Can gait patterns be explained by joint structure in people with and without radiographic knee osteoarthritis? Data from the IMI-APPROACH cohort.

OBJECTIVE: To determine the association between joint structure and gait in patients with knee osteoarthritis (OA). METHODS: IMI-APPROACH recruited 297 clinical knee OA patients. Gait data was collected (GaitSmart®) and OA-related joint measures determined from knee radiographs (KIDA) and MRIs (qMRI/MOAKS). Patients were divided into those with/without radiographic OA (ROA). Principal component analyses (PCA) were performed on gait parameters; linear regression models were used to evaluate whether image-based structural and demographic parameters were associated with gait principal components. RESULTS: Two hundred seventy-one patients (age median 68.0, BMI 27.0, 77% female) could be analyzed; 149 (55%) had ROA. PCA identified two components: upper leg (primarily walking speed, stride duration, hip range of motion [ROM], thigh ROM) and lower leg (calf ROM, knee ROM in swing and stance phases). Increased age, BMI, and radiographic subchondral bone density (sclerosis), decreased radiographic varus angle deviation, and female sex were statistically significantly associated with worse lower leg gait (i.e. reduced ROM) in patients without ROA (R2 = 0.24); in ROA patients, increased BMI, radiographic osteophytes, MRI meniscal extrusion and female sex showed significantly worse lower leg gait (R2 = 0.18). Higher BMI was significantly associated with reduced upper leg function for non-ROA patients (R2 = 0.05); ROA patients with male sex, higher BMI and less MRI synovitis showed significantly worse upper leg gait (R2 = 0.12). CONCLUSION: Structural OA pathology was significantly associated with gait in patients with clinical knee OA, though BMI may be more important. While associations were not strong, these results provide a significant association between OA symptoms (gait) and joint structure.

"You don't put it down to arthritis": A qualitative study of the first symptoms recalled by individuals with knee osteoarthritis.

Objective: As part of the first phase of the OARSI Early-stage Symptomatic Knee Osteoarthritis (EsSKOA) initiative, we explored the first symptoms and experiences recalled by individuals with knee osteoarthritis (OA). Design: This qualitative study, informed by qualitative description, was a secondary analysis of focus groups (n â€‹= â€‹17 groups) and one-on-one interviews (n â€‹= â€‹3) conducted in 91 individuals living with knee OA as part of an international study to better understand the OA pain experience. In each focus group or interview, participants were asked to describe their first symptoms of knee OA. We inductively coded these transcripts and conducted thematic analysis. Results: Mean age of participants was 70 years (range 47-92) and 68 â€‹% were female. We developed four overarching themes: Insidious and Episodic Onset, Diverse Early Symptoms, Must be Something Else, and Adjustments. Participants described the gradual and intermittent way in which symptoms of knee OA developed over many years; many could not identify a specific starting point. Participants described diverse initial knee symptoms, including activity-exacerbated joint pain, stiffness and crepitus. Most participants dismissed early symptoms or rationalized their presence, employing various strategies to enable continued participation in recreational and daily activities. Few sought medical attention until physical functioning was demonstrably impacted. Conclusions: The earliest symptoms of knee OA are frequently insidious in onset, episodic and present long before individuals present to health professionals. These results highlight challenges to identifying people with knee OA early and support the development of specific classification criteria for EsSKOA to capture individuals at an early stage.

Prolonged morning stiffness is common in hand OA and does not preclude a diagnosis of hand osteoarthritis.

OBJECTIVE: Prolonged morning stiffness (>60 min) is considered a symptom of inflammatory arthritis, but has a poor discriminative ability. Knowledge about morning stiffness in patients with hand osteoarthritis (OA) is lacking. We therefore studied morning stiffness in patients with hand OA. DESIGN: Patients with primary hand OA according to their treating rheumatologist in the Hand OSTeoArthritis in Secondary care (HOSTAS) cohort were studied. Severity of morning stiffness was examined with Australian/Canadian hand OA index (AUSCAN) and presence and duration of morning stiffness were examined with a standardized questionnaire. Association of patient and disease characteristics with prolonged morning stiffness (>60 min) were analyzed with logistic regression. RESULTS: In total 519 of 538 patients had available data about duration of morning stiffness, of whom 89 (17%) had prolonged morning stiffness. Severity of stiffness was mild in 158 of 525 (30%), intermediate in 194 (37%), severe in 97 (18%) and extreme in 19 (4%) patients. Patients with prolonged morning stiffness reported more pain, worse physical function and had a reduced mental and physical quality of life. Patients with prolonged morning stiffness also had more severe radiographic disease, although the association did not reach statistical significance. CONCLUSIONS: Prolonged and severe morning stiffness are frequently present in patients with hand OA. Patients with these symptoms report more pain in general and have a lower quality of life than patients that do not report these symptoms. Prolonged morning stiffness does not preclude a diagnosis of hand OA.

Test-retest precision and longitudinal cartilage thickness loss in the IMI-APPROACH cohort.

OBJECTIVE: To investigate the test-retest precision and to report the longitudinal change in cartilage thickness, the percentage of knees with progression and the predictive value of the machine-learning-estimated structural progression score (s-score) for cartilage thickness loss in the IMI-APPROACH cohort - an exploratory, 5-center, 2-year prospective follow-up cohort. DESIGN: Quantitative cartilage morphology at baseline and at least one follow-up visit was available for 270 of the 297 IMI-APPROACH participants (78% females, age: 66.4 ± 7.1 years, body mass index (BMI): 28.1 ± 5.3 kg/m2, 55% with radiographic knee osteoarthritis (OA)) from 1.5T or 3T MRI. Test-retest precision (root mean square coefficient of variation) was assessed from 34 participants. To define progressor knees, smallest detectable change (SDC) thresholds were computed from 11 participants with longitudinal test-retest scans. Binary logistic regression was used to evaluate the odds of progression in femorotibial cartilage thickness (threshold: -211 µm) for the quartile with the highest vs the quartile with the lowest s-scores. RESULTS: The test-retest precision was 69 µm for the entire femorotibial joint. Over 24 months, mean cartilage thickness loss in the entire femorotibial joint reached -174 µm (95% CI: [-207, -141] µm, 32.7% with progression). The s-score was not associated with 24-month progression rates by MRI (OR: 1.30, 95% CI: [0.52, 3.28]). CONCLUSION: IMI-APPROACH successfully enrolled participants with substantial cartilage thickness loss, although the machine-learning-estimated s-score was not observed to be predictive of cartilage thickness loss. IMI-APPROACH data will be used in subsequent analyses to evaluate the impact of clinical, imaging, biomechanical and biochemical biomarkers on cartilage thickness loss and to refine the machine-learning-based s-score. GOV IDENTIFICATION: NCT03883568.

The genetic contribution to hand osteoarthritis.

OBJECTIVE: To estimate the genetic contribution to doctor-diagnosed hand osteoarthritis (OA). METHODS: Using data from the Swedish Twin Registry and National Patient Register, we conducted a 20-year population-based longitudinal cohort study including 59,970 twins aged 35 years or older. We studied inpatient and outpatient doctor-diagnosed hand OA using ICD-10 codes from 1997 until 2016, including both the distal/proximal interphalangeal (DIP/PIP) joints and/or the first carpometacarpal (CMC-1) joints. We calculated intra-pair correlation, estimated the heritability (i.e., the percentage variation in hand OA that can be explained by genetic factors) as well as a genetic risk. RESULTS: Among 59,970 included persons, 936 had a hand OA diagnosis registered during the study period. The heritabilities of hand OA (any joint), CMC-1 OA and DIP/PIP OA were ∼87%, 86% and 48%, respectively, yet the two latter should be interpreted with care due to low numbers. Hand OA in any joint in both twins in a pair occurred more frequently in identical twins (54/554 = 9.7%, intra-pair correlation = 0.54, 95% CI = 0.44-0.63) than in fraternal twins (18/1,246 = 1.4%, intra-pair correlation = 0.10, 95% CI = -0.01-0.22). Identical twins who were diagnosed with hand OA in any joint had a far higher risk than fraternal twins with hand OA to also have their co-twin diagnosed with hand OA in any joint (Hazard Ratio = 6.98, 95% CI = 3.08-15.45). CONCLUSION: The genetic contribution to hand OA is high and likely varying between 48% and 87%. Potential differential heritability by hand OA phenotypes should be further explored.

The association of the lipid profile with knee and hand osteoarthritis severity: the IMI-APPROACH cohort.

OBJECTIVE: To investigate the association of the lipidomic profile with osteoarthritis (OA) severity, considering the outcomes radiographic knee and hand OA, pain and function. DESIGN: We used baseline data from the Applied Public-Private Research enabling OsteoArthritis Clinical Headway (APPROACH) cohort, comprising persons with knee OA fulfilling the clinical American College of Rheumatology classification criteria. Radiographic knee and hand OA severity was quantified with Kellgren-Lawrence sum scores. Knee and hand pain and function were assessed with validated questionnaires. We quantified fasted plasma higher order lipids and oxylipins with liquid chromatography with tandem mass spectrometry (LC-MS/MS)-based platforms. Using penalised linear regression, we assessed the variance in OA severity explained by lipidomics, with adjustment for clinical covariates (age, sex, body mass index (BMI) and lipid lowering medication), measurement batch and clinical centre. RESULTS: In 216 participants (mean age 66 years, mean BMI 27.3 kg/m2, 75% women) we quantified 603 higher order lipids (triacylglycerols, diacylglycerols, cholesteryl esters, ceramides, free fatty acids, sphingomyelins, phospholipids) and 28 oxylipins. Lipidomics explained 3% and 2% of the variance in radiographic knee and hand OA severity, respectively. Lipids were not associated with knee pain or function. Lipidomics accounted for 12% and 6% of variance in hand pain and function, respectively. The investigated OA severity outcomes were associated with the lipidomic fraction of bound and free arachidonic acid, bound palmitoleic acid, oleic acid, linoleic acid and docosapentaenoic acid. CONCLUSIONS: Within the APPROACH cohort lipidomics explained a minor portion of the variation in OA severity, which was most evident for the outcome hand pain. Our results suggest that eicosanoids may be involved in OA severity.

Reliability and agreement of proton density-weighted vs. gadolinium-enhanced T1-weighted MRI in hand osteoarthritis. An OMERACT MRI special interest group reliability exercise.

OBJECTIVES: To compare reliabilities of assessing synovitis in hand osteoarthritis (OA) using Magnetic Resonance Imaging (MRI) with/without gadolinium (Gd). METHODS: Three readers scored synovitis on non-enhanced two-dimensional (2D) proton density (PD)-weighted MRI and Gd-enhanced (3D) MRI of hand joints in 20 patients. Inter-reader reliabilities were examined. RESULTS: Reliability was good for Gd-enhanced MRI, but poor for non-enhanced PD-weighted MRI (intraclass correlation coefficient 0.83 and 0.21, respectively). Agreement between the two sequences was poor (weighted kappa 0.18). CONCLUSION: Gd-enhanced MRI was more reliable than PD-weighted MRI for assessing synovitis. Gd-enhancement, but also resolution and tissue contrast, might have contributed to this.

Detection of subclinical skin manifestation in patients with psoriasis and psoriatic arthritis by fluorescence optical imaging.

OBJECTIVES: To investigate the frequency of subclinical skin inflammation in both hands by fluorescence optical imaging (FOI) in patients with psoriasis/psoriatic arthritis (Pso/PsA) vs. rheumatoid arthritis (RA) and healthy individuals, and to correlate these findings with cardiovascular (CV) risk factors. PATIENTS AND METHODS: The FOI scans were analyzed retrospectively to detect clinically invisible skin enhancement (0-3 scale) in both hands without relationship to underlying joints or blood vessels. We further characterized the FOI patterns and sorted the scans into groups based on the assumed diagnosis (Pso/PsA, RA, and healthy controls), which was compared with the physician's diagnosis. Furthermore, the associations between CV risk factors and imaging findings were investigated by regression analyses. RESULTS: We included FOI scans of patients with Pso/PsA (n = 80), RA (n = 78), and healthy controls (n = 25). Subclinical skin enhancement on the back of their hands was more common in Pso/PsA (72.5%) than in RA patients (20.5%) and healthy individuals (28.0%) (p < 0.001). Based on the FOI pattern, the majority of patients with Pso/PsA (72.5%), RA (76.9%), and healthy controls (68.0%) were classified correctly using the physician-based diagnosis as reference (overall agreement of 74%, kappa = 0.57). No CV risk factors except body weight (kg) were associated with subclinical skin enhancement (OR 1.04, 95% CI 1.02-1.06; p < 0.001). CONCLUSION: Subclinical subdermal skin inflammation was common in Pso/PsA patients using FOI. Based on the FOI pattern, most patients with Pso/PsA and were classified with the correct diagnosis. We demonstrated an important influence of the body weight on our FOI results. FOI may be a helpful novel tool to study microcirculation in rheumatic diseases with skin involvement.

Evaluation of three scoring methods for Fluorescence Optical Imaging in erosive hand osteoarthritis and rheumatoid arthritis.

Objective: Fluorescence Optical Imaging (FOI) demonstrates indocyanine green (ICG)-enhanced microcirculation in wrist and finger joints, as a sign of inflammation. We wanted to assess the reliability of three FOI scoring methods from Berlin, Stockholm, and Copenhagen, to assess the validity of FOI with MRI as reference and to compare enhancement in hand joints in erosive hand osteoarthritis (OA) vs. rheumatoid arthritis (RA). Design: Five readers scored all finger and wrist joints of 26 patients with erosive hand OA and RA on semi-quantitative 0-3 scales using three different FOI scoring methods. To evaluate inter-reader reliability, we calculated the intraclass correlation coefficients (ICC) for sum scores and prevalence and bias adjusted kappa values for ordinal scales (Pabak-OS) on joint level. Enhancement in joint groups in erosive hand OA vs. RA was compared using Mann-Whitney test. Sensitivities and specificities of FOI was calculated with MRI as reference for hand OA patients only. Results: We found moderate to good inter-reader reliability for all FOI scoring methods (Pabak-OS: 0.50-0.78, ICC: 0.43-0.85) and different patterns of enhancement in erosive hand OA vs. RA with significantly more FOI enhancement in DIP joints in erosive hand OA across all methods. With MRI as reference the different FOI scoring methods reached similar sensitivities (63-65%) and specificities (76-91%). Conclusion: FOI enhancement can be measured reliably in erosive hand OA and RA using three different scoring methods. More DIP enhancement in erosive hand OA patients and good agreement with MRI support the diagnostic performance of FOI.

OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis

To update and expand upon prior Osteoarthritis Research Society International (OARSI) guidelines by developing patient-focused treatment recommendations for individuals with Knee, Hip, and Polyarticular osteoarthritis (OA) that are derived from expert consensus and based on objective review of high-quality meta-analytic data. We sought evidence for 60 unique interventions. A systematic search of all relevant databases was conducted from inception through July 2018. After abstract and full-text screening by two independent reviewers, eligible studies were matched to PICO questions. Data were extracted and meta-analyses were conducted using RevMan software. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Evidence Profiles were compiled using the GRADEpro web application. Voting for Core Treatments took place first. Four subsequent voting sessions took place via anonymous online survey, during which Panel members were tasked with voting to produce recommendations for all joint locations and comorbidity classes. We designated non-Core treatments to Level 1A, 1B, 2, 3, 4A, 4B, or 5, based on the percentage of votes in favor, in addition to the strength of the recommendation. Core Treatments for Knee OA included arthritis education and structured land-based exercise programs with or without dietary weight management. Core Treatments for Hip and Polyarticular OA included arthritis education and structured land-based exercise programs. Topical non-steroidal anti-inflammatory drugs (NSAIDs) were strongly recommended for individuals with Knee OA (Level 1A). For individuals with gastrointestinal comorbidities, COX-2 inhibitors were Level 1B and NSAIDs with proton pump inhibitors Level 2. For individuals with cardiovascular comorbidities or frailty, use of any oral NSAID was not recommended. Intra-articular (IA) corticosteroids, IA hyaluronic acid, and aquatic exercise were Level 1B/Level 2 treatments for Knee OA, dependent upon comorbidity status, but were not recommended for individuals with Hip or Polyarticular OA. The use of Acetaminophen/Paracetamol (APAP) was conditionally not recommended (Level 4A and 4B), and the use of oral and transdermal opioids was strongly not recommended (Level 5). A treatment algorithm was constructed in order to guide clinical decision-making for a variety of patient profiles, using recommended treatments as input for each decision node. These guidelines offer comprehensive and patient-centered treatment profiles for individuals with Knee, Hip, and Polyarticular OA. The treatment algorithm will facilitate individualized treatment decisions regarding the management of OA.

Biomarkers of cardiovascular risk across phenotypes of osteoarthritis.

BACKGROUND: The objective of this study was to explore the associations between ultrasonographic and radiographic joint scores and levels of arterial CVD risk markers in patients with osteoarthritis (OA). Secondly, to compare the levels of arterial CVD risk markers between OA phenotypes and controls. METHOD: The "Musculoskeletal pain in Ullensaker" Study (MUST) invited residents of Ullensaker municipality with self-reported OA to a medical examination. OA was defined according to the American College of Rheumatology (ACR) criteria and phenotyped based on joint distribution. Joints of the hands, hips and knees were examined by ultrasonography and conventional radiography, and scored for osteosteophytes. Hands were also scored for inflammation by grey scale (GS) synovitis and power Doppler (PD) signal. Control populations were a cohort of inhabitants of Oslo (OCP), and for external validation, a UK community-based register (UKPC).Pulse pressure augmentation index (AIx) and pulse wave velocity (PWV) were measured using the Sphygmocor apparatus (Atcor®). Ankel-brachial index (ABI) was estimated in a subset of patients. In separate adjusted regression models we explored the associations between ultrasonography and radiograph joint scores and AIx, PWV and ABI. CVD risk markers were also compared between phenotypes of OA and controls in adjusted analyses. RESULTS: Three hundred and sixty six persons with OA were included (mean age (range); 63.0 (42.0-75.0)), (females (%); 264 (72)). Of these, 155 (42.3%) had isolated hand OA, 111 (30.3%) had isolated lower limb OA and 100 (27.3%) had generalized OA. 108 persons were included in the OCP and 963 persons in the UKPC; (mean age (range); OCP: 57.2 (40.4-70.4), UKPC: 63.9 (40.0-75.0), females (%); OCP: 47 (43.5), UKPC: 543 (56.4%). Hand osteophytes were associated with AIx while GS and PD scores were not related to CVD risk markers. All OA phenotypes had higher levels of AIx compared to OCP in adjusted analyses. External validation against UKPC confirmed these findings. CONCLUSIONS: Hand osteophytes might be related to higher risk of CVD. People with OA had higher augmented central pressure compared to controls.Words 330.

OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis.

OBJECTIVE: To update and expand upon prior Osteoarthritis Research Society International (OARSI) guidelines by developing patient-focused treatment recommendations for individuals with Knee, Hip, and Polyarticular osteoarthritis (OA) that are derived from expert consensus and based on objective review of high-quality meta-analytic data. METHODS: We sought evidence for 60 unique interventions. A systematic search of all relevant databases was conducted from inception through July 2018. After abstract and full-text screening by two independent reviewers, eligible studies were matched to PICO questions. Data were extracted and meta-analyses were conducted using RevMan software. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Evidence Profiles were compiled using the GRADEpro web application. Voting for Core Treatments took place first. Four subsequent voting sessions took place via anonymous online survey, during which Panel members were tasked with voting to produce recommendations for all joint locations and comorbidity classes. We designated non-Core treatments to Level 1A, 1B, 2, 3, 4A, 4B, or 5, based on the percentage of votes in favor, in addition to the strength of the recommendation. RESULTS: Core Treatments for Knee OA included arthritis education and structured land-based exercise programs with or without dietary weight management. Core Treatments for Hip and Polyarticular OA included arthritis education and structured land-based exercise programs. Topical non-steroidal anti-inflammatory drugs (NSAIDs) were strongly recommended for individuals with Knee OA (Level 1A). For individuals with gastrointestinal comorbidities, COX-2 inhibitors were Level 1B and NSAIDs with proton pump inhibitors Level 2. For individuals with cardiovascular comorbidities or frailty, use of any oral NSAID was not recommended. Intra-articular (IA) corticosteroids, IA hyaluronic acid, and aquatic exercise were Level 1B/Level 2 treatments for Knee OA, dependent upon comorbidity status, but were not recommended for individuals with Hip or Polyarticular OA. The use of Acetaminophen/Paracetamol (APAP) was conditionally not recommended (Level 4A and 4B), and the use of oral and transdermal opioids was strongly not recommended (Level 5). A treatment algorithm was constructed in order to guide clinical decision-making for a variety of patient profiles, using recommended treatments as input for each decision node. CONCLUSION: These guidelines offer comprehensive and patient-centered treatment profiles for individuals with Knee, Hip, and Polyarticular OA. The treatment algorithm will facilitate individualized treatment decisions regarding the management of OA.

Cartilage evaluation in finger joints in healthy controls and early hand osteoarthritis patients using high-resolution MRI.

OBJECTIVE: To compare direct evaluation of cartilage with high resolution MRI (hrMRI) to indirect cartilage evaluation using MRI inter-bone distance in hand OA patients and healthy controls. DESIGN: 41 hand OA patients and 18 healthy controls underwent hrMRI of the 2nd and 3rd metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. The images were read by two independent readers using OMERACT hand OA MRI inter-bone distance score (0-3 scale) and a new hrMRI cartilage score with direct evaluation of the cartilage (0-3 scale). Inter-reader and intra-reader reliability was calculated using exact and close agreement and kappa values. The prevalence of abnormal scores and agreement between methods was assessed in both hand OA patients and healthy controls. RESULTS: The intra- and inter-reader reliability of both scores was comparable, with exact agreement in 73-83% and close agreement in 95-100%. In hand OA patients 27% of 161 joints had both cartilage damage and loss of inter-bone distance, cartilage damage by hrMRI only was present in 20% of joints and reduced inter-bone distance only in 4% of joints. In the healthy controls, 1 of 71 joints were scored as abnormal by both hrMRI and inter bone distance scoring, 1 joint was scored as abnormal using the hrMRI cartilage score only, whereas 15% of joints had only reduced inter bone distance. CONCLUSIONS: Direct cartilage evaluation of MCP and PIP joints using hrMRI has a good reliability, and the higher prevalence of hrMRI cartilage damage in hand OA patients and the lower prevalence in healthy controls in comparison to evaluation of inter-bone distance suggests a better validity.

Incident hand OA is strongly associated with reduced peripheral blood leukocyte telomere length.

OBJECTIVE: To evaluate the relationship of telomere length to the prevalence and incidence of hand osteoarthritis in a longitudinal cohort. DESIGN: We conducted a cross-sectional and longitudinal analysis of data from a subset of participants in the Osteoarthritis Initiative (OAI) recruited between February 2004 and May 2006. 274 individuals were eligible for the study based on availability of both baseline and 48-month hand radiographs and peripheral blood leucocyte telomere length data. Mean telomere length of peripheral blood leukocytes (PBL)s from the DNA samples was determined using a validated quantitative polymerase chain reaction (PCR)-based assay, and hand radiographs were analyzed and graded using the Kellgren-Lawrence scale. RESULTS: In joint -level analyses, prevalent Interphalangeal Joint Osteoarthritis (IPJOA) was significantly associated with PBL telomere length in the baseline sample in unadjusted analyses (RR = 2.84; 95% CI:0.87-9.29) or in models adjusted for age, sex, and body mass index (aRR = 1.10; 95% CI: 0.96-1.27). The association in crude and adjusted analyses appeared slightly stronger with incident IPJOA, especially in the subset with normal hands at baseline (aRR = 1.62; 95% CI: 1.02-2.57). PBL telomere length was also associated with prevalent HOA at baseline (significant in unadjusted analysis: RR = 1.22; 95% CI 1.06-1.42), but not after adjusting for covariates: aRR = 1.12; 95% CI: 0.96-1.30). The magnitude of association was stronger for incident HOA, especially incident symptomatic HOA (aRR = 1.53; 95% CI: 1.09-2.15). CONCLUSIONS: In summary, the results of this exploratory analysis are confirmatory of previous work showing a cross-sectional relationship between telomere length and HOA and add to the field by demonstrating an even stronger association with incident IPJOA, both radiographic and symptomatic.

Enhanced angiogenesis and increased bone turnover characterize bone marrow lesions in osteoarthritis at the base of the thumb.

OBJECTIVES: Little is known about tissue changes underlying bone marrow lesions (BMLs) in non-weight-bearing joints with osteoarthritis (OA). Our aim was to characterize BMLs in OA of the hand using dynamic histomorphometry. We therefore quantified bone turnover and angiogenesis in subchondral bone at the base of the thumb, and compared the findings with control bone from hip OA. METHODS: Patients with OA at the base of the thumb, or the hip, underwent preoperative MRI to assess BMLs, and tetracycline labelling to determine bone turnover. Three groups were compared: trapezium bones removed by trapeziectomy from patients with thumb base OA (n = 20); femoral heads with (n = 24); and those without (n = 9) BMLs obtained from patients with hip OA who underwent total hip arthroplasty. RESULTS: All trapezium bones demonstrated MRI-defined BMLs. Compared with femoral heads without BMLs, the trapezia demonstrated significantly higher bone turnover (mean sd 0.2 (0.1) versus 0.01 (0.01) µm3/µm2/day), mineralizing surface (18.5% (13.1) versus 1.4% (1.3)) and vascularity (5.2% (1.1) versus 1.2% (0.6)). Femoral heads with BMLs exhibited higher bone turnover (0.3 (0.2) versus 0.2 (0.1) µm3/µm2/day), a higher mineralization rate (26.6% (10.6) versus 18.6% (11.9)) and greater trabecular thickness (301.3 µm (108) versus 163.6 µm (24.8)) than the trapezia. CONCLUSION: Bone turnover and angiogenesis were enhanced in BMLs of both the thumb base and hip OA, of which the latter exhibited the highest bone turnover. Thus, the increase in bone turnover in weight-bearing joints like the hip may be more pronounced than less mechanically loaded osteoarthritic joints demonstrating BMLs. The histological changes observed may explain the water signal from BMLs on MRI.Cite this article: M. Shabestari, N. J. Kise, M. A. Landin, S. Sesseng, J. C. Hellund, J. E. Reseland, E. F. Eriksen, I. K. Haugen. Enhanced angiogenesis and increased bone turnover characterize bone marrow lesions in osteoarthritis at the base of the thumb. Bone Joint Res 2018;7:406-413. DOI: 10.1302/2046-3758.76.BJR-2017-0083.R3.

Trabecular bone texture detected by plain radiography is associated with MRI-defined osteophytes in finger joints of women without radiographic osteoarthritis.

OBJECTIVE: To examine associations between trabecular bone (TB) texture and magnetic resonance imaging (MRI)-defined osteophytes in finger joints without radiographic osteoarthritis (OA) using an augmented variance orientation transform (AVOT) method. DESIGN: In a cross-sectional study, associations of the TB texture and osteophytes were examined in 21 women with mean (standard deviation) age of 69.9 (5.3) from the Oslo Hand OA cohort. The AVOT was applied to distal and proximal TB regions selected on hand radiographs of the subjects. The regions were adjacent to 57 finger joints (24 distal and 33 proximal interphalangeal) without radiographic OA (Kellgren-Lawrence [KL] grade 0), without MRI-defined joint space narrowing (JSN), bone marrow lesions (BMLs), attrition, erosion, cysts, sclerosis, malalignment (all MRI grades 0) and without or only with mild synovitis (MRI grade 0 or 1). Bone texture parameters were calculated: mean fractal dimension (FDMEAN), FDs in the horizontal (FDH) and vertical (FDV) directions, and along the roughest part (FDSta). Associations between the parameters categorized into groups using tertiles and osteophytes were evaluated using logistic regression adjusted for age. RESULTS: Lower FDSta and FDV in the distal TB regions were associated with increased odds of MRI-defined osteophytes (P < 0.037 for linear trend). No statistically significant associations were found for the proximal regions. CONCLUSIONS: Lower mean roughness and lower roughness in vertical and roughest directions of the proximal TB texture are associated with MRI-defined osteophytes in finger joints without radiographic OA. These findings suggest that TB texture may be a useful marker for detecting early hand OA.

A randomised double-blind placebo-controlled crossover trial of HUMira (adalimumab) for erosive hand OsteoaRthritis - the HUMOR trial.

OBJECTIVE: To assess the efficacy of adalimumab in patients with erosive hand osteoarthritis (OA). METHOD: Patients >50 years old, meeting the American College of Rheumatology (ACR) criteria for hand OA, with pain >50 on 100 mm visual analogue scale (VAS), morning stiffness >30 min and ≥1 erosive joint on X-ray with synovitis present on magnetic resonance imaging (MRI) were included in a randomised double-blind placebo-controlled crossover trial. Patients were randomised to adalimumab (40 mg subcutaneous injections every other week) or identical placebo injections for 12 weeks followed by an 8-week washout and then crossed over treatment groups for another 12 weeks. The primary outcome was change in VAS hand pain over 12 weeks. Secondary outcomes included change in Australian/Canadian Hand OA Index (AUSCAN) pain, function and stiffness subscales from baseline to 4, 8 and 12 weeks, change in MRI-detected synovitis and bone marrow lesions (BMLs) from baseline to 12 weeks and change in VAS from baseline to 4 and 8 weeks. RESULTS: We recruited 51 patients and 43 were randomised to either Group 1 (N = 18, active then placebo) or Group 2 (N = 25, placebo then active). At 12 weeks there was no difference between the groups on the primary outcome measure (mean decrease in VAS pain of 3.2 mm standard deviation (SD 16.7) for adalimumab vs 0.8 mm (SD 29.6) for placebo). The adjusted treatment effect was -0.7 mm (95% confidence interval (CI) -9.3 to 8.0), P = 0.87. No statistically significant differences were found for any secondary outcomes. CONCLUSION: Adalimumab did not show any effect on pain, synovitis or BMLs in patients with erosive hand OA with MRI-detected synovitis as compared to placebo after 12 weeks. CLINICAL TRIAL REGISTRATION NUMBER: ACTRN12612000791831.

Smoking and alcohol use are associated with structural and inflammatory hand osteoarthritis features.

OBJECTIVES: To explore whether smoking and alcohol use are associated with hand osteoarthritis (OA) features in two different OA cohorts. METHOD: We studied 530 people with radiographic hand OA from the Musculoskeletal pain in Ullensaker STudy (MUST) and 187 people from the Oslo hand OA cohort [mean (sd) age 65 (8.0) and 62 (5.7) years, 71% and 91% women, respectively]. Smoking, alcohol use and hand pain were self-reported. Participants underwent conventional hand radiographs and ultrasound examination of 30 hand joints. The Kellgren-Lawrence sum score for radiographic OA severity (0-120 scale) and the proportion of participants having at least one joint with grey-scale synovitis (grade ≥1) were calculated. We studied whether smoking and alcohol use were cross-sectionally associated with radiographic OA, synovitis, and pain using adjusted linear and logistic regression analyses. RESULTS: Smoking was associated with less radiographic OA in both cohorts [ß = -4.71, 95% confidence interval (CI) -8.36 to -1.06 for current smoking in MUST and ß = -0.15, 95% CI -0.29 to -0.02 for smoking pack-years in the Oslo hand OA cohort]. Stratified analyses indicated that the association was present in men only. Being a monthly drinker (examined in MUST only) was significantly associated with present synovitis compared to never drinkers (odds ratio = 2.35, 95% CI 1.27 to 4.34) (no gender differences). Neither smoking nor alcohol was associated with hand pain. CONCLUSIONS: Smoking was associated with less radiographic hand OA whereas alcohol consumption was associated with present joint inflammation in hand OA. Future longitudinal studies are needed to explore the causal associations and explanatory mechanisms behind gender differences.

Frequency of temporomandibular joint osteoarthritis and related symptoms in a hand osteoarthritis cohort.

OBJECTIVE: The prevalence of osteoarthritis (OA) in the temporomandibular joints (TMJs) in hand OA patients is largely unknown. Our aims were to explore (1) The frequency of TMJ-related symptoms and clinical findings; (2) The TMJ OA frequency defined by cone beam computed tomography (CBCT); and (3) The relationship between TMJ-related symptoms/clinical findings and CBCT-defined TMJ OA, in a hand OA cohort. METHODS: We calculated the frequencies of TMJ-related symptoms, clinical findings and diagnosis of TMJ OA by CBCT and clinical examination in 54 patients from the Oslo hand OA cohort (88% women, mean (range) age 71 (61-83) years). Participants with and without CBCT-defined TMJ OA were compared for differences in proportions (95% confidence interval (CI)) of symptoms and clinical findings. Sensitivity and specificity of the clinical TMJ OA diagnosis were calculated using CBCT as reference. RESULTS: Self-reported symptoms and clinical findings were found in 24 (44%) and 50 (93%) individuals (93%), respectively, whereas 7 (13%) had sought healthcare. Individuals with CBCT-defined TMJ OA (n = 36, 67%) reported statistically significantly more pain at mouth opening (22%, 95% CI 4-40%), clicking (33%, 95% CI 14-52%) and crepitus (25%, 95% CI 4-46%). By clinical examination, only crepitus was more common in TMJ OA (33%, 95% CI 29-77%). Clinical diagnosis demonstrated low sensitivity (0.42) and high specificity (0.93). CONCLUSIONS: CBCT-defined TMJ OA was common in hand OA patients, suggesting that TMJ OA may be part of generalized OA. Few had sought healthcare, despite high burden of TMJ-related symptoms/findings. Clinical examination underestimated TMJ OA frequency.

Hand osteoarthritis: current knowledge and new ideas.

Hand osteoarthritis (OA) is a prevalent disease that can lead to substantial pain and physical disability. Currently, no disease-modifying drugs exist for the treatment of OA. Most OA research has been conducted on knee OA and we have limited knowledge about disease mechanisms in hand OA. During her research career, Ida K Haugen (IKH) has focused on the epidemiology of hand OA and imaging techniques. She has established a large international network, providing the opportunity to study the epidemiology of hand OA in large international OA cohorts. In the Framingham study, she found that symptomatic hand OA was present in 16% of women and 8% of men aged between 40 and 84 years. In her PhD thesis, IKH studied the reliability and validity of magnetic resonance imaging (MRI) in hand OA. In collaboration with OMERACT (Outcome Measures in Rheumatology), an MRI scoring system for hand OA was developed. MRI is more sensitive than radiographs for detecting structural abnormalities. Synovitis, as detected by both MRI and ultrasound, is associated with pain and predicts future disease progression. Hence, synovitis may represent a treatment target in hand OA. Her future research plans include the observational Nor-Hand study and a placebo-controlled randomized trial on methotrexate (MTX) in hand OA. The data collection of 300 patients in the Nor-Hand study is ongoing, and focuses on causes of pain and novel imaging techniques to assess inflammation in hand OA. In a future clinical trial, patients with moderate to severe long-lasting pain and inflammation will be treated with MTX and the effect on pain and inflammation will be explored.