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Objective: The purpose of this study is to examine the course of hand osteoarthritis (HOA) and its relationship with cardiovascular disease (CVD) and diabetes (DM)., Methods: Data were collected at 3 timepoints from 845 Johnston County Osteoarthritis Project participants (two-thirds women, one-third African Americans, mean age 60 yrs) with and without HOA, CVD, or DM. A diagnosis of radiographic HOA (rHOA) required a Kellgren-Lawrence severity grade of ≥ 2 in at least 3 joints in each hand. A 4-state progressive model included transitions based on rHOA and pain or function as defined using the Australian/Canadian HOA Index (AUSCAN). Markov multistate models estimated HR (aHR) and 95% CI for associations between DM or CVD and specific state transitions, adjusting for baseline and time-varying covariates., Results: Participants with DM (vs those without DM) were more likely to experience worsening pain with rHOA. Individuals who had or developed CVD (vs those who did not) were significantly less likely to experience symptomatic improvement, regardless of rHOA status. Those with DM or CVD (vs those without these comorbidities) were less likely to experience improvement in function, although this was statistically significant only for those with DM and no rHOA., Conclusion: Overall, having or developing DM and/or CVD reduced the likelihood of symptomatic and functional improvement over time, suggesting an effect of comorbid CVD and DM on the clinical and radiographic course of HOA. Additional studies are needed to confirm these findings.

Background: This cross-sectional study evaluated associations of joint hypermobility and multiple joint osteoarthritis (MJOA) in a community-based cohort of adults 45+ years of age., Methods: MJOA and joint hypermobility data were from 1677 participants (mean age 69 years, 68% women) who completed research clinic visits during 2003-2010. Prevalent MJOA was defined in four ways. Radiographic OA (rOA) was defined as Kellgren-Lawrence (KL) > 2 at any included study joint; symptomatic OA (sxOA) required both symptoms and rOA in a joint. Joint hypermobility was defined as a Beighton score of > 4. Separate logistic regression models were used to estimate odds ratios (OR) between joint hypermobility and each MJOA definition, adjusting for age, sex, race, body mass index, and baseline visit., Results: In this cohort, 4% had Beighton score > 4 and 63% met any definition of MJOA. Joint hypermobility was associated with significantly lower odds of radiographic and symptomatic MJOA-1 (multiple joint OA-definition 1: involvement of > 1 IP (interphalangeal) nodes and > 2 sites of hip, knee, and spine; 74 and 58% lower, respectively). However, for the other MJOA definitions (i.e., MJOA-2:involvement of > 2 IP joints, > 1 carpometacarpal [CMC] joints, and knee or hip sites; MJOA-3: involvement of > 5 joint sites from among distal interphalangeal, proximal interphalangeal, CMC, hip, knee, or spine sites; and MJOA-4:involvement of > 2 lower body sites (hip, knee, or spine), there were no statistically significant associations. For associations between site-specific hypermobility and any MJOA definition, most adjusted ORs were less than one, but few were statistically significant., Conclusions: Overall, joint hypermobility was not positively associated with any definition of prevalent MJOA in this cohort, and an inverse association existed with one definition of MJOA. Longitudinal studies are needed to determine the contribution of hypermobility to the incidence and progression of MJOA outcomes.

Objective: To explore associations of joint hypermobility (a condition where range of motion is greater than normal) with ankle and foot radiographic osteoarthritis (OA) and symptoms in a large community-based cohort of African American and white adults ages 55-94 years old., Methods: Ankle and foot radiographs and joint hypermobility data (Beighton score for joint hypermobility criteria) were available for 848 participants (from 2003 to 2010) in this cross-sectional study. General joint hypermobility was defined as a Beighton score ≥4 (range 0-9); knee hypermobility was defined as hyperextension of at least 1 knee. Standing anteroposterior and lateral foot radiographs were read with standard atlases for Kellgren-Lawrence grade, osteophytes, and joint space narrowing (JSN) at the tibiotalar joint, and for osteophytes and JSN to define OA at 5 foot joints. Ankle or foot symptoms were self-reported. Separate person-based logistic regression models were used to estimate associations of ankle and foot OA and symptom outcomes with hypermobility measures, adjusting for age, sex, race, body mass index, and history of ankle/foot injury., Results: This sample cohort included 577 women (68%) and 280 African Americans (33%). The mean age of the participants was 71 years, with a mean body mass index of 31 kg/m 2 . The general joint hypermobility of the participants was 7% and knee hypermobility was 4%. Having a history of ankle injury was 11.5%, and foot injury was 3.8%. Although general joint hypermobility was not associated with ankle and foot outcomes, knee hypermobility was associated with ankle symptoms, foot symptoms, and talonavicular OA (adjusted odds ratios of 4.4, 2.4, and 3.0, respectively)., Conclusion: Knee joint hypermobility may be related to talonavicular OA and to ankle and foot symptoms., (© 2018, American College of Rheumatology.)

Objective: Symptomatic hand osteoarthritis (OA) is a common condition that affects hand strength and function, and causes disability in activities of daily living. Prior studies have estimated that the lifetime risk of symptomatic knee OA is 45% and that of hip OA is 25%. The objective of the present study was to estimate the overall lifetime risk of symptomatic hand OA, and the stratified lifetime risk according to potential risk factors., Methods: Data were obtained from 2,218 adult subjects (ages ≥45 years) in the Johnston County Osteoarthritis Project, a population-based prospective cohort study among residents of Johnston County, North Carolina. Data for the present study were collected from 2 of the follow-up cycles (1999-2004 and 2005-2010). Symptomatic hand OA was defined as the presence of both self-reported symptoms and radiographic OA in the same hand. Lifetime risk, defined as the proportion of the population who will develop symptomatic hand OA in at least 1 hand by age 85 years, was estimated from models using generalized estimating equations., Results: Overall, the lifetime risk of symptomatic hand OA was 39.8% (95% confidence interval [95% CI] 34.4-45.3%). In this population, nearly 1 in 2 women (47.2%, 95% CI 40.6-53.9%) had an estimated lifetime risk of developing symptomatic hand OA by age 85 years, compared with 1 in 4 men (24.6%, 95% CI 19.5-30.5%). Race-specific symptomatic hand OA risk estimates were 41.4% (95% CI 35.5-47.6%) among whites and 29.2% (95% CI 20.5-39.7%) among African Americans. The lifetime risk of symptomatic hand OA among individuals with obesity (47.1%, 95% CI 37.8-56.7%) was 11 percentage points higher than that in individuals without obesity (36.1%, 95% CI 29.7-42.9%)., Conclusion: These findings demonstrate the substantial burden of symptomatic hand OA overall and in sociodemographic and clinical subgroups. Increased use of public health and clinical interventions is needed to address its impact., (© 2017, American College of Rheumatology.)

Purpose: To determine associations between multiple joint symptoms and radiographic osteoarthritis (rOA) and functional outcomes., Method: Complete cross-sectional data for multi-joint symptoms and radiographs, Health Assessment Questionnaire (HAQ) scores, and gait speed were available for 1307 Johnston County Osteoarthritis Project participants (34% men, 32% African American, mean age 66 years). Factor analysis of symptom scores and radiographic grades for the lumbosacral spine, bilateral hands, knees, and hips provided composite scores. Regression models were used to determine associations between composite scores, HAQ, and gait speed, adjusting for age, body mass index, gender, and race., Results: Five rOA factors were identified: (1) IP/CMC factor (carpometacarpal [CMC] and all interphalangeal [IP] joints); (2) MCP factor (metacarpophalangeal joints 2-5); (3) Knee factor (tibiofemoral and patellofemoral joints); (4) Spine factor (L1/2 to L5/S1); and (5) Symptom factor. After adjustment, only the Symptom composite was significantly associated with HAQ and gait speed; a 1-standard deviation increase in Symptom score was associated with 9 times higher odds of having poorer function on the HAQ (odds ratio 9.32, 95% confidence interval [CI] 6.80, 12.77), and a clinically significant decline in gait speed (0.06 m/s, 95% CI -0.07, -0.05)., Conclusions: A novel Symptom composite score was associated with poorer functional outcomes., Implications for Rehabilitation: Osteoarthritis (OA) commonly affects multiple joints and is the most common form of arthritis. Symptomatic assessments, which can be easily executed by rehabilitation practitioners, are more closely related to self-reported and performance-based functional status than are less accessible and more costly radiographs. Symptomatic assessments are likely to be more informative for understanding, treating, and potentially preventing functional limitations than radiographic assessments.

Objective: To determine differences in the phenotypes (patterns) of multiple-joint symptomatic osteoarthritis (OA) involvement by race and sex., Methods: A cross-sectional analysis of symptomatic OA phenotypes was performed in a community-based cohort, comprising subjects for whom data were collected from 4 sites of symptomatic OA involvement (the hands, knees, hips, and lumbosacral [LS] spine) at a single visit (2003-2010). Mutually exclusive phenotypes describing all combinations of these 4 sites were compared by race and by sex, using Fisher's exact tests. For those phenotypes occurring in >40 subjects, logistic regression was performed, with adjustments for race, sex, age, and body mass index (BMI), and interactions of race and sex were assessed., Results: The sample included 1,650 participants, of whom 36% were men and 32% were African American. The mean age of the subjects was 66 years, and the mean BMI was 31 kg/m(2). Overall, in this sample, 13% of subjects had symptomatic hand OA, 25% had symptomatic knee OA, 11% had symptomatic hip OA, and 28% had symptomatic LS spine OA. African Americans, as compared with Caucasians, were less likely to have involvement of symptomatic OA in the hand only, or in some combination of the hand and other sites, but were more likely to have involvement of the knee only. Men, as compared to women, were less likely to have involvement of the hand only, but were more likely to have involvement of the LS spine only., Conclusion: There are differences in the phenotypes of multiple-joint symptomatic OA involvement by race and by sex that may influence the definitions of multiple-joint, or generalized, OA., (Copyright © 2013 by the American College of Rheumatology.)

Objective: To define and contrast multiple joint radiographic osteoarthritis (OA) phenotypes describing hand and whole-body radiographic OA among African Americans and Caucasians., Methods: We conducted a cross-sectional analysis in the Johnston County Osteoarthritis Project, using radiographic data for the hands, tibiofemoral (TF) joints, patellofemoral joints, hips, and lumbosacral (LS) spine. Radiographs were read for OA by a single radiologist using standard atlases. Fisher's exact test, with correction for multiple comparisons, was used to compare phenotype frequencies by race and sex. Logistic regression was used to provide odds ratios, which were adjusted for sex, age, and body mass index (BMI)., Results: Sixteen mutually exclusive hand (n = 2,083) and 32 whole-body (n = 1,419) radiographic OA phenotypes were identified. We found that in comparison to Caucasians, African Americans had significantly less frequent radiographic OA of the distal interphalangeal joints, both in isolation and in combination with other hand joint sites, but had comparable frequencies of radiographic OA for other hand joint sites. Moreover, African Americans had less frequent radiographic OA of the hand, both in isolation and in combination with other joint sites, as compared to Caucasians. In contrast, African Americans had more than twice the odds of isolated OA of the TF joint and 77% higher odds of radiographic OA of the TF joint and LS spine together as compared to Caucasians., Conclusion: Even after adjustment for sex, age, and BMI, African Americans were less likely than Caucasians to have hand radiographic OA phenotypes, but more likely to have knee radiographic OA phenotypes involving the TF joint. African Americans may have a higher burden of multiple large-joint OA involvement not captured by most definitions of "generalized OA.", (Copyright © 2011 by the American College of Rheumatology.)

Purpose: To examine associations between biomarkers of joint tissue metabolism and whole blood lead (Pb), separately for men and women in an African American and Caucasian population, which may reflect an underlying pathology., Methods: Participants in the Johnston County Osteoarthritis Project Metals Exposure Sub-Study (329 men and 342 women) underwent assessment of whole blood Pb and biochemical biomarkers of joint tissue metabolism. Urinary cross-linked N telopeptide of type I collagen (uNTX-I) and C-telopeptide fragments of type II collagen (uCTX-II), serum cleavage neoepitope of type II collagen (C2C), serum type II procollagen synthesis C-propeptide (CPII), and serum hyaluronic acid (HA) were measured using commercially available kits; the ratio of [C2C:CPII] was calculated. Serum cartilage oligomeric matrix protein (COMP) was measured by an in-house assay. Multiple linear regression models were used to examine associations between continuous blood Pb and biomarker outcomes, adjusted for age, race, current smoking status, and body mass index. Results are reported as estimated change in biomarker level for a 5-unit change in Pb level., Results: The median Pb level among men and women was 2.2 and 1.9μg/dL, respectively. Correlations were noted between Pb levels and the biomarkers uNTX-I, uCTX-II, and COMP in women, and between Pb and uCTX-II, COMP, CPII, and the ratio [C2C:CPII] in men. In adjusted models among women, a 5-unit increase in blood Pb level was associated with a 28% increase in uCTX-II and a 45% increase in uNTX-I levels (uCTX-II: 1.28 [95% CI: 1.04-1.58], uNTX-I: 1.45 [95% CI:1.21-1.74]). Among men, levels of Pb and COMP showed a borderline positive association (8% increase in COMP for a 5-unit change in Pb: 1.08 [95% CI: 1.00-1.18]); no other associations were significant after adjustment., Conclusions: Based upon known biomarker origins, the novel associations between blood Pb and biomarkers appear to be primarily reflective of relationships to bone and calcified cartilage turnover among women and cartilage metabolism among men, suggesting a potential gender-specific effect of Pb on joint tissue metabolism that may be relevant to osteoarthritis., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Introduction: The purpose of this study was to examine data from the Johnston County Osteoarthritis (OA) Project for independent associations of educational attainment, occupation and community poverty with tibiofemoral knee OA., Methods: A cross-sectional analysis was conducted on 3,591 individuals (66% Caucasian and 34% African American). Educational attainment (< 12 years or ≥12 years), occupation (non-managerial or not), and census block group household poverty rate (< 12%, 12 to 25%, > 25%) were examined separately and together in logistic models adjusting for covariates of age, gender, race, body mass index (BMI), smoking, knee injury and occupational activity score. Outcomes were presence of radiographic knee OA (rOA), symptomatic knee OA (sxOA), bilateral rOA and bilateral sxOA., Results: When all three socioeconomic status (SES) variables were analyzed simultaneously, low educational attainment was significantly associated with rOA (odds ratio (OR) = 1.44, 95% confidence interval (CI) 1.20, 1.73), bilateral rOA (OR = 1.43, 95% CI 1.13, 1.81), and sxOA (OR = 1.66, 95% CI 1.34, 2.06), after adjusting for covariates. Independently, living in a community of high household poverty rate was associated with rOA (OR = 1.83, 95% CI 1.43, 2.36), bilateral rOA (OR = 1.56, 95% CI 1.12, 2.16), and sxOA (OR = 1.36, 95% CI 1.00, 1.83). Occupation had no significant independent association beyond educational attainment and community poverty., Conclusions: Both educational attainment and community SES were independently associated with knee OA after adjusting for primary risk factors for knee OA.

Introduction: Although osteoarthritis (OA) commonly involves multiple joints, no widely accepted method for quantifying whole-body OA burden exists. Therefore, our aim was to apply factor analytic methods to radiographic OA (rOA) grades across multiple joint sites, representing both presence and severity, to quantify the burden of rOA., Methods: We used cross-sectional data from the Johnston County Osteoarthritis Project. The sample (n = 2092) had a mean age of 65 ± 11 years, body mass index (BMI) 31 ± 7 kg/m2, with 33% men and 34% African Americans. A single expert reader (intra-rater κ = 0.89) provided radiographic grades based on standard atlases for the hands (30 joints, including bilateral distal and proximal interphalangeal [IP], thumb IP, metacarpophalangeal [MCP] and carpometacarpal [CMC] joints), knees (patellofemoral and tibiofemoral, 4 joints), hips (2 joints), and spine (5 levels [L1/2 to L5/S1]). All grades were entered into an exploratory common factor analysis as continuous variables. Stratified factor analyses were used to look for differences by gender, race, age, and cohort subgroups., Results: Four factors were identified as follows: IP/CMC factor (20 joints), MCP factor (8 joints), Knee factor (4 joints), Spine factor (5 levels). These factors had high internal consistency reliability (Cronbach's α range 0.80 to 0.95), were not collapsible into a single factor, and had moderate between-factor correlations (Pearson correlation coefficient r = 0.24 to 0.44). There were no major differences in factor structure when stratified by subgroup., Conclusions: The 4 factors obtained in this analysis indicate that the variables contained within each factor share an underlying cause, but the 4 factors are distinct, suggesting that combining these joint sites into one overall measure is not appropriate. Using such factors to reflect multi-joint rOA in statistical models can reduce the number of variables needed and increase precision.

ObjectiveHip shape by statistical shape modeling (SSM) is associated with hip radiographic osteoarthritis (rOA). We examined associations between hip shape and knee rOA given the biomechanical interrelationships between these joints.MethodsBilateral baseline hip shape assessments [for those with at least 1 hip with a Kellgren-Lawrence arthritis grading scale (KL) 0 or 1] from the Johnston County Osteoarthritis Project were available. Proximal femur shape was defined on baseline pelvis radiographs and evaluated by SSM, producing mean shape and continuous variables representing independent modes of variation (14 modes = 95% of shape variance). Outcomes included prevalent [baseline KL ≥ 2 or total knee replacement (TKR)], incident (baseline KL 0/1 with followup ≥ 2), and progressive knee rOA (KL increase of ≥ 1 or TKR). Limb-based logistic regression models for ipsilateral and contralateral comparisons were adjusted for age, sex, race, body mass index (BMI), and hip rOA, accounting for intraperson correlations.ResultsWe evaluated 681 hips and 682 knees from 342 individuals (61% women, 83% white, mean age 62 yrs, BMI 29 kg/m(2)). Ninety-nine knees (15%) had prevalent rOA (4 knees with TKR). Lower modes 2 and 3 scores were associated with ipsilateral prevalent knee rOA, and only lower mode 3 scores were associated with contralateral prevalent knee rOA. No statistically significant associations were seen for incident or progressive knee rOA.ConclusionVariations in hip shape were associated with prevalent, but not incident or progressive, knee rOA in this cohort, and may reflect biomechanical differences between limbs, genetic influences, or common factors related to both hip shape and knee rOA.

ObjectiveTo investigate hip shape by active shape modeling (ASM) as a potential predictor of incident radiographic hip osteoarthritis (RHOA) and symptomatic hip osteoarthritis (SRHOA).MethodsAll hips developing RHOA from baseline (Kellgren/Lawrence [K/L] grade 0/1) to mean 6-year followup (K/L grade ≥2, 190 hips) and 1:1 control hips (K/L grade 0/1 at both times, 192 hips) were included. Proximal femur shape was defined on baseline anteroposterior pelvis radiographs and submitted to ASM, producing a mean shape and continuous variables representing independent modes of shape variation. Mode scores (n = 14, explaining 95% of shape variance) were simultaneously included in logistic regression models with incident RHOA and SRHOA as dependent variables, adjusted for intraperson correlations, sex, race, body mass index (BMI), baseline K/L grade, and/or symptoms.ResultsWe evaluated 382 hips from 342 individuals: 61% women and 83% white, with mean age 62 years and mean BMI 29 kg/m(2) . Several modes differed by sex and race, but no modes were associated with incident RHOA overall. Among men only, modes 1 and 2 were significantly associated (for a 1-SD decrease in mode 1 score: odds ratio [OR] 1.7 [95% confidence interval (95% CI) 1.1-2.5] and for a 1-SD increase in mode 2 score: OR 1.5 [95% CI 1.0-2.2]) with incident RHOA. A 1-SD decrease in mode 2 or 3 score increased the odds of SRHOA by 50%.ConclusionThis study confirms other reports that variations in proximal femur shape have a modest association with incident hip OA. The observation of proximal femur shape associations with hip symptoms requires further investigation.

Objective. We applied a precision medicine-based machine learning approach to discover underlying patient characteristics associated with differential improvement in knee osteoarthritis symptoms following standard physical therapy (PT), internet-based exercise training (IBET), and a usual care/wait list control condition. Methods. Participants (n = 303) were from the Physical Therapy vs Internet-Based Training for Patients with Knee Osteoarthritis trial. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score at 12-month follow-up. Random forest-informed tree-based learning was applied to identify patient characteristics that were critical to improving outcomes, and patients with those features were grouped. Results. Age, BMI, and Brief Fear of Movement (BFOM) score, all at baseline, were identified as characteristics that effectively divided participants, creating 6 subgroups. Assigning treatments according to these models, compared to assigning a single best treatment to all patients, resulted in greater improvements of the average WOMAC at 12 months (P = 0.01). Key patterns were that IBET was the optimal treatment for patients of younger age and low BFOM, whereas PT was the optimal treatment for patients of older age, high BFOM, and BMI (kg/m²) between 26.3 and 37.2. Conclusion. These results suggest that easily assessed patient characteristics including age, fear of movement, and BMI could be used to guide patients toward either home-based exercise or PT, though additional studies are needed to confirm these findings. (ClinicalTrials.gov: NCT02312713) [ABSTRACT FROM AUTHOR]

Introduction: Biochemical biomarkers may provide insight into musculoskeletal pain reported at individual or multiple body sites. The purpose of this study was to determine if biomarkers or pressure-pain threshold (PPT) were associated with individual or multiple sites of pain. Methods: This cross-sectional analysis included 689 community-based participants. Self-reported symptoms (ie, pain, aching, or stiffness) were ascertained about the neck, upper back/thoracic, low back, shoulders, elbows, wrist, hands, hips, knees, ankles, and feet. Measured analytes included CXCL-6, RANTES, HA, IL-6, BDNF, OPG and NPY. A standard dolorimeter measured PPT. Logistic regression was used determine the association between biomarkers and PPT with individual and summed sites of pain. Results: Increased IL-6 and HA were associated with knee pain (OR=1.30, 95% CI 1.03, 1.64) and (OR=1.32, 95% CI 1.01, 1.73) respectively; HA was also associated with elbow/wrist/hand pain (OR=1.60, 95% CI 1.22, 2.09). Those with increased NPY levels were less likely to have shoulder pain (OR=0.56, 95% CI 0.33, 0.93). Biomarkers HA (OR=1.50, 95% CI 1.07, 2.10), OPG (OR=1.74, 95% CI 1.00, 3.03), CXCL-6 (OR=1.75, 95% CI 1.02, 3.01) and decreased PPT (OR=3.97, 95% CI 2.22, 7.12) were associated with multiple compared to no sites of pain. Biomarker HA (OR=1.57, 95% CI 1.06, 2.32) and decreased PPT (OR=3.53, 95% CI 1.81, 6.88) were associated with multiple compared to a single site of pain. Conclusion: Biomarkers of inflammation (HA, OPG, IL-6 and CXCL-6), pain (NPY) and PPT may help to understand the etiology of single and multiple pain sites. [ABSTRACT FROM AUTHOR]

Objective: To apply biclustering, a methodology originally developed for analysis of gene expression data, to simultaneously cluster observations and clinical features to explore candidate phenotypes of knee osteoarthritis (KOA) for the first time. Methods: Data from the baseline Osteoarthritis Initiative (OAI) visit were cleaned, transformed, and standardized as indicated (leaving 6461 knees with 86 features). Biclustering produced submatrices of the overall data matrix, representing similar observations across a subset of variables. Statistical validation was determined using the novel SigClust procedure. After identifying biclusters, relationships with key outcome measures were assessed, including progression of radiographic KOA, total knee arthroplasty, loss of joint space width, and worsening Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, over 96 months of follow-up. Results: The final analytic set included 6461 knees from 3330 individuals (mean age 61 years, mean body mass index 28 kg/m2, 57% women and 86% White). We identified 6 mutually exclusive biclusters characterized by different feature profiles at baseline, particularly related to symptoms and function. Biclusters represented overall better (#1), similar (#2, 3, 6), and poorer (#4, 5) prognosis compared to the overall cohort of knees, respectively. In general, knees in biclusters #4 and 5 had more structural progression (based on Kellgren-Lawrence grade, total knee arthroplasty, and loss of joint space width) but tended to have an improvement in WOMAC pain scores over time. In contrast, knees in bicluster #1 had less incident and progressive KOA, fewer total knee arthroplasties, less loss of joint space width, and stable pain scores compared with the overall cohort. Significance: We identified six biclusters within the baseline OAI dataset which have varying relationships with key outcomes in KOA. Such biclusters represent potential phenotypes within the larger cohort and may suggest subgroups at greater or lesser risk of progression over time. [ABSTRACT FROM AUTHOR]

Objective: To describe point prevalence of knee symptoms, radiographic knee osteoarthritis (rKOA), severe rKOA, and symptomatic rKOA at four time points in the longitudinal, population‐based Johnston County Osteoarthritis Project (JoCo OA). Methods: Data were from 2573 JoCo OA participants with up to 18 years of follow‐up (1999‐2018) and standardized fixed‐flexion knee radiographs read by a single, reliable expert musculoskeletal radiologist. The four outcomes were 1) self‐reported knee symptoms, defined by "On most days, do you have pain, aching, or stiffness in your right/left knee?"; 2) rKOA, defined as a Kellgren‐Lawrence grade (KLG) of 2 to 4); 3) severe rKOA, defined as a KLG of 3 or 4; and 4) symptomatic rKOA, defined as both symptoms and rKOA in the same joint. Weighted prevalence estimates and 95% confidence intervals (CIs) were generated overall and by age group, sex, race, and body mass index (BMI). Results: Most recently (2017‐2018, T4), the overall prevalence (percentage) of knee symptoms, rKOA, severe rKOA, and symptomatic rKOA was 41% (95% CI: 35‐47%), 61% (95% CI: 56‐67%), 35% (95% CI: 30‐40%), and 30% (95% CI: 24‐35%), respectively. From time point T1 to T4, prevalence increased for rKOA, severe rKOA, and symptomatic rKOA but not for knee symptoms. The prevalence of both severe rKOA (17‐39%) and symptomatic rKOA (23‐30%) was consistently higher among women. The prevalence of all outcomes was higher among those with higher BMI and among Black participants at all time points, particularly rKOA (35‐69%) and severe rKOA (22‐46%). Conclusion: These updated estimates demonstrate a large and increasing burden of knee OA, particularly among women and Black individuals. [ABSTRACT FROM AUTHOR]

Objective: To apply a precision medicine approach to determine the optimal treatment regime for participants in an exercise (E), dietary weight loss (D), and D + E trial for knee osteoarthritis that would maximize their expected outcomes.Methods: Using data from 343 participants of the Intensive Diet and Exercise for Arthritis (IDEA) trial, we applied 24 machine-learning models to develop individualized treatment rules on 7 outcomes: Short Form 36 physical component score, weight loss, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain/function/stiffness scores, compressive force, and interleukin-6 level. The optimal model was selected based on jackknife value function estimates that indicate improvement in the outcomes if future participants follow the estimated decision rule compared to the optimal single, fixed treatment model.Results: Multiple outcome random forest was the optimal model for the WOMAC outcomes. For the other outcomes, list-based models were optimal. For example, the estimated optimal decision rule for weight loss indicated assigning the D + E intervention to participants with baseline weight not exceeding 109.35 kg and waist circumference above 90.25 cm, and assigning D to all other participants except those with a history of a heart attack. If applied to future participants, the optimal rule for weight loss is estimated to increase average weight loss to 11.2 kg at 18 months, contrasted with 9.8 kg if all participants received D + E (P = 0.01).Conclusion: The precision medicine models supported the overall findings from IDEA that the D + E intervention was optimal for most participants, but there was evidence that a subgroup of participants would likely benefit more from diet alone for 2 outcomes. [ABSTRACT FROM AUTHOR]

Context: Gait biomechanics are linked to biochemical changes that contribute to the development of posttraumatic knee osteoarthritis in individuals with anterior cruciate ligament reconstruction (ACLR). It remains unknown if modifying peak loading during gait using real-time biofeedback will result in acute biochemical changes related to cartilage metabolism. Objective: To determine if acutely manipulating peak vertical ground reaction force (vGRF) during gait influences acute changes in serum cartilage oligomeric matrix protein concentration (sCOMP) among individuals with ACLR. Design: Crossover study. Patients or Other Participants: Thirty individuals with unilateral ACLR participated (70% female, age = 20.43 ± 2.91 years old, body mass index = 24.42 ± 4.25, months post-ACLR = 47.83 ± 26.97). Additionally, we identified a subgroup of participants who demonstrated an increase in sCOMP after the control or natural loading condition (sCOMPCHANGE > 0 ng/mL, n = 22, 70% female, age = 20.32 ± 3.00 years old, body mass index = 24.73 ± 4.33, months post-ACLR = 47.27 ± 29.32). Main Outcome Measure(s): Serum was collected both prior to and immediately after each condition to determine SCOMPCHANGE. Intervention(s): All participants attended 4 sessions that involved 20 minutes of walking on a force-measuring treadmill consisting of a control condition (natural loading) followed by random ordering of 3 loading conditions with real-time biofeedback: (1) symmetric vGRF between limbs, (2) a 5% increase in vGRF (high loading) and (3) a 5% decrease in vGRF (low loading). A general linear mixed model was used to determine differences in sCOMPchange between altered loading conditions and the control group in the entire cohort and the subgroup. Results: The sCOMPCHANGE was not different across loading conditions for the entire cohort (F3.29 = 1.34, P = .282). Within the subgroup, sCOMPCHANGE was less during high loading (1.95 ± 24.22 ng/mL, t21 = -3.53, P = .005) and symmetric loading (9.93 ± 21.45 ng/mL, t21 =-2.86, P= .025) compared with the control condition (25.79 ± 21.40 ng/mL). Conclusions: Increasing peak vGRF during gait decreased sCOMP in individuals with ACLR who naturally demonstrated an increase in sCOMP after 20 minutes of walking. [ABSTRACT FROM AUTHOR]

Objective: In individuals with knee osteoarthritis (OA), self-reported physical function is poorer in African Americans than in whites, but whether this difference holds true for objective assessments is unclear. The purpose of this study was to examine racial differences in performance-based physical function as well as potential underlying factors contributing to these racial differences.Methods: Participants with knee OA from a randomized controlled trial completed the 2-minute step test (2MST), timed-up-and-go (TUG), and 30-second chair stand (30s-CST) at baseline. Race differences in performance-based function were assessed by logistic regression. Separate models were adjusted for sets of demographic, socioeconomic, psychological health, and physical health variables.Results: In individuals with knee OA (n = 322; 72% women, 22% African American, mean ± SD age 66 ± 11 years, mean ± SD body mass index 31 ± 8 kg/m2 ), African Americans (versus whites) had greater unadjusted odds of poorer function (30s-CST odds ratio [OR] 2.79 [95% confidence interval (95% CI) 1.65-4.72], 2MST OR 2.37 [95% CI 1.40-4.03], and TUG OR 3.71 [95% CI 2.16-6.36]). Relationships were maintained when adjusted for demographic and psychological health covariates, but they were either partially attenuated or nonsignificant when adjusted for physical health and socioeconomic covariates.Conclusion: African American adults with knee OA had poorer unadjusted performance-based function than whites. Physical health and socioeconomic characteristics diminished these differences, emphasizing the fact that these factors may be important to consider in mitigating racial disparities in function. [ABSTRACT FROM AUTHOR]

Objective: This study sought to develop and employ a comprehensive and standardized ultrasound (US) protocol and scoring atlas for the evaluation of features relevant to knee osteoarthritis (KOA) in a community‐based cohort in the United States, with the goals of demonstrating feasibility, reliability, and validity. Methods: We utilized data from the fourth follow‐up (2016‐2018) of the Johnston County OA Project, which includes individuals with (~50%) and without radiographic KOA. All participants underwent standardized knee radiography and completed standard questionnaires including the Knee Injury and Osteoarthritis Outcome Score (KOOS). Bilateral knee US images were obtained by a trained sonographer using a standardized protocol and scored by trained rheumatologists using an atlas developed for this study. A total of 396 knees were each scored by two readers according to the atlas. Associations between US features, radiographic findings (graded by an expert radiologist), and KOOS scores were assessed. Results: Overall interreader reliability for US scoring was fair to moderate. The strongest correlations between US and radiographic features were seen for osteophytes, and similarly strong correlations were seen between US osteophytes and overall radiographic Kellgren‐Lawrence Grade, demonstrating criterion validity. Features of effusion/synovitis and osteophytes were most associated with KOOS pain and impaired function. Conclusion: US is a feasible, reliable, and valid method to assess features relevant to KOA in clinical and research settings. The protocol and atlas developed in this study can be utilized to evaluate KOA in a standardized fashion in future clinical studies, enabling greater utilization of this valuable modality in osteoarthritis. [ABSTRACT FROM AUTHOR]

The purpose of this work is to determine the relationship between biomarkers of inflammation, structure, and pain with radiographic disc space narrowing (DSN) in community‐based participants. A total of 74 participants (37 cases and 37 controls) enrolled in the Johnston County Osteoarthritis Project during 2006–2010 were selected. The cases had at least mild radiographic DSN and low back pain (LBP). The controls had neither radiographic evidence of DSN nor LBP. The measured analytes from human serum included N‐cadherin, Keratin‐19, Lumican, CXCL6, RANTES, IL‐17, IL‐6, BDNF, OPG, and NPY. A standard dolorimeter measured pressure‐pain threshold. The coefficients of variation were used to evaluate inter‐ and intra‐assay reliability. Participants with similar biomarker profiles were grouped together using cluster analysis. The binomial regression models were used to estimate risk ratios (RR) and 95% confidence intervals (CI) in propensity score‐matched models. Significant associations were found between radiographic DSN and OPG (RR = 3.90; 95% CI: 1.83, 8.31), IL‐6 (RR = 2.54; 95% CI: 1.92, 3.36), and NPY (RR = 2.06 95% CI: 1.62, 2.63). Relative to a cluster with low levels of biomarkers, a cluster representing elevated levels of OPG, RANTES, Lumican, Keratin‐19, and NPY (RR = 3.04; 95% CI: 1.22, 7.54) and a cluster representing elevated levels of NPY (RR = 2.91; 95% CI: 1.15, 7.39) were significantly associated with radiographic DSN. Clinical Significance: These findings suggest that individual and combinations of biochemical biomarkers may reflect radiographic DSN. This is just one step toward understanding the relationships between biochemical biomarkers and DSN that may lead to improved intervention delivery. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:1027‐1037, 2020 [ABSTRACT FROM AUTHOR]

Background and Purpose: Knee osteoarthritis (KOA) is a common disease that hinders activity participation in older adults. Associated symptoms and physiological changes can increase risk of falling in individuals with KOA. Balance training can decrease fall risks in older adults. Limited evidence exists regarding utilization of balance training in physical therapy (PT) for this population. This secondary data analysis investigated the proportion of participants at high risk for falling in the PhysicAl THerapy vs. INternet-based Exercise Training for Patients with Osteoarthritis (PATH-IN) study and the frequency with which balance training was utilized as an intervention in PT. Methods: PATH-IN study participants (N = 344) performed the Four-Stage Balance Test and the Timed Up and Go (TUG) test during baseline assessment. Participants were randomly allocated to PT, an Internet-based exercise program, or a control group. Participants were classified as being at high risk for falling if they did not progress to the single-leg stance (SLS) during the Four-Stage Balance Test, were unable to maintain SLS for 5 seconds, or took longer than 13.5 seconds to complete the TUG test. The proportion of participants at high risk for falling was calculated for all participants and separately for those allocated to PT. In addition, PT notes were coded for balance training and the frequency of balance training utilization was calculated. Results and Discussion: Upon enrollment, 35.5% (N = 122) of all participants and 36.2% (N = 50) of those allocated to PT were at high risk for falling. Of participants allocated to PT with documentation available for coding (N = 118), 35.5% (N = 42) were at high risk for falling. Balance training was provided to 62.7% (N = 74) during at least one PT session. Of those classified as being at high risk for falling, 33.3% (N = 14) did not receive balance training. Conclusions: The finding of high fall risks in more than one-third of all participants with KOA is consistent with previous reports of a higher risk of falling in this population. Many PT participants did receive some balance training; however, one-third of participants at high risk for falling did not. Balance training for individuals with KOA at high risk for falling may be underutilized. [ABSTRACT FROM AUTHOR]

Background Physical therapy is essential for conservative management of symptomatic knee osteoarthritis (OA). However, physical therapy utilization data are limited for knee OA. Objective The purpose of this study is to identify correlates of physical therapy utilization among adults with symptomatic knee OA. Design The design consisted of secondary analysis using baseline data from a randomized controlled trial of 350 adults with physician-diagnosed symptomatic knee OA. Methods Patients completed baseline surveys regarding demographics, pain, function, medical history, and prior physical therapy utilization for symptomatic knee OA. Multivariable logistic regression identified correlates of physical therapy utilization, with models adjusted for body mass index and age. Interactions of race and sex with all other characteristics were evaluated. Results One hundred and eighty-one patients (52%) reported prior physical therapy utilization. Factors independently associated with increased odds of physical therapy utilization were female sex (odds ratio [OR] = 3.06, 95% CI = 1.58–5.93), bachelor degree or higher degree (OR = 2.44, 95% CI = 1.15–5.16), prior knee injury (OR = 1.86, 95% CI = 1.08–3.19), and duration of knee OA symptoms (OR = 2.16, 95% CI = 1.09–4.29 for >5–10 years; OR = 2.11, 95% CI = 1.10–4.04 for >10 years). Whites who had received a joint injection were >3 times as likely to have utilized physical therapy (OR = 3.69, 95% CI = 1.94–7.01); this relationship did not exist for non-whites who had received joint injections. Limitations A sample enrolled in an exercise study may limit generalizability. Self–report of physical therapy may misclassify utilization. It cannot be determined whether lack of utilization resulted from lack of referral or from patients choosing not to attend physical therapy. Conclusion Physical therapy is underutilized to manage symptomatic knee OA. Women and those with a bachelor degree or higher degree, prior knee injury, and longer duration of knee OA symptoms were more likely to have used therapy previously. Differences by race in the link between joint injection and physical therapy utilization may reflect a reduced likelihood of referral and decreased use of health interventions for symptomatic knee OA among non-whites, or both. [ABSTRACT FROM AUTHOR]

Objective: To compare the effectiveness of physical therapy (PT, evidence-based approach) and internet-based exercise training (IBET), each vs a wait list (WL) control, among individuals with knee osteoarthritis (OA).Design: Randomized controlled trial of 350 participants with symptomatic knee OA, allocated to standard PT, IBET and WL control in a 2:2:1 ratio, respectively. The PT group received up to eight individual visits within 4 months. The IBET program provided tailored exercises, video demonstrations, and guidance on progression. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC, range 0 [no problems]-96 [extreme problems]), assessed at baseline, 4 months (primary time point) and 12 months. General linear mixed effects modeling compared changes in WOMAC among study groups, with superiority hypotheses testing differences between each intervention group and WL and non-inferiority hypotheses comparing IBET with PT.Results: At 4-months, improvements in WOMAC score did not differ significantly for either the IBET or PT group compared with WL (IBET: -2.70, 95% Confidence Interval (CI) = -6.24, 0.85, P = 0.14; PT: -3.36, 95% (CI) = -6.84, 0.12, P = 0.06). Similarly, at 12-months mean differences compared to WL were not statistically significant for either group (IBET: -2.63, 95% CI = -6.37, 1.11, P = 0.17; PT: -1.59, 95% CI = -5.26, 2.08, P = 0.39). IBET was non-inferior to PT at both time points.Conclusions: Improvements in WOMAC score following IBET and PT did not differ significantly from the WL group. Additional research is needed to examine strategies for maximizing benefits of exercise-based interventions for patients with knee OA.Trial Registration: NCT02312713. [ABSTRACT FROM AUTHOR]

Objective: To estimate annual incidence rates (IRs) of knee symptoms and 4 knee osteoarthritis (OA) outcomes (radiographic, symptomatic, severe radiographic, and severe symptomatic), overall and stratified by sociodemographic characteristics and knee OA risk factors.Methods: We analyzed baseline (1991-1997) and first followup (1999-2003) data (n = 1,518) from the Johnston County Osteoarthritis Project. Participants were African American and white adults, ages ≥45 years, living in Johnston County, North Carolina, US. Knee symptoms were pain, aching, or stiffness on most days in a knee. Radiographic OA was Kellgren/Lawrence grade ≤2 (severe radiographic ≥3) in at least 1 knee. Symptomatic OA was defined as symptoms in a radiographically affected knee; severe symptomatic OA was defined as severe symptoms and severe radiographic OA.Results: The median followup time was 5.5 years. Average annual IRs were 6% for symptoms, 3% for radiographic OA, 2% for symptomatic OA, 2% for severe radiographic OA, and 0.8% for severe symptomatic OA. Across outcomes, IRs were highest among those with the following baseline characteristics: age ≥75 years, obese, a history of knee injury, or an annual household income ≤$15,000.Conclusion: The annual onset of knee symptoms and 4 OA outcomes in Johnston County was high. This may preview the future of knee OA in the US and underscores the urgency of clinical and public health collaborations that reduce risk factors for, and manage the impact of, these outcomes. Inexpensive, convenient, and proven strategies (e.g., physical activity, self-management education courses) complement clinical care and can reduce pain and improve quality of life for people with arthritis. [ABSTRACT FROM AUTHOR]

Background: Physical activity improves pain and function among individuals with knee osteoarthritis (OA), but most people with this condition are inactive. Physical therapists play a key role in helping people with knee OA to increase appropriate physical activity. However, health care access issues, financial constraints, and other factors impede some patients from receiving physical therapy (PT) for knee OA. A need exists to develop and evaluate other methods to provide physical activity instruction and support to people with knee OA. This study is examining the effectiveness of an internet-based exercise training (IBET) program designed for knee OA, designed by physical therapists and other clinicians.Methods/design: This is a randomized controlled trial of 350 participants with symptomatic knee OA, allocated to three groups: IBET, standard PT, and a wait list (WL) control group (in a 2:2:1 ratio, respectively). The study was funded by the Patient Centered Outcomes Research Institute, which conducted a peer review of the proposal. The IBET program provides patients with a tailored exercise program (based on functional level, symptoms, and current activity), video demonstrations of exercises, and guidance for appropriate exercise progression. The PT group receives up to 8 individual visits with a physical therapist, mirroring standard practice for knee OA and with an emphasis on a home exercise program. Outcomes are assessed at baseline, 4 months (primary time point) and 12 months (to assess maintenance of treatment effects). The primary outcome is the Western Ontario and McMaster Universities Osteoarthritis Index, and secondary outcomes include objective physical function, satisfaction with physical function, physical activity, depressive symptoms and global assessment of change. Linear mixed models will be used to compare both the IBET and standard PT groups to the WL control group, examine whether IBET is non-inferior to PT (a treatment that has an established evidence base for knee OA), and explore whether participant characteristics are associated with differential effects of IBET and/or standard PT. This research is in compliance with the Helsinki Declaration and was approved by the Institutional Review Board of the University of North Carolina at Chapel Hill.Discussion: The IBET program could be disseminated widely at relatively low cost and could be an important resource for helping patients with knee OA to adopt and maintain appropriate physical activity. This trial will provide an important evaluation of the effectiveness of this IBET program for knee OA.Trial Registration: NCT02312713. [ABSTRACT FROM AUTHOR]

Supplemental digital content is available in the text. Purpose: Aberrant walking biomechanics after anterior cruciate ligament reconstruction (ACLR) are hypothesized to be associated with deleterious changes in knee cartilage. T1ρ magnetic resonance imaging (MRI) is sensitive to decreased proteoglycan density of cartilage. Our purpose was to determine associations between T1ρ MRI interlimb ratios (ILR) and walking biomechanics 6 months after ACLR. Methods: Walking biomechanics (peak vertical ground reaction force (vGRF), vGRF loading rate, knee extension moment, knee abduction moment) were extracted from the first 50% of stance phase in 29 individuals with unilateral ACLR. T1ρ MRI ILR (ACLR limb/uninjured limb) was calculated for regions of interest in both medial and lateral femoral (LFC) and medial and lateral tibial condyles. Separate, stepwise linear regressions were used to determine associations between biomechanical outcomes and T1ρ MRI ILR after accounting for walking speed and meniscal/chondral injury (P ≤ 0.05). Results: Lesser peak vGRF in the ACLR limb was associated with greater T1ρ MRI ILR for the LFC (posterior Δ R 2 = 0.14, P = 0.05; central Δ R 2 = 0.15, P = 0.05) and medial femoral condyle (central Δ R 2 = 0.24, P = 0.01). Lesser peak vGRF loading rate in the ACLR limb (Δ R 2 = 0.21, P = 0.02) and the uninjured limb (Δ R 2 = 0.27, P = 0.01) was associated with greater T1ρ MRI ILR for the anterior LFC. Lesser knee abduction moment for the injured limb was associated with greater T1ρ MRI ILR for the anterior LFC (Δ R 2 = 0.16, P = 0.04) as well as the posterior medial tibial condyle (Δ R 2 = 0.13, P = 0.04). Conclusion: Associations between outcomes related to lesser mechanical loading during walking and greater T1ρ MRI ILR were found 6 months after ACLR. Although preliminary, our results suggest that underloading of the ACLR limb at 6 months after ACLR may be associated with lesser proteoglycan density in the ACLR limb compared with the uninjured limb. [ABSTRACT FROM AUTHOR]

Background It has been hypothesized that arthrogenic muscle inhibition is responsible for altering physical function following knee injury. The association between the onset of arthrogenic muscle inhibition, measured using voluntary quadriceps activation, and changes in muscle strength and gait biomechanics are unknown. Methods Outcomes were collected before and following a 60 ml experimental knee effusion in eighteen healthy participants. Voluntary quadriceps activation was the predictor variable, while the criterion variable included, maximal voluntary isometric strength, peak knee flexion angle, peak internal knee extension moment, and peak vertical ground reaction forces during the first half of stance phase upon stair descent. Percent change scores (Δ) were imputed into linear regression equations to determine associations between predictor and criterion variables. Findings The variance in Δ voluntary quadriceps activation significantly predicted 87% the variance in the Δ strength (R 2 = 0.87, P < 0.001; Δ strength = − 2.15 + 1.77 Δ voluntary quadriceps activation ) and 25% of the Δ vertical ground reaction force following effusion (R 2 = 0.25, P = 0.04; Δ vertical ground reaction force = − 6.1 + 0.57 Δ voluntary quadriceps activation ). After accounting for Δ knee flexion angle, Δ voluntary quadriceps activation predicted an additional 29% (Δ R 2 = 0.29, P = 0.007) of the variance in the Δ knee extension moment (R 2 = 0.54, P = 0.003, Δ knee extension moment = − 10.79 + 0.74 Δ knee flexion angle + 1.64 Δ voluntary quadriceps activation ) following knee effusion. Interpretation Immediate quadriceps activation deficits following joint effusion result in immediate alterations in muscle strength, knee extensor moment and vertical ground reaction force during gait. [ABSTRACT FROM AUTHOR]