Is the association between physical activity and fatigue mediated by physical function or depressive symptoms in symptomatic knee osteoarthritis? The Multicenter Osteoarthritis Study.

Objectives: To examine whether physical activity (PA) was associated with fatigue, and quantify the extent of potential mediation through depressive symptoms or physical function (PF) on the relationship between PA and fatigue in symptomatic knee osteoarthritis (KOA).Method: This longitudinal study used data from the Multicenter Osteoarthritis Study (n = 484), comprising subjects aged ≥ 50 years. Baseline PA was quantified via an ankle-worn accelerometer. The outcome was fatigue, measured using a 0-10 rating scale at 2 year follow-up. Mediators included gait speed as a measure of PF and depressive symptoms at 2 year follow-up. Mediation analysis was carried out after adjustment for baseline confounders. Stratified analysis by baseline fatigue status [no/low (< 4) and high (≥ 4) fatigue] was performed.Results: A significant direct association was found between PA and fatigue at 2 years [unstandardized coefficient (B) = -0.054; 95% confidence interval (CI) -0.107, -0.002, p = 0.041]. The PA-fatigue relationship was not mediated by gait speed (B = -0.006; 95% CI -0.018, 0.001) or depressive symptoms (B = 0.009; 95% CI 0.009, 0.028). In the subgroup with high baseline fatigue, direct associations were found between PA and fatigue (gait speed model:, B = -0.107; 95% CI -0.212, -0.002, p = 0.046; depressive symptoms model: B = -0.110; 95% CI -0.120, -0.020, p = 0.017); but in the no/low baseline fatigue group, no significant association was found between PA and fatigue.Conclusion: In the symptomatic KOA population, higher baseline PA was directly associated with reduced fatigue 2 years later, especially in those with high baseline fatigue. However, this relationship was not mediated by depressive symptoms or PF.

The association between walking speed from short- and standard-distance tests with the risk of all-cause mortality among adults with radiographic knee osteoarthritis: data from three large United States cohort studies.

OBJECTIVE: Adults with radiographic knee OA (rKOA) are at increased risk of mortality and walking difficulty may modify this relation. Little is known about specific aspects of walking difficulty that increase mortality risk. We investigated the association of walking speed (objective measure of walking difficulty) with mortality and examined the threshold that best discriminated this risk in adults with rKOA. METHODS: Participants with rKOA from the Johnston County Osteoarthritis Project (JoCoOA, longitudinal population-based cohort), Osteoarthritis Initiative and Multicenter Osteoarthritis Study (OAI and MOST, cohorts of individuals with or at high risk of knee OA) were included. Baseline speed was measured via 2.4-meter (m) walk test (short-distance) in JoCoOA and 20-m walk test (standard-distance) in OAI and MOST. To examine the association of walking speed with mortality risk over 9 years, hazard ratios (HR) and 95% confidence intervals (CI) were calculated from Cox regression models adjusted for potential confounders. A Maximal Likelihood Ratio Chi-square Approach was utilized to identify an optimal threshold of walking speed predictive of mortality. RESULTS: Deaths after 9 years of follow-up occurred in 23.3% (290/1244) of JoCoOA and 5.9% (249/4215) of OAI + MOST. Walking 0.2 m/s slower during short- and standard-distance walk tests was associated with 23% (aHR [95%CI]; 1.23 [1.10, 1.39]) and 25% (1.25 [1.09, 1.43]) higher mortality risk, respectively. Walking <0.5 m/s on short-distance and <1.2 m/s standard-distance walk tests, best discriminated those with and without mortality risk. CONCLUSION: Slower walking speed measured via short- and standard-distance walk tests was associated with increased mortality risk in adults with rKOA.

Examining sex differences in knee pain: the multicenter osteoarthritis study.

OBJECTIVE: To determine whether women experience greater knee pain severity than men at equivalent levels of radiographic knee osteoarthritis (OA). DESIGN AND METHODS: A cross-sectional analysis of 2712 individuals (60% women) without knee replacement or a recent steroid injection. Sex differences in pain severity at each Kellgren-Lawrence (KL) grade were assessed by knee using visual analog scale (VAS) scale and Western Ontario and McMaster Universities Arthritis Index (WOMAC) with and without adjustment for age, analgesic use, Body mass index (BMI), clinic site, comorbid conditions, depression score, education, race, and widespread pain (WSP) using generalized estimating equations. Effect sizes (Cohen's d) were also calculated. Analyses were repeated in those with and without patellofemoral OA (PFOA). RESULTS: Women reported higher VAS pain at all KL grades in unadjusted analyses (d = 0.21-0.31, P < 0.0001-0.0038) and in analyses adjusted for all covariates except WSP (d = 0.16-0.22, P < 0.0001-0.0472). Pain severity differences further decreased with adjustment for WSP (d = 0.10-0.18) and were significant for KL grade ≤2 (P = 0.0015) and 2 (P = 0.0200). Presence compared with absence of WSP was associated with significantly greater knee pain at all KL grades (d = 0.32-0.52, P < 0.0001-0.0008). In knees with PFOA, VAS pain severity sex differences were greater at each KL grade (d = 0.45-0.62, P = 0.0006-0.0030) and remained significant for all KL grades in adjusted analyses (d = 0.31-0.57, P = 0.0013-0.0361). Results using WOMAC were similar. CONCLUSIONS: Women reported greater knee pain than men regardless of KL grade, though effect sizes were generally small. These differences increased in the presence of PFOA. The strong contribution of WSP to sex differences in knee pain suggests that central sensitivity plays a role in these differences.

The relationship between quadriceps muscle weakness and worsening of knee pain in the MOST cohort: a 5-year longitudinal study.

OBJECTIVE: To determine whether quadriceps weakness is associated with elevated risk of worsening knee pain over 5 years. METHODS: The Multicenter Osteoarthritis Study (MOST) is a longitudinal study of 50-79-year-old adults with knee osteoarthritis (OA) or known risk factors for knee OA. The predictor variable was baseline isokinetic quadriceps strength. Covariates included baseline body mass index (BMI), physical activity level, and history of knee surgery. The outcome was worsening pain reported on the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index pain subscale or knee replacement surgery between baseline and 5-year follow-up. Analyses were knee-based and used generalized estimating equations, stratified by sex to assess whether the lowest compared with the highest tertile of baseline quadriceps strength was associated with an increased risk of worsening knee pain at 5-year follow-up, controlling for age, BMI, history of knee surgery, and physical activity level as well as correlation between knees within participants. RESULTS: Analyses of worsening knee pain included 4,648 knees from 2,404 participants (61% female). Men with lower quadriceps strength did not have a higher risk of worsening knee pain (RR {95% CI} = 1.01 {0.78-1.32}, P = 0.9183). However, women in the lowest compared with the highest strength tertile had a 28% increased risk of worsening knee pain (RR {95% CI} = 1.28 {1.08-1.52}, P = 0.0052). CONCLUSION: Quadriceps weakness was associated with an increased risk of worsening of knee pain over 5 years in women, but not in men.

Psychological factors predict local and referred experimental muscle pain: a cluster analysis in healthy adults.

BACKGROUND: Recent studies suggest an underlying three- or four-factor structure explains the conceptual overlap and distinctiveness of several negative emotionality and pain-related constructs. However, the validity of these latent factors for predicting pain has not been examined. METHODS: A cohort of 189 (99 female, 90 male) healthy volunteers completed eight self-report negative emotionality and pain-related measures (Eysenck Personality Questionnaire - Revised, Positive and Negative Affect Schedule, State-Trait Anxiety Inventory, Pain Catastrophizing Scale, Fear of Pain Questionnaire; Somatosensory Amplification Scale, Anxiety Sensitivity Index and Whiteley Index). Using principal axis factoring, three primary latent factors were extracted: general distress, catastrophic thinking and pain-related fear. Using these factors, individuals clustered into three subgroups of high, moderate and low negative emotionality responses. Experimental pain was induced via intramuscular acidic infusion into the anterior tibialis muscle, producing local (infusion site) and/or referred (anterior ankle) pain and hyperalgesia. RESULTS: Pain outcomes differed between clusters (multivariate analysis of variance and multinomial regression), with individuals in the highest negative emotionality cluster reporting the greatest local pain (p = 0.05), mechanical hyperalgesia (pressure pain thresholds; p = 0.009) and greater odds (2.21 odds ratio) of experiencing referred pain when compared to the lowest negative emotionality cluster. CONCLUSION: Our results provide support for three latent psychological factors explaining the majority of the variance between several pain-related psychological measures, and that individuals in the high negative emotionality subgroup are at increased risk for (1) acute local muscle pain; (2) local hyperalgesia; and (3) referred pain using a standardized nociceptive input.

Association between patella alta and the prevalence and worsening of structural features of patellofemoral joint osteoarthritis: the multicenter osteoarthritis study.

OBJECTIVE: To examine the relationship between patella alta and the prevalence and worsening at followup of structural features of patellofemoral joint (PFJ) osteoarthritis (OA) on magnetic resonance imaging (MRI). METHODS: The Multicenter Osteoarthritis Study is a cohort study of persons ages 50-79 years with or at risk for knee OA. Patella alta was measured using the Insall-Salvati ratio (ISR) on the baseline lateral radiograph, and cartilage damage, bone marrow lesions (BMLs), and subchondral bone attrition (SBA) were graded on MRI at baseline and at 30 months of followup in the PFJ. We examined the association of the ISR with the prevalence and worsening of cartilage damage, BMLs, and SBA in the PFJ using logistic regression. RESULTS: A total of 907 knees were studied (mean age 62 years, body mass index 30 kg/m(2), ISR 1.10), 63% from female subjects. Compared with knees in the lowest ISR quartile at baseline, those in the highest quartile had 2.4 (95% confidence interval [95% CI] 1.7-3.3), 2.9 (95% CI 2.0-4.3), and 3.5 (95% CI 2.3-5.5) times the odds of having lateral PFJ cartilage damage, BMLs, and SBA, respectively, and 1.5 (95% CI 1.1-2.0), 1.3 (95% CI 0.9-1.8), and 2.2 (95% CI 1.4-3.4) times the odds of having medial PFJ cartilage damage, BMLs, and SBA, respectively. Similarly, those with high ISRs were also at risk for worsening of cartilage damage and BMLs over time than those with low ISRs. CONCLUSION: A high ISR, indicative of patella alta, is associated with structural features of OA in the PFJ. Additionally, the same knees have an increased risk of worsening of these same features over time.