury and surgery, and reported hip and/or ankle pain. Conclusion Findings suggest the dynamic nature of self-reported knee confidence and addressing modifiable factors (e.g., BMI, knee strength, depressive symptoms, lower limb pain) may improve its long-term course.

Physical inactivity is a leading risk factor for developing disability. Although randomized clinical trials have demonstrated improving physical activity can reduce this risk in older adults with arthritis, these studies did not specifically evaluate inactive adults.The aim of this study was to evaluate the relationship of changes in physical activity with disability changes among initially inactive adults with or at high risk of knee osteoarthritis from Osteoarthritis Initiative.Inactive persons were identified at baseline based on the US Department of Health and Human Services classification (no [zero] 10-minute session of moderate-to-vigorous [MV] activity over 1 week) from objective accelerometer monitoring. Two years later, physical activity change status was classified as follows: (1) met Federal physical activity guidelines (≥150 MV minutes/week acquired in bouts ≥10 minutes), (2) insufficiently increased activity (some but150 MV bout minutes/week), or (3) remained inactive. Disability at baseline and 2 years was assessed by Late Life Disability Instrument limitation and frequency scores. Multiple regression evaluated the relationship of physical activity change status with baseline-to-2-year changes in disability scores adjusting for socioeconomics, health factors, and baseline disability score.Increased physical activity showed a graded relationship with improved disability scores in Late Life Disability Instrument limitation (P0.001) and frequency scores (P = 0.027). While increasing MV activity to guideline levels showed the greatest reduction, even insufficiently increased physical activity was related to reduced disability.Findings support advice to increase MV physical activity to reduce disability among inactive adults with or at high risk of knee osteoarthritis, even when guidelines are not met.

Introduction Physical activity guidelines recommend minimum thresholds. This study sought to identify evidence-based thresholds to maintain disability-free status over 4years among adults with lower extremity joint symptoms. Methods Prospective multisite Osteoarthritis Initiative accelerometer monitoring cohort data from September 2008 through December 2014 were analyzed. Adults (n=1,564) aged ≥49years at elevated disability risk because of lower extremity joint symptoms were analyzed for biennial assessments of disability-free status from gait speed ≥1meter/second (mobility disability–free) and self-report of no limitations in activities of daily living (activities of daily living disability–free). Classification tree analyses conducted in 2017–2018 identified optimal thresholds across candidate activity intensities (sedentary, light, moderate–vigorous, total light and moderate–vigorous activity, and moderate–vigorous accrued in bouts lasting ≥10 minutes). Results Minimal thresholds of 56 and 55 moderate–vigorous minutes/week best predicted disability-free status over 4years from mobility and activities of daily living disabilities, respectively, across the candidate measures. Thresholds were consistent across sex, BMI, age, and knee osteoarthritis presence. Mobility disability onset was one eighth as frequent (3% vs 24%, RR=0.14, 95% CI=0.09, 0.20) and activities of daily living disability onset was almost half (12% vs 23%, RR=0.55, 95% CI=0.44, 0.70) among people above versus below the minimum threshold. Conclusions Attaining an evidence-based threshold of approximately 1-hour moderate–vigorous activity/week significantly increased the likelihood of maintaining disability-free status over 4years. This minimum threshold tied to maintaining independent living abilities has value as an intermediate goal to motivate adults to take action towards the many health benefits of a physically active lifestyle.

This cohort study evaluates long-term levels of physical activity and inactivity among adults with or likely to develop knee osteoarthritis., Key Points Question Are long-term strenuous physical activity and extensive sitting each associated with risk for developing radiographic knee osteoarthritis in individuals at high risk for the disease? Findings In this cohort study of 1194 persons at high risk for but without radiographic evidence of knee osteoarthritis who were followed up for up to 10 years, long-term participation in strenuous physical activities was not associated with risk of incident radiographic knee osteoarthritis. Persistent extensive sitting was not associated with either elevated or reduced risk. Meaning These findings suggest that older adults at high risk for knee osteoarthritis may safely engage in strenuous physical activities at a moderate level to improve their general health., Importance Persons with knee symptoms recognize the health benefits of engaging in physical activity, but uncertainty persists about whether regular strenuous physical activity or exercise can accelerate tissue damage. A sedentary lifestyle of inactivity or underloading may also be associated with deleterious joint health. Objective To establish whether long-term strenuous physical activity participation and extensive sitting behavior are each associated with increased risk of developing radiographic knee osteoarthritis (KOA) in individuals at high risk for the disease. Design, Setting, and Participants This cohort study analyzed data from the Osteoarthritis Initiative, a prospective longitudinal cohort study of men and women with or at an increased risk of developing symptomatic, radiographic KOA. Community-dwelling adults were recruited from 4 US sites (Baltimore, Maryland; Columbus, Ohio; Pittsburgh, Pennsylvania; and Pawtucket, Rhode Island) and were followed up for up to 10 years. Individuals were included if they had a baseline Kellgren and Lawrence grade of 0 in both knees and completed a PASE (Physical Activity Scale for the Elderly) questionnaire at baseline and at least 2 follow-up visits over an 8-year interval. Data analyses were conducted from May 2018 to November 2018. Exposures Baseline to 8-year trajectories of strenuous physical activity participation and extensive sitting behavior were identified using group-based trajectory models. Main Outcomes and Measures Incident radiographic KOA, defined as Kellgren and Lawrence grade 2 or higher in either knee by the 10-year follow-up visit. Results A total of 1194 participants were included in the sample (697 women [58.4%]), with a baseline mean (SD) age of 58.4 (8.9) years and mean body mass index (BMI) of 26.8 (4.5). Four distinct trajectories of weekly hours spent in strenuous physical activities and 3 distinct trajectories of extensive sitting were identified. Long-term engagement in low-to-moderate physical activities (adjusted odds ratio [OR], 0.69; 95% CI, 0.48-1.01) or any strenuous physical activities (adjusted OR, 0.75; 95% CI, 0.53-1.07) was not associated with 10-year incident radiographic KOA. Persistent extensive sitting was not associated with incident KOA. Despite relatively mild symptoms and high function in this early-stage sample, 594 participants (49.7%) did not engage in any strenuous physical activities (ie, 0 h/wk) across 8 years, and 507 (42.5%) engaged in persistent moderate-to-high frequency of extensive sitting. Older age, higher BMI, more severe knee pain, non–college graduate educational level, weaker quadriceps, and depression were each associated with a persistent lack of engagement in strenuous physical activities. Conclusions and Relevance Results from this study appeared to show no association between long-term strenuous physical activity participation and incident radiographic KOA. The findings raise the possibility of a protective association between incident KOA and a low-to-moderate level of strenuous physical activities.

Summary Objective To test whether radiographically normal knees with contralateral radiographic knee osteoarthritis (OA), but without contralateral trauma history, display greater cartilage thickness loss than knees from subjects with bilaterally radiographically normal knees. Methods 828 radiographically normal knees (Kellgren Lawrence grade [KLG] 0) from the Osteoarthritis Initiative [OAI] were studied; 150 case knees displayed definite radiographic knee OA (KLG ≥ 2) contralaterally, and had MRI double echo steady state (DESS) images available at 12 and 48 month follow-up. 678 reference knees displayed KLG0 at the contralateral side. Cartilage thickness change was determined in femorotibial subregions and location-independent cartilage thinning scores were computed. Case and reference knees were compared using ANCOVA. Results Of the 150 KLG0 case knees, 108 had a contralateral KLG2 knee (50 without, and 58 with joint space narrowing [JSN]), 31 a KLG3 and 11 a KLG4 knee. The cartilage thinning score tended to be greater in case than reference knees; the cartilage thinning score in KLG0 case knees with contralateral radiographic JSN (−858 μm; [95% confidence interval −1016, −701 μm]) was significantly greater (P = 0.0012) than that in bilaterally KLG0 reference knees (−634 μm; [−673, −596 μm]), whereas KLG0 knees with contralateral KLG2 without JSN only showed relatively small thinning scores (−530 μm, [−631, −428 μm]). Region-specific analysis suggested greater rates of cartilage loss in case than in reference knees in the lateral, rather than medial, femorotibial compartment. Conclusions Radiographically normal knees with contralateral JSN may serve as a human model of early OA, for testing disease modifying drugs in clinical trials designed to prevent cartilage loss before the onset of radiographic change. Clinicaltrials.gov identification NCT00080171 .

Summary Objective Test the hypothesis that greater baseline peak external knee adduction moment (KAM), KAM impulse, and peak external knee flexion moment (KFM) during the stance phase of gait are associated with baseline-to-2-year medial tibiofemoral cartilage damage and bone marrow lesion progression, and cartilage thickness loss. Methods Participants all had knee OA in at least one knee. Baseline peak KAM, KAM impulse, and peak KFM (normalized to body weight and height) were captured and computed using a motion analysis system and six force plates. Participants underwent MRI of both knees at baseline and 2 years later. To assess the association between baseline moments and baseline-to-2-year semiquantitative cartilage damage and bone marrow lesion progression and quantitative cartilage thickness loss, we used logistic and linear regressions with generalized estimating equations (GEE), adjusting for gait speed, age, gender, disease severity, knee pain severity, and medication use. Results The sample consisted of 391 knees (204 persons): mean age 64.2 years (SD 10.0); BMI 28.4 kg/m 2 (5.7); 156 (76.5%) women. Greater baseline peak KAM and KAM impulse were each associated with worsening of medial bone marrow lesions, but not cartilage damage. Higher baseline KAM impulse was associated with 2-year medial cartilage thickness loss assessed both as % loss and as a threshold of loss, whereas peak KAM was related only to % loss. There was no relationship between baseline peak KFM and any medial disease progression outcome measures. Conclusion Findings support targeting KAM parameters in an effort to delay medial OA disease progression.

Summary Objective Among high risk individuals, whether knee lesions in tissues involved in osteoarthritis (OA) can improve prediction of knee OA is unclear. We hypothesized that models predicting (1) incident osteophytes and (2) incident osteophytes and joint space narrowing can be improved by including symptoms or function, and further improved by lesion status. Design In Osteoarthritis Initiative (OAI) participants with normal knee X-rays, we assessed cartilage damage, bone marrow lesions (BMLs), and menisci. Cox proportional hazards models were used to develop risk prediction models for risk of each outcome. Nested models (increasingly larger baseline covariable sets) were compared using likelihood ratio tests and Schwarz Bayesian Information Criterion (SBC). Model discrimination used receiver operating characteristic (ROC) curves and area under the curve (AUC). Results In 841 participants [age 59.6, body mass index (BMI) 26.7, 55.9% women] over up to 7 years follow-up, each larger set improved prediction (+hand OA, injury, surgery, activities; +symptoms/function). Prediction was further improved by including cartilage damage both compartments, BMLs both compartments, meniscal tear, meniscal extrusion, sum of lesion types, number of subregions with cartilage damage, number of subregions with BMLs, and (concurrently) subregion number with cartilage damage, subregion number with BMLs, and meniscal tear. AUCs were ≥0.80 for both outcomes for number of subregions with cartilage damage and the combined model. Conclusions Among persons at higher risk for knee OA with normal X-rays, MRI tissue lesions improved prediction of mild as well as moderate disease. These findings support that disease onset is likely occurring during the "high-risk" period and encourage a reorientation of approach.

SummaryObjectiveVarus thrust visualized during walking is associated with a greater medial knee load and an increased risk of medial knee osteoarthritis (OA) progression. Little is known about how varus thrust presence determined by visual observation relates to quantitative gait kinematic data. We hypothesized that varus thrust presence is associated with greater knee frontal plane dynamic movement during the stance phase of gait.MethodsParticipants had knee OA in at least one knee. Trained examiners assessed participants for varus thrust presence during ambulation. Frontal plane knee motion during ambulation was captured using external passive reflective markers and an 8-camera motion analysis system. To examine the cross-sectional relationship between varus thrust and frontal plane knee motion, we used multivariable regression models with the quantitative motion measures as dependent variables and varus thrust (present/absent) as predictor; models were adjusted for age, gender, body mass index (BMI), gait speed, and knee static alignment.Results236 persons [mean BMI: 28.5 kg/m2 (standard deviation (SD) 5.5), mean age: 64.9 years (SD 10.4), 75.8% women] contributing 440 knees comprised the study sample. 82 knees (18.6%) had definite varus thrust. Knees with varus thrust had greater peak varus angle and greater peak varus angular velocity during stance than knees without varus thrust (mean differences 0.90° and 6.65°/s, respectively). These patterns remained significant after adjusting for age, gender, BMI, gait speed, and knee static alignment.ConclusionVisualized varus thrust during walking was associated with a greater peak knee varus angular velocity and a greater peak knee varus angle during stance phase of gait.

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 degrees 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 degrees to 3 degrees valgus, were associated with an increased risk of lateral disease progression. In knees without radiographic OA, valgus alignment >3 degrees was associated with incidence (e. g., in the MOST, adjusted OR 2.5 [95% CI 1.0-5.9]). Valgus alignment >3 degrees 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.

Objective We evaluated whether African Americans in the Osteoarthritis Initiative (OAI) have a greater risk (versus whites) of poor 4-year function outcome within strata defined by sex, body mass index (BMI), and waist circumference. Methods Using Western Ontario and McMaster Universities Osteoarthritis Index function, 20-meter walk, and chair stand performance, poor outcome was defined as moving into a worse function group or remaining in the 2 worst groups over 4 years. Logistic regression was used to evaluate the relationship between racial group and outcome within each stratum, adjusting for age, education, and income, and then further adjusting for BMI, comorbidity, depressive symptoms, physical activity, knee pain, and osteoarthritis (OA) severity. Results In 3,695 persons with or at higher risk for knee OA, higher BMI and large waist circumference were each associated with poor outcome. Among women with high BMI and among women with large waist circumference, African Americans were at greater risk for poor outcome by every measure, adjusting for age, education, and income. From fully adjusted models, potential explanatory factors included income, comorbidity, depressive symptoms, pain, and disease severity. Findings were less consistent for men, emerging only for the 20-meter walk or chair stand outcomes, and potentially explained by age and knee pain. Conclusion Among OAI women with excess body weight, African Americans are at greater risk than whites for poor 4-year outcome. Modifiable factors that may help to explain these findings in the OAI include comorbidity, depressive symptoms, and knee pain. Targeting such factors, while supporting weight loss, may help to lessen the outcome disparity between African American and white women.

ObjectiveTo evaluate whether change in fixed-location measures of radiographic joint space width (JSW) and cartilage thickness by MRI predict knee replacement.MethodsKnees replaced between 36 and 60months' follow-up in the Osteoarthritis Initiative were each matched with one control by age, sex and radiographic status. Radiographic JSW was determined from fixed flexion radiographs and subregional femorotibial cartilage thickness from 3 T MRI. Changes between the annual visit before replacement (T0) and 2years before T0 (T-2) were compared using conditional logistic regression.ResultsOne hundred and nineteen knees from 102 participants (55.5% women; age 64.2 ± 8.7 [mean ± SD] years) were studied. Fixed-location JSW change at 22.5% from medial to lateral differed more between replaced and control knees (case-control [cc] OR = 1.57; 95% CI: 1.23-2.01) than minimum medial JSW change (ccOR = 1.38; 95% CI: 1.11-1.71). Medial femorotibial cartilage loss displayed discrimination similar to minimum JSW, and central tibial cartilage loss similar to fixed-location JSW. Location-independent thinning and thickening scores were elevated prior to knee replacement.ConclusionsDiscrimination of structural progression between knee pre-placement cases versus controls was stronger for fixed-location than minimum radiographic JSW. MRI displayed similar discrimination to radiography and suggested greater simultaneous cartilage thickening and loss prior to knee replacement.Key points• Fixed-location JSW predicts surgical knee replacement more strongly than minimum JSW. • MRI predicts knee replacement with similar accuracy to radiographic JSW. • MRI reveals greater cartilage thinning and thickening prior to knee replacement.

Objective Knee sagittal dynamic joint stiffness (DJS) describes the biomechanical interaction between change in external knee flexion moment and flexion angular excursion during gait. In theory, greater DJS may particularly stress the patellofemoral (PF) compartment and thereby contribute to PF osteoarthritis (OA) worsening. We hypothesized that greater baseline knee sagittal DJS is associated with PF cartilage damage worsening 2 years later. Methods Participants all had OA in at least one knee. Knee kinematics and kinetics during gait were recorded using motion capture systems and force plates. Knee sagittal DJS was computed as the slope of the linear regression line for knee flexion moments vs angles during the loading response phase. Knee magnetic resonance imaging (MRI) scans were obtained at baseline and 2 years later. We assessed the association between baseline DJS and baseline-to-2-year PF cartilage damage worsening using logistic regression with generalized estimating equations (GEE). Results Our sample had 391 knees (204 persons): mean age 64.2 years (SD 10.0); body mass index (BMI) 28.4 kg/m2 (5.7); 76.5% women. Baseline knee sagittal DJS was associated with baseline-to-2-year cartilage damage worsening in the lateral (OR = 5.35, 95% CI: 2.37-12.05) and any PF (OR = 2.99, 95% CI: 1.27-7.04) compartment. Individual components of baseline DJS (i.e., change in knee moment or angle) were not associated with subsequent PF disease worsening. Conclusion Capturing the concomitant effect of knee kinetics and kinematics during gait, knee sagittal DJS is a potentially modifiable risk factor for PF disease worsening.

Summary Objective To compare unbiased estimates of short- vs long-term cartilage loss in osteoarthritic knees. Method 441 knees [216 Kellgren Lawrence (KL) grade 2, 225 KL grade 3] from participants of the Osteoarthritis Initiative were studied over a 4-year period. Femorotibial cartilage thickness was determined using 3 T double echo steady state magnetic resonance imaging, the readers being blinded to time points. Because common measurement time points bias correlations, short-term change (year-1 to year-2: Y1 → Y2) was compared with long-term change (baseline to year-4: BL → Y4), and initial (BL → Y1) with subsequent (Y2 → Y4) observation periods. Results The mean femorotibial cartilage thickness change (standardized response mean) was −1.2%/−0.8% (−0.42/−0.28) over 1 (BL → Y1/Y1 → Y2), −2.1%/−2.5% (−0.56/−0.55) over 2 (BL → Y2/Y2 → Y4), −3.3% (−0.63) over 3 (Y1 → Y4), and −4.5% (−0.78) over 4 years. Spearman correlations were 0.33 for Y1 → Y2 vs BL → Y4, and 0.17 for BL → Y1 vs Y2 → Y4 change. Percent agreement between knees showing progression during Y1 → Y2 vs BL → Y4 was 59%, and 64% for BL → Y1 vs Y2 → Y4. The area under the receiver operating characteristic curve was 0.66 for using Y1 → Y2 to predict BL → Y4, and 0.59 for using BL → Y1 to predict Y2 → Y4 change. Conclusion Weak to moderate correlations and agreement were observed between individual short- vs long-term cartilage loss, and between initial and subsequent observation periods. Hence, longer observation periods are recommended to achieve robust results on cartilage loss in individual knees. At cohort and subcohort level (e.g., KLG3 vs KLG2 knees), the mean cartilage loss increased almost linearly with the length of the observation period and was constant throughout the study.

Summary Objective To examine the relationship of knee malalignment with occurrence of incident and enlarging bone marrow lesions (BMLs) and regression of BMLs. Methods Subjects from the Multicenter Osteoarthritis Study aged 50–79 years with or at high risk of knee osteoarthritis were studied. Full-limb radiographs were taken at baseline and hip–knee–ankle mechanical axis was measured. Baseline and 30-month magnetic resonance imaging (MRI) of knees ( n = 1782) were semiquantitatively assessed for BMLs. Outcome was defined as a change in BML score in femoral/tibial condyle in medial/lateral compartments. Medial compartment in varus alignment and lateral compartment in valgus alignment were combined to form ‘more loaded' compartment, while lateral compartment in valgus and medial compartment in varus were combined to form ‘less loaded' compartment. Relative risk (RR) of BML score increase or decrease in relation to malalignment was estimated using a log linear regression model with the Poisson assumption, adjusting for age, gender, body mass index, physical activity scale for the elderly, race and clinic site. Further, results were stratified by ipsilateral meniscal and cartilage status at baseline. Results Baseline varus alignment was associated with higher risk of BML score increase from baseline to follow-up in the medial compartment [adjusted RRs (95%CI): 1.5 (1.2–1.9)] and valgus alignment in the lateral compartment [1.4 (1.0–2.1)]. Increase in BML score was more likely in the more loaded compartments [1.7 (1.4–2.0)] in malaligned knees. Regardless of ipsilateral cartilage or meniscus status, adjusted RR for BML score increase was higher in the more loaded compartments of malaligned knees than those with neutral alignment. Decrease in BML score was less likely in the more loaded compartments in malaligned knees [0.8 (0.7–1.0)]. Conclusion Knee malalignment is associated with increased risk of incident and enlarging BMLs in the more loaded compartments of the tibiofemoral joint.

ObjectivesTo 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.MethodsIn the Boston OA of the Knee, Framingham OA and Multicenter OA 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°) knees were identified.ResultsThe prevalence of medial PF cartilage damage exceeded that of lateral damage in all three 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 alignment, the prevalence of lateral PF cartilage damage equalled or surpassed that of medial PF damage only when the threshold was specific to severely involved knees.ConclusionsMedial PF cartilage damage is at least as prevalent within these older adult populations as lateral PF cartilage damage.

Objective Osteoarthritis (OA) clinical practice guidelines identify a substantial therapeutic role for physical activity, but objective information about the physical activity of this population is lacking. The aim of this study was to objectively measure levels of physical activity in adults with knee OA and report the prevalence of meeting public health physical activity guidelines. Methods Cross-sectional accelerometry data from 1,111 adults with radiographic knee OA (49–84 years old) participating in the Osteoarthritis Initiative accelerometry monitoring ancillary study were assessed for meeting the aerobic component of the 2008 Physical Activity Guidelines for Americans (≥150 minutes/week moderate-to-vigorous–intensity activity lasting ≥10 minutes). Quantile regression was used to test median sex differences in physical activity levels. Results Aerobic physical activity guidelines were met by 12.9% of men and 7.7% of women with knee OA. A substantial proportion of men and women (40.1% and 56.5%, respectively) were inactive, having done no moderate-to-vigorous activity that lasted 10 minutes or more during the 7 days. Although men engaged in significantly more moderate-to-vigorous activity (average daily minutes 20.7 versus 12.3), they also spent more time in no or very-low-intensity activity than women (average daily minutes 608.2 versus 585.8). Conclusion Despite substantial health benefits from physical activity, adults with knee OA were particularly inactive based on objective accelerometry monitoring. The proportions of men and women who met public health physical activity guidelines were substantially less than those previously reported based on self-reported activity in arthritis populations. These findings support intensified public health efforts to increase physical activity levels among people with knee OA.

ObjectivesMeniscal pathology in which the aetiology is often unclear is a frequent finding on knee MRI. This study investigates potential risk factors for medial meniscal lesions or extrusion in middle-aged and elderly persons.MethodsProspective cohort study using population-based subjects from Birmingham, Alabama and Iowa City, Iowa, USA (the Multicenter Osteoarthritis Study). 644 men and women aged 50–79 years with or at high risk of knee osteoarthritis (Kellgren and Lawrence grade 0–2) but with normal medial meniscal status at baseline were studied. Paired baseline and 30-month 1.0 T knee MRI were scored for meniscal lesions and extrusion (pathology) and the following systemic, knee-specific and compartment-specific potential risk factors were evaluated: age, sex, body mass index, bony enlargement of finger joints, knee trauma, leg-length inequality and knee alignment.ResultsOf 791 knees, 77 (9.7%) had medial meniscal pathology at 30 months follow-up. 61 of the 77 (81%) had no report of trauma during follow-up. Including all potential risk factors in the multivariable model, the adjusted OR for medial meniscal pathology was 4.14 (95% CI 2.06 to 8.31) for knee trauma during follow-up, 1.64 (1.00 to 2.70) for five or more bony enlargements of finger joints (vs ≤4) and 2.00 (1.18 to 3.40) for varus alignment (vs not varus) at baseline examination. Obesity was a risk factor for the development of meniscal extrusion, OR 3.04 (1.04 to 8.93) but not for meniscal lesions, OR 1.15 (0.52 to 2.54).ConclusionsApart from knee trauma, possible generalised osteoarthritis, expressed as multiple bony enlargements of finger joints, varus alignment and obesity are risk factors for medial meniscal pathology.

Objective Physical activity measured by accelerometers requires basic assumptions to translate the output into meaningful measures. We used accelerometer data from the Osteoarthritis Initiative to investigate in the context of knee osteoarthritis (OA) the following data processing assumptions derived from the general US adult population: nonwear (a period the monitor was removed), based on zero activity exceeding 60 minutes; and a valid day of monitoring, based on wear time evidence exceeding 10 hours. Methods We examined the influence of nonwear thresholds ranging from 20 to 300 minutes of zero activity on mean daily activity minutes (counts >0), mean daily activity counts, and mean daily moderate to vigorous physical activity minutes. The effect of selecting minimums of 8, 10, or 12 wear hours to signify a valid day of monitoring on data retention was examined. Results Our sample of 3,536 days of accelerometer data from 519 persons with knee OA showed that mean daily activity minutes increased with the nonwear threshold until stabilizing at 463 minutes per day, corresponding to the 90-minute nonwear threshold. Similar patterns were observed for mean daily activity counts. Varying the nonwear threshold had no effect on mean daily moderate to vigorous physical activity minutes. Choosing the 90-minute nonwear threshold and a minimum of 10 wear hours to constitute a valid day provided 94% data retention. Conclusion Data supported applying the 90-minute nonwear threshold to the knee OA population instead of the 60-minute threshold for the general population, while retaining the 10-hour valid day threshold.

Objectives Meniscal tears have been linked to knee osteoarthritis progression, presumably by impaired load attenuation. How meniscal tears affect osteoarthritis is unclear; subregional examination may help to elucidate whether the impact is local. This study examined the association between a tear within a specific meniscal segment and subsequent 2-year cartilage loss in subregions that the torn segment overlies. Methods Participants with knee osteoarthritis underwent bilateral knee MRI at baseline and 2 years. Mean cartilage thickness within each subregion was quantified. Logistic regression with generalised estimating equations were used to analyse the relationship between baseline meniscal tear in each segment and baseline to 2-year cartilage loss in each subregion, adjusting for age, gender, body mass index, tear in the other two segments and extrusion. Results 261 knees were studied in 159 individuals. Medial meniscal body tear was associated with cartilage loss in external subregions and in central and anterior tibial subregions, and posterior horn tear specifically with posterior tibial subregion loss; these relationships were independent of tears in the other segments and persisted in tibial subregions after adjustment for extrusion. Lateral meniscal body and posterior horn tear were also associated with cartilage loss in underlying subregions but not after adjustment for extrusion. Cartilage loss in the internal subregions, not covered by the menisci, was not associated with meniscal tear in any segment. Conclusion These results suggest that the detrimental effect of meniscal tears is not spatially uniform across the tibial and femoral cartilage surfaces and that some of the effect is experienced locally.

SummaryObjectiveQuadriceps weakness has been reported with incident but not progressive knee osteoarthritis (OA) in longitudinal studies. This study examined the relationship between quadriceps strength and worsening of knee joint space narrowing (JSN) over 30 months.MethodsLongitudinal, observational study of adults aged 50–79 years with OARSI JSN score

Dunlop DD, Semanik P, Song J, Sharma L, Nevitt M, Mysiw J, Chang RW, for the Osteoarthritis Initiative Investigators. Moving to maintain function in knee osteoarthritis: evidence from the Osteoarthritis Initiative. Objectives To investigate the association between baseline physical activity and 1-year functional performance in adults with knee osteoarthritis (OA). Design Prospective cohort study of knee OA development and progression with 1-year follow-up. Setting Community. Participants Osteoarthritis Initiative public data on adults with knee OA (n=2274; age, 45–79y) who participated in functional performance assessments (timed 20-m walk and chair stand test) at baseline and 1-year follow-up. Interventions Not applicable. Main Outcome Measure A good 1-year performance outcome (separately defined for walk time and chair stand measures) was improvement from baseline quintile or maintenance in the best quintile. Results Almost 2 in 5 persons with radiographic knee OA improved or maintained high performance at 1 year. Physical activity measured by the Physical Activity Scale for the Elderly (PASE) was significantly associated with good walk rate and chair stand outcomes (odds ratio per 40 units PASE [95% confidence interval]=1.13 [1.13, 1.17] and 1.10 [1.05, 1.15], respectively), as were participation in sports/recreational activities (1.45 [1.23, 1.71] and 1.29 [1.09, 1.51], respectively) and lifestyle activities (1.11 [1.06, 1.16] and 1.09 [1.04, 1.14], respectively). An independent protective relationship for these physical activity measures approached significance after adjusting for sociodemographic and health factors. Older adults reported the least baseline physical activity and least frequent good 1-year outcomes. Conclusions These findings support public health recommendations to be physically active in order to preserve function for persons with knee OA. Physical activity messages should specifically target older adults whose low activity levels may jeopardize their ability to maintain functional performance.

Knee osteoarthritis (OA), a leading cause of functional limitation and disability in older persons, is believed to result from local mechanical factors acting within the context of a systemic susceptibility. Varus thrust is a local mechanical factor shown to be associated with a 4-fold increase in the odds of medial tibiofemoral OA progression over an 18 month follow-up period (1). Varus thrust is visualized during gait as the dynamic worsening or abrupt onset of varus (bow-leg) alignment as the limb accepts weight (stance phase), with a return to less varus and more neutral alignment during lift-off and the non-weightbearing (swing) phase of gait. A varus thrust indicates dynamic instability of the knee in the frontal plane and an acute increase in load transmitted to the medial compartment with each step of walking. Valgus thrust is the worsening or abrupt onset of valgus (knock-knee) alignment visualized during the stance phase, with a return to less valgus (more neutral) alignment during lift-off and the swing phase of gait. In theory, a valgus thrust increases load transmitted to the lateral tibiofemoral compartment, potentially contributing to lateral OA disease onset or progression. While valgus thrust is thought to be less common than varus thrust, the frequency of varus thrust and valgus thrust in persons either with knee OA or at risk to develop it is not known for any racial group. In the Johnston County Osteoarthritis Project, African-Americans were more likely than Caucasians to have lateral joint space narrowing (2), a finding that was not explained by differences in static varus-valgus alignment (3); a greater frequency of valgus thrust in African-Americans could help to explain a predisposition to lateral compartment involvement. The factors associated with varus or valgus thrust presence have not been identified. A thrust is a visible manifestation of excessive motion of one tibiofemoral surface in relation to the other under the dynamic conditions of gait. Thrust presence may represent capsuloligamentous damage and/or insufficient neuromuscular stabilization, conditions that may precede OA or develop or worsen as a result of disease. The capsular changes from static varus-valgus alignment may predispose to thrust development. Knee injury may primarily or secondarily damage stabilizing joint tissues. In theory, greater axial load from obesity may intensify a thrust in knees with compromised frontal-plane stability. Quadriceps weakness or pain-induced quadriceps inhibition may impair mechanisms of neuromuscular stabilization. To address these gaps in knowledge relating to varus and valgus thrust, we undertook an ancillary study to the Osteoarthritis Initiative (OAI) in which thrust was assessed by trained examiners. Here we analyze thrust data from African-Americans and Caucasians, the two largest racial groups in the OAI sample. The objectives of our study were: 1) to determine the frequency of varus thrust and valgus thrust in African-Americans and Caucasians for persons at high risk for but without radiographic OA in either knee and for persons with radiographic OA in one or both knees; and 2) to identify factors associated with the presence of varus and valgus thrust in persons without radiographic OA and with radiographic OA in one or both knees.

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

Objective. Malalignment is known to alter medial-to-lateral femorotibial load distribution and to affect osteoarthritis (OA) progression in the mechanically stressed compartment. We investigated the pattern of cartilage loss in neutral, varus, and valgus knees. Methods. Alignment was measured from full-limb radiographs in 174 participants with symptomatic knee OA. Coronal magnetic resonance images were acquired at baseline and a mean SD of 26.6 5.4 months later. The weight-bearing femorotibial cartilages were segmented from paired images. Cartilage volume, surface area, and thickness were determined in total cartilage plates and defined subregions using proprietary software. Results. The medial-to-lateral ratio of femorotibial cartilage loss was 1.4:1 in neutral knees (n 74), 3.7:1 in varus knees (n 57), and 1:6.0 in valgus knees (n 43). The relative contribution of cartilage thickness change tended to be greater in knees with mild cartilage loss, whereas the increase of denuded area was greater in knees with accelerated cartilage loss. In both varus and neutral knees, the greatest changes were observed in the same subregions of the medial femorotibial compartment (central and external medial tibia, and central medial femur). In valgus and neutral knees, the subregions with the greatest changes in the lateral femorotibial compartment were also similar (internal and central lateral tibia, external lateral femur). Conclusion. The medial-to-lateral rate of femorotibial cartilage loss strongly depended on alignment. Subregions of greater-than-average cartilage loss within the stressed compartment were, however, similar in neutral, varus, and valgus knees. This indicates that the medial-to-lateral loading pattern is different, but that the (sub)regional loading pattern may not differ substantially between neutral and malaligned knees.

Objective Progressive knee osteoarthritis (OA) is believed to result from local factors acting in a systemic environment. Previous studies have not examined these factors concomitantly or compared quantitative and qualitative cartilage loss outcomes. The aim of this study was to test whether meniscal damage, meniscal extrusion, malalignment, and laxity each predicted tibiofemoral cartilage loss after controlling for the other factors. Methods Laxity and alignment were measured at baseline in individuals with knee OA. Magnetic resonance imaging included spin-echo coronal and sagittal imaging for meniscal scoring and axial and coronal spoiled gradient echo sequences with water excitation for cartilage quantification. Tibial and weight-bearing femoral condylar subchondral bone area and cartilage surface were segmented. Cartilage volume, denuded bone area, and cartilage thickness were quantified in each plate, with progression defined as cartilage loss >2 times the coefficient of variation for each plate. Qualitative outcome was assessed as worsening of the cartilage score. Logistic regression analysis with generalized estimating equations yielded odds ratios for each factor, adjusting for age, sex, body mass index, and the other factors. Results We studied 251 knees in 153 persons. After full adjustment, medial meniscal damage predicted medial tibial cartilage volume loss and tibial and femoral denuded bone increase, while varus malalignment predicted medial tibial cartilage volume and thickness loss and tibial and femoral denuded bone increase. Lateral meniscal damage predicted every lateral outcome. Laxity and meniscal extrusion had inconsistent effects. After full adjustment, no factor except medial laxity predicted qualitative outcome. Conclusion Using quantitative cartilage loss assessment, local factors that independently predicted tibial and femoral loss included medial meniscal damage and varus malalignment (medially) and lateral meniscal damage (laterally). A measurement of quantitative outcome was more sensitive at revealing these relationships than a qualitative approach.

Summary Objective To examine whether the baseline ratio of a type II collagen breakdown marker to a synthesis marker, or the level of these markers individually, is associated with the likelihood of knee osteoarthritis (OA) progression between baseline and 18 months. Methods Participants were recruited from community sources and had knee OA. Blood was drawn at baseline. Collagen synthesis was measured by commercial enzyme-linked immunosorbent assay (ELISA) assay that detects c-propeptide of type II procollagen (CPII). Serum markers of collagenase cleavage of cartilage type II collagen [C2C epitope (COL2-3/4Clong mono) and C1,2C epitope (COL2-3/4Cshort)] were also assayed. Knee radiographs (semi-flexed with fluoro confirmation) were obtained at baseline and 18 months. OA progression was examined using worsening of joint space grade and worsening of Kellgren/Lawrence grade. The relationship between baseline serum markers and subsequent progression was analyzed from logistic regression. Results Baseline levels of these markers, considered individually, were not associated with a change in the odds of progression. Belonging to the low synthesis tertile was associated with a greater likelihood of progression, approaching significance (adjusted odds ratio [OR] 1.86, 95% confidence interval [CI] 0.96, 3.63). A greater C2C:CPII ratio and C1,2C:CPII ratio were each associated with an increase in the odds of joint space grade progression, which approached significance (e.g., adjusted OR of C2C:CPII ratio was 3.15, 95% CI 0.91, 10.85). Conclusion While the degradation markers individually, considered as continuous variables, did not predict OA progression, belonging to the lower synthesis marker tertile and greater degradation/synthesis marker ratios were associated with an elevation in the odds of progression albeit not achieving significance.

BackgroundWhether preradiographic lesions in knees at risk for osteoarthritis are incidental versus disease is unclear. We hypothesised, in persons without but at higher risk for knee osteoarthritis, that: 12–48 month MRI lesion status worsening is associated with 12–48 month incident radiographic osteoarthritis (objective component of clinical definition of knee osteoarthritis) and 48–84 month persistent symptoms.MethodsIn 849 Osteoarthritis Initiative participants Kellgren/Lawrence (KL) 0 in both knees, we assessed cartilage damage, bone marrow lesions (BMLs), and menisci on 12 month (baseline) and 48 month MRIs. Multivariable logistic regression was used to evaluate associations between 12–48 month worsening versus stable status and outcome (12–48 month incident KL ≥1 and KL ≥2, and 48–84 month persistent symptoms defined as frequent symptoms or medication use most days of ≥1 month in past 12 month, at consecutive visits 48–84 months), adjusting for age, gender, body mass index (BMI), injury and surgery.ResultsMean age was 59.6 (8.8), BMI 26.7 (4.2) and 55.9% were women. 12–48 month status worsening of cartilage damage, meniscal tear, meniscal extrusion, and BMLs was associated with 12–48 month incident radiographic outcomes, and worsening of cartilage damage and BMLs with 48–84 month persistent symptoms. There was a dose-response association for magnitude of worsening of cartilage damage, meniscal tear, meniscal extrusion, and BMLs and radiographic outcomes, and cartilage damage and BMLs and persistent symptoms.ConclusionsIn persons at higher risk, worsening MRI lesion status was associated with concurrent incident radiographic osteoarthritis and subsequent persistent symptoms. These findings suggest that such lesions represent early osteoarthritis, and add support for a paradigm shift towards investigation of intervention effectiveness at this stage.

ObjectivesTo provide a comprehensive simultaneous relation of various semiquantitative knee OA MRI features as well as the presence of baseline radiographic osteoarthritis (OA) to quantitative longitudinal cartilage loss.MethodsWe studied Multicenter OA Study (MOST) participants from a longitudinal observational study that included quantitative MRI measurement of cartilage thickness. These subjects also had Whole Organ MRI Score (WORMS) scoring of cartilage damage, bone marrow lesions (BMLs), meniscal pathology, and synovitis, as well as baseline radiographic evaluation for Kellgren and Lawrence (KL) grading. Knee compartments were classified as progressors when exceeding thresholds of measurement variability in normal knees. All potential risk factors of cartilage loss were dichotomized into "present" (score ≥2 for cartilage, ≥1 for others) or "absent". Differences in baseline scores of ipsi-compartmental risk factors were compared between progressor and non-progressor knees by multivariable logistic regression, adjusting for age, sex, body mass index, alignment axis (degrees) and baseline KL grade. Odds ratios (OR) and 95% CIs were calculated for medial femorotibial compartment (MFTC) and lateral femorotibial compartment (LFTC) cartilage loss. Cartilage loss across both compartments was studied using Generalized Estimating Equations.Results196 knees of 196 participants were included (age 59.8±6.3 years [mean±SD], BMI 29.5±4.6, 62% women). For combined analyses of MFTC and LFTC, baseline factors related to cartilage loss were radiographic OA (KL grade ≥2: aOR 4.8 [2.4-9.5], cartilage damage (aOR 2.3 [1.2-4.4])), meniscal damage (aOR 3.9 [2.1-7.4]) and extrusion (aOR 2.9 [1.6-5.3]), all in the ipsilateral compartment, but not BMLs or synovitis.ConclusionBaseline radiographic OA and semiquantitatively (SQ) assessed MRI-detected cartilage damage, meniscal damage and extrusion, but not BMLs or synovitis is related to quantitatively measured ipsi-compartmental cartilage thinning over 30 months.

To analyse tibial, femoral, and patellar cartilage loss in patients prior to total knee arthroplasty (TKA), and its correlation with alignment of the knee.26 patients (aged 58 to 86 years) with a clinical indication for TKA were investigated. Quantitative end points of cartilage morphology (T scores for cartilage volume normalised to total subchondral bone area) were determined from coronal and axial magnetic resonance image data, using proprietary software. The static alignment of the knee was determined from standing full limb radiographs.The magnitude of cartilage loss (T score of normalised cartilage volume) was highly variable within the knee, correlation coefficients ranging from r = 0.17 to 0.51 between cartilage plates. The correlation of cartilage loss with static alignment of the knee (as a continuous variable) was r = -0.52 (p0.05) for the medial tibia, -0.38 (not significant) for the medial femur, +0.76 (p0.001) for the lateral tibia, +0.31 (not significant) for the lateral femur, and -0.09 for the patella. When analysing alignment independent of direction (valgus or varus), the correlation for the patella increased to r = 0.30, but remained non-significant.Cartilage loss was highly variable among patients and among cartilage plates before knee arthroplasty. Its correlation with alignment was stronger for the tibia than for the femur. There was some evidence for an association of alignment and patellar cartilage loss. These findings stimulate further research on the mechanism and cause-effect relation of alignment and knee osteoarthritis using quantitative magnetic resonance imaging technology.

Objective Delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) is used to examine the distribution of glycosaminoglycan in cartilage. This study sought to characterize dGEMRIC in the evaluation of knee osteoarthritis (OA) according to various radiographically determined disease parameters, and to examine the relationship between alignment of the knee joint and the lateral:medial dGEMRIC ratio. Methods Thirty-one patients with knee OA underwent MRI with a dGEMRIC protocol at 1.5T. Semiflexed knee radiographs and full-limb radiographs were also obtained for assessment of alignment. Results Compartments of the knee joint without joint space narrowing had a higher dGEMRIC index than those with any level of narrowing (mean 408 msec versus 365 msec; P = 0.001). In knees with 1 unnarrowed (spared) and 1 narrowed (diseased) compartment, the dGEMRIC index was greater in the spared versus the diseased compartment (mean 395 msec versus 369 msec; P = 0.001). In spared compartments, there was a trend toward a lower dGEMRIC index with increasing Kellgren/Lawrence (K/L) radiographic severity grade; the spared compartments of knees with a K/L grade 2 had a higher dGEMRIC index than those of knees with a K/L grade 4 (mean 425 msec versus 371 msec; P < 0.05). There was a range of dGEMRIC values in the spared compartments within a given K/L grade, demonstrating biochemical differentiation of disease in radiographically comparable compartments. Almost all compartments with narrowing had dGEMRIC indices of

Objective To determine whether the presence of varus thrust at baseline increases the risk of progression of medial tibiofemoral osteoarthritis (OA), whether knees with thrust have a greater adduction moment, whether thrust has any additional impact on top of static varus, and whether thrust is associated with poor physical function outcome. Methods Two hundred thirty-seven patients with knee OA (definite osteophytes and symptoms) underwent baseline gait observation to assess varus thrust and full-limb radiography to assess alignment. Sixty-four of these 237 patients also underwent quantitative gait analysis to determine the maximum knee adduction moment. Two hundred thirty patients (97%) returned for followup at 18 months. At baseline and 18 months, the 230 participants had semiflexed, fluoroscopically confirmed knee radiographs (with progression defined as worsening of medial joint space grade); self-reported and performance-based measures of function were also assessed. Logistic regression with generalized estimating equations was used to estimate odds ratios (ORs) for medial OA progression, after excluding knees that were not at risk for progression. Results Varus thrust was present in 67 of 401 knees. Thrust increased 4-fold (age-, sex-, body mass index–, and pain-adjusted OR 3.96, 95% confidence interval [95% CI] 2.11–7.43) the odds of medial progression, with some reduction after further adjustment for varus alignment severity. In varus-aligned knees, thrust increased the odds of OA progression 3-fold (adjusted OR 3.17, 95% CI 1.60–6.31). In the gait substudy, the adduction moment was greater in knees with a thrust compared with knees without a thrust. Having a thrust in both knees versus neither knee was associated with a 2-fold increase in the OR for poor physical function outcome (P not significant). Conclusion Varus thrust is a potent risk factor, identifiable by simple gait observation, for disease progression in the medial compartment, the most common site of OA involvement at the knee. Varus thrust may also predict poor physical function outcome. Varus thrust increased the odds of progression among varus-aligned knees considered separately, suggesting that knees with a thrust are a subset of varus-aligned knees at particularly high risk for progression of OA.

Objective To identify factors that predict a poor physical function outcome over 3 years in individuals with knee osteoarthritis (OA), in an effort to aid in the development of strategies to prevent such functional limitations and consequential disability. Methods Community-recruited individuals with knee OA underwent baseline, 18-month, and 3-year assessments of candidate risk factors and physical function. Risk factors were age, body mass index (BMI), knee pain intensity (on a visual analog scale [VAS]), local mechanical and neuromuscular factors (varus-valgus laxity, malalignment, proprioceptive inaccuracy, quadriceps strength, hamstring strength), activity level (Physical Activity Scale for the Elderly, amount of aerobic exercise), and psychosocial factors (Short-Form 36 [SF-36] mental health and role-functioning emotional subscales, self-efficacy using the Arthritis Self-Efficacy Scale physical function subscale, and social support using the Medical Outcomes Study Social Support Survey). Outcome was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical function scale and rate of chair-stand performance. Participants were grouped by quintile of baseline WOMAC score. The baseline to 3-year outcome was considered “good” when function improved by 1 or more quintiles or remained within the 2 highest function groups, and was considered “poor” when function declined by 1 or more quintiles or remained within the 3 lowest function groups. The same approach was taken for chair-stand outcome. Logistic regression was used to evaluate both the baseline level and the baseline to 18-month change in each factor as a predictor of physical function outcome over 3 years, adjusting for age, BMI, knee pain intensity, disease severity, and additional potential confounders. Results Factors that significantly increased the likelihood of a poor WOMAC outcome were baseline laxity (crude odds ratio [OR] 1.48/3°, 95% confidence interval [95% CI] 1.02–2.14), BMI (OR 1.26/5 units, 95% CI 1.01–1.57), knee pain intensity (OR 1.21/20 mm on VAS, 95% CI 1.00–1.47), and baseline to 18-month increase in knee pain (OR 1.32/20 mm on VAS, 95% CI 1.06–1.65). Factors that significantly protected against a poor WOMAC outcome were better baseline mental health (OR 0.62/5 points, 95% CI 0.44–0.87), self-efficacy (OR 0.79/5 points, 95% CI 0.67–0.93), and social support (OR 0.86/10 points, 95% CI 0.75–0.98), and greater amount of aerobic exercise (OR 0.75/60 minutes each week, 95% CI 0.63–0.89). Factors that increased the likelihood for a poor function outcome by the chair-stand performance rate were age and proprioceptive inaccuracy, and factors that reduced the likelihood for poor chair-stand outcome were strength (attenuated after adjusting for pain intensity or self-efficacy), self-efficacy, and aerobic exercise. Individuals who sustained high function and those who sustained low function over the 3 years were described. Conclusion Factors placing individuals with knee OA at greater risk of a poor function outcome by at least 1 of the 2 function measures included the local factors laxity and proprioceptive inaccuracy, as well as age, BMI, and knee pain intensity. Factors protecting against a poor function outcome included strength, the psychosocial factors mental health, self-efficacy, and social support, and the activity level measured by the amount of aerobic exercise per week. The identification of these factors provides possible targets for rehabilitative and self-management strategies to prevent disability.

OBJECTIVES: To determine whether persons with poorer lower extremity functioning have reduced physical activity levels. DESIGN: Cross-sectional. SETTING: Three Chicago-area medical centers. PARTICIPANTS: Two hundred twenty-five people with lower extremity peripheral arterial disease (PAD) and 121 individuals without PAD. MEASUREMENTS: The summary performance score (SPS) was determined for all participants. The SPS combines data on walking velocity, time for five repeated chair rises, and standing balance. Each test is scored on a 0 to 4 scale (4 = best). Scores are summed to create the SPS (0-12 scale, 12 = best). All participants wore a vertical accelerometer for 7 days to measure physical activity. RESULTS: The SPS was associated linearly with 7-day physical activity levels of participants with (P

Investigate the relationship between sedentary behavior and physical function in adults with knee osteoarthritis (OA), controlling for moderate-vigorous physical activity (MVPA) levels.Sedentary behavior was objectively measured by accelerometer on 1,168 participants ages 49-83 years in the Osteoarthritis Initiative with radiographic knee OA at the 48-month clinic visit. Physical function was assessed using 20-meter walk and chair stand testing. Sedentary behavior was identified by accelerometer activity counts/minute100. The cross-sectional association between sedentary quartiles and physical function was examined by multiple linear regression, adjusting for demographic factors (age, sex, race/ethnicity, education level), health factors (comorbidity, body mass index, knee pain, knee OA severity, presence of knee symptoms), and average daily MVPA minutes.Adults with knee OA spent two-thirds of their daily time in sedentary behavior. The average gait speed among the most sedentary quartile was 3.88 feet/second, which was significantly slower than the speed of the less sedentary groups (4.23, 4.33, and 4.33 feet/second, respectively). The average chair stand rate among the most sedentary group was significantly lower (25.9 stands/minute) than the rates of the less sedentary behavior groups (28.9, 29.1, and 31.1 stands/minute, respectively). These trends remained significant in multivariable analyses adjusted for demographic factors, health factors, and average daily MVPA minutes.Being less sedentary was related to better physical function in adults with knee OA independent of MVPA time. These findings support guidelines to encourage adults with knee OA to decrease time spent in sedentary behavior in order to improve physical function.

Summary Quadriceps strength may protect against knee osteoarthritis (OA), but muscle activity is a major determinant of forces at the hand joints. Gripping objects is a common task during which high muscular forces are sustained, particularly at the proximal hand joints (metacarpophalangeal (MCP) joints and thumb base). The association between maximal grip strength and incident OA at different hand joints was examined in a longitudinal study of radiographic hand OA. Subjects with higher maximal grip strength were at increased risk for development of OA in the proximal interphalangeal (PIP) joints, MCP and thumb base joints in men; and in the MCP in women. No association was found between maximal grip strength and incident distal interphalangeal (DIP) joints OA in men or women. The conclusion is that increased grip strength, which is the major force of loading across proximal hand joints, increases the risk of OA in those joints.

Objective Little is known about risk factors for patellofemoral (PF) osteoarthritis (OA). The lateral vector at the PF joint increases the likelihood of lateral PF versus medial PF pathology. Both valgus and varus malalignments affect forces at the PF joint and may predispose to PF OA. We examined whether lateral PF OA is more common than medial PF OA, whether valgus malalignment is more frequent in lateral PF OA than in medial PF OA, and whether knees with PF OA are more often valgus than knees with isolated tibiofemoral (TF) OA. Methods In 292 knee OA patients, we obtained semiflexed, fluoroscopy-confirmed radiographs of the TF joint and weight-bearing, 30° flexion, axial views of the PF joint. Varus–valgus alignment (the angle formed by the intersection of the mechanical axes of the femur and tibia) was measured on a full-limb radiograph. Results Lateral PF OA was more common than medial PF OA (P < 0.0001). Forty-three of 75 knees with lateral PF OA had valgus malalignment compared with only 5 of 21 patients with medial PF OA (P = 0.0066). Conversely, varus malalignment was more likely in the medial PF OA group. Knees with isolated PF OA were more likely to have valgus malalignment than those with isolated TF OA (P = 0.0002), as were knees with mixed PF–TF OA (P = 0.0006). Conclusion Varus–valgus alignment may influence the risk of PF OA and, in particular, which compartment is affected.

Objective To investigate the public health impact of obesity and other modifiable risk factors related to physical inactivity in adults with knee osteoarthritis (OA). Methods The frequency of inactivity as defined by the US Department of Health and Human Services was assessed from objective accelerometer monitoring of 1,089 participants (ages 49–84 years) with radiographic knee OA during the Osteoarthritis Initiative 48-month visit (2008–2010). The relationship between modifiable factors (weight status, dietary fat, fiber, smoking, depressive symptoms, knee function, knee pain, and knee confidence) with inactivity was assessed using odds ratios (ORs) and attributable fractions (AFs), controlling for descriptive factors (age, sex, race, education, lives alone, employment, frequent knee symptoms, and comorbidity). Results Almost half (48.9%) of participants with knee OA were inactive. Being overweight (OR 1.8, 95% confidence interval [95% CI] 1.2–2.5) or obese (OR 3.9, 95% CI 2.6–5.7), having inadequate dietary fiber intake (OR 1.6, 95% CI 1.2–2.2), severe knee dysfunction (OR 1.9, 95% CI 1.3–2.8), and severe pain (OR 1.7, 95% CI 1.1–2.5) were significantly related to inactivity, controlling for descriptive factors. Modifiable factors with significant average AFs were being overweight or obese (AF 23.8%, 95% CI 10.5–38.6%) and inadequate dietary fiber (AF 12.1%, 95% CI 0.1–24.5%), controlling for all factors. Conclusion Being obese or overweight, the quality of the diet, severe pain, and severe dysfunction are significantly associated with physical inactivity in adults with knee OA. All components should be considered in designing physical activity interventions that target arthritis populations with low activity levels.

BACKGROUND The objective was to investigate whether baseline physical functioning, medical, psychosocial, or demographic variables predict functional outcome in patients undergoing total knee replacement. METHODS A prospective cohort study was performed between December 1991 and August 1993. Consecutive, unilateral tricompartmental total knee replacement patients aged > or = 55 yr with osteoarthritis, who met criteria, were enrolled and evaluated one month before and 3 months after total knee replacement. The primary outcome measure was the Medical Outcome Study 36 Item Short Form Health Survey (known as the SF36) Physical Functioning Scale score. The outcome evaluator was not involved in patient care. RESULTS A hierarchical multiple regression analysis was performed to calculate the contribution of baseline variables to TKR outcome. Of the 27% of outcome variance explained by the model, demographic variables accounted for 4%, psychosocial variables (motivation, role functioning-emotional, and social functioning) for 19% (p = .013), medical variables (previous reconstruction, comorbidity, body mass index, bodily pain) for 2%, and baseline physical function for 2%. CONCLUSIONS Psychosocial variables are significantly related to total knee replacement functional outcome. Assessment of baseline psychological and social functioning may identify a subset of patients at risk for worse outcome. Specific interventions for these patients should be developed and evaluated as components of patient management prior to and after the procedure.

Objective To evaluate whether low knee confidence at baseline is associated with poor baseline-to-3-year physical function outcome in the Osteoarthritis Initiative. Methods Knee confidence was assessed using an item from the Knee Injury and Osteoarthritis Outcome Score instrument. Physical function was assessed using self-report measures (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] function score and Short Form 12 physical component scale) and performance-based measures (20-meter walk and chair stand test). Poor function outcome was defined as moving into a worse function group or remaining in the 2 worst function groups between baseline and 3 years. Logistic regression was used to evaluate the relationship between baseline knee confidence level and poor baseline-to-3-year function outcome, adjusting for potential confounders. Results The sample included 3,975 men and women with or at high risk of developing osteoarthritis of the knee, of whom 37–53% had poor baseline-to-3-year function outcome. For both self-report measures, increasingly worse knee confidence was associated with a greater risk of poor function outcome, and trend tests supported a graded response (e.g., the adjusted odds ratios [95% confidence intervals] for the WOMAC function score for worsening confidence categories were 1.26 [1.07–1.49], 1.43 [1.16–1.77], and 2.05 [1.49–2.82], P for trend

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.

Objective Varus–valgus alignment has been linked to subsequent progression of osteoarthritis (OA) within the mechanically stressed (medial for varus, lateral for valgus) tibiofemoral compartment. Cartilage data from the off-loaded compartment are sparse. The purpose of this study was to examine our hypotheses that neutral and valgus (versus varus) knees each have reduced odds of cartilage loss in the medial subregions and that neutral and varus (versus valgus) knees each have reduced odds of cartilage loss in the lateral subregions. Methods Patients with knee OA underwent knee magnetic resonance imaging at baseline and 2 years. The mean cartilage thickness was quantified within 5 tibial and 3 femoral subregions. We used logistic regression with generalized estimating equations to analyze the relationship between baseline alignment and subregional cartilage loss at 2 years, adjusting for age, sex, body mass index, and disease severity. Results A reduced risk of cartilage loss in the medial subregions was associated with neutral (versus varus) alignment (external tibial, central femoral, external femoral) and with valgus (versus varus) alignment (central tibial, external tibial, central femoral, external femoral). A reduced risk of cartilage loss in the lateral subregions was associated with neutral (versus valgus) alignment (central tibial, internal tibial, posterior tibial) and with varus (versus valgus) alignment (central tibial, external tibial, posterior tibial, external femoral). Conclusion Neutral and valgus alignment were each associated with a reduction in the risk of subsequent cartilage loss in certain medial subregions and neutral and varus alignment with a reduction in the risk of cartilage loss in certain lateral subregions. These results support load redistribution as an in vivo mechanism of the long-term alignment effects on cartilage loss in knee OA.