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.

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.

Effect of Diet and Exercise on Knee Pain in Patients With Osteoarthritis and Overweight or Obesity: A Randomized Clinical Trial.

Importance: Some weight loss and exercise programs that have been successful in academic center-based trials have not been evaluated in community settings. Objective: To determine whether adaptation of a diet and exercise intervention to community settings resulted in a statistically significant reduction in pain, compared with an attention control group, at 18-month follow-up. Design, Setting, and Participants: Assessor-blinded randomized clinical trial conducted in community settings in urban and rural counties in North Carolina. Patients were men and women aged 50 years or older with knee osteoarthritis and overweight or obesity (body mass index ≥27). Enrollment (N = 823) occurred between May 2016 and August 2019, with follow-up ending in April 2021. Interventions: Patients were randomly assigned to either a diet and exercise intervention (n = 414) or an attention control (n = 409) group for 18 months. Main Outcomes and Measures: The primary outcome was the between-group difference in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee pain score (range, 0 [none] to 20 [severe]; minimum clinically important difference, 1.6) over 18 months, tested using a repeated-measures mixed linear model with adjustments for covariates. There were 7 secondary outcomes including body weight. Results: Among the 823 randomized patients (mean age, 64.6 years; 637 [77%] women), 658 (80%) completed the trial. At 18-month follow-up, the adjusted mean WOMAC pain score was 5.0 in the diet and exercise group (n = 329) compared with 5.5 in the attention control group (n = 316) (adjusted difference, -0.6; 95% CI, -1.0 to -0.1; P = .02). Of 7 secondary outcomes, 5 were significantly better in the intervention group compared with control. The mean change in unadjusted 18-month body weight for patients with available data was -7.7 kg (8%) in the diet and exercise group (n = 289) and -1.7 kg (2%) in the attention control group (n = 273) (mean difference, -6.0 kg; 95% CI, -7.3 kg to -4.7 kg). There were 169 serious adverse events; none were definitely related to the study. There were 729 adverse events; 32 (4%) were definitely related to the study, including 10 body injuries (9 in diet and exercise; 1 in attention control), 7 muscle strains (6 in diet and exercise; 1 in attention control), and 6 trip/fall events (all 6 in diet and exercise). Conclusions and Relevance: Among patients with knee osteoarthritis and overweight or obesity, diet and exercise compared with an attention control led to a statistically significant but small difference in knee pain over 18 months. The magnitude of the difference in pain between groups is of uncertain clinical importance. Trial Registration: ClinicalTrials.gov Identifier: NCT02577549.

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.

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

Objective: Describe 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. Methods: Using 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. Results: The 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. Conclusion: Clustering by biomarkers may assist in differentiating patients for specific clinical interventions aimed at decreasing LBP.

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

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

Reinvigorating an Academy of Medical Educators Using Ecological Systems Theory.

The educational framework of communities of practice postulates that early learners join medical communities as social networks that provide a common identity, role modeling and mentorship, and experiential learning. While being elected into a medical society is an honor, member engagement in these groups can falter if the society membership is seen as an honorific rather than one requiring continuing participation. As an example, Academies of Medical Educators have been established by many academic medical centers to encourage collaboration, skill development, professional identity formation, and scholarship. The University of North Carolina established the Academy of Educators in 2006 to create a diverse community of educators to promote the scholarship, teaching skills, and professional identity of educators. Despite rapid growth to over 500 members, we had less than 30 participants at events over the 2017-2018 academic year. To increase member engagement and participation, our academy leadership team used Bronfenbrenner's Ecological Systems Theory to design interventions at each layer of environmental influence, specifically at the microsystem, mesosystem, exosystem, macrosystem, and chronosystem levels. In this paper, we describe the multipronged approach used to increase the University of North Carolina Academy of Medical Educators event attendance from 30 to 1,000 faculty participants over the course of one academic year (2018-2019). This paper provides a model as to how medical societies can use ecological systems theory as a natural and comprehensive approach to plan and improve their member engagement and experience.

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.

What Cut-Point in Gait Speed Best Discriminates Community-Dwelling Older Adults With Mobility Complaints From Those Without? A Pooled Analysis From the Sarcopenia Definitions and Outcomes Consortium.

BACKGROUND: Cut-points to define slow walking speed have largely been derived from expert opinion. METHODS: Study participants (13 589 men and 5043 women aged ≥65years) had walking speed (m/s) measured over 4-6 m (mean ± SD: 1.20 ± 0.27 m/s in men and 0.94 ± 0.24 m/s in women.) Mobility limitation was defined as any self-reported difficulty with walking approximately 1/4 mile (prevalence: 12.6% men, 26.4% women). Sex-stratified classification and regression tree (CART) models with 10-fold cross-validation identified walking speed cut-points that optimally discriminated those who reported mobility limitation from those who did not. RESULTS: Among 5043 women, CART analysis identified 2 cut-points, classifying 4144 (82.2%) with walking speed ≥0.75 m/s, which we labeled as "fast"; 478 (9.5%) as "intermediate" (walking speed ≥0.62 m/s but <0.75 m/s); and 421 (8.3%) as "slow" (walking speed <0.62 m/s). Among 13 589 men, CART analysis identified 3 cut-points, classifying 10 001 (73.6%) with walking speed ≥1.00 m/s ("very fast"); 2901 (21.3%) as "fast" (walking speed ≥0.74 m/s but <1.00 m/s); 497 (3.7%) as "intermediate" (walking speed ≥0.57 m/s but <0.74 m/s); and 190 (1.4%) as "slow" (walking speed <0.57 m/s). Prevalence of self-reported mobility limitation was lowest in the "fast" or "very fast" (11% for men and 19% for women) and highest in the "slow" (60.5% in men and 71.0% in women). Rounding the 2 slower cut-points to 0.60 m/s and 0.75 m/s reclassified very few participants. CONCLUSIONS: Cut-points in walking speed of approximately 0.60 m/s and 0.75 m/s discriminate those with self-reported mobility limitation from those without.

Knee osteoarthritis and time-to all-cause mortality in six community-based cohorts: an international meta-analysis of individual participant-level data.

BACKGROUND: Osteoarthritis (OA) is a chronic joint disease, with increasing global burden of disability and healthcare utilisation. Recent meta-analyses have shown a range of effects of OA on mortality, reflecting different OA definitions and study methods. We seek to overcome limitations introduced when using aggregate results by gathering individual participant-level data (IPD) from international observational studies and standardising methods to determine the association of knee OA with mortality in the general population. METHODS: Seven community-based cohorts were identified containing knee OA-related pain, radiographs, and time-to-mortality, six of which were available for analysis. A two-stage IPD meta-analysis framework was applied: (1) Cox proportional hazard models assessed time-to-mortality of participants with radiographic OA (ROA), OA-related pain (POA), and a combination of pain and ROA (PROA) against pain and ROA-free participants; (2) hazard ratios (HR) were then pooled using the Hartung-Knapp modification for random-effects meta-analysis. FINDINGS: 10,723 participants in six cohorts from four countries were included in the analyses. Multivariable models (adjusting for age, sex, race, BMI, smoking, alcohol consumption, cardiovascular disease, and diabetes) showed a pooled HR, compared to pain and ROA-free participants, of 1.03 (0.83, 1.28) for ROA, 1.35 (1.12, 1.63) for POA, and 1.37 (1.22, 1.54) for PROA. DISCUSSION: Participants with POA or PROA had a 35-37% increased association with reduced time-to-mortality, independent of confounders. ROA showed no association with mortality, suggesting that OA-related knee pain may be driving the association with time-to-mortality. FUNDING: Versus Arthritis Centre for Sport, Exercise and Osteoarthritis and Osteoarthritis Research Society International.

How Are Neighborhood Characteristics Associated With Mental and Physical Functioning Among Older Adults With Radiographic Knee Osteoarthritis?

OBJECTIVE: To examine how neighborhood characteristics are associated with health outcomes among older adults with osteoarthritis. METHODS: In multilevel, cross-sectional, and longitudinal analyses we examined whether 4 neighborhood characteristics were associated with depressive symptoms and reported knee impact scores, and whether the neighborhood characteristics interacted with race/ethnicity among older adults with radiographic knee osteoarthritis (n = 656 for cross-sectional analyses and n = 434 for longitudinal analyses). The data came from the Johnston County Osteoarthritis Project, a prospective cohort study in North Carolina designed to examine risk factors for osteoarthritis. RESULTS: Although few longitudinal associations were found, cross-sectional results suggested that greater perceived neighborhood social cohesion (B = -0.04, P < 0.001) and perceived neighborhood resources for physical activity and walking (B = -0.03, P < 0.001) were associated with fewer depressive symptoms, and that greater perceived neighborhood resources for physical activity and walking were associated with higher (better) knee impact scores (B = 0.48, P = 0.008). We also observed 2 significant interactions among neighborhood characteristics and race/ethnicity related to depressive symptoms (P < 0.01); for African American adults, greater perceived neighborhood resources for physical activity and walking were associated with fewer depressive symptoms (B = -0.03, P < 0.001), but for White adults, greater perceived neighborhood safety was associated with fewer depressive symptoms (B = -0.04, P = 0.003). CONCLUSION: In a sample of older adults with radiographic knee osteoarthritis, neighborhood context mattered, but in nuanced ways. Interventions aiming to improve mental and physical functioning of older adults with knee osteoarthritis can look to this study as evidence for the importance of neighborhood characteristics.

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 Meta-Analysis of the Transferability of Bone Mineral Density Genetic Loci Associations From European to African Ancestry Populations.

Genetic studies of bone mineral density (BMD) largely have been conducted in European populations. We therefore conducted a meta-analysis of six independent African ancestry cohorts to determine whether previously reported BMD loci identified in European populations were transferable to African ancestry populations. We included nearly 5000 individuals with both genetic data and assessments of BMD. Genotype imputation was conducted using the 1000G reference panel. We assessed single-nucleotide polymorphism (SNP) associations with femoral neck and lumbar spine BMD in each cohort separately, then combined results in fixed effects (or random effects if study heterogeneity was high, I2 index >60) inverse variance weighted meta-analyses. In secondary analyses, we conducted locus-based analyses of rare variants using SKAT-O. Mean age ranged from 12 to 68 years. One cohort included only men and another cohort included only women; the proportion of women in the other four cohorts ranged from 52% to 63%. Of 56 BMD loci tested, one locus, 6q25 (C6orf97, p = 8.87 × 10-4 ), was associated with lumbar spine BMD and two loci, 7q21 (SLC25A13, p = 2.84 × 10-4 ) and 7q31 (WNT16, p = 2.96 × 10-5 ), were associated with femoral neck BMD. Effects were in the same direction as previously reported in European ancestry studies and met a Bonferroni-adjusted p value threshold, the criteria for transferability to African ancestry populations. We also found associations that met locus-specific Bonferroni-adjusted p value thresholds in 11q13 (LRP5, p < 2.23 × 10-4 ), 11q14 (DCDC5, p < 5.35 × 10-5 ), and 17p13 (SMG6, p < 6.78 × 10-5 ) that were not tagged by European ancestry index SNPs. Rare single-nucleotide variants in AKAP11 (p = 2.32 × 10-2 ), MBL2 (p = 4.09 × 10-2 ), MEPE (p = 3.15 × 10-2 ), SLC25A13 (p = 3.03 × 10-2 ), STARD3NL (p = 3.35 × 10-2 ), and TNFRSF11A (p = 3.18 × 10-3 ) were also associated with BMD. The majority of known BMD loci were not transferable. Larger genetic studies of BMD in African ancestry populations will be needed to overcome limitations in statistical power and to identify both other loci that are transferable across populations and novel population-specific variants. © 2020 American Society for Bone and Mineral Research (ASBMR).

Identification of Sarcopenia Components That Discriminate Slow Walking Speed: A Pooled Data Analysis.

BACKGROUND: The Sarcopenia Definitions and Outcomes Consortium (SDOC) sought to identify cut points for muscle strength and body composition measures derived from dual-energy x-ray absorptiometry (DXA) that discriminate older adults with slow walking speed. This article presents the core analyses used to guide the SDOC position statements. DESIGN: Cross-sectional data analyses of pooled data. SETTING: University-based research assessment centers. PARTICIPANTS: Community-dwelling men (n = 13,652) and women: (n = 5,115) with information on lean mass by DXA, grip strength (GR), and walking speed. MEASUREMENTS: Thirty-five candidate sarcopenia variables were entered into sex-stratified classification and regression tree (CART) models to agnostically choose variables and cut points that discriminate slow walkers (<0.80 m/s). Models with alternative walking speed outcomes were also evaluated (<0.60 and <1.0 m/s and walking speed treated continuously). RESULTS: CART models identified GR/body mass index (GRBMI) and GR/total body fat (GRTBF) as the primary discriminating variables for slowness in men and women, respectively. Men with GRBMI of 1.05 kg/kg/m2 or less were approximately four times more likely to be slow walkers than those with GRBMI of greater than 1.05 kg/kg/m2 . Women with GRTBF of less than 0.65 kg/kg were twice as likely to be slow walkers than women with GRTBF of 0.65 kg/kg or greater. Models with alternative walking speed outcomes selected only functions of GR as primary discriminators of slowness in both men and women. DXA-derived lean mass measures did not consistently discriminate slow walkers. CONCLUSION: GR with and without adjustments for body size and composition consistently discriminated older adults with slowness. CART models did not select DXA-based lean mass as a primary discriminator of slowness. These results were presented to an SDOC Consensus Panel, who used them and other information to develop the SDOC Position Statements. J Am Geriatr Soc 68:1419-1428, 2020.

Associations among neighborhood poverty, perceived neighborhood environment, and depressed mood are mediated by physical activity, perceived individual control, and loneliness.

Few studies have documented the pathways through which individual level variables mediate the effects of neighborhoods on health. This study used structural equation modeling to examine if neighborhood characteristics are associated with depressive symptoms, and if so, what factors mediated these relationships. Cross-sectional data came from a sample of mostly rural, older adults in North Carolina (n = 1,558). Mediation analysis indicated that associations among neighborhood characteristics and depressive symptoms were mediated by loneliness (standardized indirect effect = -0.19, p < 0.001), physical activity (standardized indirect effect = -0.01, p = 0.003), and perceived individual control (standardized indirect effect = -0.07, p = 0.02) with loneliness emerging as the strongest mediator. Monitoring such individual mediators in formative and process evaluations may increase the precision of neighborhood-based interventions and policies.