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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

Associations of Comorbid Conditions and Transitions Across States of Knee Osteoarthritis in a Community-Based Cohort.

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.

Incidence and progression of ankle osteoarthritis: The johnston county osteoarthritis project.

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 < 1; progressive rAOA was a ≥ 1 KLG increase at follow-up among ankles with KLG ≥ 1 at baseline. Symptoms were assessed using self-reported pain, aching, and stiffness (PAS) on most days and the Foot and Ankle Outcome Score (FAOS) symptoms subscale. Ankle-level logistic regression models were used to assess associations of ankle outcomes with covariates (age, sex, race, body mass index [BMI], smoking, number of symptomatic joints, comorbidities, prior ankle injury, and knee or foot OA). RESULTS: Among ankles without rAOA at baseline, 28% developed incident rAOA, 37% had worsening FAOS symptoms, and 7% had worsening PAS. Incident rAOA and worsening ankle symptoms were associated with higher BMI and symptoms in other joints. Among ankles with baseline rAOA, 4% had progressive rAOA, 35% had worsening of FAOS symptoms, and 9% had worsening PAS. rAOA progression was associated with ankle injury and concomitant knee or foot OA; worsening of symptoms was associated with higher BMI and other symptomatic joints. CONCLUSIONS: Not all ankle OA is post-traumatic. Smoking prevention/cessation, a healthy weight, and injury prevention may be methods for reducing the incidence and progression of rAOA.

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

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 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. RESULTS: 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. CONCLUSION: 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.

A Standardized, Pragmatic Approach to Knee Ultrasound for Clinical Research in Osteoarthritis: The Johnston County Osteoarthritis Project.

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.

Effects of Comorbid Cardiovascular Disease and Diabetes on Hand Osteoarthritis, Pain, and Functional State Transitions: The Johnston County Osteoarthritis Project.

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.

Comorbid conditions and the transition among states of hip osteoarthritis and symptoms in a community-based study: a multi-state time-to-event model approach.

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] of< 2); development of hip symptoms (self-reported hip pain, aching, or stiffness on most days) or symptomatic HOA (sxHOA; rHOA and symptoms in the same hip), and resolution of symptoms. Obesity (body mass index ≥ 30 kg/m2) 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.

Is the Association between Knee Injury and Knee Osteoarthritis Modified by the Presence of General Joint Hypermobility.

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=2,341), Genetics of Osteoarthritis (GO; N=1,872), and the population-based Johnston County Osteoarthritis Project (JoCoOA; N=1,937). 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<0.10). 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.

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.