The relation of physical activity with fatigue in persons with symptomatic knee osteoarthritis and its potential mediation by physical function or depressive symptoms: the most study

Abstract

Purpose: Depressive symptoms and impaired physical function are determinants of fatigue in symptomatic knee osteoarthritis (OA) and these factors are related to physical activity. However, potential causal pathways underlying the relationship between physical activity and fatigue are poorly understood in persons with symptomatic knee OA. We examined the association of physical activity with fatigue and quantified the extent to which the association of physical activity and fatigue could be mediated by physical function or depressive symptoms. We hypothesised that depressive symptoms or physical function would mediate the association between baseline physical activity and fatigue at follow-up in the overall population. We also hypothesised that in people with high levels of baseline fatigue, increased physical activity would be associated with decreased fatigue at follow-up. Methods: This longitudinal study included physical activity at baseline (60-month exam), fatigue at 2-year follow-up (84-month exam), depressive symptoms and physical function at baseline and follow-up from the Multicenter Osteoarthritis Study (MOST) cohort. MOST participants were classified as having symptomatic knee OA based on both the presence of radiographic whole knee OA evidence (either in tibiofemoral or patellofemoral joints) and frequent knee pain at either of the two interviews at baseline for this analysis. Exposure was defined as physical activity (i.e., average steps/day) measures by an accelerometer worn for 7 days. Outcome was defined as fatigue measurement using 0-10 visual analogue scale in the past seven days at follow-up. We defined apriori fatigue subgroup using baseline fatigue status cut-off points of no/low fatigue (<4 on 0-10 VAS) and high fatigue (>4 on 0-10 VAS) based on prior research. Potential mediators included physical function measured by gait speed using the 20-meter walk test and depressive symptoms assessed by the Center for Epidemiological Studies Depression Scale (CES-D) at follow-up. Potential confounders included baseline fatigue, gait speed, depressive symptoms, age, sex, body mass index (BMI) and study sites (University of Alabama or University of Iowa). Mediation analyses were performed with fatigue as a continuous dependent outcome and used bootstrapping method to calculate the bias corrected confidence intervals around the mediated (i.e., indirect) and direct effects with PROCESS in SPSS 23. Further, subgroup analysis of no/low baseline fatigue (<4 on 0-10 VAS) and high fatigue (>4 on 0-10 VAS) was performed. Results: Of the 591 participants with symptomatic knee OA and physical activity data at baseline, only 484 participants with complete fatigue datasets at baseline and follow-up were included in this analysis. The mean age of study participants was 67.3+7.91 years, 60% were women, and majority were white (86%). Average baseline steps/day was 8,044+3,034; baseline and follow-up fatigue scores were 3.54+2.36 and 3.43+2.29. We found no total effect of physical activity on fatigue at follow-up and also found no significant mediation by gait speed (coefficient [coef.] = -0.0057; CI = -0.0179, 0.0011) or depressive symptoms (coef. = 0.0087; -0.0087, 0.0279). In the subgroup analysis, in those with high baseline fatigue, we found total and direct associations between physical activity and fatigue at follow-up (coef. = -0.1101; -0.2153, -0.0048; coef. = -0.1072; -0.2123, -0.0022), where greater physical activity was associated with reduced fatigue if baseline fatigue was high, although no mediation effects with depressive symptoms or gait speed were found for this group. In the group with no/low baseline fatigue, we found no total and direct effect of physical activity on fatigue at follow-up and found no mediation effect with depressive symptoms (coef. = -0.0102; -0.0307, 0.0098); however, gait speed weakly mediated physical activity and fatigue relations (coef. = -0.0129; -0.0326, -0.0004). Conclusions: Our result suggested that neither depressive symptoms nor physical function mediated the effect of physical activity on fatigue in people with symptomatic knee OA. However, in the subgroup with high baseline fatigue, greater physical activity led to reduced fatigue at follow-up. In contrast, for those with no/low baseline fatigue, gait speed mediated the relationship between physical activity and fatigue. In sum, physical function may contribute to the effect of physical activity on fatigue in individuals with no/low pre-existing fatigue while greater physical activity may reduce fatigue over time in individuals with high pre-existing fatigue. In individuals with significant pre-existing fatigue, increasing their physical activity levels may decrease fatigue levels.