A. Mathiessen

Ultrasound-detected inflammation predicts radiographic progression in hand osteoarthritis after 5 years

Objective To examine whether ultrasound predicts radiographic hand osteoarthritis (OA) progression after 5 years. Methods We included 78 participants (71 women, mean (SD) age 67.8 (5.2) years) from the Oslo Hand OA cohort with ultrasound examination (gray-scale (GS) synovitis and power Doppler (PD) signals) at baseline and conventional radiographs and clinical examination at baseline and 5-year follow-up. Radiographic progression was defined as an increase in global OA according to the Kellgren–Lawrence (KL) scale or progression of individual radiographic OA features. We examined whether baseline ultrasound features and clinical examination predicted radiographic progression using generalised estimating equations, adjusted for age, sex, body mass index and follow-up time. Results Radiographic progression occurred in 17.9% joints for KL, 12.1% for joint space narrowing, 11.7% for osteophytes and 4.5% for erosions. Ultrasound-detected inflammation predicted KL progression, and dose–response associations were observed for GS synovitis grade 1 (OR=2.8, 95% CI 1.8 to 4.2), grade 2 (OR=3.6, 95% CI 2.2 to 5.8) and grade 3 (OR=15.2, 95% CI 6.9 to 33.6), and for PD signal grade 1 (OR=2.9, 95% CI 1.2 to 6.8) and grades 2–3 (OR=12.0, 95% CI 3.5 to 41.0). Significant associations were also observed between ultrasound inflammation and progression of all individual radiographic features, and between clinical soft tissue swelling at baseline and radiographic progression. Conclusions Ultrasound-detected GS synovitis and PD signals were significantly associated with radiographic progression after 5 years. This study supports the use of ultrasound as a tool to detect patients with hand OA who are likely to progress.

Ultrasonographic assessment of osteophytes in 127 patients with hand osteoarthritis: exploring reliability and associations with MRI, radiographs and clinical joint findings

Objective To investigate the reliability of ultrasonographic assessment of osteophytes and explore the concordance of osteophytes detected by ultrasound, MRI, conventional radiography (CR) and clinical joint examination in patients with hand osteoarthritis (HOA). Methods The study included 127 HOA patients (116 women, mean age 68.6 years (SD 5.8)) with ultrasound, CR and clinical examination of both hands and MRI of dominant hand. Osteophytes were assessed by all imaging modalities on 0–3 scales, whereas clinical bony enlargement was assessed as absent/present. An ultrasound atlas of ostephytes was developed, and the intra and inter-reader reliability of scoring ultrasound osteophytes on still images using the atlas as reference was examined. The reliability for ultrasound readings was examined with κ and percentage exact agreement (PEA) and percentage close agreement (PCA), and the sensitivity, specificity and PEA/PCA of ultrasound was calculated in comparison with MRI, CR and clinical examination. Results Ultrasound had high sensitivity (0.83) and specificity (0.75) in detecting osteophytes compared with MRI, with excellent PCA (96.1%). Moderate/large osteophytes (grade 2–3) were demonstrated more often by ultrasound (n=401) than by MRI (n=288) in 851 interphalangeal joints. Ultrasound detected more osteophytes (53.2%) than CR (30.0%) and clinical examination (36.9%). Intra and inter-reader reliability of ultrasound was excellent (PEA >88%, PCA 100% and weighted kappa >0.91). Conclusion Ultrasound can reliably assess osteophytes in patients with HOA. Good agreement was found between osteophytes detected by ultrasound and MRI, while ultrasound was more sensitive than CR and clinical examination, which could be due to a multiplanar joint demonstration by ultrasound.

Synovitis in osteoarthritis: current understanding with therapeutic implications

Modern concepts of osteoarthritis (OA) have been forever changed by modern imaging phenotypes demonstrating complex and multi-tissue pathologies involving cartilage, subchondral bone and (increasingly recognized) inflammation of the synovium. The synovium may show significant changes, even before visible cartilage degeneration has occurred, with infiltration of mononuclear cells, thickening of the synovial lining layer and production of inflammatory cytokines. The combination of sensitive imaging modalities and tissue examination has confirmed a high prevalence of synovial inflammation in all stages of OA, with a number of studies demonstrating that synovitis is related to pain, poor function and may even be an independent driver of radiographic OA onset and structural progression. Treating key aspects of synovial inflammation therefore holds great promise for analgesia and also for structure modification. This article will review current knowledge on the prevalence of synovitis in OA and its role in symptoms and structural progression, and explore lessons learnt from targeting synovitis therapeutically.

The Impact of Newer Biological Disease Modifying Anti-Rheumatic Drugs on Cardiovascular Risk Factors: A 12-Month Longitudinal Study in Rheumatoid Arthritis Patients Treated with Rituximab, Abatacept and Tociliziumab

Objectives To assess whether treatment with one of three novel biological DMARDs; rituximab, abatacept or tocilizumab reduce cardiovascular disease (CVD) risk factors in patients with rheumatoid arthritis (RA). Methods This is an open, observational and prospective study with visits at baseline, 3, 6, and 12 months. Patients were assigned to receive rituximab, abatacept or tocilizumab according to clinical indications assessed by an independent rheumatologist. Disease activity was quantified by the disease activity score (DAS28) and extensive ultrasonography. CVD risk was assessed by total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), blood pressure and arterial stiffness measurements [pulse wave velocity (PWV) and augmentation index (AIx)]. Within group change in disease activity and CVD risk over 3 months was explored using paired samples bivariate tests. Predictors of change in CVD risk at 3 months were identified in linear regression models. Changes in CVD risk markers over the 12- month follow-up in patients receiving rituximab were assessed by mixed models repeated analyses. Results 24 patients on rituximab, 5 on abatacept and 7 on tocilizumab were included. At 3 months PWV was significantly reduced in the tocilizumab group only, but at 12 months rituximab patients showed a significant reduction in PWV. Reduced inflammation at 3 months was associated with increased TC and HDL-c in the entire cohort. Conclusion Treatment with tocilizumab and rituximab reduces PWV, a marker of CVD risk, in patients with RA.

Global ultrasound assessment of structural lesions in osteoarthritis: a reliability study by the OMERACT ultrasonography group on scoring cartilage and osteophytes in finger joints

Objective Ultrasonography is sensitive for the evaluation of cartilage pathology and degree of osteophytes in patients with hand osteoarthritis (OA). High consistency of assessments is essential, and the OMERACT (Outcome Measures in Rheumatology) ultrasonography group took the initiative to explore the reliability of a global ultrasonography score in patients with hand OA using semiquantitative ultrasonography score of cartilage and osteophytes in finger joints. Methods Ten patients with hand OA were examined by 10 experienced sonographers over the course of two days. Semiquantitative scoring (0–3) was performed on osteophytes (carpo-metacarpal 1, metacarpo-phalangeal (MCP) 1–5, proximal interphalangeal 1–5 and distal interphalangeal 2–5 joints bilaterally with an ultrasonography atlas as reference) and cartilage pathology (MCP 2–5 bilaterally). A web-based exercise on static cartilage images was performed a month later. Reliability was assessed by use of weighted κ analyses. Results Osteophyte scores were evenly distributed, and the intraobserver and interobserver reliabilities were substantial to excellent (κ range 0.68–0.89 and mean κ 0.65 (day 1) and 0.67 (day 2), respectively). Cartilage scores were unevenly distributed, and the intraobserver and interobserver reliability was fair to moderate (κ range 0.46–0.66 and mean κ 0.39 (day 1) and 0.33 (day 2), respectively). The web-based exercise showed acceptable agreement for cartilage being normal (κ 0.47) or with complete loss (κ 0.68), but poor for the intermediate scores (κ 0.22–0.30). Conclusions Use of the present semiquantitative ultrasonography scoring system for cartilage pathology in hand OA is not recommended (while normal or total loss of cartilage may be assessed). However, the OMERACT ultrasonography group will endorse the use of semiquantitative scoring of osteophytes with the ultrasonography atlas as reference.

Imaging of osteoarthritis (OA): What is new?

In daily clinical practice, conventional radiography is still the most applied imaging technique to supplement clinical examination of patients with suspected osteoarthritis (OA); it may not always be needed for diagnosis. Modern imaging modalities can visualize multiple aspects of the joint, and depending on the diagnostic need, radiography may no longer be the modality of choice. Magnetic resonance imaging (MRI) provides a complete assessment of the joint and has a pivotal role in OA research. Computed tomography (CT) and nuclear medicine offer alternatives in research scenarios, while ultrasound can visualize bony and soft-tissue pathologies and is highly feasible in the clinic. In this chapter, we overview the recent literature on established and newer imaging modalities, summarizing their ability to detect and quantify the range of OA pathologies and determining how they may contribute to early OA diagnosis. This accurate imaging-based detection of pathologies will underpin true understanding of much needed structure-modifying therapies.

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 [β = −4.71, 95% confidence interval (CI) −8.36 to −1.06 for current smoking in MUST and β = −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.

Ultrasound-detected osteophytes predict the development of radiographic and clinical features of hand osteoarthritis in the same finger joints 5 years later

Background Structural pathology may be present in joints without radiographic evidence of osteoarthritis (OA). Ultrasound is a sensitive tool for early detection of osteophytes. Our aim was to explore whether ultrasound-detected osteophytes (in radiographically and clinically normal finger joints) predicted the development of radiographic and clinical hand OA 5 years later. Methods We included finger joints without radiographic OA (Kellgren-Lawrence grade (KLG)=0; n=301) or no clinical bony enlargements (n=717) at baseline and examined whether ultrasound-detected osteophytes predicted incident radiographic OA (KLG ≥1, osteophytes or joint space narrowing (JSN)) or incident clinical bony enlargement (dependent variables) in the same joints 5 years later. We applied logistic regression with generalised estimating equations adjusted for age, sex, body mass index and follow-up time. Results Ultrasound demonstrated osteophytes in 86/301 (28.6%) joints without radiographic OA and 392/717 (54.7%) joints without clinical bony enlargement. These osteophytes were confirmed in the majority of joints where MRI assessment was available. Significant associations were found between ultrasound-detected osteophytes and development of both radiographic OA (OR=4.1, 95% CI 2.0 to 8.1) and clinical bony enlargement (OR=3.5, 95% CI 2.4 to 5.1) and also incident radiographic osteophytes (OR=4.2, 95% CI 2.1 to 8.5) and JSN (OR=5.3, 95% CI 2.1 to 13.4). Conclusion Ultrasound-detected osteophytes predicted incident radiographic and clinical hand OA 5 years later. These results support the use of ultrasound for early detection of OA.

A hospital-based observational cohort study exploring pain and biomarkers in patients with hand osteoarthritis in Norway: The Nor-Hand protocol

Introduction We 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 analysis The 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 dissemination The 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 number NCT03083548; Pre-results.

Response to ‘Does inflammation predict radiographic progression in hand osteoarthritis?’ by Li et al

Dear Editor, We highly appreciate the interest Li and Liu1 show in our paper in their eLetter. The concern of Drs Li and Liu is the low number of patients with inflammation in our cohort, and they suggest carefulness when interpreting the results. Unfortunately, Li and Liu have misunderstood the results when stating that “synovitis and power Doppler were found only in 16.6% and 2.5% of the 78 included participants respectively”. These numbers are found in table 1 and refer to the number of affected joints , not patients. 2 The high prevalence of synovitis at patient level is reported in the Results section, second paragraph: ‘At baseline, …