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To evaluate the efficacy and safety of the anti-catabolic ADAMTS-5 inhibitor S201086/GLPG1972 for the treatment of symptomatic knee osteoarthritis. ROCCELLA (NCT03595618) was a randomized, double-blind, placebo-controlled, dose-ranging, phase 2 trial in adults (aged 40–75 years) with knee osteoarthritis. Participants had moderate-to-severe pain in the target knee, Kellgren–Lawrence grade 2 or 3 and Osteoarthritis Research Society International joint space narrowing (grade 1 or 2). Participants were randomized 1:1:1:1 to once-daily oral S201086/GLPG1972 75, 150 or 300 mg, or placebo for 52 weeks. The primary endpoint was change from baseline to week 52 in central medial femorotibial compartment (cMFTC) cartilage thickness assessed quantitatively by magnetic resonance imaging. Secondary endpoints included change from baseline to week 52 in radiographic joint space width, Western Ontario and McMaster Universities Osteoarthritis Index total and subscores, and pain (visual analogue scale). Treatment-emergent adverse events (TEAEs) were also recorded. Overall, 932 participants were enrolled. No significant differences in cMFTC cartilage loss were observed between placebo and S201086/GLPG1972 therapeutic groups: placebo vs 75 mg, P = 0.165; vs 150 mg, P = 0.939; vs 300 mg, P = 0.682. No significant differences in any of the secondary endpoints were observed between placebo and treatment groups. Similar proportions of participants across treatment groups experienced TEAEs. Despite enrolment of participants who experienced substantial cartilage loss over 52 weeks, during the same time period, S201086/GLPG1972 did not significantly reduce rates of cartilage loss or modify symptoms in adults with symptomatic knee osteoarthritis. [ABSTRACT FROM AUTHOR]

To assess the longer-term effect of the Good Life with osteoarthritis in Denmark (GLAD) exercise and education program relative to open-label placebo (OLP) on changes from baseline in core outcomes in individuals with knee osteoarthritis (OA). In this 1-year follow-up of an open-label, randomized trial, patients with symptomatic and radiographically confirmed knee OA were monitored after being randomized to either the 8-week GLAD program or OLP given as 4 intra-articular saline injections over 8 weeks. The primary outcome was the change from baseline in the Knee injury and Osteoarthritis Outcome Score questionnaire (KOOS) pain subscale after 1 year in the intention-to-treat population. Key secondary outcomes were the KOOS function and quality of life subscales, and Patients' Global Assessment of disease impact. 206 adults were randomly assigned: 102 to GLAD and 104 to OLP, of which only 137 (63/74 GLAD/OLP) provided data at 1 year. At one year the mean changes in KOOS pain were 8.4 for GLAD and 7.0 for OLP (Difference: 1.5 points; 95% CI −2.6 to 5.5). There were no between-group differences in any of the secondary outcomes. In this 1-year follow-up of individuals with knee OA, the 8-week GLAD program and OLP both provided minor longer-term benefits with no group difference. These results require confirmation given the significant loss to follow-up. NCT03843931. [ABSTRACT FROM AUTHOR]

To identify contextual factors that modify the treatment effect of the ' Good Life with osteoArthritis in Denmark ' (GLAD) exercise and education programme compared to open-label placebo (OLP) on knee pain in individuals with knee osteoarthritis (OA). Secondary effect modifier analysis of a randomised controlled trial. 206 participants with symptomatic and radiographic knee OA were randomised to either the 8-week GLAD programme (n = 102) or OLP given as 4 intra-articular saline injections over 8 weeks (n = 104). The primary outcome was change from baseline to week 9 in the Knee injury and Osteoarthritis Outcome Score questionnaire (KOOS) pain subscale (range 0 (worst) to 100 (best)). Subgroups were created based on baseline information: BMI, swollen study knee, bilateral radiographic knee OA, sports participation as a young adult, sex, median age, a priori treatment preference, regular use of analgesics (NSAIDs or paracetamol), radiographic disease severity, and presence of constant or intermittent pain. Participants who reported use of analgesics at baseline seem to benefit from the GLAD programme over OLP (subgroup contrast: 10.3 KOOS pain points (95% CI 3.0 to 17.6)). Participants with constant pain at baseline also seem to benefit from GLAD over OLP (subgroup contrast: 10.0 points (95% CI 2.8 to 17.2)). These results imply that patients who take analgesics or report constant knee pain, GLAD seems to yield clinically relevant benefits on knee pain when compared to OLP. The results support a stratified recommendation of GLAD as management of knee OA. ClinicalTrials.gov Identifier: NCT03843931. EudraCT number 2019-000809-71. [ABSTRACT FROM AUTHOR]

Objective: To study the impact of weight loss on inflammation in individuals with overweight and knee osteoarthritis (OA) using both static- and dynamic contrast-enhanced (DCE)-MRI and assess the association of these changes to pain.Design: Individuals with overweight (BMI > 27) and knee OA were examined before and after a >5% weight loss over 8 weeks (ClinicalTrials.gov NCT02905864). Using 3-T MRI, inflammation was quantified from non-contrast enhanced static-MRI according to MOAKS and contrast enhanced static MRI according to BLOKS and 11-point whole-knee synovitis score. DCE-MRI was used to assess the inflammation in the infra patellar fat pad (IPFP). Pain was assessed using KOOS.Results: Complete data were available in 117 participants with a mean age of 60 years, BMI of 35 kg/m2 and KOOS pain score of 64. Mean weight loss was 12 kg and KOOS pain was improved by 13 points at follow-up. Change in inflammation was not associated with weight loss in static MRI. None of the MRI variables correlated with the change in KOOS pain.Conclusion: Weight loss did not induce a significant change in inflammation in individuals with overweight and OA. The significant clinical beneficial effect of weight loss on knee pain in individuals with overweight and knee OA seems uncoupled to changes in imaging markers of synovitis. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the structural effects of weight loss on hip or knee osteoarthritis (OA) and to summarize which structural joint pathologies have been examined and the evidence for the outcome measurement instruments applied.Design: Based on a pre-specified protocol (available: PROSPERO CRD42017065263), we conducted a systematic search of the bibliographic databases, Medline, Embase and Web of Science identifying longitudinal articles reporting the effects of weight loss on structural imaging outcomes in OA of the hip or knee in people who are overweight or obese.Results: From 1625 potentially eligible records, 14 articles (from 6 cohorts) were included. 2 cohorts were derived from RCTs. Evaluated pathologies were: articular cartilage (n = 7), joint space width (n = 3), bone marrow lesions (n = 5), synovitis (n = 2), effusion (n = 1), meniscus (n = 3), bone marrow density (n = 1) and infrapatellar fat pad (IPFP; n = 2). Cartilage showed conflicting results when evaluating cartilage thickness by direct thickness measurements. Compositional dGEMRIC and T2 mapping measures in early knee OA showed trends towards reduced cartilage degeneration. Joint space width on conventional radiographs showed no change. Weight loss reduced the size of the IPFP. Synovitis and effusion were not affected. Following weight loss DXA showed bone loss at the hip.Conclusion: We did not find consistent evidence of the effects of weight loss on OA structural pathology in people who are overweight or obese. There is a need to achieve consensus on which structural pathologies and measurements to apply in weight loss and OA research. [ABSTRACT FROM AUTHOR]

Objective: To evaluate if the relative volume of bone marrow lesions (BMLs) changed in patients with knee osteoarthritis (OA) during a therapeutic study.Design: This study is a sub-study to a larger clinical trial which compared the clinical effects of intra-articular corticosteroid injection in knee OA to placebo injection, both given prior to exercise therapy. Clinical assessment using the Knee injury and Osteoarthritis Outcome Score (KOOS) and magnetic resonance imaging (MRI) examinations with BML assessments were performed at baseline and follow-up after 14 weeks and 26 weeks, respectively. The BML volume was determined using a computer assisted method focusing on participants with valid baseline and follow-up MRI examinations. Any changes in BML and KOOS were analyzed and investigated for associations.Results: Fifty participants received steroid and placebo injection, respectively, of which 41 and 45 had complete MRI examinations at week 14, and 36 and 33 at week 26, respectively. All participants received 12 weeks of exercise. A significant change in relative BML volume was observed between the corticosteroid group and the placebo group after 14 weeks [-1.1% vs 2.7%; between-group difference, 3.8% (95% CI 0.5-7.0)] but not after 26 weeks [0.8% vs 1.6%; between-group difference, 0.8% (95% CI -2.8 to 4.4)]. No significant association was found between changes in relative BML volume and KOOS.Conclusions: Despite the statistically significant difference in BML volume at 14 weeks after corticosteroid injection and 12 weeks exercise therapy compared to placebo injection and exercise, there is very little evidence on a relationship between corticosteroids and BML volume.Eu Clinical Trials Register: EudraCT number: 2012-002607-18. [ABSTRACT FROM AUTHOR]

Objective: To explore effects of weight loss and maintenance on serum cartilage biomarkers denaturation neoepitope for Collagen2 (Coll2-1) and Fibulin3 fragment (Fib3-2), as well as correlations between Coll2-1 and Fib3-2 and symptomatic improvement, in a knee osteoarthritis (KOA) population.Design: 192 obese KOA patients followed a 16 week weight loss intervention and 52 weeks weight maintenance (ClinicalTrials.gov identifier: NCT00655941). Assessments were at 0, 8, 16 and 68 weeks. Serum Coll2-1 and Fib3-2 were determined with ELISA, and symptoms by the Knee Osteoarthritis Outcome Score (KOOS) questionnaire. Changes from week 0 and association between changes from baseline in body weight and Coll2-1, Fib3-2, and the 5 KOOS domains were assessed at all time points.Results: Coll2-1 changes from baseline showed a decrease at week 8 (P = 0.0002), no change at week 16 (P = 0.49), and an increase at week 68 (P = 0.036). Fib3-2 showed an increase from baseline at week 8 (P = 0.0015) and 16 (P < 0.0001), but none at week 68 (P = 0.23). No statistically significant correlations were found between changes in body weight and Coll2-1 and Fib3-2 at any time point (r < 0.05; P > 0.49). At all time-points there were significant positive correlations between changes from baseline in Coll2-1 and in KOOSSports/Recreation (week 8, 16, 68: r = 0.17; P = 0.03; r = 0.16; P = 0.04; and r = 0.17; P = 0.04, respectively).Conclusion: The clinical improvement after a substantial weight loss and weight maintenance in KOA patients was not associated with decrease in markers of cartilage breakdown Coll2-1 or Fib3-2, even with indications of a slightly negative effect. [ABSTRACT FROM AUTHOR]

Objective: The aims of the present knee osteoarthritis (KOA)-study were to: (1) describe and compare the changes in magnetic resonance imaging (MRI)-measures of synovitis following an exercise program preceded by an intra-articular injection of either corticosteroid or isotonic saline and (2) investigate if any of the changes in patient reported outcome measures (PROMs) were associated with changes in MRI-measures of synovitis.Design: We performed a randomized, double-blinded, placebo-controlled clinical trial evaluating the effects of intra-articular corticosteroid vs placebo injections given before exercise therapy in KOA-patients. PROMs were assessed using the KOOS (knee injury and osteoarthritis outcome score). Synovitis was assessed on conventional non-contrast-enhanced, conventional contrast-enhanced (CE) and dynamic contrast-enhanced (DCE) MRI. PROMs and MRIs were obtained prior to the intra-articular injection, after termination of the exercise program (week 14-primary time point) and week 26.Results: Of 100 randomized participants (50 in each allocation group), 91 had complete MRI-data at baseline (63% female, mean age: 62 years, median Kellgren-Lawrence-grade: 3). There were no statistically significant differences between the two interventions in regards of changes in MRI-measures of synovitis at any time-point. At week 14, we found no statistical significant MRI-explanatory variables of either of the PROMs.Conclusions: The present study does not justify the use of intra-articular corticosteroids over intra-articular saline when combined with an exercise program for reduction of synovitis in KOA. The improvement in pain and function following the intervention with intra-articular corticosteroids/saline and exercise could not be explained by a decrease in synovitis on MRI indicating other pain causing/relieving mechanisms in KOA. [ABSTRACT FROM AUTHOR]

Purpose: The current narrative review covers original research related to imaging in osteoarthritis (OA) in humans published in English between April 1st 2015 and March 31st 2016, in peer reviewed journals available in Medline via PubMed (http://www.ncbi.nlm.nih.gov/pubmed/).Methods: Relevant studies in humans, subjectively decided by the authors, contributing significantly to the OA imaging field, were selected from an extensive Medline search using the terms "Osteoarthritis" in combination with "MRI", "Imaging", "Radiography", "X-rays", "Ultrasound", "Computed tomography", "Nuclear medicine", "PET-CT", "PET-MRI", "Scintigraphy", "SPECT". Publications were sorted according to relevance for the OA imaging research community with an emphasis on high impact special interest journals using the software for systematic reviews www.covidence.org.Results: An overview of newly published studies compared to studies reported previous years is presented, followed by a review of selected imaging studies of primarily knee, hip and hand OA focussing on (1) results for detection of OA and OA-related pathology (2) studies dealing with treatments and (3) studies focussing on prognosis of disease progression or joint replacement. A record high number of 1420 articles were published, among others, of new technologies and tools for improved morphological and pathophysiological understanding of OA-related changes in joints. Also, imaging data were presented of monitoring treatment effect and prognosis of OA progression, primarily using established radiographic, magnetic resonance imaging (MRI), and ultrasound (US) methods.Conclusion: Imaging continues to play an important role in OA research, where several exciting new technologies and computer aided analysis methods are emerging to complement the conventional imaging approaches. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the association between magnetic resonance imaging (MRI), macroscopic and histological assessments of synovitis in end-stage knee osteoarthritis (KOA).Methods: Synovitis of end-stage osteoarthritic knees was assessed using non-contrast-enhanced (CE), contrast-enhanced magnetic resonance imaging (CE-MRI) and dynamic contrast-enhanced (DCE)-MRI prior to (TKR) and correlated with microscopic and macroscopic assessments of synovitis obtained intraoperatively. Multiple bivariate correlations were used with a pre-specified threshold of 0.70 for significance. Also, multiple regression analyses with different subsets of MRI-variables as explanatory variables and the histology score as outcome variable were performed with the intention to find MRI-variables that best explain the variance in histological synovitis (i.e., highest R2). A stepped approach was taken starting with basic characteristics and non-CE MRI-variables (model 1), after which CE-MRI-variables were added (model 2) with the final model also including DCE-MRI-variables (model 3).Results: 39 patients (56.4% women, mean age 68 years, Kellgren-Lawrence (KL) grade 4) had complete MRI and histological data. Only the DCE-MRI variable MExNvoxel (surrogate of the volume and degree of synovitis) and the macroscopic score showed correlations above the pre-specified threshold for acceptance with histological inflammation. The maximum R2-value obtained in Model 1 was R2 = 0.39. In Model 2, where the CE-MRI-variables were added, the highest R2 = 0.52. In Model 3, a four-variable model consisting of the gender, one CE-MRI and two DCE-MRI-variables yielded a R2 = 0.71.Conclusion: DCE-MRI is correlated with histological synovitis in end-stage KOA and the combination of CE and DCE-MRI may be a useful, non-invasive tool in characterising synovitis in KOA. [ABSTRACT FROM AUTHOR]

Objective: Meta-analysis of randomized controlled trials (RCTs)--of a hip powder of Rosa canina (rosehip) preparation for symptomatic treatment of osteoarthritis (OA), in order to estimate the empirical efficacy as a pain reducing compound.Method: RCTs from systematic searches were included if they explicitly stated that OA patients were randomized to either rosehip or placebo. The primary outcome was reduction in pain calculated as effect size (ES), defined as the standardized mean difference (SMD). As secondary analysis the number of responders to therapy was analyzed as Odds Ratios (OR), and expressed as the Number Needed to Treat (NNT). Restricted Maximum Likelihood (REML) methods were applied for the meta-analyses using mixed effects models.Results: The three studies (287 patients and a median trial-duration of 3 months)--all supported by the manufacturer (Hyben-Vital International)--showed a reduction in pain scores by rosehip powder (145 patients) compared to placebo (142 patients): ES of 0.37 [95% confidence interval (CI): 0.13-0.60], P=0.002. Test for homogeneity seemed to support that the efficacy was consistent across trials (I(2)=0%). Thus it seems reasonable to assume that the three studies were measuring the same overall effect. It seemed twice as likely that a patient allocated to rosehip powder would respond to therapy, compared to placebo (OR=2.19; P=0.0009); corresponding to a NNT of six (95% CI: 4-13) patients.Conclusions: Although based on a sparse amount of data, the results of the present meta-analysis indicate that rosehip powder does reduce pain; accordingly it may be of interest as a nutraceutical, although its efficacy and safety need evaluation and independent replication in a future large-scale/long-term trial. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy of preparations with avocado-soybean unsaponifiables (ASUs) in osteoarthritis (OA) patients using meta-analysis on randomized controlled trials (RCTs).Method: RCTs from systematic searches were included if they explicitly stated that hip and/or knee OA patients were randomized to either ASU or placebo. The co-primary outcome was reduction in pain and Lequesne index, leading to effect size (ES), calculated as the standardized mean difference. As secondary analysis, the number of responders to therapy was analyzed as odds ratios (ORs). Restricted maximum likelihood methods were applied for the meta-analyses, using mixed effects models.Results: Four trials--all supported by the manufacturer--were included, with 664 OA patients with either hip (41.4%) or knee (58.6%) OA allocated to either 300 mg ASU (336) or placebo (328). Average trial duration was 6 months (range: 3-12 months). Though based on heterogeneous results, the combined pain reduction favored ASU (I(2) = 83.5%, ES = 0.39 [95% confidence intervals: 0.01-0.76], P=0.04). Applying the Lequesne index also favored ASU (I(2) = 61.0%, ES = 0.45 [0.21-0.70], P = 0.0003). Secondarily, the number of responders following ASU compared to placebo (OR = 2.19, P = 0.007) corresponded to a number needed to treat of six (4-21) patients.Conclusions: Based on the available evidence, patients may be recommended to give ASU a chance for e.g., 3 months. Meta-analysis data support better chances of success in patients with knee OA than in those with hip OA. [ABSTRACT FROM AUTHOR]

Objective: Knee osteoarthritis (KOA) is a multifactorial joint disease affecting many people worldwide. Recommended treatments for KOA include exercise and steroid injections, or a combination of these. The objective of this exploratory outcome analysis of a randomized trial was to assess changes in inflammation markers assessed by ultrasound imaging (US) in KOA secondary to intra-articular corticosteroid injection given prior to exercise therapy. Design: This study is a sub-study to a larger clinical trial which compared the clinical effects of steroid injection in KOA to placebo injection, both given prior to exercise therapy. The US outcomes were changes from baseline in US-assessed synovial size, Doppler activity presence in the synovial membrane, and numbers of US-detected Baker's cysts. US was performed at baseline, week 14 (exercise stop), and week 26 (follow-up). Results: Fifty participants received steroid injection, and 50 received placebo injection. All participants received 12 weeks of exercise. Forty-five and 44, respectively, completed the study. At week 14, the group difference in the change in synovium thickness was 2.2 mm (95%, confidence interval (CI) -0.5 to 4.8), P = 0.11. There were no group differences in the changes in distribution of patients with presence of synovial Doppler activity (P = 0.98) or Baker's cysts (P = 0.35). There were no statistically significant differences between groups at week 26 in any outcome. Conclusion: Intra-articular steroid injection of KOA-patients prior to a 3 months exercise programme did not reduce synovial hypertrophy, synovial Doppler activity, or Baker's cyst presence more than a placebo saline injection according to US-assessments. Trial Registration: EudraCT: 2012-002607-18. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between muscle perfusion in the peri-articular knee muscles assessed by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) and symptoms in patients with knee osteoarthritis (KOA).Design: In a cross-sectional setting, muscle perfusion was quantified by DCE-MRI in KOA. Regions of interest (ROI) were drawn around the peri-articular muscles, summed and averaged into one single "Total Muscle Volume" volume of interest (VOI). Symptoms were assessed via the Knee injury and Osteoarthritis Outcome Score (KOOS) (0: worst; 100: best).Results: DCE-MRI and clinical data were analyzed in 94 patients. The typical participant was a woman with a mean age of 65 years, and a body mass index (BMI) of 32 kg/m(2). Reduced multiple regression models analyzing the association between KOOS and DCE-MRI perfusion variables of Total Muscle Volume showed a statistically significant association between Nvoxel% and KOOS pain (0.41 (SE 0.14); P = 0.0048). Nvoxel% was defined as the proportion of highly perfused voxels; i.e., the voxels that show an early and rapid increase on the signal intensity vs time curves, reach a plateau state (plateau pattern) and then showing a relatively rapid decline (washout pattern) relative to the total number of voxels within the muscle VOI.Conclusions: More widespread perfusion in the peri-articular knee muscles was associated with less pain in patients with KOA. These results give rise to investigations of the effects of exercise on muscle perfusion and its possible mediating role in the causal pathway between exercise and pain improvements in the conservative management of KOA. [ABSTRACT FROM AUTHOR]

Summary The aim of this study was to assess the clinical efficacy and safety of oral ginger for symptomatic treatment of osteoarthritis (OA) by carrying out a systematic literature search followed by meta-analyses on selected studies. Inclusion criteria were randomized controlled trials (RCTs) comparing oral ginger treatment with placebo in OA patients aged >18 years. Outcomes were reduction in pain and reduction in disability. Harm was assessed as withdrawals due to adverse events. The efficacy effect size was estimated using Hedges' standardized mean difference (SMD), and safety by risk ratio (RR). Standard random-effects meta-analysis was used, and inconsistency was evaluated by the I-squared index ( I 2 ). Out of 122 retrieved references, 117 were discarded, leaving five trials (593 patients) for meta-analyses. The majority reported relevant randomization procedures and blinding, but an inadequate intention-to-treat (ITT) analysis. Following ginger intake, a statistically significant pain reduction SMD = −0.30 ([95% CI: [(−0.50, −0.09)], P = 0.005]) with a low degree of inconsistency among trials (I 2 = 27%), and a statistically significant reduction in disability SMD = −0.22 ([95% CI: ([−0.39, −0.04)]; P = 0.01; I 2 = 0%]) were seen, both in favor of ginger. Patients given ginger were more than twice as likely to discontinue treatment compared to placebo ([RR = 2.33; 95% CI: (1.04, 5.22)]; P = 0.04; I 2 = 0%]). Ginger was modestly efficacious and reasonably safe for treatment of OA. We judged the evidence to be of moderate quality, based on the small number of participants and inadequate ITT populations. Prospero: CRD42011001777. [ABSTRACT FROM AUTHOR]

Summary Objective Changes in biomarkers for bone and cartilage in knee osteoarthritis (KOA) may reflect changes in tissue turnover induced by interventions. The aim of this study was to assess the effect on osteoarthritis biomarkers of an intensive weight loss intervention in obese KOA patients. Methods 192 obese KOA patients followed a 16 weeks weight loss intervention (ClinicalTrials.gov: NCT00655941 ). Serum Cartilage Oligomeric Matrix Protein (sCOMP), Urine C-terminal telopeptide of collagen type II (uCTX-II) and type I (uCTX-I) were determined by enzyme-linked immunoassay (ELISA) at baseline and after 16 weeks. Patient-reported symptoms were assessed by the Knee Injury and Osteoarthritis Outcome Score (KOOS) Questionnaire without the sports and recreation score (KOOS-4). Change from baseline was analyzed using Analysis of CoVariance (ANCOVA) adjusting for sex, age, and body mass index (BMI). Bivariate associations were analyzed using Spearman's test of rank correlation. Results 175 patients completed the treatment and lost mean 13.4 (95% CI: 12.5–14.4) kg. sCOMP concentration decreased on average 1.1 (95% CI: −1.5 to −0.8) U/L with a correlation to weight loss ( r = −0.17, P = 0.028), but not to change in KOOS-4 ( r = −0.13, P = 0.091). uCTX-II increased significantly, mean 69 (95% CI: 31–106) ng/mmol creatinine, with no relation to weight loss ( P = 0.14). Change in uCTX-II was reversely related to change in KOOS-4 ( r = −0.28, P = 0.0003). uCTX-I increased, mean 67 (95% CI: 47–87) μg/mmol creatinine, and correlated to weight loss ( r = 0.22, P = 0.0007), while not to KOOS-4 ( P = 0.93). Conclusion A rapid substantial weight loss in obese KOA patients was weakly, while significantly associated with a reduction in sCOMP, and increases in both uCTX-II and uCTX-I. [ABSTRACT FROM AUTHOR]

Summary Objective To develop standardized musculoskeletal ultrasound (MUS) procedures and scoring for detecting knee osteoarthritis (OA) and test the MUS score's ability to discern various degrees of knee OA, in comparison with plain radiography and the ‘ Knee injury and Osteoarthritis Outcome Score ’ (KOOS) domains as comparators. Method A cross-sectional study of MUS examinations in 45 patients with knee OA. Validity, reliability, and reproducibility were evaluated. Results MUS examination for knee OA consists of five separate domains assessing (1) predominantly morphological changes in the medial compartment, (2) predominantly inflammation in the medial compartment, (3) predominantly morphological changes in the lateral compartment, (4) predominantly inflammation in the lateral compartment, and (5) effusion. MUS scores displayed substantial reliability and reproducibility, with interclass correlations coefficients ranging from 0.75 to 0.97 for the five domains. Construct validity was confirmed with statistically significant correlation coefficients (0.47–0.81, P < 0.01). Conclusion The MUS score suggested in this study was reliable and valid in detecting knee OA. In comparison with standing radiographs of the knees, the score detected all aspects of knee OA with relevant precision. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between knee pain and signs of inflammation in the infrapatellar fat pad (IPFP) in obese patients with knee osteoarthritis (KOA). Design: In a cross-sectional setting, 3-T conventional contrast-enhanced (CE) magnetic resonance imaging (MRI) and dynamic contrast-enhanced (DCE)-MRI of KOA were analysed to quantify the extent of inflammation in the IPFP, and correlated (Spearman's rank correlation) to pain and other symptoms assessed via the Knee injury and Osteoarthritis Outcome Score (KOOS) (100 = no pain, 0 = extreme pain). The extent of inflammation in the IPFP was assessed according to the MRI Osteoarthritis Knee Score (MOAKS) using CE-MRI and by DCE-MRI perfusion variables. The perfusion variable, "Inflammation", was chosen as primary perfusion variable in the analysis. Intraclass correlation coefficients for the perfusion variables ranged from 0.81 to 0.99. Results: MRI and clinical data were obtained in 95 patients. The typical patient was a woman (82%) with an average age of 65 years (SD 6.5) and a body mass index (BMI) of 32 kg/m² (SD 3.7). The bivariate association between KOOS pain and the DCE-MRI perfusion variable "Inflammation" showed a statistically significant correlation (r = -0.42, P < 0.0001). A statistically significant correlation was also found between KOOS pain and MOAKS Hoffa-synovitis (r = -0.21, P = 0.046). Conclusions: Perfusion variables on DCE-MRI reflecting the severity of inflammation in the IPFP and MOAKS Hoffa-synovitis were associated with the severity of pain in KOA. These results suggest that severe inflammation in the IPFP is associated with severe pain in KOA and that DCE-MRI is a promising method to study the impact of inflammation in KOA. [ABSTRACT FROM AUTHOR]

Summary: Objective: To compare structural knee joint changes in obese patients with knee osteoarthritis (OA) that after an intensive weight loss therapy were randomized to continuous dietetic support, a specialized knee exercise program, or ‘no attention’ for 1 year. Methods: 192 obese individuals with knee OA underwent an intensive 16-week weight loss program with subsequent randomization to one of the three treatment groups. Changes in cartilage loss, bone marrow lesions (BMLs), synovitis, and effusion were assessed using semi quantitative assessments of magnetic resonance imaging (MRI) obtained at weeks 0 and 68 applying the BLOKS score. Results: During the 52 weeks maintenance period the continuous dietary maintenance group support on average gained 1.1 kg (95% CI: −0.3:2.5) body mass, the exercise group gained 6.6 kg (95% CI 5.4:7.8) and the no-attention group gained 4.8 kg (95% CI: 2.9:6.7). There were no statistically significant between-group differences in changes in cartilage loss, synovitis or effusion at the follow-up (analysis of covariance; ANCOVA, P > 0.16), while there was an increased number of medial tibiofemoral BMLs in the exercise group (ANCOVA, P = 0.015) compared to both diet (difference: −0.21 [95%CI −0.40:−0.03]) and “no attention” (difference: −0.26 [95%CI −0.44:−0.07]) groups. Conclusion: In this 1 year follow-up after weight-loss in obese knee OA patients, we found a potentially increased number of BMLs in the exercise group compared to the diet and no attention groups, with no between-group differences in changes in cartilage loss, synovitis or effusion. These findings should be interpreted with caution for exercise compliance, MRI methodology and follow-up time. (ClinicalTrials.gov identifier: NCT00655941) [Copyright &y& Elsevier]

Summary: Objective: To investigate whether increased knee joint loading due to improved ambulatory function and walking speed following weight loss achieved over 16 weeks accelerates symptomatic and structural disease progression over a subsequent 1 year weight maintenance period in an obese population with knee osteoarthritis (OA). Methods: Data from a prospective study of weight loss in obese patients with knee OA (the CARtilage in obese knee OsteoarThritis (CAROT) study) were used to determine changes in knee joint compressive loadings (model estimated) during walking after a successful 16 week weight loss intervention. The participants were divided into ‘Unloaders’ (participants that reduced joint loads) and ‘Loaders’ (participants that increased joint loads). The primary symptomatic outcome was changes in knee symptoms, measured with the Knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire, during a subsequent 52 weeks weight maintenance period. The primary structural outcome was changes in tibiofemoral cartilage loss assessed semi-quantitatively (Boston Leeds Knee Osteoarthritis Score (BLOKS) from MRI after the 52 weight maintenance period. Results: 157 participants (82% of the CAROT cohort) with medial and/or lateral knee OA were classified as Unloaders (n = 100) or Loaders (n = 57). The groups showed similar significant changes in symptoms (group difference: −2.4 KOOS points [95% CI −6.8:1.9]) and cartilage loss (group difference: −0.06 BLOKS points [95% CI −0.22:0.11) after 1 year, with no statistically significant differences between Loaders and Unloaders. Conclusion: For obese patients undergoing a significant weight loss, increased knee joint loading for 1 year was not associated with accelerated symptomatic and structural disease progression compared to a similar weight loss group that had reduced ambulatory compressive knee joint loads. Clinicaltrials.gov: NCT00655941. [Copyright &y& Elsevier]

Objectives: To assess correlations between Kellgren & Lawrence (KL) gradings, minimum joint space width (mJSW) measurements and the Boston Leeds Osteoarthritis Knee Score (BLOKS) within a cohort of obese patients with knee osteoarthritis (KOA).Methods: 192 Participants were recruited from an outpatient clinic (ClinicalTrials.gov: NCT00655941). Inclusion criteria were age ≥50 years, body mass index (BMI) ≥30 kg/m(2) plus symptomatic and verified KOA. 1.5 T magnetic resonance imaging (MRI) scans were assessed using BLOKS and bi-plane radiography by mJSW and KL. Statistics used were Spearman rank correlation coefficients.Results: The average patient was 63 years of age, female and had a BMI of 37. KL gradings correlated to cartilage damage, bone marrow lesions and meniscus pathology (r = 0.15-0.76) and similar results were found for the relationship between BLOKS and mJSW. BLOKS assessed knee joint pathology co-segregated with compartment and grade specific KL (P < 0.0001). BLOKS variables were statistically significant correlated, particularly in the medial tibiofemoral compartment (r = 0.42-0.80). Adjusting for age, gender and BMI did not alter these associations.Conclusion: Extensive pathological damage is present even in mild radiographic KOA and BLOKS gradings and KL scores increase together. Analyses of compartment specific KL scores revealed differences in their relationship to the assessed MRI variables. Our study displays the segregation of MRI gradings with respect to location and level of radiographic scores, reveals a high inter-dependency of MRI-assessed structures, and describes some redundancy of specific BLOKS variables. [ABSTRACT FROM AUTHOR]

Summary: Objectives: To assess correlations between Kellgren & Lawrence (KL) gradings, minimum joint space width (mJSW) measurements and the Boston Leeds Osteoarthritis Knee Score (BLOKS) within a cohort of obese patients with knee osteoarthritis (KOA). Methods: 192 Participants were recruited from an outpatient clinic (ClinicalTrials.gov: NCT00655941). Inclusion criteria were age ≥50 years, body mass index (BMI) ≥30 kg/m2 plus symptomatic and verified KOA. 1.5 T magnetic resonance imaging (MRI) scans were assessed using BLOKS and bi-plane radiography by mJSW and KL. Statistics used were Spearman rank correlation coefficients. Results: The average patient was 63 years of age, female and had a BMI of 37. KL gradings correlated to cartilage damage, bone marrow lesions and meniscus pathology (r = 0.15–0.76) and similar results were found for the relationship between BLOKS and mJSW. BLOKS assessed knee joint pathology co-segregated with compartment and grade specific KL (P < 0.0001). BLOKS variables were statistically significant correlated, particularly in the medial tibiofemoral compartment (r = 0.42–0.80). Adjusting for age, gender and BMI did not alter these associations. Conclusion: Extensive pathological damage is present even in mild radiographic KOA and BLOKS gradings and KL scores increase together. Analyses of compartment specific KL scores revealed differences in their relationship to the assessed MRI variables. Our study displays the segregation of MRI gradings with respect to location and level of radiographic scores, reveals a high inter-dependency of MRI-assessed structures, and describes some redundancy of specific BLOKS variables. [ABSTRACT FROM AUTHOR]

Summary: Objective: With an increasing prevalence of older and obese citizens, the problems of knee osteoarthritis (KOA) will escalate. Weight loss is recommended for obese KOA patients and in a majority of cases this leads to symptomatic relief. We hypothesized that pre-treatment structural status of the knee joint, assessed by radiographs, 1.5 T magnetic resonance imaging (MRI) and knee-joint alignment, may influence the symptomatic changes following a significant weight reduction. Design: Patients were recruited from a Department of Rheumatology. Eligibility criteria were age above 50 years, body mass index ≥30 kg/m2, primary KOA diagnosed according to the American College of Rheumatology (ACR) criteria and having verified structural damage. Patients underwent a 16 weeks dietary programme with formula products and counselling. MRI and radiographs of the most symptomatic knee were obtained at baseline and assessed for structural damage using the Boston-Leeds Osteoarthritis of the Knee Score, minimum joint space width and Kellgren–Lawrence score. Imaging variables, muscle strength and degree of alignment, were examined as predictors of changes in Knee Osteoarthritis Outcome Score (KOOS) and Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) - Osteoarthritis Research Society International (OARSI) Responder Criterion. Results: Structural damage at baseline assessed by imaging, muscle strength or knee-joint alignment showed no statistically significant association to changes in KOOS pain and function in daily living (r ≤ 0.13; P > 0.05) or the OMERACT-OARSI Responder Criterion (OR 0.48–1.68; P-values ≥ 0.13). Conclusions: Presence of joint damage did not preclude symptomatic relief following a clinically relevant weight loss in older obese patients with KOA. Neither muscle strength nor knee-joint alignment was associated with the degree of symptomatic relief. [Copyright &y& Elsevier]

Summary: Objective: To determine the effect of an intensive weight loss program on knee joint loads during walking in obese patients with knee osteoarthritis (OA). Methods: Participants included 157 obese knee OA patients that underwent a 16-week dietary intervention. Three-dimensional gait analyses were performed before and after the intervention at the participants’ freely chosen walking speed. Knee joint compression forces, axial impulses, knee flexion angle and frontal and sagittal plane knee moments were calculated to determine the biomechanical effects of the weight loss. Results: 157 subjects (89% of the initial cohort) completed the 16-week intervention. The average weight loss of 13.7kg (P <.0001) corresponded to 13.5% of the baseline body weight. The weight loss resulted in a 7% reduction in knee joint loading, a 13% lower axial impulse, and a 12% reduction in the internal knee abductor moment (KAM). There were no clear effects on sagittal plane knee moments or peak knee flexion angle. Linear regression analyses adjusted for changes in walking speed showed that for every 1kg in weight loss, the peak knee load was reduced by 2.2kg. Thus, every kilo reduction in body weight was related to more than twice the reduction in peak knee force at a given walking speed. Conclusion: Weight loss is an excellent short-term investment in terms of joint loading for patients with combined obesity and knee OA. The effects of sustained weight loss on disease progression and symptoms in relation to biomechanical factors remain to be shown. [ABSTRACT FROM AUTHOR]

Summary: Objectives: To evaluate in a prospective, randomized clinical trial (RCT), symptom response among obese knee osteoarthritis (OA) patients following a feasible, intensive weight-loss program for 16 weeks. Methods: Eligible patients were obese [body mass index (BMI)>30kg/m2]; >50 years old, with primary knee OA. Participants were randomized to either a very-low-energy diet (VLED) or a low-energy diet (LED) (415kcal/day and 810kcal/day, respectively), using commercially available formula foods – only for the first 8 weeks, managed by dieticians. The 8 weeks were followed by an additional 8-week period of a hypo-energetic diet consisting of normal food plus meal replacements (1200kcal/day). The primary endpoint was the number of patients responding according to the Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT–OARSI) responder criterion. The statistical analysis was based on a non-responder intention-to-treat (ITT) population (baseline observation carried forward). Results: One hundred and ninety two patients (155 (80.7%) females) with a mean age 62.5 years [standard deviation (SD) 6.4; range 50–78 years]; average BMI 37.3 (SD 4.8) were included. At 16 weeks, similar proportions of the VLED and LED groups, 59 (61.5%), and 63 (65.6%) patients, respectively, met the OMERACT–OARSI responder criteria, with no statistical significant difference between the groups (P =0.55). Combining the groups the pooled estimate was 64% meeting the responder criteria [95% confidence interval (CI) 57%, 70%]. There was an overall reduction in pain, corresponding to an average pain reduction on the visual analogue scale (VAS) of 11.1 (95%CI 13.6, 8.5) in the combined groups. At week 16 weight loss in the combined groups was 12.8kg (95%CI: 11.84–13.66; P <0.001). 71% lost ≥10% body weight in both diet groups, with a pooled estimate of 74% (95%CI: 68–80%). Conclusion: No clinically significant differences were found between the 415kcal/day and 810kcal/day diets. A 16-week formula-diet weight-loss program resulted in a fast and effective weight loss with very few adverse events resulting in a highly significant improvement in symptoms in overweight patients with knee OA. ClinicalTrials.gov Identifier: NCT00655941. [Copyright &y& Elsevier]

Summary: Objective: To estimate the efficacy and safety of diacerein as a pain-reducing agent in the treatment of osteoarthritis (OA), using meta-analysis of published randomized placebo-controlled trials (RCTs). Methods: Systematic searches of the bibliographic databases Medline, Embase, Cinahl, Chemical Abstracts, Cochrane and Web of Science for RCTs concerning diacerein treatment of OA. Inclusion criteria: explicit statement about randomization to either diacerein or placebo, and co-primary outcomes being reduction in pain and improvement in function. Efficacy effect size (ES) was estimated using Hedges''s standardized mean difference. Safety was measured via the risk ratio (RR) of patients having at least one episode of diarrhoea, or withdrawal due to adverse events. Trials were combined by using random-effects meta-analysis. Consistency was evaluated via the I-squared index. Results: Six trials (seven sub-studies; 1533 patients) contributed to the meta-analysis, revealing a large degree of inconsistency among the trials (I 2 =56%) in regard to pain reduction: the combined ES was −0.24 [95% confidence intervals (CI): −0.39 to −0.08, P =0.003], favouring diacerein. The statistically significant improvement in function (P =0.01) was based on a small amount of heterogeneity (I 2 =11%), but presented a questionable clinical effect size (ES=−0.14). Risk of publication bias could not be excluded, and trials with duration of more than 6 months did not favour diacerein. There was an increased risk of diarrhoea with diacerein (RR=3.51 [2.55–4.83], P <0.0001), and some withdrawal from therapy following adverse events (RR=1.58 [1.05–2.36], P =0.03). Conclusions: Diacerein may be an alternative therapy for OA for patients who cannot take paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) because of adverse effects or lack of benefit. However, it is associated with increased risk of diarrhoea, and the symptomatic benefit after 6 months remains unknown. [Copyright &y& Elsevier]

Summary: Objective: Meta-analysis of randomized controlled trials (RCTs) – of a hip powder of Rosa canina (rosehip) preparation for symptomatic treatment of osteoarthritis (OA), in order to estimate the empirical efficacy as a pain reducing compound. Method: RCTs from systematic searches were included if they explicitly stated that OA patients were randomized to either rosehip or placebo. The primary outcome was reduction in pain calculated as effect size (ES), defined as the standardized mean difference (SMD). As secondary analysis the number of responders to therapy was analyzed as Odds Ratios (OR), and expressed as the Number Needed to Treat (NNT). Restricted Maximum Likelihood (REML) methods were applied for the meta-analyses using mixed effects models. Results: The three studies (287 patients and a median trial-duration of 3 months) – all supported by the manufacturer (Hyben-Vital International) – showed a reduction in pain scores by rosehip powder (145 patients) compared to placebo (142 patients): ES of 0.37 [95% confidence interval (CI): 0.13–0.60], P =0.002. Test for homogeneity seemed to support that the efficacy was consistent across trials (I 2 =0%). Thus it seems reasonable to assume that the three studies were measuring the same overall effect. It seemed twice as likely that a patient allocated to rosehip powder would respond to therapy, compared to placebo (OR=2.19; P =0.0009); corresponding to a NNT of six (95% CI: 4–13) patients. Conclusions: Although based on a sparse amount of data, the results of the present meta-analysis indicate that rosehip powder does reduce pain; accordingly it may be of interest as a nutraceutical, although its efficacy and safety need evaluation and independent replication in a future large-scale/long-term trial. [Copyright &y& Elsevier]

Summary: Objective: To evaluate the efficacy of preparations with avocado–soybean unsaponifiables (ASUs) in osteoarthritis (OA) patients using meta-analysis on randomized controlled trials (RCTs). Method: RCTs from systematic searches were included if they explicitly stated that hip and/or knee OA patients were randomized to either ASU or placebo. The co-primary outcome was reduction in pain and Lequesne index, leading to effect size (ES), calculated as the standardized mean difference. As secondary analysis, the number of responders to therapy was analyzed as odds ratios (ORs). Restricted maximum likelihood methods were applied for the meta-analyses, using mixed effects models. Results: Four trials – all supported by the manufacturer – were included, with 664 OA patients with either hip (41.4%) or knee (58.6%) OA allocated to either 300mg ASU (336) or placebo (328). Average trial duration was 6 months (range: 3–12 months). Though based on heterogeneous results, the combined pain reduction favored ASU (I 2 =83.5%, ES=0.39 [95% confidence intervals: 0.01–0.76], P =0.04). Applying the Lequesne index also favored ASU (I 2 =61.0%, ES=0.45 [0.21–0.70], P =0.0003). Secondarily, the number of responders following ASU compared to placebo (OR=2.19, P =0.007) corresponded to a number needed to treat of six (4–21) patients. Conclusions: Based on the available evidence, patients may be recommended to give ASU a chance for e.g., 3 months. Meta-analysis data support better chances of success in patients with knee OA than in those with hip OA. [Copyright &y& Elsevier]

Summary: Objective: Hyaluronic acid (HA) and corticosteroids are both widely used for intra-articular treatment of knee osteoarthritis (OA). We examined the effect of both drugs in intra-articular treatment for hip OA. Methods: One hundred and one patients with hip OA were included in a prospective double blind study, using a randomized controlled trial with a three-armed parallel-group design. Three ultrasound-guided, intra-articular injections were given at 14 days interval. The primary outcome measure was ‘pain on walking’, registered on a visual analogue scale (VAS). Evaluation was performed at baseline and after 14, 28 and 90 days. The study adhered to the Consolidated Standards of Reporting Trials. All analyses were based on intention-to-treat analyses, and used ‘mixed-procedures’ with the baseline-observation as covariate. Results: There were no significant interactions with respect to Treatment×Time for any of the analyzed outcome measures. There was a significant treatment effect for ‘pain on walking’ (P =0.044) due to a significant improvement following corticosteroid compared to saline with an effect-size of 0.6 (95% confidence interval: 0.1–1.1, P =0.021). By contrast, HA compared to saline had an effect size of 0.4 (−0.1 to 0.9; P =0.13). The peak-effect was obtained after 2 weeks. There was no difference between the treatment groups at endpoint. No significant side effects of the injections were observed. Conclusions: Patients treated with corticosteroids experienced significant improvement during the 3 months of intervention, with an effect size indicating a moderate clinical effect. Although a similar significant result following treatment with HA could not be shown, the effect size indicated a small clinical improvement. A higher number of patients in future HA studies would serve to clarify this point. [Copyright &y& Elsevier]