Associations of inflammatory and metabolic biomarkers with incident erosive hand osteoarthritis in the osteoarthritis initiative cohort.

OBJECTIVE: Erosive hand osteoarthritis (eHOA) is a subtype of hand osteoarthritis (OA) that develops in finger joints with pre-existing OA and is differentiated by clinical characteristics (hand pain/disability, inflammation, and erosions) that suggest inflammatory or metabolic processes. METHOD: This was a longitudinal nested case-cohort design among Osteoarthritis Initiative participants who had hand radiographs at baseline and 48-months, and biospecimens collected at baseline. We classified incident radiographic eHOA in individuals with ≥1 joint with Kellgren-Lawrence ≥2 and a central erosion present at 48-months but not at baseline. We used a random representative sample (n = 1282) for comparison. We measured serum biomarkers of inflammation, insulin resistance and dysglycemia, and adipokines using immunoassays and enzymatic colorimetric procedures, blinded to case status. RESULTS: Eighty-six participants developed incident radiographic eHOA. In the multivariate analyses adjusted for age, gender, race, smoking, and body mass index, and after adjustment for multiple analyses, incident radiographic eHOA was associated with elevated levels of interleukin-7 (risk ratio (RR) per SD = 1.30 [95% confidence interval (CI) 1.09, 1.55] p trend 0.01). CONCLUSION: This exploratory study suggests an association of elevated interleukin-7, an inflammatory cytokine, with incident eHOA, while other cytokines or biomarkers of metabolic inflammation were not associated. Interleukin-7 may mediate inflammation and tissue damage in susceptible osteoarthritic finger joints and participate in erosive progression.

Assessing the association of epigenetic age acceleration with osteoarthritis in the Multicenter Osteoarthritis Study (MOST).

PURPOSE: Advancing age is one of the strongest risk factors for osteoarthritis (OA). DNA methylation-based measures of epigenetic age acceleration may provide insights into mechanisms underlying OA. METHODS: We analyzed data from the Multicenter Osteoarthritis Study in a subset of 671 participants ages 45-69 years with no or mild radiographic knee OA. DNA methylation was assessed with the Illumina Infinium MethylationEPIC 850K array. We calculated predicted epigenetic age according to Hannum, Horvath, PhenoAge, and GrimAge epigenetic clocks, then regressed epigenetic age on chronological age to obtain the residuals. Associations between the residuals and knee, hand, and multi-joint OA were assessed using logistic regression, adjusted for chronological age, sex, clinical site, smoking status, and race. RESULTS: Twenty-three percent met criteria for radiographic hand OA, 25% met criteria for radiographic knee OA, and 8% met criteria for multi-joint OA. Mean chronological age (SD) was 58.4 (6.7) years. Mean predicted epigenetic age (SD) according to Horvath, Hannum, PhenoAge, and GrimAge epigenetic clocks was 64.9 (6.4), 68.6 (5.9), 50.5 (7.7), and 67.0 (6.2), respectively. Horvath epigenetic age acceleration was not associated with an increased odds of hand OA, odds ratio (95% confidence intervals) = 1.03 (0.99-1.08), with similar findings for knee and multi-joint OA. We found similar magnitudes of associations for Hannum epigenetic age, PhenoAge, and GrimAge acceleration compared to Horvath epigenetic age acceleration. CONCLUSIONS: Epigenetic age acceleration as measured by various well-validated epigenetic clocks based on DNA methylation was not associated with increased risk of knee, hand, or multi-joint OA independent of chronological age.

Machine-learning predicted and actual 2-year structural progression in the IMI-APPROACH cohort.

In the Innovative Medicine's Initiative Applied Public-Private Research enabling OsteoArthritis Clinical Headway (IMI-APPROACH) knee osteoarthritis (OA) study, machine learning models were trained to predict the probability of structural progression (s-score), predefined as >0.3 mm/year joint space width (JSW) decrease and used as inclusion criterion. The current objective was to evaluate predicted and observed structural progression over 2 years according to different radiographic and magnetic resonance imaging (MRI)-based structural parameters. Radiographs and MRI scans were acquired at baseline and 2-year follow-up. Radiographic (JSW, subchondral bone density, osteophytes), MRI quantitative (cartilage thickness), and MRI semiquantitative [SQ; cartilage damage, bone marrow lesions (BMLs), osteophytes] measurements were obtained. The number of progressors was calculated based on a change exceeding the smallest detectable change (SDC) for quantitative measures or a full SQ-score increase in any feature. Prediction of structural progression based on baseline s-scores and Kellgren-Lawrence (KL) grades was analyzed using logistic regression. Among 237 participants, around 1 in 6 participants was a structural progressor based on the predefined JSW-threshold. The highest progression rate was seen for radiographic bone density (39%), MRI cartilage thickness (38%), and radiographic osteophyte size (35%). Baseline s-scores could only predict JSW progression parameters (most P>0.05), while KL grades could predict progression of most MRI-based and radiographic parameters (P<0.05). In conclusion, between 1/6 and 1/3 of participants showed structural progression during 2-year follow-up. KL scores were observed to outperform the machine-learning-based s-scores as progression predictor. The large amount of data collected, and the wide range of disease stage, can be used for further development of more sensitive and successful (whole joint) prediction models. Trial Registration: Clinicaltrials.gov number NCT03883568.

Structural tissue damage and 24-month progression of semi-quantitative MRI biomarkers of knee osteoarthritis in the IMI-APPROACH cohort.

BACKGROUND: The IMI-APPROACH cohort is an exploratory, 5-centre, 2-year prospective follow-up study of knee osteoarthritis (OA). Aim was to describe baseline multi-tissue semiquantitative MRI evaluation of index knees and to describe change for different MRI features based on number of subregion-approaches and change in maximum grades over a 24-month period. METHODS: MRIs were acquired using 1.5 T or 3 T MRI systems and assessed using the semi-quantitative MRI OA Knee Scoring (MOAKS) system. MRIs were read at baseline and 24-months for cartilage damage, bone marrow lesions (BML), osteophytes, meniscal damage and extrusion, and Hoffa- and effusion-synovitis. In descriptive fashion, the frequencies of MRI features at baseline and change in these imaging biomarkers over time are presented for the entire sample in a subregional and maximum score approach for most features. Differences between knees without and with structural radiographic (R) OA are analyzed in addition. RESULTS: Two hundred eighty-nine participants had readable baseline MRI examinations. Mean age was 66.6 ± 7.1 years and participants had a mean BMI of 28.1 ± 5.3 kg/m2. The majority (55.3%) of included knees had radiographic OA. Any change in total cartilage MOAKS score was observed in 53.1% considering full-grade changes only, and in 73.9% including full-grade and within-grade changes. Any medial cartilage progression was seen in 23.9% and any lateral progression on 22.1%. While for the medial and lateral compartments numbers of subregions with improvement and worsening of BMLs were very similar, for the PFJ more improvement was observed compared to worsening (15.5% vs. 9.0%). Including within grade changes, the number of knees showing BML worsening increased from 42.2% to 55.6%. While for some features 24-months change was rare, frequency of change was much more common in knees with vs. without ROA (e.g. worsening of total MOAKS score cartilage in 68.4% of ROA knees vs. 36.7% of no-ROA knees, and 60.7% vs. 21.8% for an increase in maximum BML score per knee). CONCLUSIONS: A wide range of MRI-detected structural pathologies was present in the IMI-APPROACH cohort. Baseline prevalence and change of features was substantially more common in the ROA subgroup compared to the knees without ROA. TRIAL REGISTRATION: Clinicaltrials.gov identification: NCT03883568.

Association Between Race and Radiographic, Symptomatic, and Clinical Hand Osteoarthritis: A Propensity Score-Matched Study Using Osteoarthritis Initiative Data.

OBJECTIVE: To determine the associations between Black race and the presence of radiographic, symptomatic, and clinical hand osteoarthritis (OA). METHODS: Using available hand radiographs from the Osteoarthritis Initiative cohort (total 4,699; n = 849 Black subjects [18.1%], n = 3,850 non-Black subjects [81.9%]), a propensity score-matching method was used to match Black subjects with non-Black subjects for known potential risk factors of hand OA (age, sex, body mass index, smoking status, cardiovascular disease, osteoporosis, excessive occupation- or recreation-related hand use, and knee OA). Posteroanterior radiographs of subjects' dominant hands were reviewed by a musculoskeletal radiologist in a blinded manner. To assess the severity of hand OA, the modified Kellgren/Lawrence (K/L) radiographic OA scoring scale (grades 0-4) was used, and the presence of erosive OA in the hand joints was recorded. Associations between race and the severity of hand OA (measured as the summed modified K/L grade), presence of radiographic hand OA (modified K/L grade ≥2), presence of erosive hand OA, presence of symptomatic hand OA (radiographic OA with hand pain), and presence of clinical hand OA (indicated by clinical findings of Heberden's nodes in the hands) were studied using regression models. In these models, beta coefficients or odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated for the associations between Black race and any of these radiographic and symptomatic hand OA phenotypes. RESULTS: Black subjects had less severe hand OA (ß = -1.93 [95% CI -2.53, -1.34]), as well as a lower risk of developing radiographic hand OA (OR 0.79 [95% CI 0.66, 0.94]), erosive hand OA (OR 0.23 [95% CI 0.11, 0.47]), symptomatic hand OA (OR 0.63 [95% CI 0.49, 0.82]), and clinical hand OA (OR 0.49 [95% CI 0.41, 0.60]), as compared to non-Black subjects. CONCLUSION: In contrast to the well-established association between Black race and knee or hip OA, the findings of this study suggest that the risk of hand OA is lower in Black subjects compared to non-Black subjects, which is not mediated by known hand OA risk factors. Future studies are warranted to determine the mediating protective factors for hand OA among Black subjects.

Patient Goals and Motivation for Thumb Carpometacarpal Osteoarthritis Surgery.

BACKGROUND: Knowledge is lacking on patient goals and motivation for carpometacarpal joint osteoarthritis (CMCJ OA) surgery. The objective of this study was to explore patient goals and motivation for surgery, whether patient goals were reflected in self-reports of pain and function, and factors characterizing patients highly motivated for surgery. METHODS: This cross-sectional study included 180 patients referred from their general practitioner for CMCJ surgical consultation. Goals for surgery were collected with an open-ended question, categorized with the International Classification of Functioning, Disability and Health coding system, and compared to self-reports of pain and function. Motivation for surgery was rated with a Numeric Rating Scale (NRS, 0-10, 0 = not motivated). Factors characterizing patients highly motivated for surgery (NRS ≥ 8) were explored with multivariate regression analyses. RESULTS: The mean age of the participants was 63 years (SD = 7.6), and 142 (79%) were women. The most common goals for surgery were to reduce pain and improve arm and hand use, but these were not reflected in self-reports of pain and function. Fifty-six (31%) of the patients were characterized as highly motivated for surgery. High motivation for surgery was strongly associated with reporting more activity limitations (odds ratio [OR] = 4.00, P = .008), living alone (OR = 3.18, P = .007), and a young age (OR = 0.94, P = .002). CONCLUSIONS: Decisions on CMCJ OA surgery should be based on assessment and discussion of patients' life situation, hand pain, activity limitations for, and goals and motivation for surgery. According to the european league against rheumatism (EULAR) recommendations, previously received conservative and pharmacological treatment should also be evaluated.

Characteristics of persons with hand osteoarthritis visiting complementary and alternative medicine providers.

Objective: To examine the frequency of Complementary and Alternative Medicine (CAM) in a hand osteoarthritis (OA) population, and to compare demographic and clinical characteristics between persons with hand OA visiting vs. not visiting CAM providers. Methods: 300 persons with hand OA from the Nor-Hand study responded to questionnaires concerning demographic information, medical assessments and their use of CAM and other therapies. In addition, they answered questions about health-related quality of life, comorbidities, psychological health and joint symptoms. The characteristics of persons visiting vs. not visiting CAM providers were compared using chi-square tests and t-tests or Mann-Whitney tests, as appropriate. Results: In total 227 (75.7%) persons with hand OA had used CAM for their joint symptoms and 68 (22.7%) had visited CAM providers. Persons visiting CAM providers reported more severe joint pain when taking all joints into account (mean 4.5 vs. 3.9 on a 0-10 Numerical Rating Scale, p â€‹= â€‹0.05) and more frequent use of non-pharmacological interventions, conventional analgesics, opioids, and previous surgery on ligaments and joints compared with persons not visiting CAM providers. Persons visiting CAM providers also reported more comorbidities and anxiety symptoms and they were characterized by having a more approach-seeking behaviour. Conclusion: Persons with hand OA in secondary care were frequently visiting CAM providers. Persons visiting CAM providers were characterized by more severe joint symptoms despite the use of non-pharmacological and pharmacological interventions compared with persons not visiting CAM providers.

Cohort profile: The Applied Public-Private Research enabling OsteoArthritis Clinical Headway (IMI-APPROACH) study: a 2-year, European, cohort study to describe, validate and predict phenotypes of osteoarthritis using clinical, imaging and biochemical markers.

PURPOSE: The Applied Public-Private Research enabling OsteoArthritis Clinical Headway (APPROACH) consortium intends to prospectively describe in detail, preselected patients with knee osteoarthritis (OA), using conventional and novel clinical, imaging, and biochemical markers, to support OA drug development. PARTICIPANTS: APPROACH is a prospective cohort study including 297 patients with tibiofemoral OA, according to the American College of Rheumatology classification criteria. Patients were (pre)selected from existing cohorts using machine learning models, developed on data from the CHECK cohort, to display a high likelihood of radiographic joint space width (JSW) loss and/or knee pain progression. FINDINGS TO DATE: Selection appeared logistically feasible and baseline characteristics of the cohort demonstrated an OA population with more severe disease: age 66.5 (SD 7.1) vs 68.1 (7.7) years, min-JSW 2.5 (1.3) vs 2.1 (1.0) mm and Knee injury and Osteoarthritis Outcome Score pain 31.3 (19.7) vs 17.7 (14.6), except for age, all: p<0.001, for selected versus excluded patients, respectively. Based on the selection model, this cohort has a predicted higher chance of progression. FUTURE PLANS: Patients will visit the hospital again at 6, 12 and 24 months for physical examination, pain and general health questionnaires, collection of blood and urine, MRI scans, radiographs of knees and hands, CT scan of the knee, low radiation whole-body CT, HandScan, motion analysis and performance-based tests.After two years, data will show whether those patients with the highest probabilities for progression experienced disease progression as compared to those wit lower probabilities (model validation) and whether phenotypes/endotypes can be identified and predicted to facilitate targeted drug therapy. TRIAL REGISTRATION NUMBER: NCT03883568.

Does occupational therapy delay or reduce the proportion of patients that receives thumb carpometacarpal joint surgery? A multicentre randomised controlled trial.

Objectives: To evaluate whether occupational therapy, provided in the period between referral and surgical consultation, might delay or reduce the need of surgery in thumb carpometacarpal joint (CMCJ) osteoarthritis and to explore predictors for CMCJ surgery. Methods: This multicentre randomised controlled trial included patients referred for surgical consultation due to CMCJ osteoarthritis. An occupational therapy group received hand osteoarthritis education, assistive devices, CMCJ orthoses and exercises. A control group received only hand osteoarthritis information. Primary outcome was the proportion of patients that had received CMCJ surgery after 2 years. We examined the primary outcome and predictors for surgery with regression models, and time to surgery with the log-rank test and cox regression analyses. Results: Of 221 patients screened for eligibility, 180 were randomised. Information on the primary outcome was collected from medical records for all included patients. Surgery was performed on 22 patients (24%) that had received occupational therapy and 29 (32%) control patients (OR 0.56, 95% CI 0.26 to 1.21; p=0.14). Median time to surgery was 350 days (IQR 210-540) in the occupational therapy group and 296 days (IQR 188-428) in the control group (p=0.13). Previous non-pharmacological treatment (OR 2.72, 95% CI 1.14 to 6.50) and higher motivation for surgery (OR 1.25, 95% CI 1.09 to 1.43) were significant predictors for CMCJ surgery. Conclusions: Occupational therapy showed a small non-significant tendency to delay and reduce the need for surgery in CMCJ osteoarthritis. Previous non-pharmacological treatment and higher motivation for surgery were significant predictors for surgery.

Heberden's Nodes and Knee Osteoarthritis-Related Osseous Structural Damage: Exploratory Study From the Osteoarthritis Initiative.

OBJECTIVE: To explore whether Heberden's nodes (HNs) could predict magnetic resonance imaging (MRI)-based knee osteoarthritis (OA)-related osseous structural progression. METHODS: Five hundred seventy-five subjects from the Foundation for the National Institutes of Health project underwent clinical examination to evaluate HNs at baseline and knee MRI at baseline and 24 months. The MRI was read according to the semiquantitative MRI OA Knee Score and quantitative periarticular bone morphology measures. Adjusted linear/logistic regression models were implemented to assess the association between the presence of HNs at baseline examination and worsening of MRI-defined osseous structural damage, and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. RESULTS: Comparing patients with HNs (n = 395) and patients without HNs (n = 180), more periarticular bone area expansion in the knee joint was seen in the patients with HNs over 24 months (adjusted OR [ORadj ] 1.39 [95% CI 1.06, 1.83], corrected P [Pcorr ] = 0.019), especially in the medial femur (ORadj 1.49 [95% CI 1.05, 2.13], Pcorr = 0.026) and lateral femur (ORadj 2.51 [95% CI 1.58, 3.97], Pcorr < 0.001), femoral notch (ORadj 1.37 [95% CI 1.02, 1.84], Pcorr = 0.04), and lateral trochlea (ORadj 1.44 [95% CI 1.08, 1.9], Pcorr = 0.012). However, a trend toward less osteophyte worsening was seen in patients with HNs in the whole knee joint (ORadj 0.63 [95% CI 0.40, 1.02], Pcorr = 0.058), particularly in the femur region (ORadj 0.54 [95% CI 0.31, 0.95], Pcorr = 0.03), compared to patients without HNs. CONCLUSION: The presence of HNs was associated with increased MRI-based periarticular bone area expansion, but less osteophyte worsening over 24 months in the knee joint, especially in the femoral region.

2018 update of the EULAR recommendations for the management of hand osteoarthritis.

Since publication of the European League Against Rheumatism (EULAR) recommendations for management of hand osteoarthritis (OA) in 2007 new evidence has emerged. The aim was to update these recommendations. EULAR standardised operating procedures were followed. A systematic literature review was performed, collecting the evidence regarding all non-pharmacological, pharmacological and surgical treatment options for hand OA published to date. Based on the evidence and expert opinion from an international task force of 19 physicians, healthcare professionals and patients from 10 European countries formulated overarching principles and recommendations. Level of evidence, grade of recommendation and level of agreement were allocated to each statement. Five overarching principles and 10 recommendations were agreed on. The overarching principles cover treatment goals, information provision, individualisation of treatment, shared decision-making and the need to consider multidisciplinary and multimodal (non-pharmacological, pharmacological, surgical) treatment approaches. Recommendations 1-3 cover different non-pharmacological treatment options (education, assistive devices, exercises and orthoses). Recommendations 4-8 describe the role of different pharmacological treatments, including topical treatments (preferred over systemic treatments, topical non-steroidal anti-inflammatory drugs (NSAIDs) being first-line choice), oral analgesics (particularly NSAIDs to be considered for symptom relief for a limited duration), chondroitin sulfate (for symptom relief), intra-articular glucocorticoids (generally not recommended, consider for painful interphalangeal OA) and conventional/biological disease-modifying antirheumatic drugs (discouraged). Considerations for surgery are described in recommendation 9. The last recommendation relates to follow-up. The presented EULAR recommendations provide up-to-date guidance on the management of hand OA, based on expert opinion and research evidence.

Validation of a Knowledge Transfer Tool According to the OMERACT Filter: Does Web-based Real-time Iterative Calibration Enhance the Evaluation of Bone Marrow Lesions in Hip Osteoarthritis?

OBJECTIVE: To assess reliability and feasibility of using a Web-based interface and interactive online calibration tool for magnetic resonance imaging (MRI) scoring of bone marrow lesions (BML) in osteoarthritis (OA), applied to the Hip MR Inflammation Scoring System (HIMRISS). METHODS: Seven readers new to HIMRISS (3 radiologists, 4 rheumatologists) scored coronal short-tau inversion recovery MRI from a hip OA observational study obtained pre- and 8-week poststeroid injection (n = 40 × 2 scans × 2 hips = 160 hips). By crossover design, Group B (4 readers) scored 20 patients (40 hips) using conventional spreadsheet-based methods and then another 20 using a Web-based interface and an online real-time iterative calibration (RETIC) training module. Group A (3 readers) reversed the order, scoring the first 20 subjects by the new method and the final 20 conventionally. Outcomes included ICC and reader survey. RESULTS: Interobserver reliability for BML status was high by both spreadsheet and Web-based methods (0.84-0.90), regardless of the order in which scoring was performed. Reliability of change scores was moderate and improved with training. Improvement was greater in readers who began with the spreadsheet method and then used the Web-based method than in those who began with the Web-based method, especially at the acetabulum. Readers found Web-based/RETIC scoring more user-friendly and nearly 50% faster than traditional spreadsheet methods. CONCLUSION: HIMRISS offers reliable BML scoring in OA, whether by conventional spreadsheet-based scoring or by a Web-based interface with interactive feedback. The new method allowed faster readings, provided a consistent training environment that helped inexperienced readers achieve reliability equivalent to that of conventional methods, and was preferred by the readers.

The Prevalence, Incidence, and Progression of Hand Osteoarthritis in Relation to Body Mass Index, Smoking, and Alcohol Consumption.

OBJECTIVE: To estimate the extent that overweight/obesity, smoking, and alcohol are associated with prevalence and longitudinal changes of radiographic hand osteoarthritis (OA). METHODS: Participants from the Osteoarthritis Initiative (n = 1232) were included, of whom 994 had 4-year followup data. In analyses on incident hand OA, only persons without hand OA at baseline were included (n = 406). Our exposure variables were overweight/obesity [body mass index (BMI), waist circumference], smoking (current/former, smoking pack-yrs), and alcohol consumption (drinks/week). Using linear and logistic regression analyses, we analyzed possible associations between baseline exposure variables and radiographic hand OA severity, erosive hand OA, incidence of hand OA, and radiographic changes. Analyses were adjusted for age, sex, and education. RESULTS: Neither overweight nor obesity were associated with hand OA. Current smoking was associated with less hand OA in cross-sectional analyses, whereas longitudinal analyses suggested higher odds of incident hand OA in current smokers (OR 2.20, 95% CI 1.02-4.77). Moderate alcohol consumption was associated with higher Kellgren-Lawrence sum score at baseline (1-3 drinks: 1.55, 95% CI 0.43-2.67) and increasing sum score during 4-year followup (4-7 drinks: 0.33, 95% CI 0.01-0.64). Moderate alcohol consumption (1-7 drinks/week) was associated with 2-fold higher odds of erosive hand OA, which was statistically significant. Additional adjustment for BMI gave similar strengths of associations. CONCLUSION: Overweight/obesity were not associated with hand OA. Contrasting results were observed for smoking and hand OA, suggesting lack of association. Moderate alcohol consumption was associated with hand OA severity, radiographic changes, and erosive hand OA, warranting further investigation.

Validation of a Knowledge Transfer Tool for the Knee Inflammation MRI Scoring System for Bone Marrow Lesions According to the OMERACT Filter: Data from the Osteoarthritis Initiative.

OBJECTIVE: To assess feasibility and reliability of scoring bone marrow lesions (BML) on knee magnetic resonance imaging (MRI) in osteoarthritis using the Outcome Measures in Rheumatology Knee Inflammation MRI Scoring System (KIMRISS), with a Web-based interface and online training with real-time iterative calibration. METHODS: Six readers new to the KIMRISS (3 radiologists, 3 rheumatologists) scored sagittal T2-weighted fat-saturated MRI in 20 subjects randomly selected from the Osteoarthritis Initiative data, at baseline and 1-year followup. In the KIMRISS, the reader moves a transparent overlay grid within a Web-based interface to fit bones, then clicks or touches each region containing BML per slice, to score 1 if BML is present. Regional and total scores are automatically calculated. Outcomes include the interreader intraclass correlation coefficients (ICC) and the smallest detectable change (SDC). RESULTS: Scoring took 3-12 min per scan and all readers rated the process as moderately to very user friendly. Despite a low BML burden (average score 2.8% of maximum possible) and small changes, interobserver reliability was moderate to high for BML status and change in the femur and tibia (ICC 0.78-0.88). Four readers also scored the patella reliably, whereas 2 readers were outliers, likely because of image artifacts. SDC of 1.5-5.6 represented 0.7% of the maximum possible score. CONCLUSION: We confirmed feasibility of knee BML scoring by new readers using interactive training and a Web-based touch-sensitive overlay system, finding high reliability and sensitivity to change. Further work will include adjustments to training materials regarding patellar scoring, and study in therapeutic trial datasets with higher burden of BML and larger changes.

Development and Reliability of the OMERACT Thumb Base Osteoarthritis Magnetic Resonance Imaging Scoring System.

OBJECTIVE: To develop the Outcome Measures in Rheumatology (OMERACT) thumb base osteoarthritis (OA) magnetic resonance imaging (MRI) scoring system (TOMS) for the assessment of inflammatory and structural abnormalities in this hand OA subset, and test its cross-sectional reliability. METHODS: Included features and their scaling were agreed upon by members of the OMERACT MRI Task Force using the Hand OA MRI scoring system as a template. A reliability exercise was performed in which 3 readers participated, using a preliminary atlas with examples to facilitate reading. Each reader independently scored a set of 20 MRI (coronal and axial T1- and T2-weighted fat-suppressed images, of which 5 included T1-weighted fat-suppressed post-Gadolinium images). Intra- and inter-reader reliability were assessed using ICC, percentage exact agreement (PEA), and percentage close agreement (PCA). RESULTS: The TOMS assessed the first carpometacarpal (CMC-1) and scaphotrapeziotrapezoid (STT) joints for synovitis, subchondral bone defects (including erosions, cysts, and bone attrition), osteophytes, cartilage, and bone marrow lesions on a 0-3 scale (normal to severe). Subluxation was evaluated only in the CMC-1 joint (absent/present). Reliability of scoring for both joints was comparable. Interreader ICC were good for all features (0.77-0.99 and 0.74-0.96 for CMC-1 and STT joints, respectively). Intrareader reliability analyses gave similar results. PCA was ≥ 65% for all features. PEA was low to moderate, with better performance for subchondral bone defects, subluxation, and bone marrow lesions. CONCLUSION: A thumb base OA MRI scoring system has been developed. The OMERACT TOMS demonstrated good intrareader and interreader reliability. Longitudinal studies are warranted to investigate reliability of change scores and responsiveness.

MRI findings predict radiographic progression and development of erosions in hand osteoarthritis.

OBJECTIVES: To examine whether MRI features predict radiographic progression including erosive evolution in patients from the Oslo hand osteoarthritis (OA) cohort, which is the first longitudinal hand OA study with available MRI. METHODS: We included 74 patients (91% female, mean (SD) age of 67.9 (5.3) years) with MRI of the dominant hand and conventional radiographs taken at baseline and 5-year follow-up. Baseline MRIs were read according to the Oslo hand OA MRI score. We used three definitions of radiographic progression: Progression of joint space narrowing (JSN, grades 0-3), increased Kellgren-Lawrence score (grades 0-4) or incident erosions (absent/present). For each definition, we examined whether MRI features predicted radiographic progression in the same joint using Generalised Estimating Equations. We adjusted for age, sex, Body Mass Index, follow-up time and other erosive joints (the latter for analyses on incident erosions only). RESULTS: MRI-defined moderate/severe synovitis (OR=3.52, 95% CI 1.29 to 9.59), bone marrow lesions (BML) (OR=2.73, 95% CI 1.29 to 5.78) and JSN (severe JSN: OR=11.05, 95% CI 3.22 to 37.90) at baseline predicted progression of radiographic JSN. Similar results were found for increasing Kellgren-Lawrence score, except for weaker association for JSN. Baseline synovitis, BMLs, JSN, bone damage, osteophytes and malalignment were significantly associated with development of radiographic erosions, of which malalignment showed the strongest association (OR=10.18, 95% CI 2.01 to 51.64). CONCLUSIONS: BMLs, synovitis and JSN were the strongest predictors for radiographic progression. Malalignment was associated with incident erosions only. Future studies should explore whether reducing BMLs and inflammation can decrease the risk of structural progression.

Increasing synovitis and bone marrow lesions are associated with incident joint tenderness in hand osteoarthritis.

OBJECTIVES: To explore whether changes of MRI-defined synovitis and bone marrow lesions (BMLs) are related to changes in joint tenderness in a 5-year longitudinal study of the Oslo hand osteoarthritis (OA) cohort. METHODS: We included 70 patients (63 women, mean (SD) age 67.9 (5.5) years). BMLs and contrast-enhanced synovitis in the distal and proximal interphalangeal joints were evaluated on 0-3 scales in n=69 and n=48 patients, respectively. Among joints without tenderness at baseline, we explored whether increasing/incident synovitis and BMLs were associated with incident joint tenderness using generalised estimating equations. Among joints with tenderness at baseline, we explored whether decreasing or resolution of synovitis and BMLs were associated with loss of joint tenderness. We adjusted for age, sex, body mass index, follow-up time and changes in radiographic OA. RESULTS: Among joints without tenderness at baseline, increasing/incident synovitis and BMLs were seen in 45 of 220 (20.5%) and 47 of 312 (15.1%) joints, respectively. Statistically significant associations to incident joint tenderness were found for increasing/incident synovitis (OR=2.66, 95% CI 1.38 to 5.11) and BMLs (OR=2.85, 95% CI 1.23 to 6.58) independent of structural progression. We found a trend that resolution of synovitis (OR=1.72, 95% CI 0.80 to 3.68) and moderate/large decreases of BMLs (OR=1.90, 95% CI 0.57 to 6.33) were associated with loss of joint tenderness, but these associations were non-significant. CONCLUSIONS: The Oslo hand OA cohort is the first study with longitudinal hand MRIs. Increasing synovitis and BMLs were significantly associated with incident joint tenderness, whereas no significant associations were found for decreasing or loss of synovitis and BMLs.

The Longitudinal Reliability and Responsiveness of the OMERACT Hand Osteoarthritis Magnetic Resonance Imaging Scoring System (HOAMRIS).

OBJECTIVE: To evaluate the interreader reliability of change scores and the responsiveness of the OMERACT Hand Osteoarthritis (OA) Magnetic Resonance Image (MRI) Scoring System (HOAMRIS). METHODS: Paired MRI (baseline and 5-yr followup) from 20 patients with hand OA were scored with known time sequence by 3 readers according to the HOAMRIS: Synovitis, erosive damage, cysts, osteophytes, cartilage space loss, malalignment, and bone marrow lesions (BML; 0-3 scales with 0.5 increments for synovitis, erosive damage, and BML). Interreader reliability for status and change scores were assessed by intraclass correlation coefficients (ICC), percentage exact agreement and percentage close agreement (PEA/PCA), and smallest detectable change (SDC). Responsiveness was assessed by standardized response means (SRM). RESULTS: Cross-sectional interreader ICC were good to very good (≥ 0.74) for all features except synovitis, cysts, and malalignment (ICC 0.50-0.58). The range of change values was small, leading to low ICC for change scores. The SDC values for sum scores (total range 0-24) varied between 1.97-3.05 (except 1.08 for malalignment). For status scores, PEA/PCA on scores in individual joints across the readers were 8.1-50.0 and 43.8-78.1, respectively. Similarly, PEA/PCA for change scores were 20.6-63.8 and 66.3-93.1, respectively. All features except cysts and BML demonstrated good responsiveness with higher SRM for sum scores (range 0.46-1.62) than for scores in individual joints (range 0.24-0.73). CONCLUSION: Good to very good interreader ICC values were found for cross-sectional readings, whereas the longitudinal reliability was lower because of a smaller range of change scores. All features, except cysts and BML, showed good responsiveness.

The OMERACT MRI in Arthritis Working Group - Update on Status and Future Research Priorities.

OBJECTIVE: To provide an update on the status and future research priorities of the Outcome Measures in Rheumatology (OMERACT) magnetic resonance imaging (MRI) in arthritis working group. METHODS: A summary is provided of the activities of the group within rheumatoid arthritis (RA), psoriatic arthritis (PsA), and osteoarthritis (OA), and its research priorities. RESULTS: The OMERACT RA MRI score (RAMRIS) evaluating bone erosion, bone edema (osteitis), and synovitis is now the standard method of quantifying articular pathology in RA trials. Cartilage loss is another important part of joint damage, and at the OMERACT 12 conference, we provided longitudinal data demonstrating reliability and sensitivity to change of the RAMRIS JSN component score, supporting its use in future clinical trials. The MRI group has previously developed a PsA MRI score (PsAMRIS). At OMERACT 12, PsAMRIS was evaluated in a randomized placebo-controlled trial of patients with PsA, demonstrating the responsiveness and discriminatory ability of applying the PsAMRIS to hands and feet. A hand OA MRI score (HOAMRIS) was introduced at OMERACT 11, and has subsequently been further validated. At OMERACT 12, good cross-sectional interreader reliability, but variable reliability of change scores, were reported. Potential future research areas were identified at the MRI session at OMERACT 12 including assessment of tenosynovitis in RA and enthesitis in PsA and focusing on alternative MRI techniques. CONCLUSION: MRI has been further developed and validated as an outcome measure in RA, PsA, and OA. The group will continue its efforts to optimize the value of MRI as a robust biomarker in rheumatology clinical trials.

Hand osteoarthritis in relation to mortality and incidence of cardiovascular disease: data from the Framingham heart study.

OBJECTIVES: To study whether hand osteoarthritis (OA) is associated with increased mortality and cardiovascular events in a large community based cohort (Framingham Heart Study) in which OA, mortality and cardiovascular events have been carefully assessed. METHODS: We examined whether symptomatic (≥1 joint(s) with radiographic OA and pain in the same joint) and radiographic hand OA (≥1 joint(s) with radiographic OA without pain) were associated with mortality and incident cardiovascular events (coronary heart disease, congestive heart failure and/or atherothrombotic brain infarction) using Cox proportional hazards models. In the adjusted models, we included possible confounding factors from baseline (eg, metabolic factors, medication use, smoking/alcohol). We also adjusted for the number of painful joints in the lower limb and physical inactivity. RESULTS: We evaluated 1348 participants (53.8% women) with mean (SD) age of 62.2 (8.2) years, of whom 540 (40.1%) and 186 (13.8%) had radiographic and symptomatic hand OA, respectively. There was no association between hand OA and mortality. Although there was no significant relation to incident cardiovascular events overall or a relation of radiographic hand OA with events, we found a significant association between symptomatic hand OA and incident coronary heart disease (myocardial infarction/coronary insufficiency syndrome) (HR 2.26, 95% CI 1.22 to 4.18). The association remained after additional adjustment for pain in the lower limb or physical inactivity. CONCLUSIONS: Symptomatic hand OA, but not radiographic hand OA, was associated with an increased risk of coronary heart disease events. The results suggest an effect of pain, which may be a possible marker of inflammation.