Bone edema scored on magnetic resonance imaging scans of the dominant carpus at presentation predicts radiographic joint damage of the hands and feet six years later in patients with rheumatoid arthritis

OBJECTIVE: Magnetic resonance imaging (MRI) is capable of revealing synovitis and tendinitis in early rheumatoid arthritis (RA), as well as bone edema and erosion. These features are visible before radiographic joint damage occurs. We sought to examine whether MRI of one body region (the wrist) can be used to predict whole-body radiography scores reflecting joint damage at 6 years. METHODS: We conducted a 6-year prospective study of a cohort of patients who fulfilled the criteria for RA at presentation, using clinical parameters, radiographs, and MRI scans of the dominant wrist. Of the 42 patients enrolled at baseline, full MRI, radiographic, and clinical data were available for 31 at 6-year followup. MRI scans were scored by 2 radiologists, using a validated scoring system. Radiographs of the hands and feet were graded using the modified Sharp scoring method. MRI and radiography scores obtained at baseline and 6 years were compared, and baseline MRI scores were examined for their ability to predict radiographic outcome at 6 years. RESULTS: At 6 years, the total Sharp score correlated significantly with the total MRI score and the MRI erosion score (r = 0.81, P < 0.0001 and r = 0.79, P < 0.0001, respectively). The 6-year Sharp score also correlated with the baseline total MRI and MRI erosion scores (r = 0.56, P < 0.0001 and r = 0.33, P = 0.03, respectively). MRI synovitis and bone edema scores remained constant for the group as a whole over 6 years, but bone erosion scores progressed (P = 0.0001), consistent with radiographic deterioration. Erosions on 6-year MRI scans were frequently preceded by MRI bone edema at baseline (odds ratio 6.5, 95% confidence interval 2.78-18.1). Regression models indicated that the baseline MRI bone edema score was predictive of the 6-year total Sharp score (P = 0.01), as was the C-reactive protein (CRP) level (P = 0.0002). Neither shared epitope status nor swollen or tender joint counts predicted radiographic outcome in this cohort. A model incorporating baseline MRI scores for erosion, bone edema, synovitis, and tendinitis plus the CRP level and the erythrocyte sedimentation rate explained 59% of the variance in the 6-year total Sharp score (R(2) = 0.59, adjusted R(2) = 0.44). CONCLUSION: MRI scans performed at the first presentation of RA can be used to help predict future radiographic damage, allowing disease-modifying therapy to be targeted to patients with aggressive disease.     

Magnetic resonance imaging of the wrist in early rheumatoid arthritis reveals progression of erosions despite clinical improvement

OBJECTIVES: To investigate the progression of joint damage in early rheumatoid arthritis (RA) using magnetic resonance imaging (MRI) of the wrist and determine whether this technique can be used to predict prognosis. METHODS: An inception cohort of 42 early patients has been followed up prospectively for one year. Gadolinium enhanced MRI scans of the dominant wrist were obtained at baseline and one year and scored for synovitis, tendonitis, bone marrow oedema, and erosions. Plain radiographs were performed concurrently and scored for erosions. Patients were assessed clinically for disease activity and HLA-DRB1 genotyping was performed. RESULTS: At one year, MRI erosions were found in 74% of patients (31 of 42) compared with 45% at baseline. Twelve patients (28.6%) had radiographic erosions at one year. The total MRI score and MRI erosion score increased significantly from baseline to one year despite falls in clinical measures of inflammation including erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and swollen joint count (p < 0.01 for all). Baseline findings that predicted carpal MRI erosions at one year included a total MRI score of 6 or greater (sensitivity: 93.3%, specificity 81.8%, positive predictive value 93.3%, p = 0.000007), MRI bone oedema (OR = 6.47, p < 0.001), MRI synovitis (OR = 2.14, p = 0.003), and pain score (p = 0.01). Radiological erosions at one year were predicted by a total MRI score at baseline of greater than 13 (OR = 12.4, p = 0.002), the presence of MRI erosions (OR = 11.6, p = 0.005), and the ESR (p = 0.02). If MRI erosions were absent at baseline and the total MRI score was low, radiological erosions were highly unlikely to develop by one year (negative predictive value 0.91 and 0.92 respectively). No association was found between the shared epitope and erosions on MRI (p = 0.4) or radiography (p = 1.0) at one year. CONCLUSIONS: MRI scans of the dominant wrist are useful in predicting MRI and radiological erosions in early RA and may indicate the patients that should be managed aggressively. Discordance has been demonstrated between clinical improvement and progression of MRI erosion scores.     

Ability of hand radiographs to predict a further diagnosis of rheumatoid arthritis in patients with early arthritis.

OBJECTIVE: To evaluate the ability of hand radiographs collected at study inclusion to predict a diagnosis of rheumatoid arthritis (RA) 2 years later, in a cohort of patients with early arthritis. METHODS: We evaluated 270 patients with arthritis of less than one year duration. At the first visit, all patients underwent a standardized evaluation including laboratory tests and radiographs. Followup was 30+/-11.3 mo. The hand radiographs were read by observers blinded to patient data who looked for item 7 of the 1987 ACR criteria for RA and used Sharp's method to score erosions and joint space narrowing. RESULTS: The kappa coefficient for ACR item 7 was < 0.65 for bony decalcification and > 0.8 for erosions. Intra and interobserver correlation coefficients for Sharp score ranged from 0.90 to 0.95. The "erosion" component of ACR item 7 was more specific than the full item 7 (96% versus 87.5%; p = 0.02). Sharp erosion score was not better than the erosion component of item 7 (sensitivity 17%; specificity 96%). CONCLUSION: Regardless of the criterion used, hand radiographs were of limited value to predict which patients would be considered as having RA 2 years later. Diagnostic performance was similar for the "erosions" component of the 1987 ACR item 7 and for Sharp erosion score. The full 1987 ACR item 7 (erosions or bony decalcification) performed less well.     

What is the fate of erosions in early rheumatoid arthritis? Tracking individual lesions using x rays and magnetic resonance imaging over the first two years of disease

OBJECTIVES: To investigate the progression of erosions at sites within the carpus, in patients with early rheumatoid arthritis (RA), using magnetic resonance imaging (MRI) and plain radiology over a two year period. METHODS: Gadolinium enhanced MRI scans of the dominant wrist were performed in 42 patients with RA at baseline (within six months of symptom onset) and one year. Plain wrist radiographs (x rays) and clinical data were obtained at baseline, one year, and two years. Erosions were scored by two musculoskeletal radiologists on MRI and x ray at 15 sites in the wrist. A patient centred analysis was used to evaluate the prognostic value of a baseline MRI scan. A lesion centred analysis was used to track the progression of individual erosions over two years. RESULTS: The baseline MRI erosion score was predictive of x ray erosion score at two years (p=0.004). Patients with a "total MRI score" (erosion, bone oedema, synovitis, and tendonitis) > or =13 at baseline were significantly more likely to develop erosions on x ray at two years (odds ratio 13.4, 95% CI 2.65 to 60.5, p=0.002). Baseline wrist MRI has a sensitivity of 80%, a specificity of 76%, a positive predictive value of 67%, and a high negative predictive value of 86% for the prediction of wrist x ray erosions at two years. A lesion centred analysis, which included erosions scored by one or both radiologists, showed that 84% of baseline MRI erosions were still present at one year. When a more stringent analysis was used which required complete concordance between radiologists, all baseline lesions persisted at one year. The number of MRI erosion sites in each patient increased from 2.1 (SD 2.7) to 5.0 (4.6) (p<0.0001) over the first year of disease. When MRI erosion sites were tracked, 21% and 26% were observed on x ray, one and two years later. A high baseline MRI synovitis score, Ritchie score, and erythrocyte sedimentation rate were predictive of progression of MRI erosions to x ray erosions over one year (p=0.005, 0.01, and 0.03 respectively), but there was no association with the shared epitope. Progression of MRI erosions to x ray erosions was not seen in those with transient polyarthritis. CONCLUSIONS: MRI scans of the wrist, taken when patients first present with RA, can predict radiographic erosions at two years. MRI may have a role in the assessment of disease prognosis and selection of patients for more or less aggressive treatment. However, only one in four MRI erosions progresses to an x ray erosion over one year, possibly owing to healing, observer error, or technical limitations of radiography at the carpus. Progression of MRI erosions to x ray erosions is greatest in those with high baseline disease activity.     

MRI bone oedema predicts eight year tendon function at the wrist but not the requirement for orthopaedic surgery in rheumatoid arthritis

OBJECTIVE: To investigate the role of early magnetic resonance imaging (MRI) of the wrist in predicting functional outcome in rheumatoid arthritis. METHODS: MRI scans of the dominant wrist were scored for synovitis, tendon inflammation, bone oedema, and erosion at first presentation (n = 42), at 1 year (n = 42), and at 6 years (n = 31). At 8 years, clinical reassessment (n = 28) was undertaken. Tendon function was graded 0-3 for movement, tendon sheath swelling, and pain on resistance at nine flexor and extensor tendons of the hand. Hand function was also assessed using the Sollerman grip test. The requirement for joint or tendon surgery by 8 years was determined by telephone survey in 39 of the original 42 patients. RESULTS: At 8 years, tendon function was highly correlated with hand function (Sollerman score, R = -0.51, p = 0.005) and global function (health assessment questionnaire score, R = 0.53, p = 0.004). Using a model incorporating baseline and 1 year MRI scores, the MRI bone oedema score was strongly predictive of tendon function at 8 years (chi(2)(2) = 15.3, p = 0.0005), as was the MRI bone erosion score (chi(2)(2) = 9.23, p = 0.01). Hand function was also predicted by the baseline MRI erosion score (p = 0.02). MRI variables did not predict the requirement for surgery, but patients who had surgery were more likely to show progression of MRI bone erosion scores between baseline and 1 year (p = 0.008). CONCLUSIONS: Extensive MRI bone oedema and erosions at the wrist in early rheumatoid arthritis predict tendon dysfunction and impaired hand function in the medium term but not the requirement for joint or tendon surgery.     

Rheumatoid arthritis bone erosion volumes on CT and MRI: reliability and correlations with erosion scores on CT, MRI and radiography

OBJECTIVES: To investigate intramodality and intermodality agreements of CT and MRI erosion volumes in metacarpophalangeal (MCP) joints in rheumatoid arthritis (RA), and to compare the volumes with erosion scores for CT, MRI and radiography. METHODS: In total, 17 patients with RA and four healthy controls underwent unilateral CT, MRI and radiography of second to fifth MCP joints in one hand. Erosion volumes (using OSIRIS software) and scores were determined from CT, MRI and radiography (scores only). RESULTS: CT, MRI and radiography detected 77, 62 and 12 erosions, respectively. On CT, the mean erosion volume was 26 mm(3) (median 10; range 0 to 248) and 30 mm(3) (18; 1 to 163) on MRI. Total erosion volumes (per patient/control) were 97 mm(3) (29; 0 to 485) on CT and 90 mm(3) (46; 0 to 389) on MRI. For volumes, Spearman correlation coefficients were 0.96 to 0.99 (CT vs CT), 0.95 to 0.98 (MRI vs MRI) and 0.64 to 0.89 (CT vs MRI), all p<0.01. MRI erosion volumes correlated with the Outcome Measures in Rheumatology Clinical Trials/Rheumatoid Arthritis Magnetic Resonance Imaging Score (OMERACT RAMRIS) erosion scores (0.91 to 0.99; p<0.01) and the Sharp/van der Heijde erosion score (0.49 to 0.63; p<0.01). CONCLUSION: Very high intramodality and high intermodality agreements of CT and MRI erosion volumes were found, encouraging further testing in longitudinal studies. A close correlation with CT and MRI erosion volumes supports the OMERACT RAMRIS erosion score as a valid measure of joint destruction in RA.     

Identification of wrist and metacarpophalangeal joint erosions using a portable magnetic resonance imaging system compared to conventional radiographs

OBJECTIVE: To compare magnetic resonance (MR) images obtained using a portable MR system to radiographs for identifying bone erosions in the wrists and metacarpophalangeal (MCP) joints of patients with inflammatory arthropathy. METHODS: MR imaging and radiographs were performed in wrists (n = 227) and 2nd and 3rd MCP (n = 188) of 132 patients with inflammatory arthritis to identify erosions. MR imaging was performed using a portable MR system. Findings per body location and per patient were calculated and compared. Additionally, intraobserver and interobserver reliabilities were calculated. RESULTS: MR imaging identified bony erosions in 125 (95%) patients and in 315 (78%) body locations. By comparison, radiographs identified erosions in 78 (59%; p < 0.05) patients and in 156 (39%; p < 0.05) body locations. Intraobserver reliability (K = 0.564) and interobserver reliability (K = 0.429) exhibited moderate agreement, with reader agreement in 80% of the joints scored. CONCLUSION: There was superior sensitivity to bone damage using the portable MR system compared to radiographs of the wrists and MCP joints, suggesting that this scanner is extremely promising for assessment of inflammatory arthritis.     

Bone oedema predicts erosive progression on wrist MRI in early RA--a 2-yr observational MRI and NC scintigraphy study

OBJECTIVES: To investigate if disease assessment by contrast-enhanced dynamic and static magnetic resonance imaging (MRI) and quantitative nanocolloid (NC) scintigraphy gives useful additional information in early rheumatoid arthritis (RA). METHODS: Twenty-seven patients with early RA (disease duration < or =12 months) were followed up for 1 yr and 24 of them for 2 yrs with contrast-enhanced MRI and NC scintigraphy of the wrist joint. Synovial inflammation was assessed by measuring time-dependent enhancement rates (E-rate) from dynamic MRI scans and technetium(99m)-labelled nanocolloid ((99m)Tc-NC) uptake from scintigraphy scans. Synovial membrane hypertrophy, bone oedema and erosions were semiquantitatively scored according to the Outcome Measures in Rheumatology Clinical Trials RA-MRI scoring system from static MR images. Response to the treatment was evaluated based on whether or not > or = 50% improvement was achieved in the tender and swollen joint scores and the Health Assessment Questionnaire score, with normal C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) levels. Progression of the erosion score on wrist MRI was evaluated as the outcome. RESULTS: The baseline MRI bone oedema score (rho= 0.67), MRI synovitis score (rho= 0.57), ESR (rho= 0.56), CRP (rho= 0.48), E-rate (rho= 0.47) and (99m)Tc-NC uptake (rho= 0.45) were related with the change in the MRI erosion score from baseline to 2 yrs (rho= Spearman's correlation). In the multivariate logistic regression model, the bone marrow oedema score was the only baseline variable that predicted erosive progression at 2 yrs' follow-up (OR 4.2, 95% CI 1.3-13.8). The median (interquartile range) change in the erosion score from baseline to 2 yrs was 0 (0, 0) and 4 (2, 5) in the patients with (n= 9) and without (n= 15) a persistent clinical response over the 2 yrs, respectively (P= 0.001). The non-responders who presented with erosive progression from 1 yr to 2 yrs had higher MRI synovitis scores, bone oedema scores, E-rate and (99m)Tc-NC uptake at 1-yr follow-up than the non-responders without progressive bone damage. CONCLUSION: The degree of local synovial inflammation at baseline, evaluated by dynamic and static MRI and quantitative NC scintigraphy, is closely related to the progression of wrist joint erosions during the first 2 yrs of the disease. Furthermore, at follow-up, if no persistent clinical response is achieved, these imaging methods may help to predict future erosiveness and help in clinical therapeutic decision making.     

Increased radiographic damage scores at the onset of seropositive rheumatoid arthritis in older patients are associated with osteoarthritis of the hands, but not with more rapid progression of damage

OBJECTIVE: To investigate the impact of patient age at symptom onset on radiographic joint damage at study entry, and on subsequent progression of damage in a cohort of patients with early seropositive rheumatoid arthritis (RA). METHODS: We studied 186 patients with RA of <15 months' duration. All patients had active disease and had not received disease-modifying antirheumatic drugs. At study entry and during followup, total Sharp scores (TSS), RA-associated joint space narrowing (RA-JSN), and erosions were determined on hand and foot radiographs. Baseline radiographs were also scored for osteoarthritis (OA)-related JSN (OA-JSN) and osteophytes. Older patients (>55 years) and younger patients (相似文献   

MRI of the wrist in early rheumatoid arthritis can be used to predict functional outcome at 6 years

OBJECTIVES: To determine whether magnetic resonance (MR) scans of the dominant wrist of patients with early rheumatoid arthritis (RA) can be used to predict functional outcome at 6 years' follow up. METHODS: Dominant wrist MR scans were obtained in 42 patients with criteria for RA at first presentation. Patients were followed up prospectively for 6 years, and further scans obtained at 1 year (42 patients) and 6 years (31 patients). Two radiologists scored scans for synovitis, tendonitis, bone oedema, and erosions. The Stanford Health Assessment Questionnaire (HAQ) score, indicating functional outcome, and standard measures of disease activity were assessed at 0, 1, 2, and 6 years. The physical function component of the SF-36 score (PF-SF36) was also used as a functional outcome measure at 6 years. RESULTS: Baseline MR parameters, including bone oedema score and the total baseline MR score, were predictive of the PF-SF36 at 6 years (R2 = 0.22, p = 0.005 and R2 = 0.16, p = 0.02, respectively). The PF-SF36 score correlated strongly with the HAQ score at 6 years (rs = -0.725, p<0.0001); none of the baseline MR parameters predicted the 6 year HAQ score. The total MR score obtained at 1 year was predictive of the 6 year HAQ (R2 = 0.04, p = 0.01). Standard clinical and radiographic measures at baseline were not predictive of the 6 year PF-SF36, but when combined in a model with baseline MR oedema score, prediction increased from 0.09 to 0.23, or 23% of the 6 year variance. CONCLUSION: MR imaging of the wrist in patients with early RA can help to predict function at 6 years and could be used to plan aggressive management at an earlier stage.     

OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Studies. Exercise 3: an international multicenter reliability study using the RA-MRI Score

We examined inter-reader agreement of the revised OMERACT 5 Rheumatoid Arthritis MRI Score (RAMRIS v3). Magnetic resonance (MR) images of 10 sets of metacarpophalangeal (MCP) joints 2-5 and 8 sets of rheumatoid arthritis (RA) wrists [1.5 T, coronal and axial T1 and T2 spin-echo, +/- fat saturation (FS), +/- intravenous gadolinium (Gd)] were scored for (1) synovitis using a global score (0-3) and a direct measurement of synovial thickness (mm) and (2) three bone lesions: erosions, defects and edema, (score 0-10 by the volume of the lesion as a proportion of the "assessed bone volume" by 10% increments). Six readers from 5 multinational centers performed all scoring. Three statistical methods were used to analyze the data: (1) single-measure fixed effects intraclass correlations (sICC) and average-measure fixed effects ICC (avICC), (2) percentage exact and close agreement, and (3) the smallest detectable difference (SDD). The sICC were moderate to good (between 0.60 and 0.91) for half of the joint sites for the 2 synovitis scoring methods, and for bone erosions and bone edema. After adjusting for 6 readers, the avICC was very good to excellent (0.80-0.98) for two-thirds of the joint sites by lesion, excluding bone defects that performed relatively poorly, primarily because few readers scored these lesions. The aggregated scores with the best reliability were those with a wide range of scores, high ICC, low SDD, and low percentage SDD (< 33%). The metacarpophalangeal (MCP) bone erosion (sICC 0.58, avICC 0.89, %SDD +/- 27), wrist bone erosion scores (0.72, 0.94, +/- 31%), the wrist synovitis global (0.74, 0.94, +/- 32%), and synovial maximal thickness (0.6, 0.94, +/- 32%) met these conditions. MCP joint synovitis global (0.76, 0.95, +/-35%), MCP joint bone edema (0.63, 0.91, +/- 34%), and wrist bone edema (0.78, 0.95, +/- 38%) performed marginally less well. Bone defects performed poorly (MCP joint 0.18, 0.46, +/- 56%; wrist 0.06, 0.24, +/- 55%). The revised OMERACT 5 RAMRIS has acceptable inter-reader reliability for measures of disease activity (synovitis global and bone edema scores) and damage (bone erosion score). Whether the score is sensitive to change will be determined by its performance in longitudinal and intervention studies.     

Validation of a radiographic damage index in chronic gout

OBJECTIVE: To identify a valid method to measure radiographic damage in patients with chronic gout. METHODS: The scoring method that best represented radiographic damage in individual joints was analyzed by comparing a gold standard rheumatologist consensus global score with recognized scoring methods, including the Sharp/van der Heijde erosion and narrowing scores, Ratingen destruction score, and Steinbrocker score. Ninety-five proximal interphalangeal joints from 12 patients with gout were included in this analysis. Scoring of hand and feet radiographs from an additional 35 patients with gout was used to analyze the sites to be included in a scoring system and the additional features to be recorded. RESULTS: For individual joints, the combination of the Sharp/van der Heijde erosion and narrowing scores correlated best with the consensus global score. In addition, the limits of agreement were narrowest for the combined Sharp/van der Heijde erosion and narrowing score. All joint areas in the Sharp/van der Heijde rheumatoid arthritis score and the distal interphalangeal joints were affected by chronic gout and contributed to the total score. Additional features (extraarticular erosions, joint space widening, and ankylosis) occurred infrequently, and scoring of these features did not increase the reliability of the total score. The reliability of the total score was high: intraclass correlation coefficient for intraobserver reproducibility was 0.993-0.998 and for interobserver reproducibility was 0.963-0.966. The modified Sharp/van der Heijde score was able to discriminate between early and advanced disease. CONCLUSION: A modified Sharp/van der Heijde system accurately and reliably represents radiographic joint damage in chronic gout.     

Use of the Sharp and Larsen scoring methods in the assessment of radiographic progression in juvenile idiopathic arthritis

OBJECTIVE: To investigate the applicability of the Sharp and Larsen scoring methods for radiographic damage in juvenile idiopathic arthritis (JIA). METHODS: Wrist/hand radiographs of 25 patients with polyarthritis obtained at first observation and then yearly for 4-5 years were assessed independently by 2 pediatric rheumatologists according to the Sharp and Larsen methods. To facilitate score assignment, each patient radiograph was compared with a bone age-related standard. A third pediatric rheumatologist measured the Poznanski score, and a pediatric radiologist provided a semiquantitative assessment of radiographic damage severity. RESULTS: Interobserver and intraobserver agreement on longitudinal scores were good for both Sharp and Larsen methods, with intraclass correlation coefficient >0.9. Agreement on change assessment was good for the Sharp method and moderate for the Larsen method. Both methods yielded a steady increase in scores during the study, with score change being more marked in the first year. Sharp and Larsen scores were highly correlated (r(s) = 0.96). Correlations of both scores with the Poznanski score were moderate to high (r(s) from -0.62 to -0.72). Radiologist score was correlated at borderline-high level with both Sharp (r(s) = 0.70) and Larsen (r(s) = 0.71) scores. Sharp and Larsen score change from baseline to final visit was moderately to highly correlated with the number of joints with active arthritis and restricted motion and the Childhood Health Assessment Questionnaire score at final visit. CONCLUSION: Our results demonstrate that the Sharp and Larsen scoring systems are potentially reliable and valid for assessment of radiographic progression in patients with polyarticular JIA.     

The EULAR-OMERACT rheumatoid arthritis MRI reference image atlas: the wrist joint

This paper presents the wrist joint MR images of the EULAR-OMERACT rheumatoid arthritis MRI reference image atlas. Reference images for scoring synovitis, bone oedema, and bone erosions according to the OMERACT RA MRI scoring (RAMRIS) system are provided. All grades (0-3) of synovitis are illustrated in each of the three wrist joint areas defined in the scoring system--that is, the distal radioulnar joint, the radiocarpal joint, and the intercarpal-carpometacarpal joints. For reasons of feasibility, examples of bone abnormalities are limited to five selected bones: the radius, scaphoid, lunate, capitate, and a metacarpal base. In these bones, grades 0-3 of bone oedema are illustrated, and for bone erosion, grades 0-3 and examples of higher grades are presented. The presented reference images can be used to guide scoring of wrist joints according to the OMERACT RA MRI scoring system.     

Use of digital x ray radiogrammetry in the assessment of joint damage in rheumatoid arthritis

OBJECTIVE: To compare digital x ray radiogrammetry (DXR) with manual radiography for assessing bone loss in RA and examine the relationship of the scores obtained with other disease indices. METHODS: 225 consecutive consenting subjects attending the RA clinic were enrolled. An x ray examination was carried out; demographic details recorded; a self assessment questionnaire completed; blood taken for ESR measurement; and an assessment made by a trained nurse. All x ray films were scored manually using the modified Sharp technique by a single observer; 20 films were rescored by three readers. Films were assessed with the Pronosco X-Posure system, version 2.0. Analysis included chi2 tests, independent t tests, multiple linear regression, and partial correlations, as appropriate. The smallest detectable difference (SDD), coefficient of variation (CV), and coefficient of repeatability (CR) were determined from Bland and Altman plots. RESULTS: The DXR precision varied: SDD = 0.002-0.9; CV = 0.09-5.9%; CR = 0.002-0.792, but was better than that of the intra- and interobserver Sharp scores: SDD = 73.9; CV = 27.8%; CR = 33.0-47.6. The DXR measurements, bone mineral density (R2 = 0.210), metacarpal index (R2 = 0.222), and cortical thickness (R2 = 0.215), significantly predicted Sharp scores. In women, DXR measurements significantly correlated with modified HAQ scores but with no other disease indices. Sharp scores significantly correlated with assessor's global assessment, swollen and tender joint counts, pain, HAQ, and DAS28. CONCLUSION: DXR measurements are more precise than Sharp scores; both are related to long term disease activity in RA. DXR is simple to use, does not require intensive training, and may identify subjects not responding to standard treatment.     

Anti-cyclic citrullinated peptide antibody in rheumatoid arthritis: relation with disease aggressiveness

OBJECTIVES: To analyse the value of the anti-cyclic citrullinated peptide antibody (anti-CCP) in patients with rheumatoid arthritis (RA) as a prognostic factor, as well as its relationship with disease activity. METHODS: A cross-sectional study was made on 89 patients with RA. The following values were assessed: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-CCP, Disease Activity Score 28 (DAS 28), Modified Health Assessment Questionnaire score (M-HAQ) and simplified radiologic score of Sharp/Van der Heijde (SENS: simple erosion narrowing score). RESULTS: Sixty-four percent of the patients were anti-CCP positive, from which 36.8% were negative for RF. Among negative RF patients, 48.3% had anti-CCP antibody. The average value of DAS 28 in anti-CCP positive patients was 4.31 (SD 1.27) compared to 3.30 (SD 1.55) for anti-CCP negative (p 200 U/ml) had higher SENS (p < 0.05). There was no correlation between M-HAQ and anti-CCP. CONCLUSION: Prevalence of anti-CCP was higher among patients with higher activity. Patients with higher levels of anti-CCP antibody had more aggressive disease, with greater activity (elevated values in DAS 28 and CRP) and more severe radiological damage (more erosions and higher radiological damage, SENS).     

The relationship between focal erosions and generalized osteoporosis in postmenopausal women with rheumatoid arthritis

Objective

Among rheumatoid arthritis (RA) patients who have had the disease for 10 years, more than half have focal erosions, and the risk of fracture is doubled. However, there is little information about the potential relationship between focal erosions and bone mineral density (BMD). The aim of this study was to determine whether lower BMD is associated with higher erosion scores among patients with RA.

Methods

We enrolled 163 postmenopausal women with RA, none of whom were taking osteoporosis medications. Patients underwent dual x‐ray absorptiometry at the hip and spine and hand radiography, and completed a questionnaire. The hand radiographs were scored using the Sharp method, and the relationship between BMD and erosions was measured using Spearman's correlation coefficients and adjusted linear regression models.

Results

Patients had an average disease duration of 13.7 years, and almost all were taking a disease‐modifying antirheumatic drug. Sixty‐three percent were rheumatoid factor (RF) positive. The median modified Health Assessment Questionnaire score was 0.7, and the average Disease Activity Score in 28 joints was 3.8. The erosion score was significantly correlated with total hip BMD (r = −0.33, P < 0.0001), but not with lumbar spine BMD (r = −0.09, P = 0.27). Hip BMD was significantly lower in RF‐positive patients versus RF‐negative patients (P = 0.02). In multivariable models that included age, body mass index, and cumulative oral glucocorticoid dose, neither total hip BMD nor lumbar spine BMD was significantly associated with focal erosions.

Conclusion

Our results suggest that hip BMD is associated with focal erosions among postmenopausal women with RA, but that this association disappears after multivariable adjustment. While BMD and erosions may be correlated with bone manifestations of RA, their relationship is complex and influenced by other disease‐related factors.

     

Denosumab prevents metacarpal shaft cortical bone loss in patients with erosive rheumatoid arthritis

Objective

Osteoclast‐mediated bone loss in the hand predicts future bone erosions in patients with rheumatoid arthritis (RA). Osteoclast activity depends on RANKL, which is inhibited by denosumab, an investigational fully human monoclonal antibody against RANKL. We measured metacarpal shaft cortical bone thickness using a novel computer‐based technique, digital x‐ray radiogrammetry (DXR), to evaluate the effects of denosumab on cortical bone in RA.

Methods

Patients (n = 227) with active, erosive RA were randomized to receive subcutaneous denosumab 60 mg or 180 mg or placebo every 6 months. All patients received stable doses of methotrexate and daily calcium and vitamin D. For this blinded post hoc analysis (n = 218), cortical bone loss was determined by DXR using computer‐assisted measurement of cortical thickness and shaft width at 21 midshaft levels of the second through fourth metacarpal bones of both hands.

Results

At 12 months, patients receiving denosumab had significantly less metacarpal bone loss versus placebo (denosumab 60 mg: ?0.0034, denosumab 180 mg: 0.0001 gain, placebo: ?0.0108; P ≤ 0.01 for both denosumab doses). Twelve‐month decreases from baseline greater than the smallest detectable change occurred in 2 patients in the denosumab 180 mg group, 9 patients in the denosumab 60 mg group, and 12 patients in the placebo group. Negative correlation was significant between static cortical thickness ratios and static erosion scores (6 and 12 months), and for placebo, between changes in erosion scores and changes in cortical thickness ratio.

Conclusion

Twice‐yearly injections of denosumab with ongoing methotrexate treatment significantly reduced cortical bone loss in RA patients for up to 12 months. These results add to the growing evidence supporting the clinical utility of DXR.

     

Association of tumor necrosis factor alpha polymorphism, but not the shared epitope, with increased radiographic progression in a seropositive rheumatoid arthritis inception cohort

OBJECTIVE: To determine whether the tumor necrosis factor alpha (TNFA) -308 guanine-to-adenosine polymorphism and/or the shared epitope (SE) is associated with radiographic damage in patients with early rheumatoid arthritis (RA). METHODS: The cohort consisted of 189 patients with early seropositive RA (median 5.6 months since symptom onset) who had active disease, no previous disease-modifying antirheumatic drug treatment, and >or=2 sets of scored radiographs of the hands/wrists and forefeet. TNFA -308 polymorphism was analyzed by polymerase chain reaction pyrosequencing. The SE was defined as presence of any 1 of the following HLA-DRB1 alleles: *0101, *0102, *0401, *0404, *0405, *0408, *0410, *1001, *1402, or *1406. Radiographic progression was assessed by the total Sharp score. RESULTS: Using a weighted least-squares regression analysis, patients with the -308 TNFA AA plus AG genotypes (n=49) had significantly higher rates of progression in erosion scores (median 0.84 versus 0.48 units/year), joint space narrowing (JSN) scores (0.42 versus 0.04), and total Sharp scores (1.70 versus 0.61) compared with patients with the TNFA GG genotype (n=140). Presence of the SE (n=137) was associated with significantly lower progression rates (per year) for total Sharp scores (median 0.9 versus 1.25 units/year) and JSN scores (0.04 versus 0.41), but not for erosion scores (0.50 versus 0.61) compared with patients without the SE (n=52). In a least-squares multiple linear regression model, the presence of the AA plus AG genotypes was associated with a significantly higher progression rate after adjusting for the presence of the SE, interaction between the SE and the AA plus AG genotypes, baseline log C-reactive protein level, Health Assessment Questionnaire Disability Index, total Sharp score, swollen joint count, and presence of osteophytes (osteoarthritis). There was a strong linkage disequilibrium between DRB1*0301 and TNFA polymorphism (D'=0.84, r2=0.45, P<0.001). CONCLUSION: This study showed an association between the TNFA -308 polymorphism and progression of radiographic damage in patients with early seropositive RA. This association appeared to be independent of the SE, but might be dependent on other genetic variants in linkage disequilibrium with the -308 TNFA A allele and DRB1*0301. Further studies should be conducted to validate these results in both longitudinal observational cohorts and randomized clinical trials.     

Periarticular bone structure in rheumatoid arthritis patients and healthy individuals assessed by high‐resolution computed tomography

Objective

To define the nature of structural bone changes in patients with rheumatoid arthritis (RA) compared with those in healthy individuals by using the novel technique of high‐resolution microfocal computed tomography (micro‐CT).

Methods

Fifty‐eight RA patients and 30 healthy individuals underwent a micro‐CT scan of the proximal wrist and metacarpophalangeal joints. Bone lesions such as cortical breaks, osteophytes, and surface changes were quantified on 2‐dimensional (2‐D) slices as well as by using 3‐D reconstruction images, and exact localization of lesions was recorded.

Results

Micro‐CT scans could detect bone lesions <0.5 mm in width or depth. Small erosions could be observed in healthy individuals and RA patients, whereas lesions >1.9 mm in diameter were highly specific for RA. Cortical breaks were mostly found along the radial sites of the metacarpal heads. No significant difference in the presence of osteophytes between healthy individuals and RA patients was found. Cortical surface changes, presumably cortical thinning and fenestration, became evident from 3‐D reconstructions and were more pronounced in RA patients.

Conclusion

Micro‐CT allows exact detection of morphologic changes of juxtaarticular bone in healthy individuals and RA patients. Even healthy individuals occasionally show bone changes, but the severity of these lesions, with the exception of osteophytes, is greater in RA patients. Thus, micro‐CT allows accurate differentiation among physiologic bone changes in joints and among types of pathologic bone damage resulting from RA.