A consensus-based framework for conducting and reporting osteoarthritis phenotype research

Background The concept of osteoarthritis (OA) heterogeneity is evolving and gaining renewed interest. According to this concept, distinct subtypes of OA need to be defined that will likely require recognition in research design and different approaches to clinical management. Although seemingly plausible, a wide range of views exist on how best to operationalize this concept. The current project aimed to provide consensus-based definitions and recommendations that together create a framework for conducting and reporting OA phenotype research. Methods A panel of 25 members with expertise in OA phenotype research was composed. First, panel members participated in an online Delphi exercise to provide a number of basic definitions and statements relating to OA phenotypes and OA phenotype research. Second, panel members provided input on a set of recommendations for reporting on OA phenotype studies. Results Four Delphi rounds were required to achieve sufficient agreement on 11 definitions and statements. OA phenotypes were defined as subtypes of OA that share distinct underlying pathobiological and pain mechanisms and their structural and functional consequences. Reporting recommendations pertaining to the study characteristics, study population, data collection, statistical analysis, and appraisal of OA phenotype studies were provided. Conclusions This study provides a number of consensus-based definitions and recommendations relating to OA phenotypes. The resulting framework is intended to facilitate research on OA phenotypes and increase combined efforts to develop effective OA phenotype classification. Success in this endeavor will hopefully translate into more effective, differentiated OA management that will benefit a multitude of OA patients

Is synovitis detected on non-contrast-enhanced magnetic resonance imaging associated with serum biomarkers and clinical signs of effusion? Data from the Osteoarthritis Initiative.

ObjectivesTo determine the relationship between synovitis detected on non-contrast-enhanced (non-CE) magnetic resonance imaging (MRI), biochemical markers of inflammation, and clinical assessment of effusion in people with knee osteoarthritis (OA).MethodWe examined data from the OA Biomarkers Consortium within the Osteoarthritis Initiative (n = 600). Non-CE MRIs were semi-quantitatively scored (grades 0-3) for severity of Hoffa synovitis and effusion synovitis. Serum (s) matrix metalloproteinase-3 (sMMP-3), hyaluronic acid (sHA), and nitrated epitope of the α-helical region of type II collagen (sColl2-1NO2) were quantified. The bulge and patellar tap clinical tests were performed at baseline and performance characteristics were assessed for the detection of effusion synovitis on MRI. Multinomial logistic regression adjusted for covariates was used to assess the association between biochemical and imaging markers at baseline and over 12 and 24 months.ResultsAt baseline, sHA and sMMP-3 were associated with moderate to large (score ≥ 2, n = 117) effusion synovitis, with odds ratio = 1.35 and 1.30 per 1 standard deviation in biochemical markers (95% confidence intervals 1.07, 1.71 and 1.00, 1.69), c-statistics 0.640 and 0.626, respectively. The c-statistics for the presence of Hoffa synovitis (score ≥ 2) were 0.693, 0.694, and 0.694 for sHA, sMMP-3, and sColl2-1NO2, respectively. There was no significant association between biochemical markers (baseline and 12 and 24 month time-integrated concentrations) and changes in MRI markers. The bulge and patellar tap signs were 22.0% and 4.3% sensitive and 88.8% and 94.8% specific, respectively, for detecting effusion synovitis (score ≥ 1) on MRI.ConclusionssHA and sMMP-3 were modestly associated with effusion synovitis at baseline. Clinical signs of effusion are insensitive but highly specific for the presence of any effusion synovitis on non-CE MRI

Is Heel Height Associated with Pain Exacerbations in Hip Osteoarthritis Patients?-Results from a Case-Crossover Study

The etiology of osteoarthritis (OA) pain exacerbations is not well understood. The purpose of this study is to evaluate the association of heel height and duration of wearing shoes with higher heels with pain exacerbations in people with hip OA. Eligible participants with symptomatic hip OA were instructed to complete online questionnaires every 10 days over a 90-day follow-up period. They were required to complete the questionnaire whenever they were experiencing hip pain exacerbation. Of 252 participants recruited, 137 (54.4%) contributed both case and control period data, and were included in the analysis. Wearing shoes with a heel height ≥ 2.5 cm during the past 24 h was associated with lower odds of pain exacerbations (OR: 0.54, 95% CI: 0.30 to 0.99). A longer duration (>6 h) of wearing shoes with heel height ≥ 2.5 cm was also associated with a lower risk of hip pain exacerbations (p for linear trend = 0.003). Wearing shoes with heel height ≥ 2.5 cm and longer duration in the past 24 h may be protective against hip pain exacerbations in people with symptomatic hip OA. Given the observational study nature, it would be prudent for this to be replicated in an independent data set

Clinimetrics of ultrasound pathologies in osteoarthritis: systematic literature review and meta-analysis

Objective; The aims of this study were to systematically review clinimetrics of commonly assessed ultrasound pathologies in knee, hip and hand osteoarthritis (OA), and to conduct a meta-analysis for each clinimetric. Methods; Medline, Embase, and Cochrane Library databases were searched from their inceptions to September 2016. According to the Outcome Measures in Rheumatology (OMERACT) Instrument Selection Algorithm, data extraction focused on ultrasound technical features and performance metrics. Methodological quality was assessed with modified 19-item Downs and Black score and 11-item Quality Appraisal of Diagnostic Reliability (QAREL) score. Separate meta-analyses were performed for clinimetrics: (1) inter-rater/intra-rater reliability; (2) construct validity; (3) criteria validity; and (4) internal/external responsiveness. Statistical Package for the Social Sciences (SPSS), Excel and Comprehensive Meta-analysis were used. Result; Our search identified 1126 records; of these, 100 were eligible, including a total of 8542 patients and 32,373 joints. The average Downs and Black score was 13.01, and average QAREL was 5.93. The stratified meta-analysis was performed only for knee OA, which demonstrated moderate to substantial reliability [minimum kappa > 0.44(0.15,0.74), minimum intraclass correlation coefficient (ICC) > 0.82(0.73–0.89)], weak construct validity against pain (r = 0.12 to 0.27), function (r = 0.15 to 0.23), and blood biomarkers (r = 0.01 to 0.21), but weak to strong correlation with plain radiography (r = 0.13 to 0.60), strong association with Magnetic Resonance Imaging (MRI) [minimum r = 0.60(0.52,0.67)] and strong discrimination against symptomatic patients (OR = 3.08 to 7.46). There was strong criterion validity against cartilage histology [r = 0.66(−0.05,0.93)], and small to moderate internal [standardized mean difference(SMD) = 0.20 to 0.58] and external (r = 0.35 to 0.43) responsiveness to interventions. Conclusion; Ultrasound demonstrated strong criterion validity with cartilage histology, poor to strong correlation with patient findings and MRI, moderate reliability, and low responsiveness to interventions. PROSPERO registration no. CRD4201603995

Is synovitis detected on non-contrast-enhanced magnetic resonance imaging associated with serum biomarkers and clinical signs of effusion? Data from the Osteoarthritis Initiative

ObjectivesTo determine the relationship between synovitis detected on non-contrast-enhanced (non-CE) magnetic resonance imaging (MRI), biochemical markers of inflammation, and clinical assessment of effusion in people with knee osteoarthritis (OA).MethodWe examined data from the OA Biomarkers Consortium within the Osteoarthritis Initiative (n = 600). Non-CE MRIs were semi-quantitatively scored (grades 0-3) for severity of Hoffa synovitis and effusion synovitis. Serum (s) matrix metalloproteinase-3 (sMMP-3), hyaluronic acid (sHA), and nitrated epitope of the α-helical region of type II collagen (sColl2-1NO2) were quantified. The bulge and patellar tap clinical tests were performed at baseline and performance characteristics were assessed for the detection of effusion synovitis on MRI. Multinomial logistic regression adjusted for covariates was used to assess the association between biochemical and imaging markers at baseline and over 12 and 24 months.ResultsAt baseline, sHA and sMMP-3 were associated with moderate to large (score ≥ 2, n = 117) effusion synovitis, with odds ratio = 1.35 and 1.30 per 1 standard deviation in biochemical markers (95% confidence intervals 1.07, 1.71 and 1.00, 1.69), c-statistics 0.640 and 0.626, respectively. The c-statistics for the presence of Hoffa synovitis (score ≥ 2) were 0.693, 0.694, and 0.694 for sHA, sMMP-3, and sColl2-1NO2, respectively. There was no significant association between biochemical markers (baseline and 12 and 24 month time-integrated concentrations) and changes in MRI markers. The bulge and patellar tap signs were 22.0% and 4.3% sensitive and 88.8% and 94.8% specific, respectively, for detecting effusion synovitis (score ≥ 1) on MRI.ConclusionssHA and sMMP-3 were modestly associated with effusion synovitis at baseline. Clinical signs of effusion are insensitive but highly specific for the presence of any effusion synovitis on non-CE MRI

Disease modification in OA — will we ever get there?

No drugs are currently approved that change the natural course of osteoarthritis (OA) and translate to long-term, clinically relevant benefits. Two-stage clinical trial designs for OA have now received FDA approval, but remaining challenges lie in defining suitable study populations, surrogate outcomes and pivotal long-term, clinically relevant trial endpoints