Objective. To develop a feasible magnetic resonance imaging (MRI)-based scoring system for sacroiliac joint inflammation in patients with ankylosing spondylitis (AS) that requires minimal scan time, does not require contrast enhancement, evaluates lesions separately at each articular surface, and limits the number of sacroiliac images that are scored. Methods. A scoring method based on the assessment of increased signal denoting bone marrow edema on T2-weighted STIR sequences was used. MRI films were assessed blindly in random order at 2 sites by multiple readers. Intra-and interreader reliability was assessed by intraclass correlation coefficient (ICC); the 24-week response of patients with AS randomized to placebo:infliximab (3:8) was assessed by effect size and standardized response mean. The reliability and responsiveness of the scoring method were compared for STIR and gadolinium diethylenetriaminepentaacetic (Gd-DTPA)-enhanced MRI sequences. Results. We scanned 11 patients with AS with clinically active disease and 11 additional patients randomized to the trial of infliximab therapy. ICC for total sacroiliac joint STIR score ranged from 0.90 to 0.98 (P < 0.00001) and interobserver ICC for combined readers from the 2 sites was 0.84 (P < 0.0001). ICC for change scores was lower for STIR (ICC 0.53) than for Gd-DTPA-enhanced sequences (ICC 0.79). Responsiveness was poor, although fusion was evident in one-third of patients who received treatment (placebo:infliximab) and inflammation scores were low. Conclusion. The Spondyloarthritis Research Consortium of Canada MRI index is a feasible and reproducible index for measuring sacroiliac joint inflammation in patients with AS.

AS patients with enthesitis constitute a more severe subset of disease, and the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index is feasible and reliable for measurement of this condition. Discrimination requires further study in larger trials.

Objective. To develop a feasible magnetic resonance imaging (MRI)-based scoring system for spinal inflammation in patients with spondylarthropathy that requires minimal scan time, does not require contrast enhancement, evaluates the extent of lesions in 3 dimensional planes, and limits the number of vertebral levels that are scored because MRI demonstrates characteristic inflammatory lesions in the spine of patients with ankylosing spondylitis (AS) prior to the development of typical features on plain radiographic. Methods. Our scoring method was based entirely on the assessment of increased signal denoting bone marrow edema on T2-weighted STIR sequences. Blinded MRI films were assessed in random order at 2 sites by 3 blinded readers at each of the 2 sites (the Universities of Alberta and Toronto). Intra-and interreader reliability was assessed by intraclass correlation coefficient. The 24-week response of patients with AS randomized to infliximab:placebo (8:3) was assessed by effect size and standardized response mean.Results. An initial analysis of all discovertebral units (DVUs) in the spine of 11 patients demonstrated a mean of 3.2 (95% confidence interval 3.2, 5.2) affected units, while limiting the scoring to a maximum of 6 units captured most of the affected units. We scanned 11 patients with AS with clinically active disease and 20 additional patients randomized to a 24-week trial of either infliximab or placebo. Intraobserver reproducibility for the 6-DVU STIR score ranged from 0.93 to 0.98 (P < 0.0001). Interobserver reproducibility of scores by readers from both sites was 0.79 (P < 0.0001) for status score and 0.82 (P < 0.0001) for change score. Analysis of pretreatment and posttreatment scores for all 20 patients randomized to infliximab/placebo showed a large degree of responsiveness (standardized response mean ‫؍‬ 0.87). Reproducibility and responsiveness were only slightly improved by using contrast enhancement with gadolinium diethylenetriaminepentaacetic acid. Conclusion. The Spondyloarthritis Research Consortium of Canada MRI index is a feasible, reproducible, and responsive index for measuring spinal inflammation in AS.

Although results moderately support the idea that the three tools are measuring a similar underlying construct, the tools are not interchangeable because they are scaled differently and produce varying results. These findings have potential implications for the interpretation and comparability of health outcome studies and economic analyses. Possible approaches are sensitivity analysis or standardization of scores before calculation of QALYs.

Objective. Focal fat infiltration is frequently visible on magnetic resonance imaging (MRI) of the spine in patients with ankylosing spondylitis (AS) and likely reflects postinflammatory tissue metaplasia. To support the concept of coupling between inflammation and new bone formation, we tested the hypothesis that focal fat infiltration at a vertebral corner is more likely to evolve into a de novo syndesmophyte.Methods. MRI scans were obtained at baseline and radiographs were obtained at baseline and 2 years in 100 AS patients from 2 cohorts: a clinical trial cohort (n ‫؍‬ 38) and an observational cohort (n ‫؍‬ 62). In the clinical trial cohort, patients were randomized to receive anti-tumor necrosis factor (anti-TNF) therapy or placebo for 12-24 weeks and then open-label treatment for 2 years. In the observational cohort, patients received either standard therapy (n ‫؍‬ 36) or anti-TNF therapy (n ‫؍‬ 26) for 2 years. Vertebral corner inflammation and fat infiltration were assessed independently by pairs of readers who were blinded with regard to the radiographic findings.Results. New syndesmophytes developed significantly more frequently in vertebral corners with fat in both the clinical trial (10.2%) and the observational (6.5%) cohort as compared to those without either Conclusion. Our data lend support to the hypothesis that inflammatory lesions evolve into new bone through a process of tissue metaplasia that includes fat infiltration.A hallmark of ankylosing spondylitis (AS) is the development of new bone in the spine, which typically leads to ankylosis across the disc spaces. Bone proliferation typically starts at the vertebral rim and grows in the direction of the anulus fibrosus, parallel to the vertebral axis. Ossification may extend across the vertical length of the anulus and becomes visible on radiographs as a syndesmophyte.Until recently, it was hypothesized that ankylosis occurred in response to inflammation and following a reparative process that included cartilage metaplasia. However, data from animal models of spondylarthritis (SpA), principally ankylosing enthesitis, directly challenged this hypothesis by demonstrating that anti-tumor necrosis factor ␣ (anti-TNF␣) therapy did not prevent the development of ankylosis (1). An alternative hypothesis was then proposed whereby pathogenetic factors such as altered gene expression, biomechanical factors, and bacteria trigger the concomitant expression of inflammation and new bone formation, which then proceed

Objective. In prospective studies, only baseline radiographic damage has been identified as an independent predictor of radiographic progression in ankylosing spondylitis (AS). Several biomarkers have been identified as independent predictors of radiographic progression in rheumatoid arthritis, however, and these may be of use in AS. This study was undertaken to analyze serologic biomarkers as predictors of radiographic progression in AS.Methods. We measured a panel of biomarkers reflecting cartilage turnover and osteoclasis. These biomarkers were cartilage oligomeric matrix protein, human cartilage gp-39 (YKL-40), type II collagen epitopes detected by the C2C and C1,2C degradation assays and the CPII synthesis assay, aggrecan 846 epitope, osteoprotegerin, and matrix metalloproteinase 3 (MMP-3). The analysis was performed in a cohort of AS patients from the Netherlands, Belgium, and France enrolled in a longitudinal study, the Outcome Assessments in Ankylosing Spondylitis International Study. We examined 2-year radiographic progression data scored using the modified Stoke AS Spine Score (mSASSS).Results. Complete data were available on 97 patients. Only the biomarkers YKL-40 and MMP-3 showed weak to moderate univariate correlation with 2-year progression. After adjustment for sex, age, disease duration, C-reactive protein level, and baseline mSASSS, only MMP-3 was significantly associated with 2-year progression (␤ ‫؍‬ 0.29, P ‫؍‬ 0.004). Logistic regression analysis revealed MMP-3 (cutoff 68 ng/ml; odds ratio 9.4 [95% confidence interval 1.6-56]) and baseline mSASSS (cutoff 10 mSASSS units; odds ratio 18.6 [95% confidence interval 2.5-138]) as the only independent predictors of 2-year progression (cutoff 3 mSASSS units; model R 2 ‫؍‬ 50%). MMP-3 was primarily contributory in patients who already had substantial baseline damage (>10 mSASSS units).Conclusion. These results indicate that MMP-3 is a significant independent predictor of radiographic progression in patients with AS, particularly in those with preexisting radiographic damage.Ankylosing spondylitis (AS) is characterized by the presence of inflammation in the spine and the development of ankylosis in the facet joints and intervertebral discs, which leads to immobility and functional impairment. The degree and rate of progression of radiographic changes can be reliably assessed using a validated scoring method, the modified Stoke AS Spine Score (mSASSS), which records structural changes in

Objective. To determine the efficacy of fluoroscopically guided corticosteroid injection for hip osteoarthritis (OA) in a randomized, double-blind, placebocontrolled trial.Methods. Fifty-two patients with symptomatic hip OA were randomly allocated to receive placebo (10 mg bipuvicaine, 2 ml saline) (n ‫؍‬ 21) or corticosteroid treatment (10 mg bipuvicaine, 40 mg triamcinolone hexacetonide) (n ‫؍‬ 31). Patients were followed up for 1, 2, 3, and 6 months. The primary outcome measure was the pain improvement response, defined as a 20% decrease in the Western Ontario and McMaster Universities OA Index (WOMAC) pain score (on 5 100-mm visual analog scales [VAS]) (WOMAC20) from baseline to 2 months postinjection. Secondary outcomes were a 50% decrease in the WOMAC pain score (WOMAC50), changes in other WOMAC subscale scores, patient's global assessment of health (on a 100-mm VAS), and Short Form 36 (SF-36) quality of life indices. Analyses were based on the intent-to-treat principle.Results. The mean WOMAC pain score fell 49.2% (decreasing from 310.1 mm to 157.4 mm) at 2 months postinjection in patients receiving corticosteroid, compared with a decrease of 2.5% (from 314.3 mm to 306.5 mm) in the placebo group (P < 0.0001). The proportion of WOMAC20 responders at 2 months' followup was significantly higher in the corticosteroid group (67.7%) compared with the placebo group (23.8%) (P ‫؍‬ 0.004); similar proportions of WOMAC50 responders were observed between groups (61.3% in the corticosteroid group versus 14.3% in the placebo group; P ‫؍‬ 0.001). Response differences were maintained at 3 months' followup (58.1% responders in the corticosteroid group versus 9.5% responders in the placebo group; P ‫؍‬ 0.004). Significant differences in the WOMAC stiffness and physical function scores (P < 0.0001), patient's global health scores (P ‫؍‬ 0.005), and SF-36 physical component scores (P ‫؍‬ 0.04) were observed, with patients in the corticosteroid group showing greater improvements. There were no differences in the frequency of adverse events between groups.Conclusion. This placebo-controlled trial confirms that corticosteroid injection can be an effective treatment of pain in hip OA, with benefits lasting up to 3 months in many cases. Future studies should address questions related to the benefits of repeated steroid injection and the effects of this treatment on disease modification.Osteoarthritis (OA) affects all vertebrates, and the prevalence of the disease increases exponentially with age. Estimates of the prevalence of hip OA in humans range from 2% at age 35 years to 35% at age 85 years or older (1), and autopsies have shown that cartilage degeneration can be detected in patients as early as the second decade of life (2). A disease prevalence estimate of 3% among North Americans older than age 55 years has been commonly quoted, but this may well be an underestimate of the true burden of hip OA in the general population (3,4). The prevalence of the disease has significant fiscal implications, since it has

Our data supports the hypothesis that new bone formation is more likely in advanced inflammatory lesions and proceeds through a process of fat metaplasia, supporting a window of opportunity for disease modification.