Knee rOA Research Articles

TNF-α Carried by Plasma Extracellular Vesicles Predicts Knee Osteoarthritis Progression.

ObjectivesTo identify plasma extracellular vesicles (EVs) associated with radiographic knee osteoarthritis (OA) progression.MethodsEVs of small (SEV), medium (MEV) and large (LEV) sizes from plasma of OA participants (n=30) and healthy controls (HCs, n=22) were profiled for surface markers and cytokine cargo by high-resolution flow cytometry. The concentrations of cytokines within (endo-) and outside (exo-) EVs were quantified by multiplex ELISA. EV associations with knee radiographic OA (rOA) progression were assessed by multivariable linear regression (adjusted for baseline clinical variables of age, gender, BMI and OA severity) and receiver operating characteristic (ROC) curve analysis.ResultsBased on integrated mean fluorescence intensity (iMFI), baseline plasma MEVs carrying CD56 (corresponding to natural killer cells) predicted rOA progression with highest area under the ROC curve (AUC) 0.714 among surface markers. Baseline iMFI of TNF-α in LEVs, MEVs and SEVs, and the total endo-EV TNF-α concentration, predicted rOA progression with AUCs 0.688, 0.821, 0.821, 0.665, respectively. In contrast, baseline plasma exo-EV TNF-α (the concentration in the same unit of plasma after EV depletion) did not predict rOA progression (AUC 0.478). Baseline endo-EV IFN-γ and exo-EV IL-6 concentrations were also associated with rOA progression, but had low discriminant capacity (AUCs 0.558 and 0.518, respectively).ConclusionsPlasma EVs carry pro-inflammatory cargo that predict risk of knee rOA progression. These findings suggest that EV-associated TNF-α may be pathogenic in OA. The sequestration of pathogenic TNF-α within EVs may provide an explanation for the lack of success of systemic TNF-α inhibitors in OA trials to date.

Association between serum immunoglobulin E levels and knee osteoarthritis in Korean adults

The objective of this study was to examine whether osteoarthritis (OA) in the knees was associated with total immunoglobulin E (IgE), allergen-specific IgE, or allergic sensitizations in a nationally representative population. The study population comprised of 785 adults aged 50 years or more in the Korea National Health and Nutrition Examination Survey 2010. OA was diagnosed as radiographic (rOA) and symptomatic osteoarthritis (sxOA). We performed multivariable logistic regression analyses to investigate relationships of OA in a knee with serum total IgE, allergen (Dermatophagoides farinae, cockroach, and dog allergens)-specific IgE, and allergic sensitizations. Participants with the highest tertile of the total IgE had 92% and 242% increased risk of knee rOA and sxOA, respectively. Those with D.farinae-specific IgE had 2.2 times increased risk of knee sxOA compared to the lowest tertile. Participants with high total IgE (>150kU/L) had a 60% increased risk of knee rOA. Those with D.farinae-specific sensitization (>0.35kU/L) had 2.0 times increased risk of knee sxOA in compared to those without sensitization. Population-attributable fractions of knee rOA caused by high total IgE and knee sxOA caused by D.farinae-specific sensitization were 9.8% and 15.3%, respectively. Total IgE and D.farinae-specific IgE were significantly associated with OA in knees of Korean adults. High total IgE and D.farinae-specific sensitization were also associated with their OA.

Is the association between knee injury and knee osteoarthritis modified by the presence of general joint hypermobility?

To evaluate whether joint hypermobility modifies the association between knee joint injury and knee osteoarthritis (OA) among adults. 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). 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. In a general adult population, the presence of joint hypermobility may not modify the strong association between knee injury and OA.

The relationships of blood lead level, body mass index, and osteoarthritis in postmenopausal women

ObjectivesIt is unclear whether blood lead level (BLL) is associated with osteoarthritis (OA). The objectives of this study were to address the relationship between BLL and OA and to assess whether degree of obesity, evaluated as body mass index (BMI), mediates BLL-related OA. Study designThis study was performed using data obtained from 884 postmenopausal women (≥55 years old) in the Korea National Health and Nutrition Examination Survey 2010-2012. OA in back, hip, and knee was assessed by radiographic examination (rOA) and radiographic examination and symptoms (sxOA). Multivariable logistic regression analyses were performed to investigate the BLL–OA relationship. Mediation analyses were performed to address the contribution of BMI to BLL-related OA. ResultsOdds ratio (OR) for knee rOA with the highest tertile of BLL was 1.56 [95% confidence interval (CI) = 1.08–2.25] compared with the lowest tertile; there were significant linear trends across tertiles. With adjustments for confounders without BMI, continuous BLL was significantly associated with rOA (OR = 1.89, 95% CI = 1.27–2.80) and sxOA (OR = 1.69, 95% CI = 1.03–2.80) in the knee. After further adjusting for BMI, however, these significances were attenuated or disappeared. BMI was significantly associated with BLL, rOA of knee, and sxOA of knee and back. BMI significantly mediated the BLL–rOA association of the knee (21.1%) and back (46.5%) and the BLL–sxOA association of the knee (22.0%). The population-attributable fraction of rOA caused by BLL greater than the median (2.216 μg/dL) was 8.7% (95% CI = 1.1%–16.2%, P value = 0.024). ConclusionsBLL was significantly associated with knee OA in Korean postmenopausal women. BMI considerably mediated the effects of BLL on knee OA.

The impact of painful knee osteoarthritis on mortality: a community-based cohort study with over 24 years of follow-up

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

Knee and hip OA as risk factors for development of CVD and diabetes in a community based longitudinal study

Purpose: Osteoarthritis (OA) and comorbid conditions such as cardiovascular disease (CVD) and diabetes often occur together. However, the temporal relationship between them is unclear. Therefore, we sought to explore whether OA is associated with the development of CVD and diabetes in a longitudinal cohort. Methods: We carried out a longitudinal analysis using data from baseline assessment and up to two follow-up periods in the Johnston County OA Project. African American and Caucasian men and women aged 45 years or older at study entry who were free of CVD (n=3,560) or diabetes (n=3,740) at baseline were included in analyses. There were two dichotomous outcomes of interest: self-reported CVD or self-reported diabetes. Knee and hip rOA were defined as a Kellgren-Lawrence (KL) grade of ≥2 in either knee or hip at baseline clinical assessment. Severe rOA was defined as a KL grade of ≥3, and symptomatic rOA (sxOA) and severe sxOA were subsets of those with rOA and severe rOA, respectively, who also had symptoms in the same joint. Population-averaged models for non-normal (binomial) repeated measures using generalized estimating equations (GEE) were used to estimate odds ratios (OR) and 95% confidence intervals (CI) and determine associations between knee and hip OA measures and development of CVD and diabetes at a later follow up period. All models were adjusted for age, BMI, sex, race, and education (less than or at least High School [HS]); any self-reported knee or hip injury (depending on the OA outcome) during at least one time-point; enrollment cohort (original or enrichment); and years of follow-up from baseline. Results: At baseline, the mean age was 61.5 years, 64.6% were women, 32.1% African American, 31.9% did not complete high school, and had a mean BMI of 29.7. There were 27.4% of participants who had knee rOA and 17.2% had knee sxOA, while 29.4% had hip rOA and 10.4% had hip sxOA. Adjusted odds of CVD increased for those with knee and hip sxOA (aOR=1.18, 95% CI=1.02-1.37; aOR=1.29, 95% CI=1.09-1.53, respectively) and severe sxOA (aOR=1.24, 95% CI=1.04-1.48; aOR=1.64, 95% CI=1.05-2.56, respectively). Additionally, those with rOA in both hips were at increased odds of developing CVD (aOR=1.27, 95% CI=1.06-1.51). There were no associations observed for knee or hip OA as a factor in development of diabetes. Conclusions: In our large cohort of individuals free of CVD at baseline, we observed that knee and hip OA were independently associated with development of CVD at later time points. Results from this study may suggest that knee and hip OA may lead to development of CVD and therefore may be an important for clinicians to be aware of this increased risk and to provide targeted interventions.TableAdjusted1 ORs and 95% CI for the association between knee and hip rOA and incident CVD and DiabetesCVD2Diabetes2Knee rOA1.02 (0.90–1.17)0.95 (0.80–1.13)Single knee rOA0.90 (0.76–1.07)0.95 (0.76–1.17)Both knees rOA1.14(0.98–1.33)0.96 (0.79–1.17)Symptomatic Knee rOA1.18 (1.02–1.37)0.98 (0.82–1.18)Severe Knee rOA1.06 (0.91–1.23)0.93 (0.77–1.12)Severe Symptomatic Knee rOA1.24 (1.04–1.48)0.94 (0.76–1.18)Hip rOA1.07 (0.94–1.21)0.96 (0.82–1.13)Single Hip rOA0.97 (0.84–1.12)0.93 (0.77–1.12)Both Hips rOA1.27 (1.06–1.51)1.03 (0.82–1.30)Symptomatic Hip rOA1.29 (1.09–1.53)1.06 (0.85–1.32)Severe Hip rOA1.08 (0.80–1.44)0.79 (0.52–1.22)Severe Symptomatic Hip rOA1.64 (1.05–2.56)0.73 (0.34–1.54)1Adjusted for baseline cohort, age, gender, race, education, BMI, joint injury, high blood pressure and CVD/diabetes.2Includes both knee and hip measures as predictors in same model Open table in a new tab 1Adjusted for baseline cohort, age, gender, race, education, BMI, joint injury, high blood pressure and CVD/diabetes. 2Includes both knee and hip measures as predictors in same model

The Effect of Widespread Pain on Knee Pain Worsening, Incident Knee Osteoarthritis (OA), and Incident Knee Pain: The Multicenter OA (MOST) Study.

Whether widespread pain (WSP) affects the risk of developing knee pain or knee osteoarthritis (OA) is unknown and could enhance understanding of pain mechanisms in OA. Subjects from the Multicenter OA (MOST) study, a US National Institutes of Health-funded prospective cohort of older adults with or at risk of knee OA, were characterized regarding WSP, defined as pain above and below the waist on both sides of the body and axially using a standard homunculus, excluding knee pain at 60 months (baseline). Followup occurred 2 years later. We assessed the relation of WSP to odds of knee pain worsening (≥ 2-point increase in the Western Ontario and McMaster Universities Arthritis Index pain subscale) using logistic regression, and to odds of incident radiographic knee OA (ROA; Kellgren-Lawrence arthritis scale ≥ grade 2 of either knee among those free of ROA at baseline) and incident consistent frequent knee pain (CFKP; knee pain on most days during the past month among participants free of knee pain at baseline) in 1 or both knees using multinomial regression adjusting for potential confounders. There were 1752 participants available for analysis [mean age (SD) 67.0 yrs (7.7), body mass index 30.5 kg/m2 (5.9), 59% women]. Baseline presence of WSP was not associated with worsened knee pain (adjusted OR 1.15, 95% CI 0.89-1.48, p = 0.30), ROA (adjusted OR 0.86, 95% CI 0.46-1.63, p = 0.65), or incident CFKP (adjusted OR 1.69, 95% CI 0.96-2.96, p = 0.07). WSP was not significantly associated with worsening knee pain, incident ROA, or CFKP. Development of knee pain and ROA does not appear to be influenced by underlying WSP.

Variations in Hip Shape Are Associated with Radiographic Knee Osteoarthritis: Cross-sectional and Longitudinal Analyses of the Johnston County Osteoarthritis Project

Hip shape by statistical shape modeling (SSM) is associated with hip radiographic osteoarthritis (rOA). We examined associations between hip shape and knee rOA given the biomechanical interrelationships between these joints. Bilateral baseline hip shape assessments [for those with at least 1 hip with a Kellgren-Lawrence arthritis grading scale (KL) 0 or 1] from the Johnston County Osteoarthritis Project were available. Proximal femur shape was defined on baseline pelvis radiographs and evaluated by SSM, producing mean shape and continuous variables representing independent modes of variation (14 modes = 95% of shape variance). Outcomes included prevalent [baseline KL ≥ 2 or total knee replacement (TKR)], incident (baseline KL 0/1 with followup ≥ 2), and progressive knee rOA (KL increase of ≥ 1 or TKR). Limb-based logistic regression models for ipsilateral and contralateral comparisons were adjusted for age, sex, race, body mass index (BMI), and hip rOA, accounting for intraperson correlations. We evaluated 681 hips and 682 knees from 342 individuals (61% women, 83% white, mean age 62 yrs, BMI 29 kg/m(2)). Ninety-nine knees (15%) had prevalent rOA (4 knees with TKR). Lower modes 2 and 3 scores were associated with ipsilateral prevalent knee rOA, and only lower mode 3 scores were associated with contralateral prevalent knee rOA. No statistically significant associations were seen for incident or progressive knee rOA. Variations in hip shape were associated with prevalent, but not incident or progressive, knee rOA in this cohort, and may reflect biomechanical differences between limbs, genetic influences, or common factors related to both hip shape and knee rOA.

Associations Between Pressure–Pain Threshold, Symptoms, and Radiographic Knee and Hip Osteoarthritis

To determine the association between generalized evoked pressure pain sensitivity with distal pressure-pain threshold (PPT) and the presence, severity, or number of involved knee/hip joints with radiographic osteoarthritis (rOA) or related symptoms. Data for these cross-sectional analyses come from the second followup (2008-11) of the Johnston County Osteoarthritis Project (n = 1,602). PPT measurements were averaged over 2 trials from both the left and right trapezius. Outcomes of radiographic knee and hip OA were both defined by a Kellgren/Lawrence score of 2-4 and site-specific symptoms were ascertained at clinical interview. Associations were determined with multiple logistic regression models and two-way interactions were tested at P < 0.05. The sample was 67.2% women and 31.0% African American. Participants' mean ± SD age was 67.9 ± 9.0 years, mean ± SD body mass index was 31.5 ± 7.1 kg/m(2) , mean ± SD Center for Epidemiologic Studies Depression Scale score was 6.5 ± 7.4, and mean ± SD total PPT was 3.6 ± 0.7 kg. Significant associations were found between PPT and self-reported knee/hip symptoms. No significant associations were found between PPT and presence, severity, or number of joints with knee and hip rOA without accompanying symptoms. No significant interactions were found with demographic or clinical characteristics. PPT was significantly associated with self-reported single and multijoint symptoms. In contrast, after adjustment, PPT measured at the trapezius was not associated with asymptomatic knee or hip rOA. As such, PPT may prove to be a useful indicator of rOA pain processing and of why individuals respond favorably and others do not to treatments targeting rOA.

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

BackgroundThe 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).MethodsCross-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.ResultsIn analyses among all individuals with rOA, models which included individual SES measures were observed to show that occupation was significantly associated with WOMAC Function (β =2.91, 95% Confidence Interval (CI) = 0.68-5.14), WOMAC Pain (β =0.93, 95% CI = 0.26-1.59) and WOMAC Total scores (β =4.05, 95% CI = 1.04-7.05), and education was significantly associated with WOMAC Function (β =3.57, 95% CI = 1.25-5.90) and WOMAC Total (β =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 (β =2.83, 95% CI = 0.38-5.28) and WOMAC Total (β =3.48, 95% CI = 0.18-6.78), as well as for the association between occupation and WOMAC Pain (β =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 (β =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 (β =1.35, 95% CI = 0.06-2.64).ConclusionsLower individual and community SES are both associated with worse function and pain among adults with knee rOA.

Development of radiological knee osteoarthritis in patients with knee complaints

ObjectivesIt is currently impossible to identify which patients with knee complaints presenting to the general practitioner will develop knee osteoarthritis (OA) pathology at a later stage. This study examines the...

Whole blood lead levels are associated with radiographic and symptomatic knee osteoarthritis: a cross-sectional analysis in the Johnston County Osteoarthritis Project

IntroductionLead (Pb) is known to affect bone, and recent evidence suggests that it has effects on cartilage as well. As osteoarthritis (OA) is a highly prevalent disease affecting bone and cartilage, we undertook the present analysis to determine whether whole blood Pb levels are associated with radiographic and symptomatic OA (rOA and sxOA, respectively) of the knee.MethodsThe analysis was conducted using cross-sectional data from the Johnston County Osteoarthritis Project, a rural, population-based study, including whole blood Pb levels, bilateral posteroanterior weight-bearing knee radiography and knee symptom data. rOA assessment included joint-based presence (Kellgren-Lawrence (K-L) grade 2 or higher) and severity (none, K-L grade 0 or 1; mild, K-L grade 2; moderate or severe, K-L grade 3 or 4), as well as person-based laterality (unilateral or bilateral). SxOA was deemed present (joint-based) in a knee on the basis of K-L grade 2 or higher with symptoms, with symptoms rated based on severity (0, rOA without symptoms; 1, rOA with mild symptoms; 2, rOA with moderate or severe symptoms) and in person-based analyses was either unilateral or bilateral. Generalized logit or proportional odds regression models were used to examine associations between the knee OA status variables and natural log-transformed blood Pb (ln Pb), continuously and in quartiles, controlling for age, race, sex, body mass index (BMI), smoking and alcohol drinking.ResultsThose individuals with whole blood Pb data (N = 1,669) had a mean (±SD) age of 65.4 (±11.0) years and a mean BMI of 31.2 (±7.1) kg/m2, including 66.6% women and 35.4% African-Americans, with a median blood Pb level of 1.8 μg/dl (range, 0.3 to 42.0 μg/dl). In joint-based analyses, for every 1-U increase in ln Pb, the odds of prevalent knee rOA were 20% higher (aOR, 1.20; 95% CI, 1.01 to 1.44), while the odds of more severe rOA were 26% higher (aOR, 1.26; 95% CI, 1.05 to 1.50, under proportional odds). In person-based analyses, the odds of bilateral rOA were 32% higher for each 1-U increase in ln Pb (aOR, 1.32; 95% CI, 1.03 to 1.70). Similarly for knee sxOA, for each 1-U increase in ln Pb, the odds of having sxOA were 16% higher, the odds of having more severe symptoms were 17% higher and the odds of having bilateral knee symptoms were 25% higher. Similar findings were obtained with regard to ln Pb in quartiles.ConclusionsIncreases in the prevalence and severity measures for both radiographically and symptomatically confirmed knee OA (although statistically significant only for rOA) were observed with increasing levels of blood Pb, suggesting that Pb may be a potentially modifiable environmental risk factor for OA.

Die Prävalenz der radiologischen Gonarthrose in Bezug zu Lebensalter, Geschlecht, Jahrgangskohorte und ethnischer Zugehörigkeit. Eine Metaanalyse

This metaanalysis was performed to evaluate the prevalence of the radiological assessed knee osteoarthritis in the whole community. Medical databases (Medline, EMBASE, Cochrane) were searched for the strategy: ["Osteoarthritis" and "Knee" and "Prevalence"]. The deadline for the search was 31.12.2009. Two investigators (first and senior author) independently made the selection from 17 studies (from a total of 1428) according to the inclusion criteria: a cross-sectional study of the whole community, radiological investigation and definition of knee ROA by an established radiological score. Only studies in English or German language were evaluated. Effect sizes (event rate, odds ratio [OR] and confidence interval [CI]) were calculated by the software "Comprehensive Metaanalysis V2". Study heterogeneity (I2) was determined accordingly to Higgins. The kappa index for interobserver validity was k = 0.948. All studies judged the grade of osteoarthritis according to the Kellgren-Lawrence (KL) score. For calculation of knee ROA KL grades 2+ were estimated only. The total prevalence of knee ROA was 24.3 % (CI 23.4-25.2 %). The whole prevalence in male patients was 24.3 % (CI 23.4-25.2 %); I2 = 59.4 (p = 0.002) and in female patients 32.6 % (CI 31.8-33.4 %); I2 = 49,1 (p < 0.001). Younger male patients (age 50-) had a prevalence of 5.6 (CI 4.5-6.8). In older patients (80+) the male prevalence was 44.5 % (CI 39.6-49.5 %). In this age group female patients had a prevalence of 71.6 % (CI 67.6-75.3 %). The higher prevalence of knee ROA in female patients was significant (OR = 1.8 [1.7-1.9]; I2 = 46.0 [p < 0.001]). The prevalence of knee ROA was higher in male Asians compared with male Caucasians (OR = 1.1, CI 0.9-1.2; p = 0.080) in tendency. This difference was significant in female patients (OR = 2.2; CI 2.0-2.4; p < 0.001). Furthermore another trend was evaluated. Female patients (70-79 years) from the birth-year cohort 1920- had a prevalence of 37.8 % (CI 35.9-39.7)%. In contrast female patients from the birth-year cohort 1920 had a prevalence of 62.8 % (CI 60.8-64.8 %) at 70-79 years. This difference was significant (OR = 2.8; CI 2.5-3.1; p < 0.001). This investigation confirms the high prevalence of knee ROA. The evaluated data may serve as a reference for medical or scientific investigations in the future.

Hazard of Incident and Progressive Knee and Hip Radiographic Osteoarthritis and Chronic Joint Symptoms in Individuals with and without Limb Length Inequality

To examine the hazard of incident and progressive radiographic osteoarthritis (rOA) and chronic joint symptoms at the hip and knee by limb length inequality (LLI) in a large, community-based sample. A longitudinal cohort completed baseline (1991-97) clinical evaluation and identical followup assessment (1999-2003) (median followup time 5.9 yrs, range 3.0-13.1 yrs). LLI was defined at baseline as a measured difference between limbs ≥ 2 cm. The study groups with LLI data comprised 1583 participants with paired (baseline and followup) knee radiographs and 1453 participants with paired hip radiographs. Multivariable Cox regression models were used to examine the hazard of incident and progressive knee and hip rOA and chronic joint symptoms, with adjustment for demographic and clinical factors. The hazard of developing incident knee or hip rOA was 20%-30% higher and of developing progressive knee or hip rOA was 35%-83% higher among participants with LLI, but results were only statistically significant for progressive knee rOA (adjusted hazard ratio = 1.83, 95% CI 1.10-3.05). The hazards of progressive chronic knee symptoms and incident and progressive chronic hip symptoms were 13%-59% higher among participants with LLI, but were not statistically significant. LLI was associated with progressive knee rOA and was nonsignificantly associated with incident knee or hip rOA and progressive hip rOA, progressive chronic knee symptoms, and incident and progressive chronic hip symptoms. Longer studies may strengthen these associations and help determine whether LLI is a risk factor or marker of these outcomes.

Patellar skin surface temperature by thermography reflects knee osteoarthritis severity.

Background:Digital infrared thermal imaging is a means of measuring the heat radiated from the skin surface. Our goal was to develop and assess the reproducibility of serial infrared measurements of the knee and to assess the association of knee temperature by region of interest with radiographic severity of knee Osteoarthritis (rOA).Methods:A total of 30 women (15 Cases with symptomatic knee OA and 15 age-matched Controls without knee pain or knee OA) participated in this study. Infrared imaging was performed with a Meditherm Med2000™ Pro infrared camera. The reproducibility of infrared imaging of the knee was evaluated through determination of intraclass correlation coefficients (ICCs) for temperature measurements from two images performed 6 months apart in Controls whose knee status was not expected to change. The average cutaneous temperature for each of five knee regions of interest was extracted using WinTes software. Knee x-rays were scored for severity of rOA based on the global Kellgren-Lawrence grading scale.Results:The knee infrared thermal imaging procedure used here demonstrated long-term reproducibility with high ICCs (0.50–0.72 for the various regions of interest) in Controls. Cutaneous temperature of the patella (knee cap) yielded a significant correlation with severity of knee rOA (R = 0.594, P = 0.02).Conclusion:The skin temperature of the patellar region correlated with x-ray severity of knee OA. This method of infrared knee imaging is reliable and as an objective measure of a sign of inflammation, temperature, indicates an interrelationship of inflammation and structural knee rOA damage.

No clear association between female hormonal aspects and osteoarthritis of the hand, hip and knee: a systematic review

Incidence of OA rises steeply in women of age >50 years; the climacteric period for women. The simultaneous occurrence of these events suggests an association between OA and changes in female hormonal aspects. This systematic review studies the assumed association between OA and aspects concerning the fertile period (duration, endogenous hormones, age at menarche/menopause) and the menopause [menopausal status, years since menopause (YSM) and surgical menopause]. Medline and EMBASE were searched for articles assessing associations between hand/hip/knee OA and female hormonal aspects. Methodological quality was assessed systematically, and results were summarized in a best-evidence synthesis. Sixteen studies were included in the present study. For most hormonal aspects no association was found. Conflicting evidence was found for an association of age at menarche with Herberden's nodes (HNs) and hand ROA, YSM with knee ROA and ovariectomy with hip OA. An increased risk was seen for low estradiol serum levels in the early follicular phase with incident knee ROA, age at menarche being < or =11 years old with total hip replacement, being post-menopausal and YSM with the presence of HN. A protective effect was seen for age at menopause being > or =52 years with total knee replacement. Evidence level was limited for all. The assumed relationship between the female hormonal aspects and OA was not clearly observed in this review. The relationship is perhaps too complex, or other aspects, yet to be determined, play a role in the increased incidence in women aged >50 years.

Static Knee Alignment Measurements among Caucasians and African Americans: The Johnston County Osteoarthritis Project

To determine if knee alignment measures differ between African Americans and Caucasians without radiographic knee osteoarthritis (rOA). A single knee was randomly selected from 175 participants in the Johnston County Osteoarthritis Project without rOA in either knee. Anatomic axis, condylar, tibial plateau, and condylar plateau angles were measured by 1 radiologist; means were compared and adjusted for age and body mass index (BMI). There were no significant differences in knee alignment measurements between Caucasians and African Americans among men or women. Observed differences in knee rOA occurrence between African Americans and Caucasians are not explained by differences in static knee alignment.

Failure of serum transforming growth factor-beta (TGF-β1) as a biomarker of radiographic osteoarthritis at the knee and hip: a cross-sectional analysis in the Johnston County Osteoarthritis Project

To assess associations between serum transforming growth factor-beta (TGF-beta1) and radiographic knee and hip osteoarthritis (rOA) in African American (AA) and White men and women. Baseline data from 330 participants in the Johnston County Osteoarthritis Project were used in the analysis. Radiographs were scored with the Kellgren-Lawrence scale and rOA defined as grade> or =2. Individual radiographic features (IRFs) were rated 0-3. TGF-beta1 was measured using a sandwich enzyme-linked immunosorbent assay (ELISA). General linear models were used to estimate associations between lnTGF-beta1 and rOA presence, laterality or severity, and IRF presence and severity, adjusting for age, gender, race and body mass index. Interactions by race and gender were considered significant at P<0.1. Mean lnTGF-beta1 levels were higher among AAs compared to Whites, and among women compared to men (P<0.009). Mean lnTGF-beta1 levels were higher in those with knee osteophytes (OST), but this association was not significant after adjustment. There were no other significant differences in mean lnTGF-beta1 levels by presence, laterality, or severity of knee or hip rOA or IRFs. No race or gender interactions were identified, although a borderline significant association between lnTGF-beta1 and knee OST was seen among AAs (P<0.06). Although serum TGF-beta1 varied by race and gender and several rOA variables, there were no independent significant associations with presence, laterality, or severity of knee or hip rOA by K-L grade or IRFs, suggesting that serum TGF-beta1 is unlikely to be useful as a stand-alone biomarker in OA studies. A possible association between TGF-beta1 and OST in AAs cannot be excluded.

Gender difference in symptomatic radiographic knee osteoarthritis in the Knee Clinical Assessment – CAS(K): A prospective study in the general population

BackgroundA recent study of adults aged ≥50 years reporting knee pain found an excess of radiographic knee osteoarthritis (knee ROA) in symptomatic males compared to females. This was independent of age, BMI and other clinical signs and symptoms. Since this finding contradicts many previous studies, our objective was to explore four possible explanations for this gender difference: X-ray views, selection, occupation and non-articular conditions.MethodsA community-based prospective study. 819 adults aged ≥50 years reporting knee pain in the previous 12 months were recruited by postal questionnaires to a research clinic involving plain radiography (weight-bearing posteroanterior semiflexed, supine skyline and lateral views), clinical interview and physical examination. Any knee ROA, ROA severity, tibiofemoral joint osteoarthritis (TJOA) and patellofemoral joint osteoarthritis (PJOA) were defined using all three radiographic views. Occupational class was derived from current or last job title. Proportions of each gender with symptomatic knee ROA were expressed as percentages, stratified by age; differences between genders were expressed as percentage differences with 95% confidence intervals.Results745 symptomatic participants were eligible and had complete X-ray data. Males had a higher occurrence (77%) of any knee ROA than females (61%). In 50–64 year olds, the excess in men was mild knee OA (particularly PJOA); in ≥65 year olds, the excess was both mild and moderate/severe knee OA (particularly combined TJOA/PJOA). This male excess persisted when using the posteroanterior view only (64% vs. 52%). The lowest level of participation in the clinic was symptomatic females aged 65+. Within each occupational class there were more males with symptomatic knee ROA than females. In those aged 50–64 years, non-articular conditions were equally common in both genders although, in those aged 65+, they occurred more frequently in symptomatic females (41%) than males (31%).ConclusionThe excess of knee ROA among symptomatic males in this study seems unlikely to be attributable to the use of comprehensive X-ray views. Although prior occupational exposures and the presence of non-articular conditions cannot be fully excluded, selective non-participation bias seems the most likely explanation. This has implications for future study design.