Maria Lobo

Cellular characterisation of magnetic resonance imaging bone oedema in rheumatoid arthritis; implications for pathogenesis of erosive disease

OBJECTIVES Magnetic resonance imaging (MRI) bone oedema is an important predictor of bone erosion in rheumatoid arthritis (RA). This study aimed to determine the cellular components of MRI bone oedema, and clarify the relationship between bone erosion and MRI bone oedema. METHODS Twenty-eight bones from 11 patients with RA undergoing orthopaedic surgery were analysed by quantitative and semi-quantitative immunohistochemistry. Pre-operative contrast-enhanced MRI scans were analysed for bone oedema. RESULTS The density of osteoclasts was higher in those samples with MRI bone oedema than those without MRI bone oedema (p = 0.01). Other cells identified within bone marrow included macrophages and plasma cells, and these were more numerous in samples with MRI bone oedema (p = 0.02 and 0.05 respectively). B cells were present in lower numbers, but B cell aggregates were identified in some samples with MRI bone oedema. There was a trend to increased RANKL expression in samples with MRI bone oedema (p = 0.09). Expression of RANKL correlated with the number of osteoclasts (r = 0.592, p = 0.004). CONCLUSIONS The increased number of osteoclasts and RANKL expression in samples with MRI bone oedema supports the hypothesis that bone erosion in RA occurs through activation of local bone resorption mechanisms within subchondral bone as well as through synovial invasion into bone.

Circulating mediators of bone remodeling in psoriatic arthritis: implications for disordered osteoclastogenesis and bone erosion

IntroductionDiverse bone pathologies are observed in patients with psoriatic arthritis (PsA). Uncoupling of bone remodeling with disordered osteoclastogenesis has been implicated in the pathogenesis of PsA. The aim of this study was to examine the role of soluble mediators of bone remodeling within the circulation of patients with PsA.MethodsPatients with PsA (n = 38), with psoriasis (n = 10), and healthy controls (n = 12) were studied. Serum was obtained for testing of Dikkopf-1 (Dkk-1), macrophage-colony stimulating factor (M-CSF), osteoprotegerin (OPG), and receptor activator of nuclear factor-κB ligand (RANKL) with ELISA. Patients with PsA also had bone densitometry, plain radiographs of the hands and feet, and assessment of peripheral blood osteoclast precursors. Radiographs were scored for erosion, joint-space narrowing, osteolysis, and new bone formation.ResultsCompared with those with psoriasis and healthy controls, patients with PsA had higher circulating concentrations of Dkk-1 and M-CSF. In patients with PsA, M-CSF and RANKL, but not Dkk-1, concentrations positively correlated with radiographic erosion, joint-space narrowing, and osteolysis scores. Mediators of bone remodeling did not correlate with the number of joints with new bone formation or with total hip-bone mineral density. Peripheral blood CD14+/CD11b+ cells, and the number of osteoclast-like cells and resorptive pits after culture with RANKL and M-CSF also correlated with radiographic damage scores. Circulating M-CSF concentrations correlated with the percentage of peripheral blood CD14+/CD11b+ cells.ConclusionsSystemic expression of soluble factors that promote osteoclastogenesis is disordered in patients with PsA and may contribute to periarticular bone loss in this disease.

MRI bone oedema scores are higher in the arthritis mutilans form of psoriatic arthritis and correlate with high radiographic scores for joint damage

IntroductionThe aim of this study was to investigate the magnetic resonance imaging (MRI) features of bone disease in the arthritis mutilans (AM) form of psoriatic arthritis (PsA).MethodsTwenty-eight patients with erosive PsA were enrolled (median disease duration of 14 years). Using x-rays of both hands and feet, 11 patients were classified as AM and 17 as non-AM (erosive psoriatic arthritis without bone lysis)by two observers. MRI scans (1.5T) of the dominant hand (wrist and fingers scanned separately) were obtained using standard contrast-enhanced T1-weighted and fat-saturated T2-weighted sequences. Scans were scored separately by two readers for bone erosion, oedema and proliferation using a PsA MRI scoring system. X-rays were scored for erosions and joint space narrowing.ResultsOn MRI, 1013 bones were scored by both readers. Reliability for scoring erosions and bone oedema was high (intraclass correlation coefficients = 0.80 and 0.77 respectively) but only fair for bone proliferation (intraclass correlation coefficient = 0.42). MRI erosion scores were higher in AM patients (53.0 versus 15.0, p = 0.004) as were bone oedema and proliferation scores (14.7 versus 10.0, p = 0.056 and 3.6 versus 0.7, p = 0.003 respectively). MRI bone oedema scores correlated with MRI erosion scores and X-ray erosion and joint space narrowing scores (r = 0.65, p = 0.0002 for all) but not the disease activity score 28-C reactive protein (DAS28CRP) or pain scores.ConclusionsIn this patient group with PsA, MRI bone oedema, erosion and proliferation were all more severe in the AM-form. Bone oedema scores did not correlate with disease activity measures but were closely associated with X-ray joint damage scores. These results suggest that MRI bone oedema may be a pre-erosive feature and that bone damage may not be coupled with joint inflammation in PsA.

Development of a computed tomography method of scoring bone erosion in patients with gout: validation and clinical implications

OBJECTIVES To develop a method of scoring bone erosion in the feet of patients with gout using CT as an outcome measure for chronic gout studies, consistent with the components of the OMERACT filter. METHODS Clinical assessment, plain radiographs and CT scans of both feet were obtained from 25 patients with chronic gout. CT scans were scored for bone erosion using a semi-quantitative method based on the Rheumatoid Arthritis MRI Scoring System (RAMRIS). CT bone erosion was assessed at 22 bones in each foot (total 1100 bones) by two independent radiologists. A number of different models were assessed to determine the optimal CT scoring system for bone erosion, incorporating the frequency of involvement and inter-reader reliability for individual bones. RESULTS An optimal model was identified with low number of bones required for scoring (seven bones/foot), inclusion of bones over the entire foot, high reliability and ability to capture a high proportion of disease. This model included the following bones in each foot: first metatarsal (MT) head, second to fourth MT base, cuboid, middle cuneiform and distal tibia (range 0-140). Scores from this model correlated with plain radiographic damage scores (r = 0.86, P < 0.0001) and disease duration (r = 0.42, P < 0.05). Scores were higher in those with clinically apparent tophaceous disease than in those without tophi (P < 0.0001). CONCLUSIONS We have developed a preliminary method of assessing bone erosion in gout using conventional CT. Further testing of this method is now required, ideally in prospective studies to allow analysis of the sensitivity to change of the measure.

Functional and biomechanical characteristics of foot disease in chronic gout: A case-control study

OBJECTIVES despite the predilection of gout to the feet, the impact of gout on foot function and biomechanics is currently unknown. The aim of this study was to describe the effects of chronic gout upon function and selected biomechanical parameters associated with gait. METHODS twenty-five patients with a history of gout were compared with 25 age and gender matched control participants with no history of gout or other forms of arthritis. General function, foot specific disease activity and lower limb activities were determined using the Health Assessment Questionnaire, Foot Function Index (pain domain), and Leeds Foot Impact Scale respectively. Each patient also underwent a gait assessment that included plantar pressure measurements and an evaluation of temporal-spatial gait parameters. FINDINGS patients with chronic gout had higher levels of general and foot-specific disability, pain and impairment (P ≤0.001). Significantly lower peak plantar pressures were observed in the hallux of patients with chronic gout (P ≤0.05). Significantly higher pressure-time integrals were observed in the cases at the midfoot (P ≤0.05), but lower values were observed at the hallux (P ≤0.05). Patients with chronic gout walked slower, with longer step and stride lengths compared to the controls. INTERPRETATION patients with chronic gout experience pain and disability associated with their feet. Different toe-off strategies may account for functional changes and pain associated with foot problems in chronic gout.

Zoledronic acid does not reduce MRI erosive progression in PsA but may suppress bone oedema: the Zoledronic Acid in Psoriatic Arthritis (ZAPA) Study

Background The effect of zoledronic acid (ZA) on articular bone in patients with psoriatic arthritis (PsA) was investigated using MRI. Methods Patients with erosive PsA were randomised to receive 3-monthly infusions of ZA or placebo for 1 year. An additional ‘tests alone’ group received no infusions. Clinical assessments and MRI scans were performed at baseline and 1 year. Results Paired 1.5T MRI scans were available in 22 patients including 6 who received ZA and 16 who did not (non-ZA = 6 placebo + 10 ‘tests alone’ patients). The Disease Activity Score (28 swollen and tender joints, C reactive protein fell over 12 months to a greater degree in patients on ZA than in non-ZA patients (−1.6 vs −0.3, p=0.023). The MRI bone oedema score decreased in the ZA group (15.5 to 8.5) but increased in the non-ZA group (14.0 to 18.0) (p= 0.0056) with regression of bone oedema at 13.5% of sites in ZA patients vs 1.3% in non-ZA patients (p = 0.0073) and progression in 1.3% of sites in ZA patients vs 6.9% in non-ZA patients (p = 0.072). There was no difference between groups in change in MRI erosion score. Conclusions In this pilot study ZA reduced the progression of MRI bone oedema, indicating probable suppression of osteitis concordant with reduction in clinical measures of disease activity.

Nail Disease in Psoriatic Arthritis: Distal Phalangeal Bone Edema Detected by Magnetic Resonance Imaging Predicts Development of Onycholysis and Hyperkeratosis

Objective. To examine the association between magnetic resonance imaging (MRI) features of distal phalanx (DP) disease and the progression of nail pathology in psoriatic arthritis (PsA). Methods. Clinical nail assessment and hand MRI scans were done on 34 patients with PsA. Twenty patients had repeat nail assessments after 1 year. Results. Nails with onycholysis and hyperkeratosis at baseline were more likely to have corresponding DP bone erosion and proliferation on MRI. DP bone edema on baseline MRI was associated with development of onycholysis and hyperkeratosis in corresponding nails. Conclusion. Our data suggest that DP inflammation is central in the development of psoriatic nail disease.

Quantifying Bone Marrow Edema in the Rheumatoid Cervical Spine Using Magnetic Resonance Imaging

Objective. To determine the reliability and feasibility of a new magnetic resonance imaging (MRI) score to quantify bone marrow edema (BME), synovitis, and erosions in the cervical spine of patients with rheumatoid arthritis (RA); and to investigate the correlations among neck pain, clinical markers of RA disease activity, and MRI features of disease activity in the cervical spine. Methods. Thirty patients with RA (50% with neck pain) and a Disease Activity Score 28-joint count > 3.2 had an MRI scan of their cervical spine. STIR, VIBE, and T1-weighted postcontrast sequences were used to quantify BME. MRI scans were scored for total BME, synovitis, and erosions using a new scoring method developed by the authors and assessed for reliability and feasibility. Associations between neck pain and clinical markers of disease activity were investigated. Results. BME was present in 14/30 patients; 9/14 (64%) had atlantoaxial BME, 10/14 (71%) had subaxial BME, and 5/14 (36%) had both. Interobserver reliability for total cervical BME score was moderate [intraclass correlation coefficient (ICC) = 0.51]. ICC improved to 0.67 if only the vertebral bodies and dens were considered. There was no correlation between neck pain or clinical measures of RA disease activity and the presence of any MRI features including BME, synovitis, or erosions. Conclusion. Current RA disease activity scores do not identify activity in the cervical spine. An MRI score that quantifies BME, synovitis, and erosions in the cervical spine may provide useful information regarding inflammation and damage. This could alert clinicians to the presence of significant pathology and influence management.

Evaluating intratester reliability of manual masking of plantar pressure measurements associated with chronic gout.

BACKGROUND Plantar pressure measurements are commonly used to evaluate foot function in chronic musculoskeletal conditions. However, manually identifying anatomical landmarks is a source of measurement error and can produce unreliable data. The aim of this study was to evaluate intratester reliability associated with manual masking of plantar pressure measurements in patients with gout. METHODS Twenty-five patients with chronic gout (mean disease duration, 22 years) were recruited from rheumatology outpatient clinics. Patients were excluded if they were experiencing an acute gout flare at the time of assessment, had lower-limb amputation, or had diabetes mellitus. Manual masking of peak plantar pressures and pressure-time integrals under ten regions of the foot were undertaken on two occasions on the same day using an in-shoe pressure measurement system. Test-retest reliability was assessed by using intraclass correlation coefficients, SEM, 95% limits of agreement, and minimal detectable change. RESULTS Mean peak pressure intraclass correlation coefficients ranged from 0.92 to 0.97, with SEM of 8% to 14%. The 95% limits of agreement ranged from-150.3 to 133.5 kPa, and the minimal detectable change ranged from 30.8 to 80.6 kPa. For pressure-time integrals, intraclass correlation coefficients were 0.86 to 0.94, and SEM were 5% to 29%, with the greater errors observed under the toes. The 95% limits of agreement ranged from -48.5 to 48.8 kPa/sec, and the minimal detectable change ranged from 6.8 to 21.0 kPa/sec. CONCLUSIONS These findings provide clinicians with information confirming the errors associated with manual masking of plantar pressure measurements in patients with gout.