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Objective To evaluate quantitative joint space width (qJSW, at 10-, 30-, and 50-degree locations) in relation to incident radiographic and symptomatic hip osteoarthritis (rHOA and sxHOA, respectively) in a community-based cohort. Methods Data were from Johnston County OA Project (JoCoOA) participants with supine hip radiographs at each of 4 timepoints; all had Kellgren-Lawrence grades (KLG) and qJSW. We assessed covariates (age, race, height, weight, body mass index [BMI]) associated with qJSW, and hip-level associations between qJSW and HOA, over time using sex-stratified and multivariable-adjusted linear mixed models. A cluster analysis with logistic regression estimated associations between qJSW trajectory groups and incident rHOA and sxHOA. Results At baseline, 397 participants (784 hips, 41% men, 24% Black, mean age=57 years) had a mean BMI=29 kilograms/meter2 . Over a mean of 18 years, 20% and 12% developed incident KLG-defined rHOA or sxHOA, respectively. QJSW was more sensitive to changes over time at 50 degrees. Values were stable among men but declined over time in women. Heavier women lost more qJSW; changes in qJSW were not significantly associated with race, education, or injury in women or men. In women only, loss of qJSW over time was associated with 2-3 times higher odds of rHOA and sxHOA; among women and men, narrower baseline qJSW was associated with these outcomes. Conclusion Hip qJSW demonstrates marked sex differences, with significant loss over time only in women. Loss of qJSW over time in women, and narrower baseline qJSW in men and women, was associated with incident rHOA and sxHOA.

To determine the incidence and worsening of lumbar spine structure and low back pain (LBP) and whether they are predicted by demographic characteristics or clinical characteristics or appendicular joint osteoarthritis (OA).Paired baseline (2003-2004) and follow-up (2006-2010) lumbar spine radiographs from the Johnston County Osteoarthritis Project were graded for osteophytes (OST), disc space narrowing (DSN), spondylolisthesis, and presence of facet joint OA (FOA). Spine OA was defined as at least mild OST and mild DSN at the same level for any level of the lumbar spine. LBP, comorbidities, and back injury were self-reported. Weibull models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) of spine phenotypes accounting for potential predictors including demographic characteristics, clinical characteristics, comorbidities, obesity, and appendicular OA.Obesity was a consistent and strong predictor of incidence of DSN (HR 1.80 [95% CI 1.09-2.98]), spine OA (HR 1.56 [95% CI 1.01-2.41]), FOA (HR 4.99 [95% CI 1.46-17.10]), spondylolisthesis (HR 1.87 [95% CI 1.02-3.43]), and LBP (HR 1.75 [95% CI 1.19-2.56]), and worsening of DSN (HR 1.51 [95% CI 1.09-2.09]) and LBP (HR 1.51 [95% CI 1.12-2.06]). Knee OA was a predictor of incident FOA (HR 4.18 [95% CI 1.44-12.2]). Spine OA (HR 1.80 [95% CI 1.24-2.63]) and OST (HR 1.85 [95% CI 1.02-3.36]) were predictors of incidence of LBP. Hip OA (HR 1.39 [95% CI 1.04-1.85]) and OST (HR 1.58 [95% CI 1.00-2.49]) were predictors of LBP worsening.Among the multiple predictors of spine phenotypes, obesity was a common predictor for both incidence and worsening of lumbar spine degeneration and LBP.

OBJECTIVE. To test the hypothesis that an altered gut microbiota (dysbiosis) plays a role in obesity-associated osteoarthritis (OA). METHODS. Stool and blood samples were collected from 92 participants with BMI ≥ 30 kg/m(2) recruited from the Johnston County Osteoarthritis Project. OA cases (n=50) had hand plus knee OA (Kellgren-Lawrence [KL] grade ≥2 or arthroplasty). Controls (N=42) had no hand OA and KL grade 0–1 knees. Compositional analysis of stool samples was carried out by 16S rRNA amplicon sequencing. Alpha and beta diversity and differences in taxa relative abundances were determined. Blood samples were used for multiplex cytokine analysis and measures of lipopolysaccharide (LPS) and LPS binding protein. Germ-free mice were gavaged with case or control pooled fecal samples and placed on a 40% fat, high sucrose diet for 40 weeks. Knee OA was evaluated histologically. RESULTS. OA cases were slightly older with more females and higher BMI, WOMAC pain and KL grades than controls. There were no significant differences in alpha or beta diversity or genus level composition between cases and controls. Cases had higher plasma levels of osteopontin (p=0.01) and serum LPS (p

The association between knee injury and knee osteoarthritis (OA) is understudied relative to its importance, particularly in younger populations. This study examined the association of knee injury with radiographic features of knee OA in military officers, who have a physically-demanding profession and high rates of knee injury.Participants were recruited in 2015-2017 from an existing program that enrolled 6,452 military officers during 2004-2009. Officers with a history of knee ligament or meniscal injuries (n=117 via medical record review) were compared to officers with no history of knee injury (n=143). Bilateral posteroanterior knee radiographs were obtained using a standardized fixed-flexion positioning frame. All images were read for Kellgren-Lawrence grade (KLG), osteophyte (OST), and joint space narrowing (JSN) scores. Data were analyzed using linear-risk regression models with generalized estimating equations.Injured and non-injured participants were similar (mean age=28 years, mean body mass index=25 kg/mAt the midpoint of a projected 20-year military career, officers with a history of traumatic knee injury have a markedly increased prevalence of knee rOA compared to officers without injury. This article is protected by copyright. All rights reserved.

Osteonecrosis is a devastating complication of long-term glucocorticoid therapy that has been described in both malignant and nonmalignant diseases. Its incidence has been found to greater than 50% using magnetic resonance imaging in asymptomatic patients, thus osteonecrosis is likely underdiagnosed. Recent studies have suggested that treatment with bisphosphonates can improve pain and mobility and decrease bone marrow edema. We describe a patient with acute lymphoblastic leukemia who presented with debilitating osteonecrosis after treatment with prednisone for a total cumulative dose of 5100 mg. Magnetic resonance imaging revealed extensive infarcts of her bilateral tibiae and femora and left humerus, talus, and calcaneus consistent with osteonecrosis that had persisted for more than 2 years. Her severe knee, shoulder, and ankle pain was treated with 1 dose zolendronic acid. Despite a prolonged acute phase reaction, the patient's symptoms improved with near total resolution of pain.

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.

Objective To examine relationships between knee osteoarthritis (KOA) and obesity, diabetes mellitus (DM), and cardiovascular disease (CVD). Methods Associations of time-dependent obesity, DM, and CVD with KOA transition states over approximately 18 years were examined among 4093 participants from a community-based cohort. Transition states were 1) no knee symptoms and no radiographic KOA (rKOA; Kellgren-Lawrence grade ≥2 in at least one knee), 2) asymptomatic rKOA, 3) knee symptoms only, 4) symptomatic rKOA (sxKOA; rKOA and symptoms in same knee). Markov multistate models estimated adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for associations between comorbid conditions and transitions across states, adjusting for baseline age, sex, race, education, enrollment cohort, birth year, and time-dependent knee injury history. Results At baseline, 40% of participants had obesity, 13% had DM, and 22% had CVD (mean age = 61 years; 34% Black; 37% male). Compared with those without obesity, those with obesity had a higher hazard of worsening from no rKOA/no symptoms to asymptomatic rKOA (aHR = 1.7; 95% CI = 1.3-2.2) and from knee symptoms to sxKOA (aHR = 1.7; 95% CI = 1.3-2.3), as well as a lower hazard of symptom resolution from sxKOA to asymptomatic rKOA (aHR = 0.5 [95% = CI 0.4-0.7]). Compared with those without CVD, those with CVD had a higher hazard of worsening from no rKOA/symptoms to knee symptoms (aHR = 1.5; 95% CI = 1.1-2.1). DM was not associated with transitions of rKOA. Conclusion Prevention of obesity and CVD may limit the development or worsening of rKOA and symptoms.

Summary Objective To evaluate whether joint hypermobility modifies the association between knee joint injury and knee osteoarthritis (OA) among adults. Methods Data were from three studies: Genetics of Generalized Osteoarthritis (GOGO; N = 2341), Genetics of Osteoarthritis (GO; N = 1872), and the population-based Johnston County Osteoarthritis Project (JoCoOA; N = 1937). Knee injury was defined as a self-report of prior fracture or severe injury to either knee. OA was defined using three variables: knee pain (pain, aching, or stiffness of the knee on most days), radiographic OA (rOA; Kellgren-Lawrence grade 2–4), and symptomatic OA (sxOA; knee rOA with knee pain). Joint hypermobility was defined as Beighton score ≥4. For each study, separate logistic regression models, stratified by joint hypermobility, were used to estimate the association of knee injury with knee pain, rOA, and sxOA, adjusting for age, sex, body mass index, and race (JoCoOA only); statistical interactions between injury and hypermobility were assessed (p-value Results In all three studies, knee injury was associated with OA variables of knee pain, rOA, and sxOA (adjusted odds ratios [aOR] range 1.83–3.75). The association of knee injury with rOA and sxOA was magnified among individuals with vs. without joint hypermobility in GOGO: rOA aOR 11.0, 95% confidence interval [CI] 4.0–30.1 vs. 2.7, 95% CI 2.0–3.6, p = 0.009; sxOA aOR 9.2, 95% CI 3.5–24.3 vs. 3.3, 95% CI 2.4–4.4, p = 0.032. Interactions were not statistically significant in GO or JoCoOA. Conclusions In a general adult population, the presence of joint hypermobility may not modify the strong association between knee injury and OA.

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.

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 We examined the association of three common chronic conditions (obesity, diabetes mellitus [DM], and cardiovascular disease [CVD]) with transitions among states of hip osteoarthritis (HOA). Methods This longitudinal analysis used data from the Johnston County Osteoarthritis Project (JoCo OA, n = 3857), a community-based study in North Carolina, USA, with 18.4 ± 1.5 years of follow-up. Transitions across the following states were modeled: development of radiographic HOA (rHOA; Kellgren-Lawrence grade [KLG] of2) and self-reported DM and CVD were the time-dependent comorbid conditions of interest. Markov multi-state models were used to estimate adjusted hazard ratios and 95% confidence intervals to describe the associations between the conditions and HOA states. Results The sample included 33% African Americans, 39% men, with a mean (SD) age of 62.2 (9.8) years; the frequencies of the comorbidities increased substantially over time. When considered individually, obesity was associated with incident hip symptoms, while CVD and DM were associated with reduced symptom resolution. For those with > 1 comorbidity, the likelihood of incident sxHOA increased, while that of symptom resolution significantly decreased. When stratified by sex, the association between obesity and incident symptoms was only seen in women; among men with DM versus men without, there was a significant (~ 75%) reduction in symptom resolution in those with rHOA. When stratified by race, African Americans with DM, versus those without, were much more likely to develop sxHOA. Conclusions Comorbid chronic conditions are common in individuals with OA, and these conditions have a significant impact on the persistence and progression of HOA. OA management decisions, both pharmacologic and non-pharmacologic, should include considerations of the inter-relationships between OA and common comorbidities such as DM and CVD.

OBJECTIVE. Few studies have explored foot osteoarthritis (OA) in the general population. The purpose of this study was to determine the frequency of foot OA and identify associated factors in a cross-sectional analysis of a large community-based cohort. METHODS. Data were from the 2013-2015 study visit of the Johnston County OA Project. Radiographic OA (rOA) of the foot was defined using the La Trobe radiographic atlas (≥2 osteophytes or joint space narrowing in at least one of five joints). Symptomatic OA (sxOA) of the foot was defined as foot rOA with pain, aching, or stiffness in the same foot. At the foot-level, separate logistic regression models with generalized estimating equations to account for intra-person correlations were performed to examine associations of foot rOA or sxOA with age, body mass index (BMI), sex, race, educational attainment, and previous foot injury. RESULTS. Of 864 participants with available data (mean age 71 years, mean BMI 30 kg/m(2), 68% women, 33% African American, 13%

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/m2 . 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.

The assessment and management of a patient with a musculoskeletal condition begin with a thorough history and physical examination. In some cases, clinical laboratory information may be helpful, and in others, neurophysiologic studies may be of value. In many cases, however, the information gained from diagnostic imaging studies is indispensable and may be central to defining the condition. Modern diagnostic imaging includes many modalities, each with its own attributes and sensitivity and specificity. Conventional radiography, computed tomography, ultrasound, magnetic resonance imaging, nuclear medicine, and, on occasion, vascular imaging and interventional radiology may all have a place in musculoskeletal imaging. The selection of an imaging modality depends fundamentally on the clinical question to be answered. Imaging can be expensive and, for some modalities, is not without risk, so the selection of a modality that is safe and most likely to address the clinical concern will result in a cost-effective imaging evaluation. In most cases imaging begins with conventional radiography, and, in many cases, radiography may satisfy the imaging need. In other cases, further imaging is needed for complete characterization of the process at hand.

OBJECTIVE: To investigate the impact of hip osteoarthritis (OA) and/or hip symptoms on excess mortality. DESIGN: We analyzed data from 3,919 individuals in a community-based prospective cohort of African Americans and Caucasians age ≥45 years. Women ≥ 50 years of age and all men underwent supine anteroposterior pelvic radiography at baseline, with the participant’s feet in 15 degrees of internal rotation. Hip radiographic (rOA) was defined as a Kellgren-Lawrence grade of >2 in at least one hip. Participants completed questionnaires at baseline to determine presence of hip symptoms and covariate status. Participants with symptomatic hip rOA (SxOA) are a subset of individuals with hip rOA and symptoms in the same hip. Multiple imputation was used to impute missing values of covariates. Mortality was determined through 2015 and follow-up time was calculated from baseline assessment until death or censoring which took place when a participant was lost to follow-up or reached the end of study period. Cox proportional hazards regression was used to estimate hazard ratios and 95% confidence intervals. We carried out additional analyses stratified by sex, race, age and obesity. RESULTS: Mean follow-up time was 14.2 years during which 1762 deaths occurred. There were 29.9% participants in our population with hip rOA at baseline. Compared to those with neither hip rOA nor hip symptoms, we observed an increased risk of all-cause mortality in participants with hip symptoms alone (HR=1.28, 95% 0=1.13-1.46), but no association for hip rOA either with or without symptoms. In stratified analyses we observed increased associations for hip symptoms alone and hip sxOA in those

Summary Objective Our study analyzes the association between chemokine-ligand-2 (CCL2) serum concentrations at baseline and knee radiographic osteoarthritis (OA) (knee-rOA), knee-rOA progression, individual radiographic features and knee symptomatic OA at 5-year follow-up. Design OA outcomes were analyzed in a community-based cohort including a baseline enrollment and a 5-year follow-up. Baseline CCL2 serum concentrations were assessed by multiplex assay and associated with presence or progression of individual radiographic features at 5-year follow-up. Separate multiple logistic regression models were used to examine adjusted associations between baseline CCL2 and each of the knee OA variables at follow-up. CCL2 at baseline was modeled as an explanatory variable, whereas each of the knee OA variables at follow-up served as the response variables. Models were adjusted for age, BMI, race, and sex. Trend tests were conducted to assess any linear effect on outcomes across CCL2 tertiles. Results Participants (n = 168) had a median age of 57-years and median BMI of 29 kg/m2. About 63% of all participants were women, and 58% Caucasian (42% African American). In adjusted logistic models, continuous log-CCL2 was significantly associated with knee-rOA. For each unit increase in log CCL2, the odds of having knee-rOA at follow-up was increased by 72%. CCL2 tertiles showed significant linear associations with presence and progression of knee-rOA and medial joint space narrowing (JSN), but not with presence or progression of osteophytes, bone sclerosis, knee symptoms, or symptomatic knee-rOA. Conclusions Serum CCL2 may help to elucidate some mechanisms of joint destruction and identify individuals with higher odds of structural knee changes.

Background Injury is an important risk factor for osteoarthritis (OA), a highly prevalent and disabling joint disease. Joint shape is linked to OA, but the interplay of injury and joint shape and their combined role in OA, particularly at the ankle, is not well known. Therefore, we explored cross-sectional associations between ankle shape and injury in a large community-based cohort. Methods Ankles without radiographic OA were selected from the current data collection of the Johnston County OA Project. Ankles with self-reported prior injury were included as injury cases (n = 108) along with 1:1 randomly selected non-injured ankles. To define ankle shape, a 68 point model on weight-bearing lateral ankle radiographs was entered into a statistical shape model, producing a mean shape and a set of continuous variables (modes) representing variation in that shape. Nineteen modes, explaining 80% of shape variance, were simultaneously included in a logistic regression model with injury status as the dependent variable, adjusted for intra-person correlation, sex, race, body mass index (BMI), baseline OA radiographic grade, and baseline symptoms. Results A total of 194 participants (213 ankles) were included; mean age 71 years, BMI 30 kg/m2, 67% white and 71% women. Injured ankles were more often symptomatic and from whites. In a model adjusted only for intra-person correlation, associations were seen between injury status and modes 1, 6, 13, and 19. In a fully adjusted model, race strongly affected the estimate for mode 1 (which was no longer statistically significant). Conclusions This study showed variations in ankle shape and history of injury as well as with race. These novel findings may indicate a change in ankle morphology following injury, or that ankle morphology predisposes to injury, and suggest that ankle shape is a potentially important factor in the development of ankle OA.

Objective: A major barrier to genetic studies of OA is the need to obtain large numbers of individuals with standardized radiographic evaluations for OA. To address this gap, we performed a genome-wide association study (GWAS) of radiographically-defined tibiofemoral knee OA in 3,898 cases and 3,168 controls from four well-characterized North American cohorts, and replication analysis of published OA loci. Methods: We performed meta-analysis using a two-stage design. Stage 1 (discovery) consisted of a GWAS meta-analysis of radiographic knee OA carried out in the Osteoarthritis Initiative and the Johnston County Osteoarthritis Project. Knee OA was defined as definitive osteophytes and possible joint space narrowing or total joint replacement in one or both knees. Stage 2 (validation) was performed in the Multicenter Osteoarthritis Study and Genetics of Osteoarthritis Study. We genotyped lead meta-analysis variants (P-value

OBJECTIVE: To determine the incidence and progression of ankle osteoarthritis (OA) and associated risk factors in a community-based cohort of African Americans and whites. Methods: Data were from 541 participants who had standardized lateral and mortise radiography of the ankles in weight bearing at baseline (2013–2015) and follow-up (2017–2018). Incident radiographic ankle OA (rAOA) was defined as a Kellgren-Lawrence grade (KLG) ≥1 at follow-up among ankles with baseline KLG

Summary Objective To describe the incidence and progression of radiographic and symptomatic hand osteoarthritis (rHOA and sxHOA) in a large community-based cohort. Design Data were from the Johnston County OA Project (1999–2015, 12 ± 1.2 years follow-up, age 45+). Participants had bilateral hand radiographs each visit, read for Kellgren–Lawrence grade (KLG) at 30 joints. We defined rHOA as KLG ≥2 in ≥1 joint. SxHOA was defined in a hand/joint with rHOA and self-reported symptoms or tenderness on exam. Incidence was assessed in those without, while progression was assessed in those with, baseline rHOA. Proportions or medians are reported; differences by sex and race were assessed using models appropriate for dichotomous or continuous definitions, additionally adjusted for age, education, body mass index (BMI), and weight change. Results Of 800 participants (68% women, 32% African American, mean age 60 years), 327 had baseline rHOA and were older, more often white and female, than those without rHOA (n = 473). The incidence of HOA was high, for rHOA (60%) and for sxHOA (13%). Women were more likely than men to have incident HOA, particularly for distal interphalangeal joint radiographic osteoarthritis (DIP rOA) (adjusted odds ratios (aOR) 1.60 95% confidence intervals (95% CI) [1.03, 2.49]) and sxHOA (aOR 2.98 [1.50, 5.91]). Progressive HOA was more similar by sex, although thumb base rOA progressed more frequently in women than in men (aOR 2.56 [1.44, 4.55]). Particularly HOA incidence, but also progression, was more frequent among whites compared with African Americans. Conclusion This study provides much needed information about the natural history of HOA, a common and frequently debilitating condition, in the general population.

Background Chronic low back pain (cLBP) affects millions of Americans and costs billions. Studies suggest a link between cLBP and joint hypermobility. Methods We conducted cross-sectional primary analyses of joint hypermobility and cLBP, lumbar spine osteoarthritis (OA), and lumbar facet joint OA (FOA) in 3 large studies—the Generalized Osteoarthritis Study, Genetics of Generalized Osteoarthritis Study, and Johnston County Osteoarthritis Project (total n = 5072). Associations of joint hypermobility and Beighton trunk flexion with cLBP and lumbar OA were estimated using separate adjusted logistic regression models. Adjusted pooled odds ratios (pORs) and 95% confidence intervals (CIs) were then summarized—using random effect univariate, multivariate crude, and adjusted models—and heterogeneity was determined (I2 statistic). Results In univariate models, hypermobility was associated with symptomatic FOA (pOR = 0.64 [95% CI 0.44, 0.93]) but this result was not found in the multivariate models. In multivariate adjusted models, hypermobility was not significantly associated with cLBP and lumbar OA, but trunk flexion was inversely associated with cLBP (pOR = 0.40 [95% 0.26, 0.62]), spine OA (pOR = 0.66 [95% CI 0.50, 0.87]), symptomatic spine OA (pOR = 0.39 [95% CI 0.28, 0.53]), and symptomatic FOA (pOR = 0.53 [95% CI 0.37, 0.77]). Generally, between-study heterogeneity was moderate-high. Conclusions Hypermobility was not associated with cLBP or lumbar OA. The inverse association of trunk flexion with cLBP and lumbar OA may indicate a role for a flexible spine in avoiding or managing these conditions. Electronic supplementary material The online version of this article (10.1186/s12891-019-2523-2) contains supplementary material, which is available to authorized users.

ObjectiveTo establish reference intervals for osteoarthritis (OA)-related biomarkers used in the Foundation for the National Institutes of Health (FNIH) OA Biomarkers Consortium Project.MethodsA total of 129 ‘multijoint controls’ were selected from 2722 African-American and Caucasian men and women in the Johnston County Osteoarthritis Project. The majority (79%) of those eligible (with biospecimens and baseline data) also had one or more follow-up evaluations 5–15 years later. Multijoint controls were selected to be free of radiographic hand, hip, knee and lumbar spine osteoarthritis (OA), to have no knee or hip symptoms, and minimal hand and spine symptoms at all available time points. Eighteen biomarkers were evaluated in serum (s) and/or urine (u) by ELISA. Reference intervals and partitioning by gender and race were performed with EP Evaluator software.ResultsControls were 64% women, 33% African-Americans, mean age 59 years and mean body mass index 29 kg/m2. Three biomarkers were associated with age: sHyaluronan (positively), sN-terminal propeptide of collagen IIA (positively) and sCol2-3/4 C-terminal cleavage product of types I and II collagen (negatively). Exploratory analyses suggested that separate reference intervals may be warranted on the basis of gender for uC-terminal cross-linked telopeptide of type II collagen (uCTXII), sMatrix metalloproteinase-3, uNitrated type II collagen degradation fragment (uCol2-1 NO2) and sHyaluronan, and on the basis of race for uCTXII, sCartilage oligomeric matrix protein, sC-terminal cross-linked telopeptide of type I collagen and uCol2-1 NO2.ConclusionsTo our knowledge, this represents the best and most stringent control group ever assayed for OA-related biomarkers. These well-phenotyped controls, representing a similar age demographic to that of the OA Initiative-FNIH main study sample, provide a context for interpretation of OA subject biomarker data. The freely available data set also provides a reference for future human studies.

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.

Objective.Hip 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.Methods.Bilateral 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.Results.We evaluated 681 hips and 682 knees from 342 individuals (61% women, 83% white, mean age 62 yrs, BMI 29 kg/m2). 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.Conclusion.Variations 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.

Background Osteoarthritis (OA) is associated with worsening physical function and a high prevalence of comorbid health conditions. In particular, cardiovascular disease (CVD) risk is higher in individuals with OA than the general population. Limitations in physical function may be one pathway to the development of CVD among individuals with OA. This study evaluated associations of symptomatic knee OA (sxKOA), baseline physical function and worsening of function over time with self-reported incident CVD in a community-based cohort. Methods Our sample consisted of individuals from the Johnston County Osteoarthritis Project who did not report having CVD at baseline. Variables used to evaluate physical function were the Health Assessment Questionnaire (HAQ), time to complete 5 chair stands, and the 8-ft walk. Worsening function for these variables was defined based on previous literature and cutoffs from our sample. Logistic regression analyses examined associations of sxKOA, baseline function and worsening of function over time with self-reported incident CVD, unadjusted and adjusted for relevant demographic and clinical characteristics. Results Among 1709 participants included in these analyses, the mean age was 59.5 ± 9.5 years, 63.6% were women, 15% had sxKOA, and the follow up time was 5.9 ± 1.2 years. About a third of participants reported worsening HAQ score, about two-fifths had worsened chair stand time, half had worsened walking speed during the 8-ft walk, and 16% self-reported incident CVD. In unadjusted analyses, sxKOA, baseline function, and worsening function were all associated with self-reported incident CVD. In multivariable models including all of these variables, sxKOA was not associated with incident CVD, but worsening function was significantly associated with increased CVD risk, for all three functional measures: HAQ odds ratio (OR) = 2.49 (95% confidence interval (CI) 1.90–3.25), chair stands OR = 1.58 (95% CI 1.20–2.08), 8-ft walk OR = 1.53 (95%CI 1.15–2.04). These associations for worsening function remained in models additionally adjusted for demographic and clinical characteristics related to CVD risk. Conclusions The association between symptomatic knee osteoarthritis and cardiovascular disease risk was explained by measures of physical function. This highlights the importance of physical activity and other strategies to prevent functional loss among individuals with symptomatic knee osteoarthritis.

Background/purpose To update definitions of multiple joint osteoarthritis (MJOA), and to determine the frequency and impact of MJOA in a community-based cohort. Methods Following PRISMA guidelines and with the help of a professional research librarian, we performed a systematic review in Medline using the terms osteoarthritis, generalized, polyarticular, multiple joint, and multi-joint among others, to obtain articles related to MJOA. A total of 42 articles were included for data extraction based on multiple criteria including the requirement for a clearly stated definition of OA assessed at more than one body site. We assessed frequency of these definitions in the Johnston County OA Project (JoCo OA) cohort as well as outcomes related to general health and physical function. Results A total of 6 clearly stated definitions for MJOA were identified. These definitions were integrated with a list of 24 definitions from our previous systematic review and distilled down to produce 10 literature-derived, operationalized MJOA definitions. Based on these definitions, high frequencies of radiographic (4–74%) and symptomatic (2–52%) MJOA were found in the JoCo OA. Significant detrimental effects were seen on general health and physical function for most definitions. Conclusions We constructed a list of 10 summary MJOA definitions based in the literature that are frequent and associated with important clinical outcomes. These definitions capture some of the variability of MJOA phenotypes and provide a starting point for future analyses of both existing and newly initiated studies.

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.

Summary Objective To investigate the impact of knee osteoarthritis (OA) and/or knee pain on excess mortality. Method We analyzed data from 4,182 participants in a community-based prospective cohort study of African American and Caucasian men and women aged ≥45 years. Participants completed knee radiographs and questionnaires at baseline and at up to three follow-ups to determine knee OA (rOA), knee pain and covariate status. Mortality was determined through 2015. We used Cox proportional hazards regression with time-varying covariates (TVC) to estimate hazard ratios (HR) and 95% confidence intervals (CI). Additional analyses stratified by sex, race and age were carried out. Results Median follow-up time was 14.6 years during which 1822 deaths occurred. Baseline knee radiographic osteoarthritis (rOA) was 27.7%, 38.8% at first follow-up, 52.6% at second follow-up and 61.9% at the third follow-up. Knee rOA with pain and knee pain alone were both associated with a >15% increase in premature all-cause mortality. In analyses stratified by sex, race and age, associations between knee pain, with or without knee rOA, and all-cause death were found among women, Caucasians, those ≤65 years of age, and those with a body mass index (BMI)≥30, with observed increased risks of death between 21% and 65%. We observed similar, somewhat attenuated, results for cardiovascular disease (CVD) deaths. Conclusion In models taking into account variables that change over time, individuals who had knee pain, alone or with knee rOA, had increased mortality. These effects were particularly strong among those obese. Effective interventions to reduce knee pain, particularly those including weight management and prevention of comorbidities, could reduce mortality.

Background Osteoarthritis (OA) prevalence differs by race. General joint hypermobility (GJH) may be associated with OA, but differences by race are not known. This community-based study examined the frequency of GJH and its relationship with knee, hip, and lumbar spine OA by race (African American vs. Caucasian). Methods Data were from the Johnston County OA project, collected 2003–2010. GJH was defined as Beighton score ≥4. OA symptoms were defined as the presence of pain, aching, or stiffness on most days separately at the knee, hip, and lower back. Radiographic OA (rOA) of the knee or hip was defined as Kellgren-Lawrence grade 2–4. Lumbar spine rOA was disc space narrowing grade ≥1 and osteophyte grade ≥2 in ≥ 1 at the same lumbar level. Lumbar spine facet rOA was present in ≥ 1 lumbar levels. Separate logistic regression models stratified by race were used to examine the association between hypermobility and rOA or OA symptoms at each joint site, adjusting for age, sex, previous joint injury, and body mass index (BMI). Results Of 1987 participants, 1/3 were African-American and 2/3 were women (mean age 65 years, mean BMI 31 kg/m2). Nearly 8% of Caucasians were hypermobile vs. 5% of African-Americans (p = 0.03). Hypermobility was associated with lower back symptoms in Caucasians (adjusted odds ratio (aOR) 1.54, 95% confidence interval (CI) 1.00, 2.39), but not in African-Americans (aOR 0.77, 95% CI 0.34, 1.72). Associations between hypermobility and other knee, hip, or lumbar spine/facet OA variables were not statistically significant. Conclusions General joint hypermobility was more common in Caucasians than African-Americans. Although there were no associations between hypermobility and rOA, the association between hypermobility and lower back symptoms may differ by race. Electronic supplementary material The online version of this article (10.1186/s13075-018-1570-7) contains supplementary material, which is available to authorized users.

Objective Kashin-Beck Disease (KBD) is a rare and severe osteoarthropathy endemic to China. We evaluated the frequency and patterns of hand radiographic osteoarthritis (rOA) in adults with and without KBD. Methods Han Chinese (N = 438) from Yongshou County of central China underwent right hand radiography for determining case status. Presence of KBD was based on characteristic radiographic deformities of articular ends of bones including articular surface depression, carpal crowding, any subchondral bone deformities in the proximal end of phalanges or first metacarpal bone, or the distal ends of metacarpal bones 2–5, and any bony enlargement with deformity of the distal ends of phalanges. Hand rOA severity was determined by osteophyte (OST), joint space narrowing (JSN), and Kellgren and Lawrence (KL) grades. Results This study included 127 KBD and 311 non-KBD adults of similar mean age (39 years) and body mass index (BMI) (21 kg/m2). Inter- and intra-rater reliability for radiographic determination of case status and rOA features was high (kappa 0.72–0.96). Compared to non-KBD, KBD adults had significantly more severe hand rOA of the thumb, distal interphalangeal (DIP), proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints. Only KBD adults had end-stage carpometacapal (CMC) disease. In KBD, DIPs and PIPs were more affected than MCPs and the frequency of OSTs was significantly higher in PIPs than DIPs. Conclusions Compared with age-matched adults from the same area and farming occupation, KBD hand rOA was more widespread and severe, particularly of PIPs and CMCs. The ability to differentiate adult KBD from non-KBD hand rOA will facilitate genetic analyses of the vast majority of affected individuals.

Hallux valgus (HV) is a common deformity of the foot characterized by the progressive subluxation and medial bony enlargement of the first metatarsophalangeal joint.1 HV is a major attributable factor to orthopedic foot and ankle surgery each year,2 and is also associated with functional disability, foot pain, impaired balance, and high risk falls in older adults.3–7 Previous large studies in adults 65+ years of age4,8,9 and in clinic samples4,10 have reported the following factors associated with HV. HV has been shown to be more common in women than men8,9 and in African Americans than Caucasians.8,11 Also, the prevalence of HV was higher in individuals with older age,4,8–10 but associations between HV and body mass index (BMI)7,9,12,13 were inconsistent and appeared to vary by sex.8,9 With the pes planus foot, forces during standing and walking may be directed more medially to the first ray, contributing to disorders of the medial foot such as HV and metatarsalgia;14 however, reports of the link between HV and pes planus differ.9,15 HV has been shown to be associated with osteoarthritis (OA) of the first metatarsophalangeal joint.16 Since OA may be a multiple joint condition, HV and OA at other lower body joint sites may be related, particularly if there are biomechanical mechanisms at play, but this relationship previously has not been explored. Other related factors include wearing shoes with high heels and structural foot attributes such as long first metatarsals, round metatarsal heads and pronated foot posture.9,17 Identifying adults with HV earlier in the life course may aid in preventing later functional limitations, such as impaired balance in older populations. The overall objective of the present study was to examine potential factors related to HV in the study sample and by sex and race in a large, community-based study of African American and Caucasian men and women 50+ years of age. Inconsistences in the existing literature of factors potentially related to HV (as described above) may be explained by sex and race differences. The present study has two main purposes: 1) to determine whether HV is associated with foot pain and if this relationship differs by sex and race, and 2) to examine sex- and race-specific associations of age, BMI, pes planus, and presence of knee or hip OA with HV. We hypothesized that: 1) foot pain would be more commonly reported in individuals with HV compared to those without HV regardless of sex or race, 2) HV would be associated with female sex, African American race, greater age, greater BMI, pes planus, and the presence of knee/hip OA, and 3) associations of HV with age, BMI, pes planus, and knee/hip OA would not vary by sex or race.

OBJECTIVE: Knee and hip osteoarthritis (OA) are known risk factors for falls, but whether they together additionally contribute to falls risk is unknown. This study utilizes a biracial cohort of men and women to examine the influence of lower limb OA burden on the risk for future falls. METHODS: A longitudinal analysis was performed using data from 2 time points of a large cohort. The outcome of interest was falls at follow up. Covariates included age, sex, race, body mass index, a history of prior falls, symptomatic OA of the hip and/or knee, a history of neurologic or pulmonary diseases, and current use of narcotic medications. Symptomatic OA was defined as patient reported symptoms and radiographic evidence of OA in the same joint. Logistic regression analyses were used to determine associations between covariates and falls at follow-up. RESULTS: The odds of falling increased with an increasing number of lower limb symptomatic OA joints: those with 1 joint had 53% higher odds, those with 2 joints had 74% higher odds, those with 3-4 OA joints had 85% higher odds. When controlling for covariates, patients who had symptomatic knee or hip OA had an increased likelihood of falling (aOR 1.39 95% CI [1.02, 1.88]; aOR 1.60 95% CI [1.14, 2.24], respectively). CONCLUSIONS: This study reveals the risk for falls increases with additional symptomatic OA lower limb joints and confirms that symptomatic hip and knee OA are important risk factors for falls. © 2014 American College of Rheumatology. Language: en

OBJECTIVES: To identify genetic associations with hip osteoarthritis (HOA), we performed a meta-analysis of genome-wide association studies (GWAS) of HOA. METHODS: The GWAS meta-analysis included approximately 2.5 million imputed HapMap single nucleotide polymorphisms (SNPs). HOA cases and controls defined radiographically and by total hip replacement were selected from the Osteoporotic Fractures in Men (MrOS) Study and the Study of Osteoporotic Fractures (SOF) (654 cases and 4697 controls, combined). Replication of genome-wide significant SNP associations (p ≤5×10(-8)) was examined in five studies (3243 cases and 6891 controls, combined). Functional studies were performed using in vitro models of chondrogenesis and osteogenesis. RESULTS: The A allele of rs788748, located 65 kb upstream of the IGFBP3 gene, was associated with lower HOA odds at the genome-wide significance level in the discovery stage (OR 0.71, p=2×10(-8)). The association replicated in five studies (OR 0.92, p=0.020), but the joint analysis of discovery and replication results was not genome-wide significant (p=1×10(-6)). In separate study populations, the rs788748 A allele was also associated with lower circulating IGFBP3 protein levels (p=4×10(-13)), suggesting that this SNP or a variant in linkage disequilibrium could be an IGFBP3 regulatory variant. Results from functional studies were consistent with association results. Chondrocyte hypertrophy, a deleterious event in OA pathogenesis, was largely prevented upon IGFBP3 knockdown in chondrocytes. Furthermore, IGFBP3 overexpression induced cartilage catabolism and osteogenic differentiation. CONCLUSIONS: Results from GWAS and functional studies provided suggestive links between IGFBP3 and HOA. ispartof: ANNALS OF THE RHEUMATIC DISEASES vol:74 issue:10 pages:1861-1867 ispartof: location:England status: published

Objectives: To address knowledge gaps regarding the relationship between bone mineral density (BMD) and incident hip or knee osteoarthritis (OA); specifically, lack of information regarding hip OA or symptomatic outcomes. Methods: Using data (N=1,474) from the Johnston County Osteoarthritis (JoCo OA) Project's first (1999-2004) and second follow-up (2005-2010) of participants aged ≥45 years we examined the association between total hip BMD and both hip and knee OA. Total hip BMD was measured using dual-energy X-ray absorptiometry, and participants were classified into sex-specific quartiles (low, intermediate low, intermediate high, and high). Radiographic osteoarthritis (ROA) was defined as development of Kellgren-Lawrence grade ≥2. Symptomatic ROA (sROA) was defined as onset of both ROA and symptoms. Weibull regression modeling was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CIs). Results: Median follow-up time was 6.5 (range=4.0-10.2) years. In multivariate models, and compared with participants with low BMD, those with intermediate high and high BMD were less likely to develop hip sROA (HR (95% CIs) 0.52 (0.31- 0.86) and 0.56 (0.31 - 0.86), respectively; p-trend = 0.024); high BMD was not associated (0.69 (0.45-1.06)) with risk of hip ROA. Compared with participants with low BMD, those with intermediate low and intermediate high total hip BMD were more likely to develop knee sROA (2.15 (1.40-3.30) and 1.65 (1.02-2.67), respectively; p-trend=0.325); similar associations were seen with knee ROA. Conclusions: Our findings suggest that higher BMD may reduce the risk hip sROA, while intermediate levels may increase the risk of both knee sROA and ROA. This article is protected by copyright. All rights reserved.