Looking back on 30+ years of the Johnston County Osteoarthritis Project while looking forward with the Johnston County Health Study: A narrative review.

Over the last 30 years, knowledge of the epidemiology of osteoarthritis (OA) has dramatically advanced, and Osteoarthritis and Cartilage has been on the forefront of disseminating research findings from large OA cohort studies, including the Johnston County OA Project (JoCoOA). The JoCoOA is a population-based, prospective longitudinal cohort that began roughly 30 years ago with a key focus on understanding prevalence, incidence, and progression of OA, as well as its risk factors, in a predominantly rural population of Black and White adults 45+ years old in a county in the southeastern United States. Selected OA results that will be discussed in this review include racial differences, lifetime risk, biomarkers, mortality, and OA risk factors. The new Johnston County Health Study will also be introduced. This new cohort study of OA and comorbid conditions builds upon current OA knowledge and JoCoOA infrastructure and is designed to reflect changes in demographics and urbanization in the county and the region.

Incidence and Progression of Foot Osteoarthritis in a Longitudinal Cohort: the Johnston County Osteoarthritis Project.

INTRODUCTION: To examine the incidence and progression of foot osteoarthritis (OA), as well as associated factors, in a community-based cohort. METHODS: Baseline (2013-2015) and follow-up (2016-2018) foot radiographs were available for 541 participants (71% women, mean age 69 years; 35% Black, 53% with obesity). The LaTrobe Foot Atlas was used to examine osteophytes (OP, score 0-3) and joint space narrowing (JSN, score 0-3) at 5 joint sites. Incident foot radiographic OA (rOA) was a baseline score <2 OP and JSN in all 5 joints with ≥2 OP or JSN at follow-up in any of the joints. Progression was a worsening OP or JSN score in a joint with baseline foot rOA. At baseline and follow-up, participants reported presence/absence of foot symptoms and completed the Foot and Ankle Outcome Score (FAOS) for each foot. Joint-based logistic regression models with generalized estimating equations were used to examine associations (adjusted odds ratio [aOR], 95% confidence interval [CI]) of foot rOA incidence and progression and with covariates. RESULTS: Among 928 feet without baseline rOA, 4% developed incident foot rOA (2% of those developed symptoms). Among 154 feet with baseline foot rOA, 55% had radiographic progression (16% of those had symptoms). Women and those with higher body mass index (BMI) were more likely to have incident foot rOA (aOR [95% CI] = 4.10 [1.22, 13.8] and 1.60 [1.31, 1.97], respectively); history of gout was associated with incidence or progression of foot rOA (2.75 [1.24, 6.07]. BMI was associated with worse scores on all FAOS subscale (aORs range 1.21-1.40). CONCLUSION: Progression of foot rOA is common but not necessarily related to worsening symptoms. BMI may be a modifiable risk factor for foot OA.

Features of Knee and Multijoint Osteoarthritis by Sex and Race and Ethnicity: A Preliminary Analysis in the Johnston County Health Study.

OBJECTIVE: To evaluate knee osteoarthritis (KOA) and multijoint osteoarthritis (MJOA), and to compare features by sex and race and ethnicity in a population-based cohort. METHODS: Participants (n = 544) enrolled in the Johnston County Health Study (JoCoHS) as of January 2023 were categorized by radiographic and symptomatic KOA and MJOA phenotypes, and frequencies were compared by sex and race and ethnicity. Symptoms were assessed according to the Knee Injury and Osteoarthritis Outcome Score (KOOS) and pain, aching, and stiffness (PAS) scores at various joints. Models produced estimates (odds ratio [OR] or mean ratios [MR] and 95% CI) adjusted for age, BMI (kg/m2), and education. RESULTS: Men had twice the odds of having MJOA-6 (≥ 3 lower extremity joints affected); there were no significant differences in MJOA phenotypes by race and ethnicity. Women had 50% higher odds of having KOA or having various features of KOA. Women reported significantly worse KOOS Symptoms scores (MR 1.25). Black participants had higher odds of more severe KOA (OR 1.47), subchondral sclerosis (OR 2.06), and medial tibial osteophytes (OR 1.50). Black participants reported worse KOOS Symptoms than White participants (MR 1.18). Although not statistically significant, Hispanic participants (vs non-Hispanic participants) appeared to have lower odds of radiographic changes but reported worse symptoms. CONCLUSION: Preliminary findings in the diverse JoCoHS cohort suggest more lower extremity- predominant MJOA in men compared to women. Women and Black participants had more KOA features and more severe symptoms. Hispanic participants appear to have higher pain and symptoms scores despite having fewer structural changes. Studies in diverse populations are needed to understand the burden of OA.

Joint hypermobility is not positively associated with prevalent multiple joint osteoarthritis: a cross-sectional study of older adults.

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.

Relationship of joint hypermobility with low Back pain and lumbar spine osteoarthritis.

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.

Establishment of reference intervals for osteoarthritis-related soluble biomarkers: the FNIH/OARSI OA Biomarkers Consortium.

OBJECTIVE: To establish reference intervals for osteoarthritis (OA)-related biomarkers used in the Foundation for the National Institutes of Health (FNIH) OA Biomarkers Consortium Project. METHODS: A 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. RESULTS: Controls 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. CONCLUSIONS: To 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.

Genome-wide association and functional studies identify a role for IGFBP3 in hip osteoarthritis.

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.

Brief report: differences in multijoint symptomatic osteoarthritis phenotypes by race and sex: the Johnston County Osteoarthritis Project.

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.

Protein modification by deamidation indicates variations in joint extracellular matrix turnover.

As extracellular proteins age, they undergo and accumulate nonenzymatic post-translational modifications that cannot be repaired. We hypothesized that these could be used to systemically monitor loss of extracellular matrix due to chronic arthritic diseases such as osteoarthritis (OA). To test this, we predicted sites of deamidation in cartilage oligomeric matrix protein (COMP) and confirmed, by mass spectroscopy, the presence of deamidated (Asp(64)) and native (Asn(64)) COMP epitopes (mean 0.95% deamidated COMP (D-COMP) relative to native COMP) in cartilage. An Asp(64), D-COMP-specific ELISA was developed using a newly created monoclonal antibody 6-1A12. In a joint replacement study, serum D-COMP (p = 0.017), but not total COMP (p = 0.5), declined significantly after replacement demonstrating a joint tissue source for D-COMP. In analyses of 450 participants from the Johnston County Osteoarthritis Project controlled for age, gender, and race, D-COMP was associated with radiographic hip (p < 0.0001) but not knee (p = 0.95) OA severity. In contrast, total COMP was associated with radiographic knee (p < 0.0001) but not hip (p = 0.47) OA severity. D-COMP was higher in soluble proteins extracted from hip cartilage proximal to OA lesions compared with remote from lesions (p = 0.007) or lesional and remote OA knee (p < 0.01) cartilage. Total COMP in cartilage did not vary by joint site or proximity to the lesion. This study demonstrates the presence of D-COMP in articular cartilage and the systemic circulation, and to our knowledge, it is the first biomarker to show specificity for a particular joint site. We believe that enrichment of deamidated epitope in hip OA cartilage indicates a lesser repair response of hip OA compared with knee OA cartilage.

Independent associations of socioeconomic factors with disability and pain in adults with knee osteoarthritis.

BACKGROUND: The purpose of this study is to explore the relationship between function, pain and stiffness outcomes with individual and community socioeconomic status (SES) measures among individuals with radiographic knee osteoarthritis (rOA). METHODS: Cross-sectional data from the Johnston County Osteoarthritis Project were analyzed for adults age 45 and older with knee rOA (n = 782) and a subset with both radiographic and symptomatic knee OA (n = 471). Function, pain and stiffness were measured using the Western Ontario and McMasters Universities Index of Osteoarthritis (WOMAC). Individual SES measures included educational attainment (<12 years, ≥12 years) and occupation type (managerial, non-managerial), while community SES was measured using Census block group poverty rate (<12%, 12-25%, ≥25%). SES measures were individually and simultaneously examined in linear regression models adjusting for age, gender, race, body mass index (BMI), occupational physical activity score (PAS), comorbidity count, and presence of hip symptoms. RESULTS: In analyses among all individuals with rOA, models which included individual SES measures were observed to show that occupation was significantly associated with WOMAC Function (ß =2.91, 95% Confidence Interval (CI) = 0.68-5.14), WOMAC Pain (ß =0.93, 95% CI = 0.26-1.59) and WOMAC Total scores (ß =4.05, 95% CI = 1.04-7.05), and education was significantly associated with WOMAC Function (ß =3.57, 95% CI = 1.25-5.90) and WOMAC Total (ß =4.56, 95% CI = 1.41-7.70) scores. In multivariable models including all SES measures simultaneously, most associations were attenuated. However, statistically significant results for education remained between WOMAC Function (ß =2.83, 95% CI = 0.38-5.28) and WOMAC Total (ß =3.48, 95% CI = 0.18-6.78), as well as for the association between occupation and WOMAC Pain (ß =0.78, 95% CI = 0.08-1.48). In rOA subgroup analyses restricted to those with symptoms, we observed a significant increase in WOMAC Pain (ß =1.36, 95% CI = 0.07-2.66) among individuals living in a block group with poverty rates greater than 25%, an association that remained when all SES measures were considered simultaneously (ß =1.35, 95% CI = 0.06-2.64). CONCLUSIONS: Lower individual and community SES are both associated with worse function and pain among adults with knee rOA.

Extensive Osteonecrosis After Glucocorticoids: Clinical Response to Bisphosphonate.

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.

Association of Traumatic Knee Injury With Radiographic Evidence of Knee Osteoarthritis in Military Officers.

OBJECTIVE: The association between knee injury and knee osteoarthritis (OA) is understudied relative to its importance, particularly in younger populations. This study was undertaken to examine 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. METHODS: 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 (K/L) grade, osteophyte (OST), and joint space narrowing (JSN) scores. Data were analyzed using linear-risk regression models with generalized estimating equations. RESULTS: Injured and noninjured participants were similar (mean age 28 years, mean body mass index 25 kg/m2 , ~40% female). The mean time from first knee injury to imaging among injured participants was 9.2 years. Compared with noninjured knees, greater prevalence of radiographic OA (K/L grade ≥ 2), OST (grade ≥ 1), and JSN (grade ≥ 1) was observed among injured knees, with prevalence differences of +16% (95% confidence interval [95% CI] 10%, 22%), +29% (95% CI 20%, 38%), and + 17% (95% CI 10%, 24%), respectively. Approximately 1 in 6 officers with prior knee injury progressed to radiographic OA by age 30 years. CONCLUSION: At the midpoint of a projected 20-year military career, officers with a history of traumatic knee injury have a markedly increased prevalence of knee radiographic OA compared to officers without injury.

Differences in multijoint radiographic osteoarthritis phenotypes among African Americans and Caucasians: the Johnston County Osteoarthritis project.

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."

Biomarkers of incident radiographic knee osteoarthritis: do they vary by chronic knee symptoms?

OBJECTIVE: To explore the ability of osteoarthritis (OA)-related biomarkers to predict incident radiographic knee OA in a large sample of African American and Caucasian men and women. METHODS: Baseline levels of serum cartilage oligomeric matrix protein (COMP), hyaluronan (HA), high-sensitivity C-reactive protein (hsCRP), and keratan sulfate (KS) and baseline and followup radiographs were available for 353 knees without baseline osteophyte formation and for 446 knees without baseline joint space narrowing (JSN). Cox models estimated the hazard ratio (HR) and 95% confidence interval (95% CI) for incident knee OA for a 1-unit increase in the ln of each biomarker, with adjustment for age, race, sex, body mass index, and knee OA of the contralateral limb. Report of chronic knee symptoms was explored as a modifier of the association. RESULTS: The hazard of incident knee osteophytes (HR 2.16 [95% CI 1.39-3.37]) and incident JSN (HR 1.82 [95% CI 1.15-2.89]) increased with higher baseline ln(COMP) levels. The hazard of incident knee JSN increased with higher ln(HA) levels (HR 1.46 [95% CI 1.14-1.87]). Baseline ln(hsCRP) and ln(KS) did not predict incident knee outcomes. HRs per unit increase in ln(COMP), ln(HA), and ln(KS) were higher among knees with chronic symptoms than among those without symptoms. CONCLUSION: Higher baseline ln(COMP) and ln(HA) levels were associated with incident knee OA over an average followup period of 6.3 years. These results represent detection of a molecular stage of OA prior to radiographic manifestations. Further exploration is needed to determine how chronic knee symptoms modify the biomarker-incident knee OA association.

Osteolipoma: radiological, pathological, and cytogenetic analysis of three cases.

Osteolipoma is a rare variant of lipoma consisting of mature adipose tissue and mature lamellar bone. The presence of non-fatty elements may lead to a wide differential diagnosis on radiology including benign and malignant lipomatous and nonlipomatous entities. The pathological diagnosis is also confounded by the presence of heterologous differentiation. Fortunately, most lipomas harbor classic cytogenetic aberrations, and the finding of translocations involving 12q13-15 may aid in the correct diagnosis. We report three cases of osteolipoma with radiological, histological, and cytogenetic correlation.

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

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: Among the multiple predictors of spine phenotypes, obesity was a common predictor for both incidence and worsening of lumbar spine degeneration and LBP.

Associations Between Baseline and Longitudinal Semiautomated Quantitative Joint Space Width at the Hip and Incident Hip Osteoarthritis: Data From a Community-Based Cohort.

OBJECTIVE: To evaluate quantitative joint space width (JSW) at 10-, 30-, and 50-degree locations in relation to incident radiographic and symptomatic hip osteoarthritis (HOA) in a community-based cohort. METHODS: Data were from Johnston County OA Project participants with supine hip radiographs at each of 4 time points; all had Kellgren/Lawrence (K/L) grades and quantitative JSW. We assessed covariates (age, race, height, weight, body mass index [BMI]) associated with quantitative JSW and hip-level associations between quantitative JSW and HOA over time using sex-stratified and multivariable-adjusted linear mixed models. A cluster analysis with logistic regression estimated associations between quantitative JSW trajectory groups and incident radiographic HOA and symptomatic HOA. RESULTS: At baseline, 397 participants (784 hips, 41% men, 24% Black, mean age 57 years) had a mean BMI of 29 kg/m2 . Over a mean of 18 years, 20% and 12% developed incident K/L grade-defined radiographic HOA or symptomatic HOA, respectively. Quantitative JSW 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 quantitative JSW; changes in quantitative JSW were not significantly associated with race, education, or injury in women or men. In women only, loss of quantitative JSW over time was associated with 2-3 times higher odds of radiographic HOA and symptomatic HOA; among women and men, narrower baseline quantitative JSW was associated with these outcomes. CONCLUSION: Hip quantitative JSW demonstrates marked differences in respect to sex, with significant loss over time only in women. Loss of quantitative JSW over time in women and narrower baseline quantitative JSW in men and women were associated with incident radiographic HOA and symptomatic HOA.

Tibiofemoral knee osteoarthritis progresses symmetrically by knee compartment in the GOGO cohort.

Objective: To evaluate the degree of symmetry of knee osteoarthritis (OA) structural severity and progression of participants with a mean follow-up time of 3.8 years. Design: Participants from the Genetics of Generalized Osteoarthritis (GOGO) study (n = 705) were selected on the basis of radiographic evidence of OA in at least 1 knee, availability of radiographs at baseline and follow-up, and no history of prior knee injury or surgery. Incidence and progression of osteoarthritis were determined by radiographic Kellgren-Lawrence (KL) grade; compartmental OA progression was determined by change in joint space width of lateral and medial tibiofemoral compartments. Total OA progression was the sum of change in KL grade of both knees. Results: Compared with left knees, right knees had more severe KL grades at baseline (p = 0.0002) and follow-up (p = 0.0004), McNemar's χ2 = 34.16 and 26.08, respectively; however, both knees progressed similarly (p = 0.121, McNemar's χ2 = 10.09). Compartmental changes were symmetric across knees: medial r = 0.287, p = 0.0002; lateral r = 0.593, p = 0.0002. Change in joint space width in the medial compartment was negatively correlated with change in the lateral compartment of the same knee (left knees: r = -0.293, p = 0.021; right knees: r = -0.195, p = 0.0002). Conclusions: Although right knees tended to have more severe OA at both baseline and follow-up, radiographic progression did not differ by knee and compartmental progression correlated across knees. Given this trend in generalized OA, the risk of progression for both knees should be considered, even if only one knee has radiographic OA at baseline.

Point prevalence of Hip Symptoms, Radiographic, And Symptomatic OA at Five Time Points: The Johnston County Osteoarthritis Project, 1991-2018.

Objective: To 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). Design: Data 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). Results: At 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. Conclusion: These 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.

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 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. RESULTS: 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 ß-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 ß-diversity, but no differences in OA severity were observed. CONCLUSION: 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.