Resistive Exercise for Arthritic Cartilage Health (REACH): A randomized double-blind, sham-exercise controlled trial

<p>Abstract</p> <p>Background</p> <p>This article provides the rationale and methodology, of the first randomised controlled trial to our knowledge designed to assess the efficacy of progressive resistance training on cartilage morphology in women with knee osteoarthritis.</p> <p>Development and progression of osteoarthritis is multifactorial, with obesity, quadriceps weakness, joint malalignment, and abnormal mechanical joint forces particularly relevant to this study. Progressive resistance training has been reported to improve pain and disability in osteoarthritic cohorts. However, the disease-modifying potential of progressive resistance training for the articular cartilage degeneration characteristic of osteoarthritis is unknown. Our aim was to investigate the effect of high intensity progressive resistance training on articular cartilage degeneration in women with knee osteoarthritis.</p> <p>Methods</p> <p>Our cohort consisted of women over 40 years of age with primary knee osteoarthritis, according to the American College of Rheumatology clinical criteria. Primary outcome was blinded measurement of cartilage morphology via magnetic resonance imaging scan of the tibiofemoral joint. Secondary outcomes included walking endurance, balance, muscle strength, endurance, power, and velocity, body composition, pain, disability, depressive symptoms, and quality of life.</p> <p>Participants were randomized into a supervised progressive resistance training or sham-exercise group. The progressive resistance training group trained muscles around the hip and knee at 80% of their peak strength and progressed 3% per session, 3 days per week for 6 months. The sham-exercise group completed all exercises except hip adduction, but without added resistance or progression. Outcomes were repeated at 3 and 6 months, except for the magnetic resonance imaging scan, which was only repeated at 6 months.</p> <p>Discussion</p> <p>Our results will provide an evaluation of the disease-modifying potential of progressive resistance training for osteoarthritis.</p> <p>Trial Registration</p> <p>ANZCTR Reference No. 12605000116628</p

Structural predictors of response to intra-articular steroid injection in symptomatic knee osteoarthritis

© 2017 The Author(s). Background: The aim was to examine if structural factors could affect response to intra-articular steroid injections (IASI) in knee osteoarthritis (OA). Method: Persons with painful knee OA participated in an open-label trial of IASI where radiographic joint space narrowing (JSN) and Kellgren-Lawrence (KL) grade, whole-organ magnetic resonance imaging (MRI) scores (WORMS) and quantitative assessment of synovial tissue volume (STV) were assessed on baseline images. Participants completed the Knee Injury and Osteoarthritis Outcome Score (KOOS) and a question about knee pain with a visual analogue scale for pain during nominated activity (VAS NA ), and Outcome Measures in Rheumatology (OMERACT)-Osteoarthritis Research Society International (OARSI) criteria were used to assess responder status within 2 weeks (short term) and 6 months (longer term). Regression models were used to examine predictors of short and longer term response to IASI. Results: Subjects (n = 207) attended and had IASI. Information on responder status was available on 199 participants. Of these, 188 subjects, mean age 63.2 years (standard deviation (SD) 10.3), 97 (51.6%) female, had x-rays and 120 had MRI scans available. Based on the OMERACT-OARSI criteria, 146 (73.4%) participants responded to therapy and 40 (20.1%) were longer term responders. A few factors were associated with a reduced KOOS-pain and VAS NA response though none were associated with OMERACT-OARSI responder status in the short term. Higher MRI meniscal damage (odds ratio (OR) = 0.74; 95% CI 0.55 to 0.98), increasing KL maximal grade (OR = 0.43; 95% CI 0.23 to 0.82) and joint space narrowing (JSN) maximal score (OR = 0.60; 95% CI 0.36 to 0.99) were each associated with a lower odds of longer term responder status. Baseline synovitis was not associated with treatment response. The predicted probability of longer term response decreased from 38% to 12% as baseline maximal JSN increased from grade 0 to 3. Conclusion: Compared with those who have mild structural damage, persons with more severe knee damage on either MRI or x-ray are less likely to respond to knee IASI. Trial registration: ISRCTN.com, ISRCTN07329370. Registered 21 May 2010. Retrospectively registere

Revision 1 Size and position of the healthy meniscus, and its Correlation with sex, height, weight, and bone area- a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Meniscus extrusion or hypertrophy may occur in knee osteoarthritis (OA). However, currently no data are available on the position and size of the meniscus in asymptomatic men and women with normal meniscus integrity.</p> <p>Methods</p> <p>Three-dimensional coronal DESSwe MRIs were used to segment and quantitatively measure the size and position of the medial and lateral menisci, and their correlation with sex, height, weight, and tibial plateau area. 102 knees (40 male and 62 female) were drawn from the Osteoarthritis Initiative "non-exposed" reference cohort, including subjects without symptoms, radiographic signs, or risk factors for knee OA. Knees with MRI signs of meniscus lesions were excluded.</p> <p>Results</p> <p>The tibial plateau area was significantly larger (p < 0.001) in male knees than in female ones (+23% medially; +28% laterally), as was total meniscus surface area (p < 0.001, +20% medially; +26% laterally). Ipsi-compartimental tibial plateau area was more strongly correlated with total meniscus surface area in men (r = .72 medially; r = .62 laterally) and women (r = .67; r = .75) than contra-compartimental or total tibial plateau area, body height or weight. The ratio of meniscus versus tibial plateau area was similar between men and women (p = 0.22 medially; p = 0.72 laterally). Tibial coverage by the meniscus was similar between men and women (50% medially; 58% laterally), but "physiological" medial meniscal extrusion was greater in women (1.83 ± 1.06mm) than in men (1.24mm ± 1.18mm; p = 0.011).</p> <p>Conclusions</p> <p>These data suggest that meniscus surface area strongly scales with (ipsilateral) tibial plateau area across both sexes, and that tibial coverage by the meniscus is similar between men and women.</p

Association of IL4R single-nucleotide polymorphisms with rheumatoid nodules in African Americans with rheumatoid arthritis

Abstract Introduction To determine whether IL4R single-nucleotide polymorphisms (SNPs) rs1805010 (I50V) and rs1801275 (Q551R), which have been associated with disease severity in rheumatoid arthritis (RA) patients of European ancestry, relate to the presence of rheumatoid nodules and radiographic erosions in African Americans. Methods Two IL4R SNPs, rs1805010 and rs1801275, were genotyped in 749 patients from the Consortium for Longitudinal Evaluation of African-Americans with Early Rheumatoid Arthritis (CLEAR) registries. End points were rheumatoid nodules defined as present either by physical examination or by chest radiography and radiographic erosions (radiographs of hands/wrists and feet were scored using the modified Sharp/van der Heijde system). Statistical analyses were performed by using logistic regression modeling adjusted for confounding factors. Results Of the 749 patients with RA, 156 (20.8%) had rheumatoid nodules, with a mean age of 47.0 years, 84.6% female gender, and median disease duration of 1.9 years. Of the 461 patients with available radiographic data, 185 (40.1%) had erosions (score >0); their mean age was 46.7 years; 83.3% were women; and median disease duration was 1.5 years. Patients positive for HLA-DRB1 shared epitope (SE) and autoantibodies (rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP)) had a higher risk of developing rheumatoid nodules in the presence of the AA and AG alleles of rs1801275 (odds ratio (OR)adj = 8.08 (95% confidence interval (CI): 1.60-40.89), P = 0.01 and ORadj = 2.97 (95% CI, 1.08 to 8.17), P = 0.04, respectively). Likewise, patients positive for the HLA-DRB1 SE and RF alone had a higher risk of developing rheumatoid nodules in presence of the AA and AG alleles of rs1801275 (ORadj = 8.45 (95% CI, 1.57 to 45.44), P = 0.01, and ORadj = 3.57 (95% CI, 1.18 to 10.76), P = 0.02, respectively) and in the presence of AA allele of rs1805010 (ORadj = 4.52 (95% CI, 1.20 to 17.03), P = 0.03). No significant association was found between IL4R and radiographic erosions or disease susceptibility, although our statistical power was limited by relatively small numbers of cases and controls. Conclusions We found that IL4R SNPs, rs1801275 and rs1805010, are associated with rheumatoid nodules in autoantibody-positive African-American RA patients with at least one HLA-DRB1 allele encoding the SE. These findings highlight the need for analysis of genetic factors associated with clinical RA phenotypes in different racial/ethnic populations

Strength Training for Arthritis Trial (START): design and rationale

Background Muscle loss and fat gain contribute to the disability, pain, and morbidity associated with knee osteoarthritis (OA), and thigh muscle weakness is an independent and modifiable risk factor for it. However, while all published treatment guidelines recommend muscle strengthening exercise to combat loss of muscle mass and strength in knee OA patients, previous strength training studies either used intensities or loads below recommended levels for healthy adults or were generally short, lasting only 6 to 24 weeks. The efficacy of high-intensity strength training in improving OA symptoms, slowing progression, and affecting the underlying mechanisms has not been examined due to the unsubstantiated belief that it might exacerbate symptoms. We hypothesize that in addition to short-term clinical benefits, combining greater duration with high-intensity strength training will alter thigh composition sufficiently to attain long-term reductions in knee-joint forces, lower pain levels, decrease inflammatory cytokines, and slow OA progression. Methods/Design This is an assessor-blind, randomized controlled trial. The study population consists of 372 older (age ≥ 55 yrs) ambulatory, community-dwelling persons with: (1) mild-to-moderate medial tibiofemoral OA (Kellgren-Lawrence (KL) = 2 or 3); (2) knee neutral or varus aligned knee ( -2° valgus ≤ angle ≤ 10° varus); (3) 20 kg.m-2 ≥ BMI ≤ 45 kg.m-2; and (3) no participation in a formal strength-training program for more than 30 minutes per week within the past 6 months. Participants are randomized to one of 3 groups: high-intensity strength training (75-90% 1Repetition Maximum (1RM)); low-intensity strength training (30-40%1RM); or healthy living education. The primary clinical aim is to compare the interventions’ effects on knee pain, and the primary mechanistic aim is to compare their effects on knee-joint compressive forces during walking, a mechanism that affects the OA disease pathway. Secondary aims will compare the interventions’ effects on additional clinical measures of disease severity (e.g., function, mobility); disease progression measured by x-ray; thigh muscle and fat volume, measured by computed tomography (CT); components of thigh muscle function, including hip abductor strength and quadriceps strength, and power; additional measures of knee-joint loading; inflammatory and OA biomarkers; and health-related quality of life. Discussion Test-retest reliability for the thigh CT scan was: total thigh volume, intra-class correlation coefficients (ICC) = 0.99; total fat volume, ICC = 0.99, and total muscle volume, ICC = 0.99. ICC for both isokinetic concentric knee flexion and extension strength was 0.93, and for hip-abductor concentric strength was 0.99. The reliability of our 1RM testing was: leg press, ICC = 0.95; leg curl, ICC = 0.99; and leg extension, ICC = 0.98. Results of this trial will provide critically needed guidance for clinicians in a variety of health professions who prescribe and oversee treatment and prevention of OA-related complications. Given the prevalence and impact of OA and the widespread availability of this intervention, assessing the efficacy of optimal strength training has the potential for immediate and vital clinical impact

A prospective, single-centre, randomised study evaluating the clinical, imaging and immunological depth of remission achieved by very early versus delayed Etanercept in patients with Rheumatoid Arthritis (VEDERA)

Background Rheumatoid arthritis (RA) is a chronic inflammatory arthritis, with significant impact on quality of life and functional status. Whilst biologic disease modifying anti-rheumatic drugs (bDMARD) such as tumour necrosis factor-inhibitor (TNFi) agents have revolutionised outcomes in RA, early diagnosis with immediate conventional therapy, titrated in a treat to target approach is also associated with high remission rates. The main aim of the VEDERA study (Very Early versus Delayed Etanercept in Rheumatoid Arthritis) is to assess the depth of remission, sustainability of remission and immunological normalisation induced by very early TNFi with etanercept (ETN) or standard of care +/- delayed ETN. Methods/Design VEDERA is a pragmatic, phase IV single-centre open-label randomised superiority trial of 120 patients with early, treatment-naive RA. Patients will be randomised 1:1 to first-line ETN and methotrexate (MTX) or MTX with additional synthetic disease modifying anti-rheumatic drugs (sDMARDs) according to a treat to target (TT) protocol with further step up to ETN and MTX after 24 weeks if remission is not achieved. Participants will have regular disease activity assessments and imaging evaluation including musculoskeletal ultrasound and MRI. The main objective of this study is to assess the proportion of patients with early RA that achieve clinical remission at 48 weeks, following either treatment strategy. In addition, the participants are invited to take part in a cardio-vascular sub-study (Coronary Artery Disease in RA, CADERA), which aims to identify the incidence of cardiovascular abnormalities in early RA. Discussion The hypothesis underlining this study is that very early treatment with first-line ETN increases the proportion of patients with rheumatoid arthritis achieving clinical remission, in comparison to conventional therapy. Trial registration NCT02433184, 23/04/201