Effects of total and regional fat loss on plasma CRP and IL-6 in overweight and obese, older adults with knee osteoarthritis

SummaryObjectiveTo describe associations between total and regional body fat mass loss and reduction of systemic levels of inflammation (C-reactive protein (CRP) and interleukin-6 (IL-6)) in obese, older adults with osteoarthritis (OA), undergoing intentional weight loss.DesignData come from a single-blind, 18-month, randomized controlled trial in adults (age: 65.6 ± 6.2; Body mass index (BMI): 33.6 ± 3.7) with knee OA. Participants were randomized to diet-induced weight loss plus exercise (D + E; n = 150), diet-induced weight loss-only (D; n = 149), or exercise-only (E; n = 151). Total body and region-specific (abdomen and thigh) fat mass were measured at baseline and 18 months. High-sensitivity CRP and IL-6 were measured at baseline, six and 18 months. Intervention effects were assessed using mixed models and associations between inflammation and adiposity were compared using logistic and mixed linear regression models.ResultsIntentional total body fat mass reduction was associated with significant reductions in log-adjusted CRP (β = 0.06 (95% CI = 0.04, 0.08) mg/L) and IL-6 (β = 0.02 (95% CI = 0.01, 0.04) pg/mL). Loss of abdominal fat volume was also associated with reduced inflammation, independent of total body fat mass; although models containing measures of total adiposity yielded the best fit. The odds of achieving clinically desirable levels of CRP (<3.0 mg/L) and IL-6 (<2.5 pg/mL) were 3.8 (95% CI = 1.6, 8.9) and 2.2 (95% CI = 1.1, 4.6), respectively, with 5% total weight and fat mass loss.ConclusionsAchievement of clinically desirable levels of CRP and IL-6 more than double with intentional 5% loss of total body weight and fat mass. Global, rather than regional, measures of adiposity are better predictors of change in inflammatory burden.Clinical Trial Registration NumberNCT00381290

The Intensive Diet and Exercise for Arthritis (IDEA) Trial: 18-Month Radiographic and MRI Outcomes

SummaryPurposeReport the radiographic and magnetic resonance imaging (MRI) structural outcomes of an 18-month study of diet-induced weight loss, with or without exercise, compared to exercise alone in older, overweight and obese adults with symptomatic knee osteoarthritis (OA).MethodsProspective, single-blind, randomized controlled trial that enrolled 454 overweight and obese (body mass index, BMI = 27–41 kg m−2) older (age ≥ 55 yrs) adults with knee pain and radiographic evidence of femorotibial OA. Participants were randomized to one of three 18-month interventions: diet-induced weight loss only (D); diet-induced weight loss plus exercise (D + E); or exercise-only control (E). X-rays (N = 325) and MRIs (N = 105) were acquired at baseline and 18 months follow-up. X-ray and MRI (cartilage thickness and semi-quantitative (SQ)) results were analyzed to compare change between groups at 18-month follow-up using analysis of covariance (ANCOVA) adjusted for baseline values, baseline BMI, and gender.ResultsMean baseline descriptive characteristics of the cohort included: age, 65.6 yrs; BMI 33.6 kg m−2; 72% female; 81% white. There was no significant difference between groups in joint space width (JSW) loss; D −0.07 (SE 0.22) mm, D + E −0.27 (SE 0.22) mm and E −0.16 (SE 0.24) mm (P = 0.79). There was also no significant difference in MRI cartilage loss between groups; D −0.10(0.05) mm, D + E −0.13(0.04) mm and E −0.05(0.04) mm (P = 0.42).ConclusionDespite the potent effects of weight loss in this study on symptoms as well as mechanistic outcomes (such as joint compressive force and markers of inflammation), there was no statistically significant difference between the three active interventions on the rate of structural progression either on X-ray or MRI over 18-months

Is monocyte chemotactic protein 1 elevated in aseptic loosening of TKA? A pilot study

Item does not contain fulltextBACKGROUND: Failure of TKA from aseptic loosening is a growing concern, as TKA is performed with increasing frequency. Loosening is multifactorial and may be associated with elevated inflammatory cytokines in addition to biomechanical failure. QUESTIONS/PURPOSES: We asked whether proinflammatory cytokines and chemokines are elevated in synovial fluid from patients undergoing revision surgery as compared to those with osteoarthritis (OA) or rheumatoid arthritis (RA). METHODS: We obtained synovial fluid samples from 20 patients: six with aseptic loosening of TKA (all with bone loss), 10 with primary OA, and four with RA. A panel of cytokines/chemokines was screened using a SearchLight((R)) Array (Pierce Biotechnology, Rockford, IL, USA) in one revision sample. Using these data, we assayed the synovial fluids for monocyte chemotactic protein 1 (MCP-1) by ELISA. RESULTS: We observed an increase in synovial MCP-1 levels in samples from patients planned for TKA revision compared to those with OA or RA. In patients undergoing revision arthroplasty, the mean (+/- SD) MCP-1 concentration was 21,233 +/- 18,966 pg/mL (range, 1550-50,657 pg/mL; n = 6). In patients with OA, the mean MCP-1 level was 3012 +/- 3321 pg/mL. In patients with RA, the mean MCP-1 concentration was 690 +/- 561 pg/mL. CONCLUSIONS: All patients undergoing revision TKA showed elevated concentrations of MCP-1 compared to patients with OA and RA, suggesting MCP-1 may serve as a potential marker or predictor of bone loss in patients undergoing revision surgery. CLINICAL RELEVANCE: MCP-1 may be a novel biomarker in patients showing early symptoms of aseptic loosening of TKA