Johnston County Osteoarthritis Project Research Articles

Diminished Vibration Perception and Greater Pressure Pain Sensitivity are Associated with Worse Knee Osteoarthritis Outcomes across Sex and Race

ObjectiveTo examine associations of vibration sensitivity and pressure pain sensitivity with knee osteoarthritis (OA) outcomes across sex and race, which may relate to known sex and race disparities in clinical outcomes. DesignData were from the 2013-2015 visit of the Johnston County Osteoarthritis Project. Exposures were vibration perception threshold (VPT) measured at the bilateral medial femoral condyle (MFC) and first metatarsophalangeal joint (MTP), and pressure pain threshold (PPT) measured at the bilateral upper trapezius. Outcomes were knee pain severity and presence of knee symptoms, radiographic knee OA, and symptomatic knee OA in each knee. Cross-sectional associations of the exposures with the outcomes were examined using logistic regression models, overall and separately by sex and race. ResultsIn the VPT and PPT analyses, 851 and 862 participants (mean age 71 years, 68% female, 33% Black, body mass index 31 kg/m2) and 1585 and 1660 knees were included, respectively. Higher VPT (lower vibration sensitivity) at the MFC and first MTP joint was associated with all outcomes. Lower PPT (greater pressure pain sensitivity) was associated with greater knee pain severity. Associations of VPT and PPT with all outcomes were similar among females and males and Black and White individuals. ConclusionsDiminished vibration perception and greater pressure pain sensitivity were cross-sectionally associated with worse knee OA outcomes. Despite differences in VPT and PPT among females and males and Black and White adults, associations with knee OA outcomes did not differ by sex or race, suggesting neurophysiological differences do not relate to established disparities.

Occupational tasks associated with shoulder pain and upper extremity disability: a cross-sectional study in the Johnston County Osteoarthritis Project

BackgroundShoulder pain is a leading cause of disability. Occupations requiring high upper extremity demands may put workers at greater risk of shoulder injury and resulting pain. We examined associations of occupation with shoulder pain and upper extremity disability in the Johnston County Osteoarthritis Project.MethodsWork industry and occupational tasks for the longest job held were collected from participants. At follow-up ranging from 4–10 years later, participants were asked about shoulder symptoms (pain, aching, or stiffness occurring most days of 1 month in the last year) and given a 9-item, modified Disabilities Arm Shoulder and Hand (DASH) questionnaire to categorize disability from 0–4 (none-worst). Logistic regression and cumulative logit regression models were used to estimate associations with prevalent shoulder symptoms and with worse disability category, respectively. Models were adjusted for cohort, age, sex, race, education and time to follow-up. Sex- and race-stratified associations were evaluated.ResultsAmong 1560 included participants, mean age was 62 years (standard deviation ± 9 years); 32% were men, and 31% were Black. Compared to the managerial/professional industry, higher odds of both shoulder symptoms and worse upper extremity disability were seen for most industrial groups with physically demanding jobs, particularly the service industry. Work that often or always required lifting/moving > 10 lbs. was associated with higher odds of shoulder symptoms. Work that sometimes or always required heavy work while standing was associated with higher odds of shoulder symptoms, and this association was stronger among men and White workers.ConclusionPhysically demanding occupations were associated with increased occurrence of shoulder pain and disability. Mitigating specific physical work demands may reduce shoulder-related disability.

Tick-Borne Disease Infections and Chronic Musculoskeletal Pain

Tick-borne diseases (TBDs) other than Lyme disease, such as spotted fever group rickettsiosis, ehrlichiosis, and galactose-α-1,3-galactose (α-gal) syndrome, are an emerging public health issue. Long-term sequelae secondary to Ehrlichia or Rickettsia infection are uncommon; however, musculoskeletal symptoms are often attributed to prior tick exposure. To evaluate the potential associations between prior exposure to TBDs and musculoskeletal symptoms, including radiographic osteoarthritis. This cross-sectional study analyzed serum samples from the fourth visit (2017-2018) of the Johnston County Osteoarthritis (JoCo OA) project, an ongoing longitudinal, population-based study in Johnston County, North Carolina. Biospecimen testing and analysis were performed between May 2022 and November 2023. Participants in the JoCo OA project are noninstitutionalized White and Black Johnston County residents 45 years or older. The primary outcome was seropositivity with Ehrlichia IgG, Rickettsia IgG, and/or α-gal IgE and musculoskeletal symptoms. Secondary outcomes included risk factors associated with elevated α-gal IgE and weighted population point prevalence rates. Participants completed questionnaires, underwent physical assessments, and provided biospecimens for serological testing. Multivariable models were used to estimate associations of interest. Of the 605 participants who completed the fourth visit of the JoCo OA project, 488 (80.7%) had serum samples available for testing. The 488 participants had a median (IQR) age of 72 (68-78) years and included 336 females (68.9%) and 161 Black (33.0%) and 327 White (67.0%) individuals. The overall weighted point prevalence was 8.6% (95% CI, 5.9%-11.3%) for Ehrlichia IgG, 17.1% (95% CI, 12.6%-21.5%) for Rickettsia IgG, and 19.6% (95% CI, 15.3%-23.8%) for α-gal IgE level greater than 0.1 IU/mL. Only α-gal IgE was associated with knee pain, aching or stiffness (mean ratio, 1.30; 95% CI, 1.09-1.56). Antibodies to Rickettsia, Ehrlichia, and α-gal were not associated with symptomatic radiographic knee osteoarthritis. Male sex (odds ratio [OR], 2.63; 95% CI, 1.55-4.47), current smoker status (OR, 3.55; 95% CI, 1.38-9.18), and an attached tick bite in the past 5 years (OR, 3.99; 95% CI, 2.22-7.15) were all risk factors that were associated with α-gal IgE level greater than 0.1 IU/mL. Despite only 84 individuals (17.2%) recalling a tick bite in the past 5 years, 178 (36.5%) had evidence of prior tick-borne exposure, suggesting frequent human-tick interactions. Results of this cross-sectional study indicate no association between Ehrlichia or Rickettsia seropositivity and chronic musculoskeletal symptoms or osteoarthritis. Further investigation is needed into the pathogenesis of α-gal syndrome and interventions to reduce human-tick interactions.

Association of Foot Symptoms With Decreased Time to All-Cause Mortality: The Johnston County Osteoarthritis Project.

Adults with foot symptoms (ie, pain, aching, or stiffness) may be at increased risk of reduced time to all-cause mortality. The purpose of this study was to evaluate whether foot symptoms are independently associated with all-cause mortality in older adults. We analyzed longitudinal data from 2613 participants from the Johnston County Osteoarthritis Project, a longitudinal population-based cohort of adults 45 years of age and older. Participants completed questionnaires at baseline to determine presence of foot symptoms and covariable status. Baseline walking speed was measured via an 8-foot walk test. To examine the association of foot symptoms with time to mortality, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression models, adjusted for potential confounders. We observed 813 deaths over 4 to 14.5 years of follow-up. At baseline, 37% of participants had foot symptoms, mean age was 63 years, mean body mass index was approximately 31 kg/m2 , 65% were women, and 33% were Black. Moderate to severe foot symptoms were associated with reduced time to mortality after adjustment for demographics, comorbidities, physical activity, and knee and hip symptoms (HR=1.30, 95% CI 1.09-1.54). Importantly, this association was not modified by walking speed or diabetes. Individuals with foot symptoms had an increased hazard of all-cause mortality compared with those with no foot symptoms. These effects were independent of key confounders and were not moderated by walking speed. Effective interventions to identify and manage at least moderate foot symptoms may reduce the risk of decreased time to mortality.

Serum proteomic biomarkers diagnostic of knee osteoarthritis

To better understand the pathogenesis of knee osteoarthritis (OA) through identification of serum diagnostics. We conducted multiple reaction monitoring mass spectrometry analysis of 107 peptides in baseline sera of two cohorts: the Foundation for National Institutes of Health (NIH) (n=596 Kellgren-Lawrence (KL) grade 1-3 knee OA participants); and the Johnston County Osteoarthritis Project (n=127 multi-joint controls free of radiographic OA of the hands, hips, knees (bilateral KL=0), and spine). Data were split into (70%) training and (30%) testing sets. Diagnostic peptide and clinical data predictors were selected by random forest (RF); selection was based on association (p<0.05) with OA status in multivariable logistic regression models. Model performance was based on area under the curve (AUC) of receiver operating characteristic (ROC) and precision-recall (PR) curves. RF selected 23 peptides (19 proteins) and body mass index (BMI) as diagnostic of OA. BMI weakly diagnosed OA (ROC-AUC 0.57, PR-AUC 0.812) and only symptomatic OA cases. ACTG was the strongest univariable predictor (ROC-AUC 0.705, PR-AUC 0.897). The final model (8 serum peptides) was highly diagnostic (ROC-AUC 0.833, 95% confidence interval [CI] 0.751, 0.905; PR-AUC 0.929, 95% CI 0.876, 0.973) in the testing set and equally diagnostic of non-symptomatic and symptomatic cases (AUCs 0.830-0.835), and not significantly improved with addition of BMI. The STRING database predicted multiple high confidence interactions of the 19 diagnostic OA proteins. No more than 8 serum protein biomarkers were required to discriminate knee OA from non-OA. These biomarkers lend strong support to the involvement and cross-talk of complement and coagulation pathways in the development of OA.

Epidemiology of Hip Osteoarthritis: The Johnston County Osteoarthritis Project.

Hip osteoarthritis (OA) is common but understudied compared with knee OA, and insights into the impact of this condition on the general population are needed. This review article summarizes findings from the 30-year, longitudinal, population-based Johnston County Osteoarthritis Project cohort to address the prevalence, incidence, and progression of hip OA and differences by sex and race; similarities and differences related to other joints; and impact on morbidity and mortality.

Poor Physical Function Is Associated With Mortality Among Individuals With Knee And/Or Hip OA: The Johnston County Osteoarthritis Project

Poor Physical Function Is Associated With Mortality Among Individuals With Knee And/Or Hip OA: The Johnston County Osteoarthritis Project

Biomarkers and longitudinal changes in lumbar spine degeneration and low back pain: the Johnston County Osteoarthritis Project

To determine if baseline biomarkers are associated with longitudinal changes in the worsening of disc space narrowing (DSN), vertebral osteophytes (OST), and low back pain (LBP). Paired baseline (2003-2004) and follow-up (2006-2010) lumbar spine radiographs from the Johnston County Osteoarthritis Project were graded for severity of DSN and OST. LBP severity was self-reported. Concentrations of analytes (cytokines, proteoglycans, and neuropeptides) were quantified by immunoassay. Pressure-pain threshold (PPT), a marker of sensitivity to pressure pain, was measured with a standard dolorimeter. Binary logistic regression models were used to estimate odd ratios (OR) and 95% confidence intervals (CI) of biomarker levels with DSN, OST, or LBP. Interactions were tested between biomarker levels and the number of affected lumbar spine levels or LBP. We included participants (n=723) with biospecimens, PPT, and paired lumbar spine radiographic data. Baseline Lumican, a proteoglycan reflective of extracellular matrix changes, was associated with longitudinal changes in DSN worsening (OR=3.19 [95% CI 1.22, 8.01]). Baseline brain-derived neuropathic factor, a neuropeptide, (OR=1.80 [95% CI 1.03, 3.16]) was associated with longitudinal changes in OST worsening, which may reflect osteoclast genesis. Baseline hyaluronic acid (OR=1.31 [95% CI 1.01, 1.71]), indicative of systemic inflammation, and PPT (OR=1.56 [95% CI 1.02, 2.31]) were associated with longitudinal increases in LBP severity. These findings suggest that baseline biomarkers are associated with longitudinal changes occurring in structures of the lumbar spine (DSN vs OST). Markers of inflammation and perceived pressure pain sensitivity were associated with longitudinal worsening of LBP.

Peripheral Blood DNA Methylation-Based Machine Learning Models for Prediction of Knee Osteoarthritis Progression: Biologic Specimens and Data From the Osteoarthritis Initiative and Johnston County Osteoarthritis Project.

The lack of accurate biomarkers to predict knee osteoarthritis (OA) progression is a key unmet need in OA clinical research. The objective of this study was to develop baseline peripheral blood epigenetic biomarker models to predict knee OA progression. Genome-wide buffy coat DNA methylation patterns from 554 individuals from the Osteoarthritis Biomarkers Consortium (OABC) were determined using Illumina Infinium MethylationEPIC 850K arrays. Data were divided into model development and validation sets, and machine learning models were trained to classify future OA progression by knee pain, radiographic imaging, knee pain plus radiographic imaging, and any progression (pain, radiographic, or both). Parsimonious models using the top 13 CpG sites most frequently selected during development were tested on independent samples from participants in the Johnston County Osteoarthritis (JoCo OA) Project (n=128) and a previously published Osteoarthritis Initiative (OAI) data set (n=55). Full models accurately classified future radiographic-only progression (mean ± SEM accuracy 87 ± 0.8%, area under the curve [AUC] 0.94 ± 0.004), pain-only progression (accuracy 89 ± 0.9%, AUC 0.97 ± 0.004), pain plus radiographic progression (accuracy 72 ± 0.7%, AUC 0.79 ± 0.006), and any progression (accuracy 78 ± 0.4%, AUC 0.86 ± 0.004). Pain-only and radiographic-only progressors were not distinguishable (mean ± SEM accuracy 58 ± 1%, AUC 0.62 ± 0.001). Parsimonious models showed similar performance and accurately classified future radiographic progressors in the OABC cohort and in both validation cohorts (mean ± SEM accuracy 80 ± 0.3%, AUC 0.88 ± 0.003 [using JoCo OA Project data], accuracy 80 ± 0.8%, AUC 0.89 ± 0.002 [using previous OAI data]). Our data suggest that pain and structural progression share similar early systemic immune epigenotypes. Further studies should focus on evaluating the pathophysiologic consequences of differential DNA methylation and peripheral blood cell epigenotypes in individuals with knee OA.

Association of Biomarkers with Individual and Multiple Body Sites of Pain: The Johnston County Osteoarthritis Project.

IntroductionBiochemical 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.MethodsThis 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.ResultsIncreased 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.ConclusionBiomarkers 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.

Predictors of Lumbar Spine Degeneration and Low Back Pain in the Community: The Johnston County Osteoarthritis Project.

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.

Biomarker clusters differentiate phenotypes of lumbar spine degeneration and low back pain: The Johnston County Osteoarthritis Project

ObjectiveDescribe the association between biomarkers and lumbar spine degeneration (vertebral osteophytes [OST], facet joint osteoarthritis [FOA], and disc space narrowing [DSN]), for persons with and without low back pain (LBP) and determine whether clusters based on biomarkers differentiate lumbar spine structure with and without LBP. MethodsUsing data from the Johnston County Osteoarthritis Project (2006–2010), we measured serum N-cadherin, Keratin-19, Lumican, CXCL6, RANTES, HA, IL-6, BDNF, OPG, and NPY, and urinary CTX-II. Biomarkers were used to group participants using k-means cluster analysis. Logistic regression models were used to compare biomarker clusters. ResultsThe sample consisted of 731 participants with biospecimens and lumbar spine radiographic data. Three biomarker subgroups were identified: one characterized by structural degenerative changes; another characterized by structural degenerative changes and inflammation, with pain; and a referent cluster with lower levels of biomarkers, pain, and structural degenerative changes. Compared to the referent subgroup, the structural change subgroup was associated with DSN (OR ​= ​1.94, 95% CI 1.30–2.90) and FOA (OR ​= ​1.72, 95% CI 1.12–2.62), and the subgroup with structural degenerative change, inflammation, and pain was associated with OST with LBP (OR ​= ​1.60, 95% CI 1.04–2.46), FOA with LBP (OR ​= ​1.59, 95% CI 1.04–2.45), and LBP (OR ​= ​1.63, 95% CI 1.11–2.41). The subgroup with structural degenerative changes was more likely to have OST (OR ​= ​1.82, 95% CI 1.06–3.13) and less likely to have FOA with LBP (OR ​= ​0.62, 95% CI 0.40–0.96) compared to the group with inflammation and pain. ConclusionClustering by biomarkers may assist in differentiating patients for specific clinical interventions aimed at decreasing LBP.

PERIPHERAL BLOOD DNA METHYLATION-BASED MACHINE LEARNING MODELS ARE PREDICTIVE OF FUTURE KNEE OA PROGRESSION: BIOSPECIMENS AND DATA FROM THE OSTEOARTHRITIS INITIATIVE AND JOHNSTON COUNTY OSTEOARTHRITIS PROJECT

Purpose: Knee osteoarthritis (OA) is a heterogeneous disease characterized by a variety of clinical and molecular phenotypes, for which there exist no widely-available biomarkers. We have previously published a pilot analysis of baseline peripheral blood cell DNA methylation patterns from a small group of patients from the Osteoarthritis Initiative (OAI), demonstrating that methylation-based models could distinguish future radiographic progressors from nonprogressors. In the current study, we apply this method to the FNIH OsteoArthritis Biomarkers Consortium (OABC) subcohort of the OAI that included pain-, radiographic-, and dual- (both pain and radiographic) progressors compared to nonprogressors and to similarly constructed groups in the Johnston County Osteoarthritis Project (JoCoOA) and an independent OAI cohort from our prior work.

Point prevalence of hip symptoms, radiographic, and symptomatic OA at five time points: The Johnston County Osteoarthritis Project, 1991–2018

ObjectiveTo describe the point prevalence of hip symptoms, radiographic hip osteoarthritis (rHOA), severe rHOA, and symptomatic rHOA (sxHOA) at five time points in the longitudinal, population-based Johnston County Osteoarthritis Project (JoCoOA). DesignData were from 3068 JoCoOA participants who attended up to five study visits (1991–2018). Standardized supine pelvis radiographs were read by a single, expert musculoskeletal radiologist with high reliability. The four outcomes were: 1) self-reported hip symptoms: “On most days, do you have pain, aching, or stiffness in your right/left hip?“; 2) rHOA: Kellgren-Lawrence grade (KLG) of 2–4; 3) severe rHOA: KLG of 3–4; and 4) sxHOA: both symptoms and rHOA in the same joint. Weighted point prevalence and 95% confidence intervals (CI) were generated overall and by age group (45–54, 55–64, 65–74, 75+ years), sex, race (Black/White), and body mass index (BMI; 18.5–24.9; 25–29.9; 30+ kg/m2). ResultsAt the most recent follow-up (2017–2018), the point prevalence (%) of hip symptoms, rHOA, severe rHOA, and sxHOA were 30% (95% CI 25%, 35%), 53% (95% CI 48%, 58%), 9% (95% CI 6%, 12%), and 15% (95% CI 11%, 19%), respectively. RHOA and severe rHOA were most prevalent in those 75+ years. Women were more likely than men to have hip symptoms and sxHOA. No consistent trends were noted by race or BMI. ConclusionThese updated point prevalence estimates demonstrate a large and increasing burden of HOA in the general population, particularly with aging. Black and White individuals were affected similarly in this cohort.

Association of Increased Serum Lipopolysaccharide, But Not Microbial Dysbiosis, With Obesity-Related Osteoarthritis.

To test the hypothesis that an altered gut microbiota (dysbiosis) plays a role in obesity-associated osteoarthritis (OA). Stool and blood samples were collected from 92 participants with a body mass index (BMI) ≥30 kg/m2 , recruited from the Johnston County Osteoarthritis Project. OA patients (n = 50) had hand and knee OA (Kellgren/Lawrence [K/L] grade ≥2 or arthroplasty). Controls (n = 42) had no hand OA and a K/L grade of 0-1 for the knees. Compositional analysis of stool samples was carried out by 16S ribosomal RNA 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 patient- or control-pooled fecal samples and fed a 40% fat, high-sucrose diet for 40 weeks. Knee OA was evaluated histologically. On average, OA patients were slightly older than the controls, consisted of more women, and had a higher mean BMI, higher mean Western Ontario and McMaster Universities Osteoarthritis Index pain score, and higher mean K/L grade. There were no significant differences in α- or β-diversity or genus level composition between patients and controls. Patients had higher plasma levels of osteopontin (P = 0.01) and serum LPS (P < 0.0001) compared to controls. Mice transplanted with patient or control microbiota exhibited a significant difference in α-diversity (P = 0.02) and β-diversity, but no differences in OA severity were observed. The lack of differences in the gut microbiota, but increased serum LPS levels, suggest the possibility that increased intestinal permeability allowing for greater absorption of LPS, rather than a dysbiotic microbiota, may contribute to the development of OA associated with obesity.

Foot Osteoarthritis Frequency and Associated Factors in a Community-Based Cross-Sectional Study of White and African American Adults.

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. Data were from the 2013-2015 study visit of the Johnston County OA Project. Radiographic OA of the foot was defined using the La Trobe radiographic atlas (≥2 osteophytes or joint space narrowing in at least 1 of 5 joints). Symptomatic OA of the foot was defined as foot radiographic OA with pain, aching, or stiffness in the same foot. At the foot-level, separate logistic regression models with generalized estimating equations to account for intraperson correlations were performed to examine associations of foot radiographic OA or symptomatic OA with age, body mass index (BMI), sex, race, educational attainment, and previous foot injury. Of 864 participants with available data (mean age 71 years, mean BMI 30 kg/m2 , 68% women, 33% African American, 13% <12 years of schooling), 22% had foot radiographic OA, 20% had foot symptoms, and 5% had foot symptomatic OA. Radiographic, but not symptomatic, foot OA was more common in African American than White participants. Participants with obesity, compared to normal weight, had >2 times the odds of radiographic OA and >5 times the odds of symptomatic OA in adjusted models. Foot radiographic OA and foot symptoms were common in the sample, but both conditions simultaneously (i.e., symptomatic OA) occurred infrequently. Notably, obesity was linked with foot symptomatic OA, perhaps implicating metabolic or mechanical influences.

The Prevalence of Knee Symptoms, Radiographic, and Symptomatic Osteoarthritis at Four Time Points: The Johnston County Osteoarthritis Project, 1999-2018.

ObjectiveTo 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).MethodsData 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).ResultsMost 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%).ConclusionThese updated estimates demonstrate a large and increasing burden of knee OA, particularly among women and Black individuals.

Untargeted Fecal Metabolomics to Investigate the Role of the Microbiome and Nutrients in Osteoarthritis

Abstract Objectives The objective of this study was to determine if perturbations in gut microbial composition and the gut metabolome could be linked to individuals with obesity and osteoarthritis (OA). Methods Fecal samples were collected from 92 participants with obesity recruited from the Johnston County Osteoarthritis Project. OA cases (n = 59) had radiographic hand plus knee OA, defined as involvement of at least 3 joints across both hands, and a Kellgren-Lawrence (KL) grade 2–4 in at least one knee. Controls (n = 33) were without hand OA and with KL grade 0–1 knees. Fecal metabolomes were analyzed by a UHPLC/Q Exactive HFx mass spectrometer. Microbiome composition was determined in fecal samples by 16S ribosomal RNA amplicon sequencing (rRNA-seq). Stepwise logistic regression models were built to determine predictors of OA status. Spearman correlations were performed to determine associations between metabolites and microbiota in OA or healthy individuals. Results Untargeted metabolomics analysis indicated that OA cases had significantly higher levels of di- and tri-peptides (P &amp;lt; 0.05), and significant perturbations (P &amp;lt; 0.1) in microbial metabolites. Pathway analysis revealed several significantly perturbed pathways (P &amp;lt; 0.05) associated with OA, including leukotriene metabolism, amino acid metabolism and fatty acid utilization. Logistic regression models selected metabolites associated with the microbiota and leaky gut syndrome as significant predictors of OA status, particularly when combined with the 16S rRNA sequencing data. Omega-3/6 polyunsaturated fatty acids (PUFAs) levels were significantly correlated with the phyla Bacteriodetes and Firmicutes. Conclusions Adults with obesity and OA have distinct fecal metabolomes characterized by perturbations in microbial metabolites, PUFAs, and protein digestion compared with healthy controls. These metabolic perturbations suggest a role of intestinal inflammation and leaky gut in OA. Funding Sources Supported by the Arthritis Foundation, the National Center for Advancing Translational Sciences (NCATS) (UL1TR002489), and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR072580).

The association between walking speed from short- and standard-distance tests with the risk of all-cause mortality among adults with radiographic knee osteoarthritis: data from three large United States cohort studies

Adults with radiographic knee OA (rKOA) are at increased risk of mortality and walking difficulty may modify this relation. Little is known about specific aspects of walking difficulty that increase mortality risk. We investigated the association of walking speed (objective measure of walking difficulty) with mortality and examined the threshold that best discriminated this risk in adults with rKOA. Participants with rKOA from the Johnston County Osteoarthritis Project (JoCoOA, longitudinal population-based cohort), Osteoarthritis Initiative and Multicenter Osteoarthritis Study (OAI and MOST, cohorts of individuals with or at high risk of knee OA) were included. Baseline speed was measured via 2.4-meter (m) walk test (short-distance) in JoCoOA and 20-m walk test (standard-distance) in OAI and MOST. To examine the association of walking speed with mortality risk over 9years, hazard ratios (HR) and 95% confidence intervals (CI) were calculated from Cox regression models adjusted for potential confounders. A Maximal Likelihood Ratio Chi-square Approach was utilized to identify an optimal threshold of walking speed predictive of mortality. Deaths after 9 years of follow-up occurred in 23.3% (290/1244) of JoCoOA and 5.9% (249/4215) of OAI+MOST. Walking 0.2m/s slower during short- and standard-distance walk tests was associated with 23% (aHR [95%CI]; 1.23 [1.10, 1.39]) and 25% (1.25 [1.09, 1.43]) higher mortality risk, respectively. Walking <0.5m/s on short-distance and <1.2m/s standard-distance walk tests, best discriminated those with and without mortality risk. Slower walking speed measured via short- and standard-distance walk tests was associated with increased mortality risk in adults with rKOA.

Hip symptoms are associated with premature mortality: the Johnston County Osteoarthritis Project

To investigate the impact of hip osteoarthritis (OA) and/or hip symptoms on excess mortality. 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 (HR) and 95% confidence intervals (CI). We carried out additional analyses stratified by sex, race, age and obesity. 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% CI=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 <65 years (43% and 39% increase, respectively) and in Caucasians (34% and 21% increase, respectively). Individuals who had hip symptoms without hip rOA had an increased risk of mortality. These effects were particularly strong for those who were <65 years of age and Caucasians. Effective interventions to identify those with hip pain in order to lessen it could reduce premature mortality.