Background

Long term serum urate (SU) lowering to a target of <0.36 mmol/l (6 mg/dl) is recommended for effective gout management. However, many studies have reported low achievement of SU targets. The aim of this cross-sectional study was to examine the clinical and psychological factors associated with SU targets in patients with gout.

Methods

Patients with gout for <10 years were recruited from primary and secondary care settings. SU target was defined as SU concentration <0.36 mmol/L at the time of the study visit. Both clinical and psychological factors associated with SU target were analysed. The relationship between SU target and measures of gout activity such as flare frequency, tophi, work absences, and Health Assessment Questionnaire-II was also analysed.

Results

Of the 273 patients enrolled into the study, 89 (32.6%) had SU concentration <0.36 mmol/L. Urate-lowering therapy (ULT) use was strongly associated with SU target (p < 0.001). In those patients prescribed ULT (n = 181), allopurinol dose, patient confidence to keep SU under control, female sex, and ethnicity were independently associated with SU target. Other patient psychological measures and health-related behaviours, including adherence scores, were not independently associated with SU target in those taking ULT. Creatinine clearance, diuretic use, age, and body mass index were not associated with SU target. Patients at SU target reported lower gout flare frequency, compared with those not at target (p = 0.03).

Conclusions

ULT prescription and dosing are key modifiable factors associated with achieving SU target. These data support interventions focusing on improved use of ULT to optimise outcomes in patients with gout.

Introduction

Radiographic descriptions of gout have noted the tendency to hypertrophic bone changes. The aim of this study was to characterize the features of new bone formation (NBF) in gout, and to determine the relationship between NBF and other radiographic features of disease, particularly erosion and tophus.

Methods

Paired plain radiographs (XR) and computed tomography (CT) scans of 798 individual hand and wrist joints from 20 patients with gout were analyzed. Following a structured review of a separate set of images, films were scored for the presence of the following features of NBF: spur, osteophyte, periosteal NBF, ankylosis and sclerosis. The relationship between NBF and other radiographic features was analyzed.

Results

The most frequent forms of NBF were bone sclerosis and osteophyte. Spur and periosteal NBF were less common, and ankylosis was rare. On both XR and CT, joints with bone erosion were more likely to have NBF; for CT, if erosion was present, the odds ratios (OR) was 45.1 for spur, 3.3 for osteophyte, 16.6 for periosteal NBF, 26.6 for ankylosis and 32.3 for sclerosis, P for all < 0.01. Similarly, on CT, joints with intraosseous tophus were more likely to have NBF; if tophus was present, the OR was 48.4 for spur, 3.3 for osteophyte, 14.5 for periosteal NBF, 35.1 for ankylosis and 39.1 for sclerosis; P for all < 0.001.

Conclusions

This detailed quantitative analysis has demonstrated that NBF occurs more frequently in joints affected by other features of gout. This work suggests a connection between bone loss, tophus, and formation of new bone during the process of joint remodelling in gout.

There are many exciting new applications for advanced imaging in gout. These modalities employ multiplanar imaging and allow computerized three-dimensional rendering of bone and joints (including tophi) and have the advantage of electronic data storage for later retrieval. High-resolution computed tomography has been particularly helpful in exploring the pathology of gout by investigating the relationship between bone erosions and tophi. Magnetic resonance imaging and ultrasonography can image the inflammatory nature of gouty arthropathy, revealing synovial and soft tissue inflammation, and can provide information about the composition and vascularity of tophi. Dual-energy computerized tomography is a new modality that is able to identify tophi by their chemical composition and reveal even small occult tophaceous deposits. All modalities are being investigated for their potential roles in diagnosis and could have important clinical applications in the patient for whom aspiration of monosodium urate crystals from the joint is not possible. Imaging can also provide outcome measures, such as change in tophus volume, for monitoring the response to urate-lowering therapy and this is an important application in the clinical trial setting.

Predicting prognosis in the patient with newly diagnosed rheumatoid arthritis is of key importance so that high-cost therapies can be tailored to the needs of the individual. In a recent issue of Arthritis Research and Therapy, the prognostic significance of MRI changes at the forefoot has been studied. While progression to radiographic erosion occurred rarely in this group of patients exposed to potent disease-suppressing therapies, including TNF inhibitors, MRI bone edema, representing osteitis, has been further implicated as a forerunner to bone erosion. Early MRI scans of the forefoot were helpful in defining those with the potential to progress as well as those in a good prognosis category.

MRI bone oedema occurs in various forms of inflammatory and non-inflammatory arthritis and probably represents a cellular infiltrate within bone. It is common in early rheumatoid arthritis and is associated with erosive progression and poor functional outcome. Histopathological studies suggest that a cellular infiltrate comprising lymphocytes and osteoclasts may be detected in subchondral bone and could mediate the development of erosions from the marrow towards the joint surface. There is emerging evidence from animal models that such an infiltrate corresponds with MRI bone oedema, pointing towards the bone marrow as a site for important pathology driving joint damage in rheumatoid arthritis.

Introduction

Diverse 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.

Methods

Patients 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.

Results

Compared 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.

Conclusions

Systemic expression of soluble factors that promote osteoclastogenesis is disordered in patients with PsA and may contribute to periarticular bone loss in this disease.

Introduction

The 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).

Methods

Twenty-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.

Results

On 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.

Conclusions

In 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.