<b>OBJECTIVE: </b>To examine the effects of dietary weight loss, with and without exercise, on selected soluble biomarkers in overweight and obese older adults with symptomatic knee osteoarthritis (OA).<b>DESIGN: </b>Blood samples were analyzed from 429 participants in the Intensive Diet and Exercise for Arthritis (IDEA) trial randomized to either an 18 month exercise control group (E), weight loss diet (D), or D + E. C1M, C2M, C3M and CRPM biomarkers and interleukin-6 (IL-6) were quantitated using ELISAs. Radiographic progression was defined as a decrease in joint space width of ≥0.7 mm. Statistical modeling of group means and associations used mixed models adjusted for visit, baseline body mass index (BMI), gender, and baseline values of the outcome.<b>RESULTS: </b>Compared to the E control group, C1M was significantly lower in the D and D + E groups at both 6 and 18 months while C3M was significantly lower in D and D + E at 6 months and in D + E at 18 months. C2M did not change in any group. Using data from all groups, change in C1M (P < 0.0001), C3M (P < 0.0001), as well as CRPM (P = 0.0004) from baseline to 18 months was positively associated with change in weight. No marker was associated with change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain or radiographic progression. C3M (P = 0.008) and CRPM (P = 0.028) were positively associated with change in WOMAC function. Change in IL-6 was positively associated with change in C1M, C3M, and CRPM.<b>CONCLUSION: </b>Overweight and obese adults with knee OA who lost weight from diet and diet plus exercise reduced serum markers of interstitial matrix turnover and inflammation but not type II collagen degradation.
OBJECTIVE: To determine effects of Whole Body Vibration Exercise (WBVE) associated with quadriceps resistance exercises (QRE) versus QRE only on pain, physical function, biomarkers in serum and urine, activities of daily living (ADL), and quality of life in patients with knee osteoarthitis (OA). DESIGN: Randomized-controlled trial . SETTING: Rehabilitation medicine outpatient department of West China Hospital, Chengdu, Sichuan, People’s Republic of China. Subjects: Forty-nine patients were assigned to WBVE+QRE and 50 to QRE . Main outcome measures: Primary outcomes included pain assessed with visual analogue scale (VAS), Timed up & go test (TUG), 6-min walk distance test (6MWD), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcomes comprised range of motion, muscular strength, serum COMP and urinary CTX-II, Lequesne Index (LI), and SF-36. All outcomes were analyzed with mixed effects regression. RESULTS: Compared with QRE, WBVE+QRE showed significantly greater improvement in VAS at 4weeks (<i>p</i> = 0.03), in VAS (<i>p</i> < 0.01), 6MWD (<i>p</i> = 0.01), WOMAC pain (<i>p</i> = 0.01), and WOMAC physical function (<i>p</i> = 0.02) at 16 weeks, and in all primary outcomes at 24 weeks (all <i>p</i> < 0.01). CONCLUSION: Over a six months period, WBVE in combination with QRE was superior to QRE in most outcomes. (PsycInfo Database Record (c) 2022 APA, all rights reserved)
OBJECTIVES: The aim of this study is to investigate the effects of isokinetic and aerobic exercise training programs on serum pro-inflammatory cytokine levels, pain, and functional activity in patients with knee osteoarthritis (OA).
METHODS: Forty-two postmenopausal women and men with knee OA according to American College of Rheumatology diagnostic criteria were included. Patients were randomized into isokinetic and aerobic exercises and control groups. In intervention groups, patients were included in predetermined exercise programs 3 times per week for 6 weeks. Severity of pain, functional activity status, muscle strength, functional capacity, and serum cytokine levels were evaluated at baseline and at the 6th week.
RESULTS: At the end of 6th week, there was no statistically significant decrease in serum pro-inflammatory cytokine levels in both the exercise groups, although C-reactive protein levels exhibited a strong trend toward significance. We found a significant decrease in visual analog scale and Western Ontario McMaster Osteoarthritis Index scores, and significant increase in functional capacity and muscle strength in both the exercise groups compared with those in the control group.
The aims of this study were to observe the effect of exercise therapy on the function of the knee joint and the levels of cytokines and cytokine-related genes, specifically tumor necrosis factor-α (TNF-α), high sensitivity C-reactive protein (hs-CRP) and matrix metalloproteinase-3 (MMP-3), in the synovial joints of patients with knee osteoarthritis (KOA) and to explore its mechanism of action. A total of 100 KOA patients were divided into a treatment group (n=50) and a control group (n=50) according to the order of admission. The patients in the treatment group were treated with diclofenac sodium combined with exercise therapy and the patients in the control group were treated with diclofenac sodium only. The function of the knee joint and the therapeutic efficacy was evaluated and the TNF-α, hs-CRP and MMP-3 levels in the synovial fluid were measured following 4 weeks of treatment. The results revealed that the knee joint index score and the TNF-α, hs-CRP and MMP-3 levels in the synovial fluid decreased significantly in the KOA patients of the two groups following treatment (P<0.05). Compared with the control group, the knee joint index score and the TNF-α, hs-CRP and MMP-3 levels in the synovial joints were lower and the therapeutic efficacy was increased in the patients of the treatment group (P<0.05). In brief, exercise therapy may decrease cytokine and cytokine-related gene levels in the synovial fluid and inhibit inflammatory factor-mediated cartilage degradation in KOA patients, thus, effectively improving the clinical symptoms of KOA.
BACKGROUND: Little is known about the relationships of circulating levels of biomarkers of cartilage degradation with biomechanical outcomes relevant to knee osteoarthritis (OA) or biomarker changes following non-pharmacological interventions. The objectives of this exploratory, pilot study were to: 1) examine relationships between biomarkers of articular cartilage degradation and synthesis with measures of knee joint load during walking, and 2) examine changes in these biomarkers following 10 weeks of strengthening exercises.
METHODS: Seventeen (8 male, 9 female; 66.1 +/- 11.3 years of age) individuals with radiographically-confirmed medial tibiofemoral OA participated. All participants underwent a baseline testing session where serum and urine samples were collected, followed by a three-dimensional motion analysis. Motion analysis was used to calculate the external knee adduction moment (KAM) peak value and impulse. Following baseline testing, participants were randomized to either 10 weeks of: 1) physiotherapist-supervised lower limb muscle strengthening exercises, or 2) no exercises (control). Identical follow-up testing was conducted 11 weeks after baseline. Biomarkers included: urinary C-telopeptide of type II collagen (uCTX-II) and type II collagen cleavage neoepitope (uC2C), serum cartilage oligomeric matrix protein (sCOMP), serum hyaluronic acid (sHA) and serum C-propeptide of type II procollagen (sCPII). Linear regression analysis was used to examine relationships between measures of the KAM and biomarker concentrations as baseline, as well as between-group differences following the intervention.
RESULTS: KAM impulse predicted significant variation in uCTX-II levels at baseline (p = 0.04), though not when controlling for disease severity and walking speed (p = 0.33). KAM impulse explained significant variation in the ratio uCTX-II;sCPII even when controlling for additional variables (p = 0.04). Following the intervention, changes in sCOMP were significantly greater in the exercise group compared to controls (p = 0.04). On average those in the control group experienced a slight increase in sCOMP and uCTX-II, while those in the exercise group experienced a reduction. No other significant findings were observed.
CONCLUSIONS: This research provides initial evidence of a potential relationship between uCTX-II and knee joint load measures in patients with medial tibiofemoral knee OA. However, this relationship became non-significant after controlling for disease severity and walking speed, suggesting further research is necessary. It also appears that sCOMP is amenable to change following a strengthening intervention, suggesting a potential beneficial role of exercise on cartilage structure.
TRIAL REGISTRATION: Clinicaltrials.gov NCT01241812.
Importance: Knee osteoarthritis (OA), a common cause of chronic pain and disability, has biomechanical and inflammatory origins and is exacerbated by obesity. OBJECTIVE: To determine whether a ≥ 10% reduction in body weight induced by diet, with or without exercise, would improve mechanistic and clinical outcomes more than exercise alone. Design, Setting, and Participants: Single-blind, 18-month, randomized clinical trial at Wake Forest University between July 2006 and April 2011. The diet and exercise interventions were center-based with options for the exercise groups to transition to a home-based program. Participants were 454 overweight and obese older community-dwelling adults (age ≥ 55 years with body mass index of 27-41) with pain and radiographic knee OA. INTERVENTIONS: Intensive diet-induced weight loss plus exercise, intensive diet-induced weight loss, or exercise. Main Outcomes and Measures: Mechanistic primary outcomes: knee joint compressive force and plasma IL-6 levels; secondary clinical outcomes: self-reported pain (range, 0-20), function (range, 0-68), mobility, and health-related quality of life (range, 0-100). RESULTS: At 18 months, 399 participants (88%) completed the study. Compared with exercise participants, knee compressive forces were lower in diet participants and IL-6 levels were lower in diet and diet + exercise participants. Conclusions and Relevance: Among overweight and obese adults with knee OA, after 18 months, participants in the diet + exercise and diet groups had more weight loss and greater reductions in IL-6 levels than those in the exercise group; those in the diet group had greater reductions in knee compressive force than those in the exercise group. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
OBJECTIVE: To investigate the effects of squat exercises combined with whole-body vibration on the plasma concentration of inflammatory markers and the functional performance of elderly individuals with knee osteoarthritis (OA).
DESIGN: Clinical, prospective, randomized, single-blinded study.
SETTING: Exercise physiology laboratory.
PARTICIPANTS: Elderly subjects with knee OA (N=32) were divided into 3 groups: (1) squat exercises on a vibratory platform (platform group, n=11); (2) squat exercises without vibration (squat group, n=10); and (3) the control group (n=11).
INTERVENTIONS: The structured program of squat exercises in the platform and squat groups was conducted 3 times per week, on alternate days, for 12 weeks.
MAIN OUTCOME MEASURES: Plasma soluble tumor necrosis factor-α receptors 1 (sTNFR1) and 2 (sTNFR2) were measured using immunoassays (the enzyme-linked immunosorbent assay method). The Western Ontario and McMaster Universities Osteoarthritis Index questionnaire was used to evaluate self-reported physical function, pain, and stiffness. The 6-minute walk test, the Berg Balance Scale, and gait speed were used to evaluate physical function.
RESULTS: In the platform group, there were significant reductions in the plasma concentrations of the inflammatory markers sTNFR1 and sTNFR2 (P<.001 and P<.05, respectively) and self-reported pain (P<.05) compared with the control group, and there was an increase in balance (P<.05) and speed and distance walked (P<.05 and P<.001, respectively). In addition, the platform group walked faster than the squat group (P<.01).
CONCLUSIONS: The results suggest that whole-body vibration training improves self-perception of pain, balance, gait quality, and inflammatory markers in elderly subjects with knee OA.
We aimed to investigate whether a supplementary diet containing chicken comb extract (CCE) rich in hyaluronic acid (HA) has an effect on pain and other symptoms, as well as cartilage type II collagen (CII) metabolism in patients with knee osteoarthritis (OA). A randomized double-blind placebo-controlled study was conducted in 43 subjects with knee OA (Kellgren/Lawrence grade, mainly 1-2) comprising 22 patients receiving concurrent exercise therapy (ET) and 21 without ET (referred as ET-receivers and ET-unreceivers, respectively). Subjects were randomized to a CCE-containing diet (active diet) group administered a dose of 1,800 mg/day (containing 630 mg of CCE and approximately 60 mg of HA) and a placebo group, and the intervention was continued for 16 weeks. Symptomatic efficacy was evaluated based on the Japanese Orthopaedic Association clinical trials response criteria (JOA response criteria) and Visual analog scales (VAS) before (baseline) and during the intervention. To further examine its effect on CII metabolism, the levels of two degradation biomarkers (CTX-II and C2C) and one synthesis biomarker (CPII) were measured using urine or serum samples. Nineteen subjects (10 ET-receivers and 9 ET-unreceivers) in the active diet group and 21 subjects (10 ET-receivers and 11 ET-unreceivers) in the placebo group were finally included in the study. Compared to the baseline, subscale scores of the JOA response criteria, i.e., 'pain/walking function', 'pain/step-up and -down function' and 'aggregate total symptoms' were more intensely improved in the active diet group than in the placebo group. Moreover, subgroup analyses of ET-receivers and ET-unreceivers indicated that significant improvements were restricted to ET-receivers of the active diet group. Furthermore, VAS assessment indicated that the 'pain on pressing' subscale was significantly improved in ET-receivers of the active diet group. In addition, analysis of CII biomarkers revealed that serum C2C and CPII levels, but not the urinary CTX-II level, were increased in the active diet group. Notably, both urinary CTX-II/serum CPII and serum C2C/serum CPII ratios were reduced in the active diet group (particularly ET-unreceivers), suggesting that CII synthesis was relatively increased compared to CII degradation in the active diet group. Finally, no diet-related side effects were observed. The CCE-containing diet is likely to be effective in relieving symptoms in patients with knee OA. In addition, it has the potential to improve the balance of CII degradation/synthesis in knee OA.
OBJECTIVE: To determine the effects of exercise and weight loss interventions on serum levels of four biomarkers and to examine if changes in biomarker levels correlate with clinical outcome measures in obese and overweight adults with knee osteoarthritis (OA).
METHODS: Serum was obtained at baseline, 6 and 18 months from 193 participants in Arthritis, Diet and Activity Promotion Trial. This was a single-blind 18-month trial with subjects randomized to four groups: healthy-lifestyle (HL), diet (D), exercise (E) and diet plus exercise (D+E). Serum levels of cartilage oligomeric matrix protein (COMP), hyaluronan (HA), antigenic keratan sulfate (AgKS), and transforming growth factor-beta1 (TGF-beta1) were measured by enzyme linked immunosorbent assay.
RESULTS: At baseline there were no significant differences in biomarker levels between intervention groups. When results for all the intervention groups were combined, the levels of HA were found to be negatively correlated with medial joint space width and positively correlated with Kellgren-Lawrence scores (K-L scores) while TGF-beta1 levels negatively correlated with K-L scores. When biomarker levels measured at 6 and 18 months were adjusted for baseline values, age, gender, and body mass index, weak but significant differences between intervention groups were present for mean levels of COMP and TGF-beta1. Furthermore, AgKS levels averaged over all groups tended to decrease over time. There were no significant associations of baseline biomarkers and the follow-up outcomes. Weak associations were noted between change in the biomarkers at 18 months and change in outcome measures that included change in weight with AgKS and COMP and change in Western Ontario and McMaster Universities Osteoarthritis Index pain with AgKS.
CONCLUSION: Overall, the E and D interventions did not show a consistent effect on levels of potential OA biomarkers. The four biomarkers showed differences in correlations with outcome measures suggesting that they may measure different aspects of disease activity in OA. The strongest correlations were between serum HA and radiographic measures of OA at baseline.
To examine the effects of dietary weight loss, with and without exercise, on selected soluble biomarkers in overweight and obese older adults with symptomatic knee osteoarthritis (OA).
DESIGN:
Blood samples were analyzed from 429 participants in the Intensive Diet and Exercise for Arthritis (IDEA) trial randomized to either an 18 month exercise control group (E), weight loss diet (D), or D + E. C1M, C2M, C3M and CRPM biomarkers and interleukin-6 (IL-6) were quantitated using ELISAs. Radiographic progression was defined as a decrease in joint space width of ≥0.7 mm. Statistical modeling of group means and associations used mixed models adjusted for visit, baseline body mass index (BMI), gender, and baseline values of the outcome.
RESULTS:
Compared to the E control group, C1M was significantly lower in the D and D + E groups at both 6 and 18 months while C3M was significantly lower in D and D + E at 6 months and in D + E at 18 months. C2M did not change in any group. Using data from all groups, change in C1M (P < 0.0001), C3M (P < 0.0001), as well as CRPM (P = 0.0004) from baseline to 18 months was positively associated with change in weight. No marker was associated with change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain or radiographic progression. C3M (P = 0.008) and CRPM (P = 0.028) were positively associated with change in WOMAC function. Change in IL-6 was positively associated with change in C1M, C3M, and CRPM.
CONCLUSION:
Overweight and obese adults with knee OA who lost weight from diet and diet plus exercise reduced serum markers of interstitial matrix turnover and inflammation but not type II collagen degradation.
