Given the available evidence, depression probably has a temporal influence on RA disease progression and treatment. However, it is unclear whether these observed effects are due to a response tendency on patient-reported outcomes created from negative cognitive perceptions, immunologically mediated processes that increase inflammation or behavioural changes that lead to decreased physical activity and a greater sensitivity to pain.

Objective. To estimate the dynamic causal effects of depressive symptoms on osteoarthritis (OA) knee pain. Methods. Marginal structural models were used to examine dynamic associations between depressive symptoms and pain over 48 months among older adults (n = 2,287) with radiographic knee OA (Kellgren/Lawrence grade 2 or 3) in the Osteoarthritis Initiative. Depressive symptoms at each annual visit were assessed (threshold ≥16) using the Center for Epidemiologic Studies Depression Scale. OA knee pain was measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale, rescaled to range from 0 to 100. Results. Depressive symptoms at each visit were generally not associated with greater OA knee pain at subsequent time points. Causal mean differences in WOMAC pain score comparing depressed to nondepressed patients ranged from 1.78 (95% confidence interval [95% CI] À0.73, 4.30) to 2.58 (95% CI 0.23, 4.93) within the first and fourth years, and the depressive symptoms by time interaction were not statistically significant (P = 0.94). However, there was a statistically significant dose-response relationship between the persistence of depressive symptoms and OA knee pain severity (P = 0.002). Causal mean differences in WOMAC pain score comparing depressed to nondepressed patients were 0.89 (95% CI À0.17, 1.96) for 1 visit with depressive symptoms, 2.35 (95% CI 0.64, 4.06) for 2 visits with depressive symptoms, and 3.57 (95% CI 0.43, 6.71) for 3 visits with depressive symptoms. Conclusion. The causal effect of depressive symptoms on OA knee pain does not change over time, but pain severity significantly increases with the persistence of depressed mood.

Objective Depression is common in the rheumatoid arthritis (RA) population, yet little is known of its effect on the course of disease activity. The aim of our study was to determine if prevalent and incident depressive symptoms influenced longitudinal changes in RA disease activity. Methods RA patients with and without depressive symptoms were identified using single-item questions from an existing registry sample. Mixed-effects models were used to examine changes in disease activity over 2 years in those with and without prevalent and incident depressive symptoms. Outcome variables included composite disease activity, joint counts, global assessments, pain, function, and acute-phase reactants. Model-based outcome estimations at the index dates and corresponding 1- and 2-year changes were calculated. Results Rates of disease activity change were significantly different in patients with a lifetime prevalence of symptomology, but not incident depressive symptoms, when compared to controls. Prior symptoms were associated with slower rates of disease activity decline, evidenced by the estimated 1-year Clinical Disease Activity Index changes: −3.0 (−3.3, −2.6) and −4.0 (−4.3, −3.6) in patients with and without lifetime prevalence, respectively. Analogous results were obtained for most of the other disease activity outcomes; although, there was no temporal effect of prevalent symptoms of depression on swollen joints and acute-phase reactants. Conclusion Depressive symptoms temporally influence the evolution of RA disease activity, and the magnitude is dependent on the time of symptomatic onset. However, the effect is limited to patient-reported pain, global assessment, and function, as well as physician-reported global assessment and tender joints.

Depressive symptoms are associated with increases in pain and functional limitations in knee osteoarthritis (OA). The aim was to determine whether depressive symptoms are also associated with greater structural knee OA progression. Four years of annual radiographic and clinical assessments from the Osteoarthritis Initiative were analyzed. The Center for Epidemiological Studies Depression Scale was used to identify depressive symptoms (threshold = ≥16) at the baseline visit. Propensity scores were used to match participants with and without baseline depressive symptoms on multiple potential confounders. Assessment of radiographic knee OA was based on changes in individual radiographic features, which included osteophyte (OST) grade and joint space narrowing (JSN) grade. Mixed effect models were used to examine structural progression between depressed and non-depressed participants with definitive radiographic knee OA. Depressive symptoms were significantly associated with a higher risk of OST progression (odds ratio [OR] = 1.74; 95% confidence interval [CI]: 1.01, 3.00) and a non-significant lower risk of JSN progression (OR = 0.40; 95% CI: 0.14, 1.15) 1 year after baseline. Conversely, there was a non-significant lower risk of OST progression (OR = 0.71; 95% CI: 0.28, 1.79) and higher risk of JSN progression (OR = 1.89; 95% CI: 0.71, 5.06) from year 3 to year 4 of follow-up. However, the patterns of OST progression and JSN progression were not significantly different between the depressed and non-depressed (P = 0.25 and 0.15, respectively). The findings provide no evidence that depressive symptoms have a detectable effect on changes in radiographic disease severity in knee OA.

Objectives Osteoarthritis (OA) disease progression may lead to deteriorating psychosocial function, but it is unclear what aspects of disease severity are related to the onset of depression. This study assessed which components of OA disease progression cumulatively contribute to depression onset in persons with radiographic knee OA. Methods Osteoarthritis Initiative participants (n = 1651) with radiographic disease (Kellgren-Lawrence grade ≥2) in one or both knees and below the screening threshold for probable depression [Center for Epidemiological Studies Depression (CES-D) scale <16] at baseline were included. Disease severity was measured from baseline to the third annual follow-up visit using joint space width, 20-meter gait speed, and the Western Ontario and McMaster Universities Osteoarthritis Index pain subscale, each categorized into quintiles. Depression onset (CES-D ≥ 16) was assessed annually at four follow-up visits. Marginal structural models that account for time-dependent confounding and attrition evaluated the association between each time-varying disease severity measure and depression onset. Results Each disease severity measure exhibited a non-linear relationship concerning the probability of depression onset, with the higher quintiles generally being associated with a larger risk. The highest quintile (relative to the lowest) of joint space width and gait speed were both significantly associated with depression onset. By contrast, none of the higher pain quintiles compared with the lowest were significantly associated with the onset of depression. Conclusion Faster disease progression as measured by either worsening structural severity or decreasing physical performance corresponds to an increased risk of depression among individuals with radiographic knee OA.

Prior studies have shown that women have declines in bone structure and strength after hip fracture, but it is unclear whether men sustain similar changes. Therefore, the objective was to examine sex differences in proximal femur geometry following hip fracture. Hip structural analysis was used to derive metrics of bone structure and strength: aerial bone mineral density, cross-sectional bone area (CSA), cortical outer diameter, section modulus (SM), and buckling ratio (BR) from dual-energy x-ray absorptiometry scans performed at baseline (within 22 days of hospital admission), two, six, or twelve months after hip fracture in men and women (n=282) enrolled in the Baltimore Hip Studies 7th cohort. Weighted estimating equations were used to evaluate sex differences at the narrow neck (NN), intertrochanteric (IT), and femoral shaft (FS). Men had significantly different one year NN changes compared to women in CSA: −6.33% (−12.47, −0.20) vs. 1.37% (−3.31, 6.43), P=0.049; SM: −4.98% (−11.08, 1.10) vs. 3.94% (−2.51, 10.42), P=0.042; and BR: 7.50% (0.65, 14.36) vs. −1.20% (−6.41, 4.00), P=0.044. One year IT changes displayed similar patterns, but the sex differences were not statistically significant for CSA: −4.07% (−10.83, 2.67) vs. 0.41% (−3.41, 4.24), P=0.252; SM: −4.78% (-12.10, 5.53) vs. −0.31 (−4.74, 4.11), P=0.287; and BR: 4.59% (−0.65, 9.84) vs. 1.52% (−4.23, 7.28), P=0.425. Differences in FS geometric parameters were even smaller in magnitude and not significantly different by sex. Women generally experienced non-significant increases in bone tissue and strength following hip fracture, while men had structural declines that were statistically greater at the NN region. Reductions in the mechanical strength of the proximal femur after hip fracture could put men at higher risk for subsequent fractures of the contralateral hip.

Pain severity mediated approximately one-fifth of the association between depressive symptoms and physical performance in persons with radiographic knee OA, and the diminishing incremental effects may explain why unimodal treatment strategies with a single disease target are often ineffective in depressed OA patients.

The data suggest depressive symptom onset in RA patients is related to measures reported by the patient: pain, functional status, and global disease activity; and measures reported by providers, rather than biological markers. The magnitude of the associations, however, were greater for the patient-reported measures when compared to physician assessments, implying that patients' experience of their disease activity may be a precipitating factor of depression onset.