Subluxation of the first carpometacarpal joint and age are important factors in reduced hand strength in patients with hand osteoarthritis.

OBJECTIVE: To investigate the determinants of hand strength in patients with hand osteoarthritis (OA). METHOD: Pinch and cylinder grip strength were measured in 527 patients with hand OA diagnosed by their treating rheumatologist from the Hand OSTeoArthritis in Secondary care (HOSTAS) study. Radiographs of hands (22 joints) were scored 0-3 (scaphotrapeziotrapezoid and first interphalangeal joints 0-1) on osteophytes and joint space narrowing following the Osteoarthritis Research Society International atlas. The first carpometacarpal joint (CMC1) was scored 0-1 for subluxation. Pain was assessed with the Australian/Canadian Hand Osteoarthritis Index pain subscale, and health-related quality of life with the Short Form-36. Regression analysis served to investigate associations of hand strength with patient, disease, and radiographic features. RESULTS: Hand strength was negatively associated with female sex, age, and pain. Reduced hand strength was associated with reduced quality of life, although less after adjusting for pain. Radiographic features of hand OA were associated with reduced grip strength when solely adjusted for sex and body mass index, but only CMC1 subluxation in the dominant hand remained significantly associated with pinch grip adjusted additionally for age (-0.511 kg, 95% confidence interval -0.975; -0.046). Mediation analysis showed low and not significant percentages of mediation of hand OA in the association between age and grip strength. CONCLUSIONS: Subluxation of CMC1 is associated with reduced grip strength, whereas associations with other radiographic features seem to be confounded by age. In the relationship between age and hand strength, radiographic hand OA severity is not an important mediator.

The association of clinical and structural knee osteoarthritis with physical activity in the middle-aged population: the NEO study.

OBJECTIVE: To investigate if knee osteoarthritis (OA) is associated with lower physical activity in the general middle-aged Dutch population, and if physical activity is associated with patient-reported outcomes in knee OA. DESIGN: Clinical knee OA was defined in the Netherlands Epidemiology of Obesity population using the ACR criteria, and structural knee OA on MRI. We assessed knee pain and function with the Knee Injury and Osteoarthritis Score (KOOS), health-related quality of life (HRQoL) with the Short Form-36, and physical activity (in Metabolic Equivalent of Task (MET) hours) with the Short Questionnaire to Assess Health-enhancing physical activity. We analysed the associations of knee OA with physical activity, and of physical activity with knee pain, function, and HRQoL in knee OA with linear regression adjusted for potential confounders. RESULTS: Clinical knee OA was present in 14% of 6,212 participants, (mean age 56 years, mean BMI 27 kg/m2, 55% women, 24% having any comorbidity) and structural knee OA in 12%. Clinical knee OA was associated with 9.60 (95% CI 3.70; 15.50) MET hours per week more physical activity, vs no clinical knee OA. Structural knee OA was associated with 3.97 (-7.82; 15.76) MET hours per week more physical activity, vs no structural knee OA. In clinical knee OA, physical activity was not associated with knee pain, function or HRQoL. CONCLUSIONS: Knee OA was not associated with lower physical activity, and in knee OA physical activity was not associated with patient-reported outcomes. Future research should indicate the optimal treatment advice regarding physical activity for individual knee OA patients.

Percentile curves for the knee injury and osteoarthritis outcome score in the middle-aged Dutch population.

OBJECTIVE: To improve the interpretation of the Knee injury and Osteoarthritis Outcome Score (KOOS) in individual patients, we explored associations with age, sex, BMI, history of knee injury and presence of clinical knee osteoarthritis, and developed percentile curves. METHODS: We used cross-sectional data of middle-aged individuals from the population-based Netherlands Epidemiology of Obesity (NEO) study. Clinical knee osteoarthritis was defined using the ACR classification criteria. KOOS scores were handled according to the manual (zero = extreme problems, 100 = no problems). Patient characteristics associated with KOOS were explored using ordered logistic regression, and sex and body mass index (BMI)-specific percentile curves were developed using quantile regression with fractional polynomials. The curves were applied as a benchmark for comparison of KOOS scores of participants with knee osteoarthritis and comorbidities. RESULTS: The population consisted of 6,643 participants (56% women, mean (SD) age 56(6) years). Population-based KOOS subscale scores (median; interquartile range) near optimum: pain (100;94-100), symptoms (96;86-100), ADL function (100;96-100), sport/recreation function (100;80-100), quality of life (100;75-100). Worse KOOS scores were observed in women and in participants with higher BMI. Clinical knee osteoarthritis was defined in 15% of participants, and was, in comparison to other patient characteristics, associated with the highest odds of worse KOOS scores. Furthermore, presence of any comorbidity and cardiovascular disease specifically, was associated with worse KOOS scores, particularly in women. CONCLUSIONS: In the middle-aged Dutch population KOOS scores were generally good, but worse in women and with higher BMI. These percentile curves may be used as benchmarks in research and clinical practice.

The association of plasma fatty acids with hand and knee osteoarthritis: the NEO study.

OBJECTIVE: To investigate the association of postprandial and fasting plasma saturated fatty acid (SFAs), monounsaturated fatty acid (MUFAs) and polyunsaturated fatty acid (PUFAs) concentrations with hand and knee osteoarthritis (OA). DESIGN: In the population-based NEO study clinical hand and knee OA were defined by the ACR classification criteria. Structural knee OA was defined on MRI. Hand and knee pain was determined by Australian/Canadian Hand Osteoarthritis Index (AUSCAN) and KOOS, respectively. Plasma was sampled fasted and 150 min after a standardized meal, and subsequently analysed using a nuclear magnetic resonance platform. Logistic regression analyses were used to investigate the association of total fatty acid, SFA, MUFA, total PUFA, omega-3 PUFA and omega-6 PUFA concentrations with clinical hand and knee OA, structural knee OA and hand and knee pain. Fatty acid concentrations were standardized (mean 0, SD 1). Analyses were stratified by sex and corrected for age, education, ethnicity and total body fat percentage. RESULTS: Of the 5,328 participants (mean age 56 years, 58% women) 7% was classified with hand OA, 10% with knee OA and 4% with concurrent hand and knee OA. In men, postprandial SFAs (OR (95% CI)) 1.23 (1.00; 1.50), total PUFAs 1.26 (1.00; 1.58) and omega-3 PUFAs 1.24 (1.01; 1.52) were associated with hand OA. SFAs and PUFAs were associated with structural, but not clinical knee OA. Association of fasting fatty acid concentrations were weaker than postprandial concentrations. CONCLUSION: Plasma postprandial SFA and PUFA levels were positively associated with clinical hand and structural knee OA in men, but not in women.

In finger osteoarthritis, change in synovitis is associated with change in pain on a joint-level; a longitudinal magnetic resonance imaging study.

OBJECTIVE: To investigate determinants of decrease and increase in joint pain in symptomatic finger osteoarthritis (OA) on magnetic resonance (MR) imaging over 2 years. DESIGN: Eighty-five patients (81.2% women, mean age 59.2 years) with primary hand OA (89.4% fulfilling American College of Rheumatology (ACR) classification criteria) from a rheumatology outpatient clinic received contrast-enhanced MR imaging (1.5T) and physical examination of the right interphalangeal finger joints 2-5 at baseline and at follow-up 2 years later. MR images were scored paired in unknown time order, following the Hand OA MRI scoring system (HOAMRIS). Joint pain upon palpation was assessed by research nurses. Odds ratios (ORs; 95% confidence intervals) were estimated on joint level (n = 680), using generalized estimating equations (GEE) to account for the within patient effects. Additional adjustments were made for change in MR-defined osteophytes, synovitis, and bone marrow lesions (BMLs). RESULTS: Of 116 painful joints at baseline, at follow-up: 76 had less pain, 21 less synovitis, and 13 less BMLs. A decrease in synovitis (OR = 5.9; 1.12─31.0), but not in BMLs (OR = 0.39; 0.10─1.50), was associated with less pain. Of 678 joints without maximum baseline pain, at follow-up: 115 had increased pain, 132 increased synovitis, 96 increased BMLs, and 44 increased osteophytes. Increased synovitis (OR = 1.81; 1.11─2.94), osteophytes (OR = 2.75; 1.59─4.8), but not BMLs (OR = 1.14; 0.81─1.60), was associated with increased pain. Through stratification it became apparent that BMLs were mainly acting as effect modifier of the synovitis-pain association. CONCLUSION: Decrease in MR-defined synovitis is associated with reduced joint pain, identifying synovitis as a possible target for treatment of finger OA.

The role of leptin and adiponectin as mediators in the relationship between adiposity and hand and knee osteoarthritis.

OBJECTIVES: To investigate associations of leptin and adiponectin levels with knee and hand osteoarthritis, and explore whether these mediate the association between adiposity and osteoarthritis. METHODS: This is a cross-sectional analysis of baseline data from the population-based Netherlands Epidemiology of Obesity study. Adiposity was assessed with body mass index (BMI) and percentage total body fat (%TBF). Osteoarthritis, defined as hand or knee osteoarthritis, was determined using American College of Rheumatology criteria. Fasting serum adipokine levels were measured using immunoassays. Associations between adiposity and osteoarthritis were examined with logistic regression, adjusted for age, sex, ethnicity and education, and additionally for leptin and adiponectin as potential mediators. RESULTS: In 6408 participants (56% women, median age 56 years), prevalence of osteoarthritis was 22% (10% isolated knee and 8% isolated hand osteoarthritis). Leptin levels were positively associated with osteoarthritis, while adiponectin levels were not. Leptin partially mediated the association of adiposity with osteoarthritis (OR 1.40 (95%CI 1.30; 1.52) attenuated to 1.38 (1.24; 1.54) per 5 units BMI and OR 1.25 (1.17; 1.35) to 1.20 (1.10; 1.32) per 5 units %TBF, representing 4% and 17% mediation, respectively). Larger proportion mediation by leptin was found in knee (13%/27%) than in hand osteoarthritis (9%/18%). Sex-stratified analyses generally showed stronger associations between adiposity, leptin and osteoarthritis in women than in men. CONCLUSIONS: Serum leptin levels were associated with osteoarthritis, and partially mediated the association between adiposity and osteoarthritis, while adiponectin levels were not associated with osteoarthritis. These findings provide evidence for systemic effects of adipose tissue in osteoarthritis.

The role of inflammation in the association between overall and visceral adiposity and subclinical atherosclerosis.

BACKGROUND AND AIMS: Inflammation may underlie the association between obesity, atherosclerosis and cardiovascular disease. We investigated to what extent markers of inflammation mediate associations between overall and visceral body fat and subclinical atherosclerosis. METHODS AND RESULTS: In this cross-sectional analysis of the Netherlands Epidemiology of Obesity study we estimated total body fat (TBF) by bio-impedance analysis, carotid artery intima media thickness (cIMT) by ultrasound, C-reactive protein (hs-CRP) and glycoprotein acetyls (GlycA) concentrations in fasting blood samples (n = 5627), and visceral adipose tissue (VAT) by magnetic resonance imaging (n = 2247). We examined associations between TBF and VAT, and cIMT using linear regression, adjusted for potential confounding factors, and for mediators: cardiometabolic risk factors (blood pressure, glucose and low-density lipoprotein cholesterol), and inflammation using CRP and GlycA as proxies. Mean (SD) cIMT was 615 (90) µm. Per SD of TBF (8%), cIMT was 19 µm larger (95% confidence interval, CI: 10, 28). This association was 17 µm (95% CI: 8, 27) after adjustment for cardiometabolic risk factors, and did not change after adjustment for markers of inflammation. Per SD (56 cm2) VAT, cIMT was 9 µm larger (95% CI: 2, 16) which changed to 5 µm (95% CI: -3, 12) after adjustment for cardiometabolic risk factors, and did not change after adjustment for inflammatory markers. CONCLUSION: Our results suggest that associations between measures of overall and visceral body fat and subclinical atherosclerosis are not mediated by inflammation as measured by CRP and GlycA. Obesity may exert cardiovascular risk via other markers of systemic inflammation.

Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group.

Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals. In ancestry-specific meta-analyses, eight novel pharmacogenomic loci met the threshold for genome-wide significance (P<5 × 10-8), and a pharmacokinetic variant in CYP2C9 (rs1057910) that has been associated with sulfonylurea-related treatment effects and other adverse drug reactions in previous studies was replicated. Additional research is needed to replicate the novel findings and to understand their biological basis.

Performance of the Michigan Hand Outcomes Questionnaire in hand osteoarthritis.

OBJECTIVE: To investigate the performance of the Michigan Hand Outcomes Questionnaire (MHQ) in hand osteoarthritis (OA) by evaluating truth, discrimination and feasibility. DESIGN: Symptomatic hand OA patients from the Hand Osteoarthritis in Secondary Care (HOSTAS) cohort completed questionnaires (demographics, MHQ, Australian/Canadian Hand Osteoarthritis Index [AUSCAN], Functional Index for Hand Osteoarthritis [FIHOA] and visual analogue scale [VAS] pain) at baseline (n = 383), 1- and 2-year follow-up (n = 312, n = 293). Anchor questions at follow-up assessed whether pain/function levels were (un)acceptable and had changed compared to baseline. Correlations between MHQ and other pain/function questionnaires were calculated. Validity of unique MHQ domains (work performance, aesthetics, satisfaction), discrimination across disease stages, and responsiveness were assessed by categorizing patients by external anchors (employment, joint deformities, erosions, and anchor questions). Between-group differences were assessed with linear regression, probability plots and comparison of medians. RESULTS: MHQ pain and function subscales correlated moderately-to-good with other instruments (rs 0.63-0.81). Work performance scores were worse in patients with reduced working capacity than in employed patients. Aesthetics scores were worse in patients with more deformities. Patients with unacceptable complaints had worse satisfaction scores. All pain/function instruments discriminated between patients with acceptable vs unacceptable pain/function, while only MHQ activities of daily living (ADL), FIHOA, and MHQ aesthetics could discriminate between erosive and non-erosive disease. MHQ and AUSCAN were most responsive. CONCLUSIONS: MHQ has several unique aspects and advantages justifying its use in hand OA, including the unique assessment of work performance, aesthetics, and satisfaction. However, MHQ, AUSCAN and FIHOA appear to measure different aspects of pain and function.

In thumb base osteoarthritis structural damage is more strongly associated with pain than synovitis.

OBJECTIVE: Osteoarthritis in thumb base joints (first carpometacarpal (CMC-1), scaphotrapeziotrapezoid (STT)) is prevalent and disabling, yet focussed studies are scarce. Our aim was to investigate associations between ultrasonographic and magnetic resonance imaging (MRI) inflammatory features, radiographic osteophytes, and thumb base pain in hand osteoarthritis patients. DESIGN: Cross-sectional analyses were performed in cohorts with MRI (n = 202) and ultrasound measurements (n = 87). Pain upon thumb base palpation was assessed. Radiographs were scored for CMC-1/STT osteophytes. Synovial thickening, effusion and power Doppler signal in CMC-1 joints were assessed with ultrasound. MRIs were scored for synovitis and bone marrow lesions (BMLs) in CMC-1 and STT joints using OMERACT-TOMS. Associations between ultrasound/MRI features, osteophytes, and thumb base pain were assessed. Interaction between MRI features and osteophytes was explored. RESULTS: In 289 patients (mean age 60.2, 83% women) 139/376 thumb bases were painful. Osteophyte presence was associated with pain (MRI cohort: odds ratio (OR) 5.1 (2.7-9.8)). Ultrasound features were present in 25-33% of CMC-1 joints, though no associations were seen with pain. MRI-synovitis and BMLs grade ≥2 were scored in 25% and 43% of thumb bases, and positively associated with pain (OR 3.6 (95% CI 1.7-7.6) and 3.0 (1.6-5.5)). Associations attenuated after adjustment for osteophyte presence. Combined presence of osteophytes and MRI-synovitis had an additive effect. CONCLUSIONS: Ultrasonographic and MRI inflammatory features were often present in the thumb base. Osteophytes were more strongly associated with thumb base pain than inflammatory features, in contrast to findings in finger OA studies, supporting thumb base osteoarthritis as a distinct phenotype.

Interrelationship of the rs7903146 TCF7L2 gene variant with measures of glucose metabolism and adiposity: The NEO study.

BACKGROUND AND AIMS: We investigated the interrelationship of rs7903146-T in TCF7L2 with measures of glucose metabolism and measures of adiposity. METHODS AND RESULTS: This cross-sectional analysis was conducted in 5744 middle-aged participants (mean (standard deviation [SD]) age is 55.9 (6.0) years) from the Netherlands Epidemiology of Obesity (NEO) Study. Associations between rs7903146-T and Type 2 diabetes mellitus (T2D) were assessed with logistic regression. Additive (per-allele) associations with measures of glucose metabolism (e.g., fasting insulin) and adiposity (e.g., body mass index [BMI]) were examined with multivariable linear regression. In the total study population, rs7903146-T was associated with a higher risk of T2D (additive odds ratio: 1.42; 95% confidence interval: 1.17; 1.72), and specifically with T2D treated with insulin analogs (2.31 [1.19; 4.46]). After exclusion of participants treated with glucose-lowering medication, rs7903146-T was associated with lower mean insulin concentration (additive mean difference: -0.07 SD [-0.14; 0.00]), but not with higher mean glucose concentration (0.03 SD [-0.01; 0.07]). Furthermore, rs7903146-T was associated with, among other measures of adiposity, a lower mean BMI (-0.04 SD [-0.09; -0.00]), and a lower mean total body fat (-0.04 SD [-0.08; -0.00]). The association between rs7903146-T and T2D increased after adjustment for BMI (odds ratio: 1.51 [1.24; 1.86]); the association between rs7903146-T and fasting insulin diminished after adjustment (-0.05 SD [-0.11; 0.02]). CONCLUSION: rs7903146-T is associated with a decreased insulin concentration and increased risk of T2D with opposing effects of adjustment for adiposity.

Genetic variation in the obesity gene FTO is not associated with decreased fat oxidation: the NEO study.

BACKGROUND: The fat mass and obesity-associated (FTO) gene harbors the strongest common genetic variant associated with obesity. Recently, rs1421085-T to -C substitution mapped in FTO was shown to induce a developmental shift of human adipocytes from an energy-combusting beige to an energy-storing white phenotype in vitro. As browning of adipocytes selectively enhances fat oxidation (FatOx), we hypothesized that rs1421085-C in FTO is associated with deceased FatOx compared with carbohydrate oxidation (CarbOx) and an increased respiratory quotient (RQ). METHODS: In the Netherlands Epidemiology of Obesity study, a population-based cohort study of middle-aged individuals (45-65 years), anthropometry and genotyping was performed (n=5744), in addition to indirect calorimetry (n=1246). With linear regression analyses, we examined associations of rs1421085 genotype with FatOx, CarbOx and RQ. RESULTS: In the total study population, 36.7% carried the rs1421085-TT genotype, 47.6% rs1421085-CT and 15.7% rs1421085-CC. Mean (s.d.) age was 56 (6) years, mean (s.d.), body mass index (BMI) was 26.3 (4.4) kg m-2 and 56% of the total population were women. Measures of adiposity (difference, 95% confidence interval) were higher in CC carriers compared with that in rs1421085-TT carriers: BMI +0.56 (0.15, 0.98) kg m-2, waist circumference +1.25 (0.02, 2.49) cm and total body fat mass +1.21 (0.28, 2.14) kg. However, no differences in mean FatOx (+2.5 (-2.4, 7.4) mg min-1), CarbOx (-6.1 (-17.4, 5.2) mg min-1) or RQ (-0.01 (-0.02, 0.01)) were observed between the two genotypes. CONCLUSIONS: We observed no evidence for associations of rs1421085 in FTO with FatOx and RQ. This indicates that the rs1421085-C allele in FTO induces obesity likely via other pathways than via reduced FatOx.

Bone marrow lesions and synovitis on MRI associate with radiographic progression after 2†years in hand osteoarthritis.

OBJECTIVE: To study the association of magnetic resonance (MR) features with radiographic progression of hand osteoarthritis over 2 years. METHODS: Of 87 primary patients with hand osteoarthritis (82% women, mean age 59 years), baseline distal and proximal interphalangeal joint contrast-enhanced MR images were scored 0-3 for bone marrow lesions (BMLs) and synovitis following the Oslo score. Baseline and 2-year follow-up radiographs were scored following Kellgren-Lawrence (KL) (0-4) and OsteoArthritis Research Society International (OARSI) scoring methods (0-3 osteophytes, joint space narrowing (JSN)). Increase ≥1 defined progression. Associations between MR features and radiographic progression were explored on joint and on patient level, adjusting for age, sex, body mass index, synovitis and BML. Joints in end-stage were excluded. RESULTS: Of 696 analysed joints, 324 had baseline KL=0, 28 KL=4 and after 2 years 78 joints progressed. BML grade 2/3 was associated with KL progression (2/3 vs 0: adjusted risk ratio (RR) (95% CI) 3.3 (2.1 to 5.3)) and with osteophyte or JSN progression, as was synovitis. Summated scores were associated with radiographic progression on patient level (RR crude BML 1.08 (1.01 to 1.2), synovitis 1.09 (1.04 to 1.1), adjusted synovitis 1.08 (1.03 to 1.1)). CONCLUSIONS: BMLs, next to synovitis, show, already after 2 years, graded associations with radiographic progression, suggesting that both joint tissues could be important targets for therapy.

Bone marrow lesions on magnetic resonance imaging in hand osteoarthritis are associated with pain and interact with synovitis.

OBJECTIVE: To determine the association between bone marrow lesions (BMLs) and (teno)synovitis as assessed on magnetic resonance (MR) imaging in patients with pain in hand osteoarthritis (OA). METHODS: In 105 consecutive primary hand OA patients (83% women, mean age 59 years), who were diagnosed by rheumatologists and included in the HOSTAS (Hand OSTeoArthritis in Secondary care) cohort, contrast enhanced MR imaging of right distal and proximal interphalangeal joints were obtained. In 92 patients joint site specific pain upon palpation was assessed within 3 weeks of magnetic resonance imaging (MRI) examination. MR features were scored (0-3) following the Oslo hand OA score: BMLs, synovitis, cysts, flexor tenosynovitis (FTS). Additionally, extensor tendon inflammation (ETI) (0-3) was scored. Odds ratios (OR, 95% confidence interval (CI)) were calculated using generalized estimating equations for MR features with joint pain, adjusted for putative confounders. Stratified analyses were performed to investigate interaction. RESULTS: BMLs, synovitis, cysts, FTS and ETI were demonstrated in 56%, 90%, 22%, 16% and 30% of patients, respectively. BMLs (grade 2/3 vs 0: 3.5 (1.6-7.7)) and synovitis (3 vs 0: OR 3.6 (95% CI 1.9-6.6)) were severity-dependent associated with joint pain, but FTS and ETI were not. Stratified analyses showed that BMLs did not associate with pain in the absence of synovitis, whereas synovitis was associated with pain in the absence of BMLs. Interaction was seen between BMLs and synovitis grade 2 or 3. CONCLUSION: In hand OA patients severe synovitis is associated with joint pain, which is worsened when BMLs co-occur, suggesting synovitis as primary target of treatment.

SIPPET: methodology, analysis and generalizability.

The development of anti-FVIII neutralizing alloantibodies (inhibitors), occurring in about one-third of previously untreated patients (PUPs) with severe haemophilia A, depends on various genetic and environmental risk factors. Several previous studies have reported on the immunogenicity of FVIII concentrates, and due to differences in study design, study period, inhibitor testing frequency and follow-up duration the results were inconclusive. The first randomized trial on this unresolved question (SIPPET) included 251 previously untreated or minimally treated patients with severe haemophilia A treated with either a single plasma-derived FVIII (pdFVIII) containing VWF or a recombinant FVIII (rFVIII). The results showed an 87% higher rate of inhibitor development for rFVIII than pdFVIII during the first 50 exposure days of treatment. These results generated interest by patient organizations, physicians and regulatory agencies. This manuscript summarizes answers to the main questions that arose after the full publication of SIPPET.

Sensitivity-to-change and validity of semi-automatic joint space width measurements in hand osteoarthritis: a follow-up study.

OBJECTIVE: To assess sensitivity-to-change and validity of longitudinal quantitative semi-automatic joint space width (JSW) measurements and to compare this method with semi-quantitative joint space narrowing (JSN) scoring in hand osteoarthritis (OA) patients. DESIGN: Baseline and 2-year follow-up radiographs of 56 hand OA patients (mean age 62 years, 86% women) were used. JSN was scored 0-3 using the Osteoarthritis Research Society International atlas and JSW was quantified in millimetres (mm) in the second to fifth distal, proximal interphalangeal and metacarpal joints (DIPJs, PIPJs, MCPJs). Sensitivity-to-change was evaluated by calculating Standardized Response Means (SRMs). Change in JSW or JSN above the Smallest Detectable Difference (SDD) defined progression on joint level. To assess construct validity, progressed joints were compared by cross-tabulation and by associating baseline ultrasound variables with progression (using generalized estimating equations, adjusting for age and sex). RESULTS: The JSW method detected statistically significant mean changes over 2.6 years (-0.027 mm (95%CI -0.01; -0.04), -0.024 mm (-0.01; -0.03), -0.021 mm (-0.01; -0.03) for DIPJs, PIPJs, MCPJs, respectively). Sensitivity-to-change was low (SRMs: 0.174, 0.168, 0.211, respectively). 9.1% (121/1336) of joints progressed in JSW, but 3.6% (48/1336) widened. 83 (6.2%) joints progressed in JSW only, 36 (2.7%) in JSN only and 37 (2.8%) in both methods. Progression in JSW showed weaker associations with baseline inflammatory ultrasound features than progression in JSN. CONCLUSIONS: Assessment of progression in hand OA defined by JSW measurements is possible, but performs less well than progression defined by JSN scoring. Therefore, the value of JSW measurements in hand OA clinical trials remains questionable.

No association between impaired glucose metabolism and osteoarthritis.

OBJECTIVE: To investigate the association between markers of glucose metabolism and hand and knee osteoarthritis (OA). METHODS: This is a cross-sectional analysis of baseline measurements of the Netherlands Epidemiology of Obesity (NEO) study, a population-based prospective cohort study. Fasting glucose, insulin and glycated hemoglobulin A1c (HbA1c) concentrations were measured, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) was calculated and clinical OA was defined following the American College of Rheumatology (ACR) criteria. After exclusion of participants on glucose-lowering drugs, odds ratios (ORs) with 95% confidence intervals (CIs) for either hand, knee or both hand and knee OA were calculated (no OA as reference), as a function of each marker of glucose metabolism, with logistic regression analyses. Models were adjusted for age, ethnicity, education, height, weight and total body fat, and stratified by sex. RESULTS: In 6197 participants (age 45-65 years, 56% women, mean body mass index (BMI) 26 kg/m(2)), prevalences of hand OA, knee OA or both were 7%, 10% or 4%, respectively. In men, the adjusted OR (95%CI) for hand OA was 1.18 (1.01-1.39) per standard deviation (SD) increase in plasma glucose (0.85 mmol/L). There were no further associations of glucose, HbA1c, insulin and HOMA-IR with the different types of OA, neither in men nor in women. CONCLUSION: An impaired glucose metabolism does not seem be related to OA. In men, an association was observed for fasting glucose concentrations and hand OA. Future studies should investigate the presence of sex differences in the pathogenesis of hand OA.

Aesthetic dissatisfaction in patients with hand osteoarthritis and its impact on daily life.

OBJECTIVES: To evaluate the nature and extent of aesthetic dissatisfaction in patients with hand osteoarthritis (OA), and to investigate its impact on daily life and its determinants. METHOD: Patients with primary hand OA, consulting secondary care, underwent physical examination for the number of joints with bony joint enlargements, soft tissue swelling and deformities, and radiographs. Questionnaires were filled in to measure pain and function (Functional Index for Hand Osteoarthritis, FIHOA), dissatisfaction with the appearance of the hands and its impact (aesthetic scales from the Michigan Hand Outcomes Questionnaire, MHQ), anxiety and depression (the Hospital Anxiety and Depression Scale, HADS), and illness perceptions (the revised Illness Perception Questionnaire, IPQ-R). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using multivariate logistic regression as measures of relative risk for dissatisfaction with appearance or its impact, adjusted for age, sex, body mass index (BMI), and joint-specific abnormalities (bony joint enlargements, deformities, or radiographic severity), self-reported pain and function. RESULTS: Of 247 patients (mean age 61.6 years, 88% women), 63 (26%) were aesthetically dissatisfied and 33 (13%) reported impact on daily life due to dissatisfaction. Patients with joint-specific abnormalities were at higher risk for reporting dissatisfaction. Patients who reported impact also reported more depression and negative illness perceptions, independently from joint-specific abnormalities. CONCLUSIONS: Hand OA patients report aesthetic dissatisfaction with their hands regularly, especially in those with joint abnormalities. This dissatisfaction has a negative impact in a small group of patients who also reported more depression and negative illness perceptions. These results indicate the influence of psychosocial factors on outcome measures in patients with hand OA.

Causes of venous thrombosis.

Venous thrombosis which mainly manifests as deep vein thrombosis of the leg or pulmonary embolism occurs in 1 per 1000 per year. It occurs due to interacting genetic, environmental and behavioral risk factors. The strongest risk factors are certain types of surgery and malignancies. Over the last decade many new risk factors for venous thrombosis have been identified. Venous thrombosis has a high recurrence rate, of around 5 % per year. Whereas clinically it would be most important to identify patients at risk of recurrence, only male sex and a previous unprovoked thrombosis are established determinants of recurrent thrombosis.