IntroductionWe have limited knowledge about the underlying disease mechanisms and causes of pain in hand osteoarthritis (OA). Consequently, no disease-modifying drug exists, and more knowledge about the pathogenesis of hand OA is needed, as well as a validation of different outcome measures. Our first aim of this study is to explore the validity of various imaging modalities for the assessment of hand OA. Second, we want to gain a better understanding of the disease processes, with a special focus on pain mechanisms.Methods and analysisThe Nor-Hand study is a hospital-based observational study including 300 patients with evidence of hand OA by ultrasound and/or clinical examination. The baseline examination consists of functional tests and joint assessment of the hands, medical assessment, pain sensitisation tests, ultrasound (hands, acromioclavicular joint, hips, knees and feet), CT and MRI of the dominant hand, conventional radiographs of the hands and feet, fluorescence optical imaging of the hands, collection of blood and urine samples as well as self-reported demographic factors and OA-related questionnaires. Two follow-up examinations are planned. Cross-sectional analyses will be used to investigate agreements and associations between different relevant measures at the baseline examination, whereas the longitudinal data will be used for evaluation of predictors for clinical outcomes.Ethics and disseminationThe protocol is approved by the Norwegian Regional Committee for Medical and Health Research Ethics (Ref. no: 2014/2057). The participants receive oral and written information about the project and sign a consent form before participation. They can, whenever they want, withdraw from the study, and all de-identified data will be safely stored on the research server at Diakonhjemmet Hospital. Results will be presented at international and national congresses and in peer-reviewed rheumatology journals.Trial registration numberNCT03083548; Pre-results.

Objective To examine the association of body mass index (BMI) with pain in people with hand osteoarthritis (OA), and explore whether this association, if causal, is mediated by systemic inflammatory biomarkers. Methods In 281 Nor‐Hand study participants, we estimated associations between BMI and hand pain, as measured by the Australian/Canadian Osteoarthritis Hand Index (AUSCAN; range 0–20) and Numerical Rating Scale (NRS; range 0–10); foot pain, as measured by NRS (range 0–10); knee/hip pain, as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC; range 0–20); painful total body joint count; and pain sensitization. We fit natural‐effects models to estimate natural direct and natural indirect effects of BMI on pain through inflammatory biomarkers. Results Each 5‐unit increase in BMI was associated with more severe hand pain (on average increased AUSCAN by 0.64 [95% confidence interval (95% CI) 0.23, 1.08]), foot pain (on average increased NRS by 0.65 [95% CI 0.36, 0.92]), knee/hip pain (on average increased WOMAC by 1.31 [95% CI 0.87, 1.73]), generalized pain, and pain sensitization. Mediation analyses suggested that the effects of BMI on hand pain and painful total body joint count were partially mediated by leptin and high‐sensitivity C‐reactive protein (hsCRP), respectively. Effect sizes for mediation by leptin were larger for the hands than for the lower extremities, and were statistically significant for the hands only. Conclusion In people with hand OA, higher BMI is associated with greater pain severity in the hands, feet, and knees/hips. Systemic effects of obesity, measured by leptin, may play a larger mediating role for pain in the hands than in the lower extremities. Low‐grade inflammation, measured by hsCRP, may contribute to generalized pain in overweight/obese individuals.

Background:Overweight and obesity are well-known risk factors for osteoarthritis (OA) in weight-bearing joints. However, the role of increased body mass index (BMI) and waist circumference in OA of the non-weight-bearing joints is more controversial. Few hand OA studies have explored the associations between increased BMI/waist circumference and pain.Objectives:The aim of this study was to explore whether BMI and waist circumference were associated with self-reported pain in the hands, feet, knees and hips as well as pain sensitization in persons with hand OA. Further, we examined whether synovitis could partly explain the association between BMI/waist circumference and pain, due to a low-grade inflammatory state in overweight persons.Methods:The Nor-Hand study is an observational study of 300 participants with hand OA. We measured their height and weight in addition to their waist circumference. Participants completed Numeric Rating Scales (NRS) (0-10) about pain during the last 24 hours in their hands and feet, in addition to the Western Ontario and McMaster Universities OA Index (WOMAC) knee/hip pain subscale (0-20). Pressure pain thresholds (PPTs) (kg/cm2) were measured at both a painful and a non-painful interphalangeal joint of the hand, the left distal radioulnar joint and at the tibialis anterior and trapezius muscles. Temporal summation (TS) was measured with a weighted probe that was tapped 10 times at the left distal radioulnar joint. We considered TS to be present if the pain rating increased by ≥2 (i.e., >smallest detectable change) points on the NRS during the test. Ultrasound was used to score grey-scale synovitis on 0-3 scales in a total of 30 joints in the hands, 26 joints in the feet and the bilateral knees. We evaluated the relation of BMI and waist circumference to the pain scales and synovitis sum scores using linear regression, and to presence of pain sensitization assessed by PPT values and TS using linear and logistic regression, respectively. All analyses were adjusted for age, sex and education.Results:The majority of participants were female (n=266, 89%), and the median (IQR) age was 61 (57-66) years. Persons with higher BMI and waist circumference reported higher pain intensity in their hands, feet, knees and hips (Table). Higher BMI and waist circumference were associated with lower PPTs at the tibialis anterior muscle (Table). No associations were found between BMI/waist circumference and PPTs at the other test sites (data not shown). Persons with higher BMI and waist circumference were more likely to have TS (Table). Increased BMI and waist circumference were not associated with more synovitis in the hands, feet or knees (data not shown).Table.Data presented as B (95% CI) for the pain measures/PPT value and OR (95% CI) for presence of TS. All analyses were adjusted for age, sex and education.NRS hand pain (0-10)NRS feet pain(0-10)WOMAC knee/hip pain(0-20)PPT tibialis anterior(kg/cm2)Presenceof TSBMI per SD increase*0.5 (0.2, 0.7)0.7 (0.4, 1.0)1.3 (0.8, 1.8)-0.4 (-0.7,-0.1)1.4 (1.1, 1.8)Waist circumference per SD increase**0.5 (0.3, 0.8)0.6 (0.3, 0.9)1.3 (0.8, 1.8)-0.4 (-0.7,-0.1)1.4 (1.1, 1.8)*Standard deviation (SD)=5.0 kg/m2, **SD=12.9 cmConclusion:In the Nor-Hand cohort, persons with higher BMI and waist circumference reported higher pain intensity in their hands, feet, knees and hips. This relation was not explained by higher levels of synovitis in the joints. However, the association may at least partly be driven by a higher prevalence of central pain sensitization in persons with higher BMI. Due to the cross-sectional study design we cannot conclude about causality.Disclosure of Interests:Marthe Gløersen: None declared, Pernille Steen Pettersen: None declared, Tuhina Neogi Grant/research support from: Pfizer/Lilly, Consultant of: Pfizer/Lilly, EMD-Merck Serono, Novartis, Tore K. Kvien Grant/research support from: Received grants from Abbvie, Hospira/Pfizer, MSD and Roche (not relevant for this abstract)., Consultant of: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Paid instructor for: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Speakers bureau: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Karin Magnusson: None declared, Hilde Berner Hammer Consultant of: Has received fees as consultant from Roche, AbbVie and Novartis., Speakers bureau: Has received fees for speaking from AbbVie, BMS, Pfizer, UCB, Roche, MSD and Novartis, Ida K. Haugen: None declared

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Objective.To examine the validity of a modified Intermittent and Constant Osteoarthritis Pain (ICOAP) questionnaire for assessment of pain in hand osteoarthritis (OA).Methods.The modified ICOAP-hand questionnaire was administered to 300 patients [89% female, median (interquartile range) age: 61 (57–66) yrs] in the Nor-Hand observational cohort study. The questionnaire was completed twice by 31 patients and test-retest reliability was assessed by intraclass correlation coefficients (ICC) for sum scores and weighted κ scores for individual items. Internal consistency was assessed by Cronbach’s alpha coefficient and item-total correlations. Correlations between the ICOAP-hand questionnaire, the Australian/Canadian Hand OA Index (AUSCAN) hand pain subscale, and pain on a numerical rating scale (NRS) were analyzed using Spearman correlation analyses.Results.We found a substantial overlap between constant and intermittent pain (46% reporting constant + intermittent pain and 33% reporting no pain). Test-retest reliability analysis of ICOAP-hand showed an ICC of 0.89 for the total scale and weighted κ values between 0.39–0.70 for the individual items. Principal component analysis revealed one component with an eigenvalue of 7.9, explaining 72% of the total variance. Cronbach’s alpha coefficient values > 0.93 and strong item-total correlations proved high internal consistency. ICOAP-hand was strongly correlated with NRS hand pain and the AUSCAN pain subscale.Conclusion.ICOAP-hand is a reliable pain index that correlates with other available pain questionnaires. However, our results indicate that constant and intermittent pain do not represent separate constructs in hand OA, questioning the usefulness of the 2 subscales. [ClinicalTrials.gov: NCT03083548]

Purpose: The Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP) questionnaire is specially developed to assess both constant and intermittent pain in knee and hip osteoarthritis (OA). There are few validated questionnaires to assess pain in hand OA, including the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) and numerical rating scales (NRS). They measure the pain intensity only, do not cover other important aspects of the nature of pain, and the AUSCAN questionnaire is not available for free. Hence, the aim of this study was to explore the test-retest reliability and internal consistency of a modified version of the ICOAP questionnaire (ICOAP-hand) for assessment of pain in hand OA, as well as the correlations with AUSCAN and NRS pain. Methods: A total of 301 patients (89% female, median age 60.9 years (56.6e65.9), mean BMI 26.5 (5.0), 93% fulfilling the ACR hand OA criteria) were examined in the Nor-Hand study, which is an observational cohort study of patients with hand OA. The patients completed the AUSCAN pain subscale (5 questions about hand pain last 48 h, each rated on 0e4 scales), NRS hand pain last 24 h (0e10 scale) and ICOAP-hand questionnaire (5 questions about constant pain and 6 questions about intermittent pain in the hands during the last week, each on a 0e4 scale). The test-retest reliability was calculated using the intraclass correlation coefficients (ICC). Internal consistency was assessed by Cronbach's alpha and item-total correlations. In addition, correlations between ICOAP-hand, AUSCAN pain and NRS pain were calculated using Spearman correlation coefficients. Results: The questionnaire was completed twice by 45 patients, and the median (min, max) time interval between the first and second assessment was 6 (0, 80) days. Test-retest reliability was good for all questionnaires, with ICCs ranging from 0.63 (AUSCAN pain) to 0.80 (ICOAP total pain). High internal consistency was found for the ICOAP constant pain, intermittent pain and total pain subscales (Cronbach's alpha: 0.93e0.96). The item-total correlations ranged between 0.75 and 0.87 for the constant pain subscale and 0.71e0.86 for the intermittent pain subscale. Strong correlations were found between ICOAP-hand, AUSCAN pain and NRS pain (table 1), which were all statistically significant (P < 0.001). Conclusions: The modified ICOAP questionnaire for assessment of hand OA pain showed good test-retest reliability, high internal consistency and strong correlations with AUSCAN pain and NRS pain. The ICOAPhand questionnaire may be an important tool to gain knowledge about the nature of pain in hand OA. In contrast to the AUSCAN index, the questionnaire is available for free. However, longitudinal studies are needed to explore the sensitivity to change before ICOAP-hand can be recommended for use in clinical trials.

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