Gait characteristics of patients with knee osteoarthritis.

The knee kinematics and kinetics of 139 patients (47 males and 92 females) with Grade II knee osteoarthritis (OA) were measured during level walking, stair ascent and stair descent. There was no significant difference in knee motion between the patients and normal subjects. The patients with knee OA had a significantly reduced internal knee extensor moment compared to normal subjects. This difference reflects the patient's compensation to reduce the knee joint loading. Further, subjects with OA and a higher body mass index have a lower knee extensor moment. The female subjects had significantly greater knee flexion and a greater knee extensor moment. This gender difference may partially explain the increased prevalence of OA in females. Most tests of OA treatments are assessed by criteria that do not reflect functional activities. This study demonstrates that objective gait analysis can be used to document gait adaptations used by patients with knee OA.     

Association of chemerin levels in synovial fluid with the severity of knee osteoarthritis

Context: Chemerin has been implicated to be correlated with inflammation.

Objective: This study aims to determine the association of chemerin levels in serum and synovial fluid (SF) with the disease severity of patients with knee Osteoarthritis (OA).

Methods: 124 patients with knee OA and 76 healthy controls were enrolled in this study.

Results: Chemerin levels in serum were significant higher with regard to paired SF. Chemerin levles in SF of knee OA patients were correlated with disease severity evaluated by KL grading criteria.

Conclusion: Chemerin levels may be involved in the pathophysiology of the development and progression of OA.     

Changes in knee joint muscle activation patterns during walking associated with increased structural severity in knee osteoarthritis

PurposeTo determine whether alterations in knee joint muscle activation patterns during gait were related to structural severity determined by Kellgren–Lawrence (KL) radiographic grades, for those with a moderate knee OA classification.ScopeEighty-two individuals with knee OA, classified as moderate using a functional and clinical criterion were stratified on KL-grade (KL II, KL III and KL IV). Thirty-five asymptomatic individuals were matched for age and walking velocity. Lower limb motion and surface electromyograms from rectus femoris plus lateral and medial sites for the gastrocnemii, vastii and hamstring muscles were recorded during self-selected walking. Gait velocity and characteristics from sagittal plane knee angular displacement waveforms were calculated. Principal component analysis extracted amplitude and temporal features from electromyographic waveform. Analysis of variance models tested for main effects (group, muscle) and interactions (α = 0.05) for these features. No differences in anthropometrics, velocity, knee muscle strength and symptoms were found among the three OA groups (p > 0.05). Specific features from medial gastrocnemius, lateral hamstring and quadriceps amplitude and temporal patterns were significantly different among OA groups (p < 0.05).ConclusionsSystematic alterations in specific knee joint muscle activation patterns were associated with increasing structural severity based on KL-grades whereas other alterations were associated with the presence of OA.     

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

Introduction  

Lead (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.     

Quadriceps neuromuscular function and self-reported functional ability in knee osteoarthritis

The purposes of this study were to determine 1) the relationships of self-reported function scores in patients with knee osteoarthritis (OA) to both maximal isometric torque and to isotonic power at a variety of loads, and 2) the degree to which muscle volume (MV) or voluntary activation (VA) are associated with torque and power measures in this population. Isometric maximal voluntary contraction (MVC) torque and isotonic power [performed at loads corresponding to 10, 20, 30, 40, and 50% MVC, and a minimal load ("Zero Load")] were measured in 40 participants with knee OA. Functional ability was measured with the Western Ontario and McMaster Osteoarthritis Index (WOMAC) function subscale. MV was determined with magnetic resonance imaging, and VA was measured with the interpolated twitch technique. In general, power measured at lower loads (Zero Load and 10-30% MVC, r(2) = 0.21-0.28, P < 0.05) predicted a greater proportion of the variance in function than MVC torque (r(2) = 0.18, P < 0.05), with power measured at Zero Load showing the strongest association (r(2) = 0. 28, P < 0.05). MV was the strongest predictor of MVC torque and power measures in multiple regression models (r(2) = 0.42-0.72). VA explained only 6% of the variance in MVC torque and was not significantly associated with power at any load (P > 0.05). Quadriceps MVC torque and power are associated with self-reported function in knee OA, but muscle power at lower loads is more predictive of function than MVC torque. The variance in MVC torque and power between participants is due predominantly to differences in MV and has little to do with deficits in VA.     

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

Lead (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. The 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. Those 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. Increases 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.     

Strain-related differences in antibody-mediated changes in gene expression are associated with differences in capsule and location of binding

We recently established that antibody (Ab)-binding can induce gene expression changes in a serotype A strain (H99) of the pathogenic yeast, Cryptococcus neoformans. That study showed that monoclonal antibodies (mAbs) differing in epitope specificity and protective efficacy elicited differences in gene expression. Because many mAbs bind to serotypes A and D strains differently, we now investigate the binding of one mAb to two strains representing these serotypes. Cells of the serotype A strain H99 and the serotype D strain 24067 were incubated with near saturating concentrations of the IgG1 capsule-binding mAb 18B7 or MOPC, an irrelevant mAb matched control. Comparative immunofluorescence analysis of mAb 18B7 binding revealed that it bound closer to the cell wall in H99 than 24067, where it was associated with decreased or increased cell diameter, respectively. A comparison of encapsulated cell compressibility showed that strain 24067 was more compressible than that of strain H99. RNA was extracted and used for gene expression analysis using the C. neoformans JEC21 genomic microarray. After 1h incubation with mAb 18B7, there were just 2 gene expression changes observed with strain 24067 or strain JEC21, unlike the 43 seen with strain H99. After 4h incubation with mAb 18B7, there were 14 and 140 gene expression changes observed with strain 24067 and JEC21, respectively. Thus, C. neoformans strains differ both in the response and the time of response to mAb binding and these differences may reflect differences in the location of Ab binding, Ab-mediated changes in cell diameter and compressibility of the capsular polysaccharide.     

Sagittal plane hip motion reversals during walking are associated with disease severity and poorer function in subjects with hip osteoarthritis

A midstance reversal of sagittal plane hip motion during walking, or motion discontinuity (MD), has previously been observed in subjects with endstage hip osteoarthritis (OA) and in patients with femoroacetabular impingement. The goal of the present study was to evaluate whether this gait pattern is a marker of OA presence or radiographic severity by analyzing a large IRB approved motion analysis data repository. We also hypothesized that subjects with the MD would show more substantial gait impairments than those with normal hip motion. We identified 150 subjects with symptomatic unilateral hip OA and Kellgren-Lawrence OA severity data on file, and a control group of 159 asymptomatic subjects whose ages fell within 2 standard deviations of the mean OA group age. From the gait data, the MD was defined as a reversal in the slope of the hip flexion angle curve during midstance. Logistic regressions and general linear models were used to test the association between the MD and OA presence, OA severity and, other gait variables. 53% of OA subjects compared to 7.5% of controls had the MD (p<0.001); occurrence of the MD was associated with OA severity (p=0.009). Within the OA subject group, subjects with the MD had reduced dynamic range of motion, peak, extension, and internal rotation moments compared to those who did not (MANCOVA p ≤ 0.042) after controlling for walking speed. We concluded that sagittal plane motion reversals are indeed associated with OA presence and severity, and with more severe gait abnormalities in subjects with hip OA.     

Elevated serum leptin levels are associated with low vitamin D,sarcopenic obesity,poor muscle strength,and physical performance in knee osteoarthritis*

Context: The associations between serum leptin, vitamin D status, sarcopenic obesity, muscle strength and physical performance in osteoarthritis (OA) remain uncertain.

Objective: To analyse the relationships between serum leptin, vitamin D status, muscle strength and physical performance in OA patients.

Methods: A total of 208 knee OA patients were enrolled. Serum leptin, vitamin D, muscle strength and physical performance were evaluated.

Results: OA patients with sarcopenic obesity had significantly higher serum leptin levels than those with non-sarcopenic obesity. In addition, knee OA patients with sarcopenic obesity displayed low grip strength and poor physical performance. Furthermore, high serum leptin was negatively associated with vitamin D and physical performance.

Conclusions: Serum leptin levels were correlated with low vitamin D, reduced muscle strength and functional impairment, suggesting that serum leptin might serve as a biomarker reflecting physical performance in OA patients.     

Mechanical contributors to sex differences in idiopathic knee osteoarthritis

The occurrence of knee osteoarthritis (OA) increases with age and is more common in women compared with men, especially after the age of 50 years. Recent work suggests that contact stress in the knee cartilage is a significant predictor of the risk for developing knee OA. Significant gaps in knowledge remain, however, as to how changes in musculoskeletal traits disturb the normal mechanical environment of the knee and contribute to sex differences in the initiation and progression of idiopathic knee OA. To illustrate this knowledge deficit, we summarize what is known about the influence of limb alignment, muscle function, and obesity on sex differences in knee OA. Observational data suggest that limb alignment can predict the development of radiographic signs of knee OA, potentially due to increased stresses and strains within the joint. However, these data do not indicate how limb alignment could contribute to sex differences in either the development or worsening of knee OA. Similarly, the strength of the knee extensor muscles is compromised in women who develop radiographic and symptomatic signs of knee OA, but the extent to which the decline in muscle function precedes the development of the disease is uncertain. Even less is known about how changes in muscle function might contribute to the worsening of knee OA. Conversely, obesity is a stronger predictor of developing knee OA symptoms in women than in men. The influence of obesity on developing knee OA symptoms is not associated with deviation in limb alignment, but BMI predicts the worsening of the symptoms only in individuals with neutral and valgus (knock-kneed) knees. It is more likely, however, that obesity modulates OA through a combination of systemic effects, particularly an increase in inflammatory cytokines, and mechanical factors within the joint. The absence of strong associations of these surrogate measures of the mechanical environment in the knee joint with sex differences in the development and progression of knee OA suggests that a more multifactorial and integrative approach in the study of this disease is needed. We identify gaps in knowledge related to mechanical influences on the sex differences in knee OA.     

Climate is associated with prevalence and severity of radiographic hand osteoarthritis

The aim of this study was to evaluate whether geographic location and climatic factors are associated with prevalence and severity of radiographic hand osteoarthritis (OA) in several samples of the same ethnicity.The total sample included 2079 ethnic Russians (900 males and 1179 females), belonging to 7 samples from different geographic locations in the former USSR. Places of residence were characterized by latitude, longitude, altitude and climatic parameters (mean temperatures, humidity, and daylight duration of January and July). Radiographs of the left hand were obtained from each individual. Osteoarthritis (OA) was evaluated in 14 hand joints according to Kellgren and Lawrence's grading system. OA was characterized by the presence of at least one affected joint and its severity by the number of affected joints (NAJ). Statistical analysis included prevalence estimation, polynomial and logistic regressions, ANOVA and correlation analyses.Prevalence of hand OA and NAJ were significantly associated with latitude and altitude and with most climatic parameters (except the inter-seasonal temperature amplitude and the mean atmospheric pressure of January and July). The highest correlations of hand OA prevalence were found with altitude (r = 0.29, p < 0.001), annual precipitation (r = −0.26, p < 0.001) and the mean temperatures of July (r = 0.26, p < 0.001). The highest correlations of NAJ were found with altitude (r = 0.51, p < 0.001), mean humidity in January (r = −0.44, p < 0.001) and the mean day duration in January (r = 0.0.37, p < 0.001).The present study demonstrates that the differences in prevalence and severity of radiographic hand OA among Russian samples are most likely dependent on climatic conditions in the place of residence.     

Fundamental subchondral bone changes in spontaneous knee osteoarthritis

Osteoarthritis has an unknown aetiology, and tissue samples from early stage human osteoarthritis tissue cannot be reliably obtained. Therefore understanding the development of OA relies on using animal models: such as the spontaneous changes seen in the Dunkin-Hartley guinea pig strain, which are biochemically, histologically and radiologically similar to human OA. We investigated the role of bone change in early OA development using the non-OA developing Bristol strain-2 as control from 3 to 36 weeks by standard microfocal X-ray imaging and histological techniques. The patella, tibia and femur epiphyseal region and immediate subchondral area were analysed for bone density at all ages. We found that both radiological and histological osteoarthritis scores increased progressively for the Dunkin-Hartley, but not for the BS2 demonstrating its value as a control. The Dunkin-Hartley had a higher bone density and greater subchondral bone thickness from 24 weeks of age. We conclude that prior to any gross osteoarthritis pathology the Dunkin-Hartley are undergoing subchondral bone remodelling, thus demonstrating the fundamental role of early bone remodelling in the development of osteoarthritis.     

Sex differences in physiological cardiac hypertrophy are associated with exercise-mediated changes in energy substrate availability

Exercise-induced cardiac hypertrophy has been recently identified to be regulated in a sex-specific manner. In parallel, women exhibit enhanced exercise-mediated lipolysis compared with men, which might be linked to cardiac responses. The aim of the present study was to assess if previously reported sex-dependent differences in the cardiac hypertrophic response during exercise are associated with differences in cardiac energy substrate availability/utilization. Female and male C57BL/6J mice were challenged with active treadmill running for 1.5 h/day (0.25 m/s) over 4 wk. Mice underwent cardiac and metabolic phenotyping including echocardiography, small-animal PET, peri-exercise indirect calorimetry, and analysis of adipose tissue (AT) lipolysis and cardiac gene expression. Female mice exhibited increased cardiac hypertrophic responses to exercise compared with male mice, measured by echocardiography [percent increase in left ventricular mass (LVM): female: 22.2 ± 0.8%, male: 9.0 ± 0.2%; P < 0.05]. This was associated with increased plasma free fatty acid (FFA) levels and augmented AT lipolysis in female mice after training, whereas FFA levels from male mice decreased. The respiratory quotient during exercise was significantly lower in female mice indicative for preferential utilization of fatty acids. In parallel, myocardial glucose uptake was reduced in female mice after exercise, analyzed by PET {injection dose (ID)/LVM [%ID/g]: 36.8 ± 3.5 female sedentary vs. 28.3 ± 4.3 female training; P < 0.05}, whereas cardiac glucose uptake was unaltered after exercise in male counterparts. Cardiac genes involved in fatty acid uptake/oxidation in females were increased compared with male mice. Collectively, our data demonstrate that sex differences in exercise-induced cardiac hypertrophy are associated with changes in cardiac substrate availability and utilization.     

Extracellular vesicle features are associated with COVID-19 severity

COVID-19 is heterogeneous; therefore, it is crucial to identify early biomarkers for adverse outcomes. Extracellular vesicles (EV) are involved in the pathophysiology of COVID-19 and have both negative and positive effects. The objective of this study was to identify the potential role of EV in the prognostic stratification of COVID-19 patients. A total of 146 patients with severe or critical COVID-19 were enrolled. Demographic and comorbidity characteristics were collected, together with routine haematology, blood chemistry and lymphocyte subpopulation data. Flow cytometric characterization of the dimensional and antigenic properties of COVID-19 patients' plasma EVs was conducted. Elastic net logistic regression with cross-validation was employed to identify the best model for classifying critically ill patients. Features of smaller EVs (i.e. the fraction of EVs smaller than 200 nm expressing either cluster of differentiation [CD] 31, CD 140b or CD 42b), albuminemia and the percentage of monocytes expressing human leukocyte antigen DR (HLA-DR) were associated with a better outcome. Conversely, the proportion of larger EVs expressing N-cadherin, CD 34, CD 56, CD31 or CD 45, interleukin 6, red cell width distribution (RDW), N-terminal pro-brain natriuretic peptide (NT-proBNP), age, procalcitonin, Charlson Comorbidity Index and pro-adrenomedullin were associated with disease severity. Therefore, the simultaneous assessment of EV dimensions and their antigenic properties complements laboratory workup and helps in patient stratification.     

Addressing the gaps: sex differences in osteoarthritis of the knee

An introduction to the accompanying three papers.