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Objective: Arthritic cartilage is primed for mechanical damage. Joint biochemical markers (JBM) could provide insight into the impact of mechanical stimulation on joint tissue turnover in osteoarthritis (OA) of potential use in clinical OA research and practice. However, existing studies of the acute impact of physical activities (PA) on JBM often contain risks of substantial bias. The purpose of this scoping review was to critically review and discuss existing reports of acute joint tissue turnover as reflected in JBM in relation to PA in OA and propose considerations for future research. Design: We searched PubMed, Embase, and Scopus and reference lists for original reports on the acute impact of PA on JBM in human OA. Identified studies were reviewed by two reviewers forming the basis for the discussion of methodology. Results: Search in databases resulted in nine eligible papers after full-text evaluation. Two additional papers were identified through reference lists, resulting in 11 papers included in this review. Ten investigated knee OA and one investigated hand OA. Biomarkers described were related to turnover of type II collagen, aggrecan, and cartilage oligomeric matrix protein. Conclusions: The literature is dominated by small, simplistic studies, but suggests that mechanical stimulation can induce acute changes in joint biomarkers. In order to diminish the existing bias in future studies, it is important to recognize methodological considerations e.g. patient and biomarker selection as well as peri-interventional control. Common potential sources of bias include the acute shift in plasma volume due to cardiovascular stress and postural changes.

Introduction: Plasma volume (PV) changes in response to physical activity, possibly as a consequence of adrenergic activation. We estimated changes in PV in response to common exercise modalities; cycling and running as well as adrenaline infusion and control at rest.Methods: On separate days, forty circulatory healthy subjects [aged 60 years (range: 42–75)] with knee osteoarthritis underwent moderate-high intensity cycling, running, and intravenous adrenaline infusion to mimic the circulatory response to exercise. Blood samples were obtained from peripheral veins taken at several pre-defined time points before, during, and after the interventions. PV changes were estimated using venous hemoglobin and the derived hematocrit. The temporal associations between PV and selected biomarkers were explored.Results: Changes in PV were observed during all four interventions, and the response to cycling and running was similar. Compared to rest, PV decreased by -14.3% (95% CI: -10.0 to -18.7) after cycling, -13.9% (95% CI: -10.9 to -17.0) after running, and -7.8% (95% CI: -4.2 to -11.5) after adrenaline infusion.Conclusion: PV decreased in response to moderate-high intensity running and cycling. Adrenaline infusion mimicked the PV change observed during exercise, suggesting a separate influence of autonomic control on blood volume homeostasis. In perspective, a temporal association between PV and biomarker dynamics suggests that consideration of PV changes could be relevant when reporting plasma/serum constituents measured during exercise, but more research is needed to confirm this.

Abstract. Introduction:. Visual Analogue Scale (VAS) and the pain subscale of the Western Ontario and McMaster Universities Arthritis Index (WOMAC) are commonly used measuring tools of osteoarthritis (OA) pain. Objectives:. The objective of this cross-sectional study was to explore the associations between single-question VAS pain and the weight-bearing and non–weight-bearing domains of WOMAC pain. Methods:. Data from 2093 patients with OA participating in 2 phase 3 clinical trials were included for post hoc analyses. Univariate Pearson correlations and comparison of r values were made using z statistics obtained using the Fisher r to z test for all items of the VAS pain scale, the WOMAC pain subscale, the weight-bearing and non–weight-bearing constructs of WOMAC pain subscale, and by subgroups of WOMAC pain quintiles and Kellgren–Lawrence grades. Results:. The correlations between VAS pain and WOMAC pain were significant (r = 0.67, P < 0.001) with a slope of 0.57 (95% confidence interval [CI]: 0.54–0.61). A similar correlation was found for weight-bearing pain (r = 0.68, P < 0.001, slope: 0.62 (95% CI: 0.59–0.65) but significantly lower for non–weight-bearing pain (r = 0.55, P < 0.001, slope: 0.49 (95% CI: 0.46–0.52). The degree of disagreement between the 2 instruments seemed to be lesser in the extreme ends of the scales, and the observed association between Kellgren–Lawrence grade and disagreement between VAS and WOMAC was driven by non–weight-bearing pain. Conclusion:. In conclusion, VAS pain and WOMAC pain subscale correlation was found to be moderate and the VAS pain scale correlated more accurately with the WOMAC pain weight-bearing questions. This constitutes novel insight into patient with OA pain reporting.

Summary: Objective: To propose a standardized model for exercise-induced cartilage turnover and investigate residual levels and dynamics of biomarker serum ARGS (sARGS) in primary osteoarthritis (OA) patients and a supportive group of young healthy subjects. Method: The trial is a randomized, cross-over, exploratory study with interventions of exercise and inactivity. 20 subjects with knee OA, as well as 20 young healthy subjects (mean age 25.7 years (range; 19–30), 50% male), underwent cycling, running and resting interventions on separate days one week apart. Blood samples were taken at baseline, immediately, 1, 2, 3 and 24 h after activity start. sARGS was measured by sandwich ELISA. Results: Intraclass correlation between visits were 0.97 and 0.77 for the OA and healthy group, respectively. An acute drop in sARGS in response to high-intensity exercise was observed in both groups. Minute acute sARGS increase was observed in OA subjects in response to moderate intensity running and cycling, which normalized within 24 h. In healthy subjects an acute drop in sARGS was seen immediately after running, but not cycling, and no other changes were observed. A negative correlation between baseline Kellgren-Lawrence (KL) grade and baseline sARGS (r = −0.69, p = 0.002) in OA was found. A negative correlation between age and sARGS was found in healthy subjects (r = −0.67, p =

Abstract Background Change in forced expiratory volume in one second (FEV1) is important for defining severity of chronic obstructive pulmonary disease (COPD). Serological neoepitope markers of collagen turnover may predict rate of change in FEV1. Methods One thousand COPD subjects from the observational, multicentre, three-year ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) study (NCT00292552, trial registration in February 2006) were included. Matrix metalloproteinase (MMP)-generated fragments of collagen type I, and type VI (C1M and C6M) were assessed in month six serum samples. A random-coefficient model with both a random intercept and a random slope was used to test the ability of the markers to predict post-dose bronchodilator FEV1 (PD-FEV1) change over two years adjusting for sex, age, BMI, smoking, bronchodilator reversibility, prior exacerbations, emphysema and chronic bronchitis status at baseline. Results Annual change of PD-FEV1 was estimated from a linear model for the two-year study period. Serum C1M and C6M were independent predictors of lung function change (p = 0.007/0.005). Smoking, bronchodilator reversibility, plasma hsCRP and emphysema were also significant predictors. The effect estimate between annual change in PD-FEV1 per one standard deviation (1SD) increase of C1M and C6M was +10.4 mL/yr. and +8.6 mL/yr. C1M, and C6M, had a significant association with baseline FEV1. Conclusion We demonstrated that markers of tissue turnover were significantly associated with lung function change. These markers may function as prognostic biomarkers and possibly as efficacy biomarkers in clinical trials focusing on lung function change in COPD. Trial registration NCT00292552 , Retrospectively registered, trial registration in February 2006.