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Objectives: In 2015, the 20-item Tophus Impact Questionnaire (TIQ-20) was developed as a tophus-specific patient-reported outcome measure. The aim of this study was to determine whether TIQ-20 scores change during urate-lowering therapy., Methods: We analysed data from a 2-year clinical trial of allopurinol dose escalation using a treat-to-target serum urate approach. For participants with tophaceous gout, the longest diameter of up to three index tophi was measured, using Vernier calipers, and the TIQ-20 was recorded at study visits. Participants at the one site were invited to participate in a dual-energy CT (DECT) substudy. Participants were included in this analysis if they had tophaceous gout and TIQ-20 scores available at baseline, Year 1 and Year 2 (n = 58, 39 with DECT data). Data were analysed using a mixed-model approach to repeated measures., Results: Improvements were observed in all tophus measures over the 2-year period. The mean (s.d.) TIQ-20 scores reduced over 2 years from 3.59 (1.77) to 2.46 (1.73), P < 0.0001, and the mean (95% CI) TIQ-20 change over the 2 years was -1.13 (-1.54, -0.71). The effect size (Cohen's d) for the change in the sum of the index tophi diameter over 2 years was 0.68, for the DECT urate volume was 0.50, and for the TIQ-20 was 0.71., Conclusion: For people with tophaceous gout treated with allopurinol using a treat-to-target serum urate approach, improvements in TIQ-20 occurred, as did improvements in physical and imaging tophus measures. These findings demonstrate that the TIQ-20 is a responsive patient-reported instrument of tophus impact., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Dual energy computed tomography (DECT) allows direct visualization of monosodium urate crystal deposition in gout. However, DECT urate volume data are often highly skewed (mostly small volumes with the remainder considerably larger), making statistical analyses challenging in longitudinal research. The aim of this study was to explore the ability of various analysis methods to normalise DECT urate volume data and determine change in DECT urate volumes over time., Methods: Simulated datasets containing baseline and year 1 DECT urate volumes for 100 people with gout were created from two randomised controlled trials. Five methods were used to transform the DECT urate volume data prior to analysis: log-transformation, Box-Cox transformation, log(X-(min(X)-1)) transformation; inverse hyperbolic sine transformation, and rank order. Linear regression analyses were undertaken to determine the change in DECT urate volume between baseline and year 1. Cohen's d were calculated as a measure of effect size for each data treatment method. These analyses were then tested in a validation clinical trial dataset containing baseline and year 1 DECT urate volumes from 91 people with gout., Results: No data treatment method successfully normalised the distribution of DECT urate volumes. For both simulated and validation data sets, significant reductions in DECT urate volumes were observed between baseline and Year 1 across all data treatment methods and there were no significant differences in Cohen's d effect sizes., Conclusions: Normalising highly skewed DECT urate volume data is challenging. Adopting commonly used transformation techniques may not significantly improve the ability to determine differences in measures of central tendency when comparing the change in DECT urate volumes over time., Competing Interests: Declaration of Competing Interest Lisa Stamp reports grants or contracts from Health Research Council of New Zealand, personal royalties or licenses from UptoDate, and consulting fees from Pharmac. Nicola Dalbeth reports grants or contracts from Health Research Council of New Zealand and Novotech, personal consulting fees from AstraZeneca, Dyve Biosciences, Horizon, Selecta, Arthrosi, JW Pharmaceutical Corporation, PK Med, PTC Therapeutics, Protalix, Cello Health, JPI, Unlocked Labs, and LG, payment or honoraria from Novartis and Hikma. The other authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Objective: The gouty tophus is an organized structure composed of monosodium urate (MSU) crystals and chronic inflammatory soft tissue. This dual-energy computed tomography (DECT) study aimed to determine whether the composition of the tophus changes during urate-lowering therapy., Methods: Serial DECT scans from 32 people with gout were obtained over 2 years of allopurinol therapy, dose-escalated to serum urate of <0.36 mmoles/liter. Up to 5 index tophi were selected for each patient, with 103 separate tophi included in the analysis. Using manual outlining methods of conventional CT and DECT scans, the same index tophi were serially measured for total tophus volume and urate volume. For each tophus, the soft tissue volume was then calculated by subtracting the urate volume from the total tophus volume., Results: The mean ± SD serum urate reduced from 0.43 ± 0.03 mmoles/liter at baseline to 0.31 ± 0.02 mmoles/liter at year 2. The mean ± SD total tophus volume reduced over the 2-year period from 5.17 ± 5.55 cm 3 to 2.61 ± 2.73 cm 3 (P < 0.0001). Greater reductions in tophus urate volumes than tophus soft tissue volumes were observed; the tophus urate volume decreased by 70.6%, and tophus soft tissue volume decreased by 37.8% (P < 0.0001). The mean tophus urate:soft tissue ratio reduced from 0.15 at baseline to 0.05 at year 2 (P < 0.001)., Conclusion: The composition of the tophus is dynamic and changes during urate-lowering therapy for gout management. The soft tissue component of the tophus is slower to respond and may persist without measurable MSU crystal deposition., (© 2023 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: To determine whether a therapeutic approach of intensive serum urate lowering results in improved bone erosion scores in patients with erosive gout., Methods: We undertook a 2-year, double-blind randomized controlled trial of 104 participants with erosive gout who were receiving serum urate-lowering therapy orally and who had serum urate levels of ≥0.30 mmoles/liter at baseline. Participants were randomly assigned to either an intensive serum urate target of <0.20 mmoles/liter or a standard target of <0.30 mmoles/liter (considered the standard according to rheumatology guidelines). Oral serum urate-lowering therapy was titrated to target using a standardized protocol (with the maximum approved doses of allopurinol, probenecid, febuxostat, and benzbromarone). The primary end point was the total computed tomography (CT) bone erosion score. Outcome Measures in Rheumatology (OMERACT) gout core outcome domains were secondary end points., Results: Although the serum urate levels were significantly lower in the intensive target group compared to the standard target group over the study period (P = 0.002), fewer participants in the intensive target group achieved the randomized serum urate target level by year 2 (62% versus 83% of patients in the standard target group; P < 0.05). The intensive target group required higher doses of allopurinol (mean ± SD 746 ± 210 mg/day versus 497 ± 186 mg/day; P < 0.001) and received more combination therapy (P = 0.0004) compared to the standard target group. We observed small increases in CT bone erosion scores in both serum urate target groups over 2 years, with no between-group difference (P = 0.20). OMERACT core outcome domains (gout flares, tophi, pain, patient's global assessment of disease activity, health-related quality of life, and activity limitation) improved in both groups over 2 years, with no between-group differences. Adverse event and serious adverse event rates were similar between the groups., Conclusion: Compared to a serum urate target of <0.30 mmoles/liter, more intensive serum urate lowering is difficult to achieve with an oral urate-lowering therapy. Intensive serum urate lowering leads to a high medication burden and does not improve bone erosion scores in patients with erosive gout., (© 2021 American College of Rheumatology.)

Background: Features of new bone formation (NBF) are common in tophaceous gout. The aim of this project was to develop a plain radiographic scoring system for NBF in gout., Methods: Informed by a literature review, scoring systems were tested in 80 individual 1st and 5th metatarsophalangeal joints. Plain radiography scores were compared with computed tomography (CT) measurements of the same joints. The best-performing scoring system was then tested in paired sets of hand and foot radiographs obtained over 2 years from an additional 25 patients. Inter-reader reproducibility was assessed using intraclass correlation coefficients (ICC). NBF scores were correlated with plain radiographic erosion scores (using the gout-modified Sharp-van der Heijde system)., Results: Following a series of structured reviews of plain radiographs and scoring exercises, a semi-quantitative scoring system for sclerosis and spur was developed. In the individual joint analysis, the inter-observer ICC (95% CI) was 0.84 (0.76-0.89) for sclerosis and 0.81 (0.72-0.87) for spur. Plain radiographic sclerosis and spur scores correlated with CT measurements (r = 0.65-0.74, P < 0.001 for all analyses). For the hand and foot radiograph sets, the inter-observer ICC (95% CI) was 0.94 (0.90-0.98) for sclerosis score and 0.76 (0.65-0.84) for spur score. Sclerosis and spur scores correlated highly with plain radiographic erosion scores (r = 0.87 and 0.71 respectively), but not with change in erosion scores over 2 years (r = -0.04-0.15)., Conclusion: A semi-quantitative plain radiographic scoring method for the assessment of NBF in gout is feasible, valid, and reproducible. This method may facilitate consistent measurement of NBF in gout., (© 2021. The Author(s).)

Background/purpose: Disordered osteoclast activity has been implicated in the pathogenesis of gouty bone erosion. We sought to determine if the addition of denosumab (a monoclonal antibody targeting the receptor activator of nuclear factor kappa-B ligand - RANKL) to intensive urate-lowering therapy (ULT) improves gouty bone erosion., Methods: Open-label, parallel-group pilot randomized controlled trial in which 20 participants with gout with at least one confirmed conventional radiographic foot bone erosion were assigned in a 1:1 allocation to receive denosumab (60 mg subcutaneous every 6 months) added to intensive ULT (serum urate ≤5 mg/dL or 300 µmol/L at the time of randomization and continued for the duration of the study), or intensive ULT alone. The primary outcome was the change in the bilateral foot and ankle computed tomography (CT) bone erosion score from baseline to 12 months, assessed by an experienced musculoskeletal radiologist blinded to study assignment. Secondary outcomes included change in serum C-terminal telopeptide (CTX), and patient reported outcomes of pain and function., Results: Although serum CTX declined markedly in the denosumab/ULT group compared with the ULT alone group, there was no interval change in CT erosion score in either the denosumab/ULT or ULT alone group after one year of follow-up. Other secondary outcomes did not differ between groups. There were two severe adverse events: One patient developed atrial fibrillation (on denosumab/ULT) and another atrial flutter (on ULT alone)., Conclusions: In this pilot study, denosumab did not offer additional benefit to intensive urate lowering therapy for gouty bone erosion., Competing Interests: Declaration of Competing Interest Consultant for Arthrosi, Atom Bioscience, Horizon, Inflazome, LG Pharma, Mallinkrodt, SOBI, Takeda; research grants from Horizon, SOBI, and Shanton (KGS). Nicola Dalbeth reports consulting fees from AstraZeneca, Dyve, Selecta, Horizon, Arthrosi, and Cello Health, and speaker fees from Abbvie and Janssen. No other authors report conflicts of interests., (Published by Elsevier Inc.)

Objective: To examine whether allopurinol dose escalation to achieve serum urate (SU) target can influence bone erosion or monosodium urate (MSU) crystal deposition, as measured by dual-energy computed tomography (DECT) in patients with gout., Methods: We conducted an imaging study of a 2-year randomized clinical trial that compared immediate allopurinol dose escalation to SU target with conventional dosing for 1 year followed by dose escalation to target, in gout patients who were receiving allopurinol and who had an SU level of ≥0.36 mmoles/liter. DECT scans of feet and radiographs of hands and feet were obtained at baseline, year 1, and year 2 visits. DECT scans were scored for bone erosion and urate volume., Results: Paired imaging data were available for 87 patients (42 in the dose-escalation group and 45 in the control group). At year 2, the progression in the CT erosion score was higher in the control group than in the dose-escalation group (+7.8% versus +1.4%; P = 0.015). Changes in plain radiography erosion or narrowing scores did not differ between groups. Reductions in DECT urate volume were observed in both groups. At year 2, patients in the control group who had an SU level of <0.36 mmoles/liter and patients in the dose-escalation group had reduced DECT urate volume (-27.6 to -28.3%), whereas reduction in DECT urate volume was not observed in control group patients with an SU level of ≥0.36 mmoles/liter (+1.5%) (P = 0.023)., Conclusion: These findings provide evidence that long-term urate-lowering therapy using a treat-to-SU-target strategy can influence structural damage and reduce urate crystal deposition in gout., (© 2019, American College of Rheumatology.)

The objective of the study was to determine clinical factors associated with activity limitation and predictors of a change in activity limitation after 1 year in people with gout. Two hundred ninety-five participants with gout (disease duration < 10 years) attended a baseline assessment which included medical and disease-specific history, pain visual analog score and plain radiographs scored for erosion and narrowing. Activity limitation was assessed using the Health Assessment Questionnaire-II (HAQ-II). After 1 year, participants were invited to complete a further HAQ-II; follow-up questionnaires were available for 182 participants. Fully saturated and stepwise regression analyses were used to determine associations between baseline characteristics and HAQ-II at baseline and 1 year, and to determine predictors of worsening HAQ-II in those with normal baseline scores. Median (range) baseline HAQ-II was 0.20 (0-2.50) and 0.20 (0-2.80) after 1 year of follow-up. Pain score was the strongest independent predictor of baseline HAQ-II, followed by radiographic narrowing score, type 2 diabetes, swollen joint count, BMI, age and urate (model R 2  = 0.51, P < 0.001). Baseline HAQ-II was the strongest predictor of change in HAQ-II at 1 year, followed by tender joint count (model R 2  = 0.19, P < 0.001). Of those with HAQ-II scores of 0 at baseline (n = 59, 32% of those with follow-up data), most did not progress (n = 52, 88%); however, baseline pain score, type 2 diabetes and flare frequency were significant predictors of worsening HAQ-II in this group (R 2  = 0.34, P < 0.001). People with gout experience a wide range of activity limitation, and levels of activity limitation are, on average, stable over a 1-year period. Baseline pain scores are strongly associated with activity limitation and predict development of activity limitation in those with normal HAQ-II scores at baseline.

Imaging tests are in clinical use for diagnosis, assessment of disease severity and as a marker of treatment response in people with gout. Various imaging tests have differing properties for assessing the three key disease domains in gout: urate deposition (including tophus burden), joint inflammation and structural joint damage. Dual-energy CT allows measurement of urate deposition and bone damage, and ultrasonography allows assessment of all three domains. Scoring systems have been described that allow radiological quantification of disease severity and these scoring systems may play a role in assessing the response to treatment in gout. This article reviews the properties of imaging tests, describes the available scoring systems for quantification of disease severity and discusses the challenges and controversies regarding the use of imaging tools to measure treatment response in gout., (© The Author 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: Imaging and pathology studies have established a close relationship between tophus and bone erosion in gout. The tophus is an organized structure consisting of urate crystals and chronic inflammatory tissue. The aim of this work was to examine the relationship between bone erosion and each component of the tophus., Methods: Plain radiographs and dual energy CT scans of the feet were prospectively obtained from 92 people with tophaceous gout. The 10 MTP joints were scored for erosion score, tophus urate and soft tissue volume. Data were analysed using generalized estimating equations and mediation analysis., Results: Tophus was visualized in 80.2% of all joints with radiographic (XR) erosion [odds ratio (OR) = 7.1 (95% CI: 4.8, 10.6)] and urate was visualized in 78.6% of all joints with XR erosion [OR = 6.6 (95% CI: 4.7, 9.3)]. In mediation analysis, tophus urate volume and soft tissue volume were directly associated with XR erosion score. About a third of the association of the tophus urate volume with XR erosion score was indirectly mediated through the strong association between tophus urate volume and tophus soft tissue volume., Conclusion: Urate and soft tissue components of the tophus are strongly and independently associated with bone erosion in gout., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background/aims: Radiographic damage is frequently observed in patients with longstanding gout. The aim of this prospective observational study was to determine factors associated with change in radiographic damage scores in gout., Methods: People with gout and disease duration <10 years were recruited into this prospective observational study. At the baseline visit, structured assessment was undertaken in 290 participants including detailed clinical examination and plain radiographs (XR) of the hands and feet. Participants were invited to attend a further study visit with repeat XR 3 years after the baseline visit. XR were scored for erosion and joint space narrowing according to the gout-modified Sharp/van der Heijde XR damage score., Results: Age, subcutaneous tophus count and tender joint count were independently associated with XR damage score at the baseline visit. Paired serial XR were available for 140 participants. In stepwise linear regression analysis, change in total damage score over 3 years was positively associated with change in subcutaneous tophus count and baseline XR damage score, and inversely associated with baseline subcutaneous tophus count (model R 2 =0.39, p<0.001). Change in subcutaneous tophus count contributed most to the change in erosion score (partial R 2 change=0.31, p<0.001), and baseline XR damage score contributed most to the change in narrowing score (partial R 2 change=0.31, p<0.001)., Conclusions: Development of new subcutaneous tophi and baseline radiographic damage are associated with progressive joint damage scores in people with gout. These data provide further evidence that the tophus plays a central role in bone erosion in gout., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: It is currently unknown whether bone erosion in gout occurs through an 'inside-out' mechanism due to direct intra-osseous crystal deposition or through an 'outside-in' mechanism from the surface of bone. The aim of this study was to examine the mechanism ('outside-in' vs. 'inside-out') of monosodium urate (MSU) crystal deposition in bone erosion in gout. Specifically, we used three-dimensional dual-energy computed tomography (DECT) to analyse the positional relationship between bone and MSU crystal deposition in tophaceous gout, and to determine whether intra-osseous crystal deposition occurs in the absence of erosion., Methods: One hundred forty-four participants with gout and at least one palpable tophus had a DECT scan of both feet. Two readers independently scored all metatarsal heads (1433 bones available for scoring). For bones in contact with urate, the bone was scored for whether urate was present within an erosion, on the surface of bone or within bone only (true intra-osseous deposit). Data were analysed using generalised estimating equations., Results: Urate in contact with bone was present in 370 (54.3 %) of 681 joints with urate deposition. For those bones in contact with urate, deposition was present on the surface of bone in 143 (38.6 %) of 370 joints and within erosion in 227 (61.4 %) of 370. True intra-osseous urate deposition was not observed at any site (p < 0.0001). For all bones with apparent intra-osseous deposition in one plane, examination in other planes revealed urate deposition within an en face erosion., Conclusions: In tophaceous gout, MSU crystal deposition is present within the joint, on the bone surface and within bone erosion, but it is not observed within bone in the absence of a cortical break. These data support the concept that MSU crystals deposit outside bone and contribute to bone erosion through an 'outside-in' mechanism.

Objective: The purpose of this study was to investigate whether monosodium urate (MSU) deposits could be identified within the abdomen and axial skeleton of patients with tophaceous gout using dual-energy CT (DECT)., Conclusion: DECT of the abdomen, chest wall, and spine revealed extensive MSU deposits in costal cartilages and, to a lesser extent, intervertebral disks in the male patients with gout in our study. These were quantified volumetrically. However, age-matched control subjects showed similar deposits, indicating this was not a disease-specific finding. Thus, MSU deposition in the axial skeleton may be physiologic in middle-aged men.

Objective: To determine the relationship between tophus, erosion and bone remodeling factors in gout., Methods: Computed tomography bone erosion and circulating bone factors were measured in adults with tophaceous gout. Multiple regression modeling and path analysis were used to determine predictors of erosion., Results: Tophus number, Māori or Pacific ethnicity, creatinine, receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), and sclerostin were independently associated with erosion. Path analysis showed a direct effect of tophus number on erosion, partially mediated through OPG, RANKL, and sclerostin., Conclusion: Tophus number is strongly associated with bone erosion in gout. Circulating RANKL, OPG, and sclerostin are potential mediators of tophus-related erosion.

Introduction: Magnetic resonance imaging (MRI) is useful for detecting joint inflammation and damage in the inflammatory arthropathies. This study aimed to investigate MRI cartilage damage and its associations with joint inflammation in patients with gout compared with a group with rheumatoid arthritis (RA)., Methods: Forty patients with gout and 38 with seropositive RA underwent 3T-MRI of the wrist with assessment of cartilage damage at six carpal sites, using established scoring systems. Synovitis and bone oedema (BME) were graded according to Rheumatoid Arthritis MRI Scoring System criteria. Cartilage damage was compared between the groups adjusting for synovitis and disease duration using logistic regression analysis., Results: Compared with RA, there were fewer sites of cartilage damage and lower total damage scores in the gout group (P = 0.02 and 0.003), adjusting for their longer disease duration and lesser degree of synovitis. Cartilage damage was strongly associated with synovitis in both conditions (R = 0.59, P < 0.0001 and R = 0.52, P = 0.0045 respectively) and highly correlated with BME in RA (R = 0.69, P < 0.0001) but not in gout (R = 0.095, P = 0.56)., Conclusions: Cartilage damage is less severe in gout than in RA, with fewer sites affected and lower overall scores. It is associated with synovitis in both diseases, likely indicating an effect of pro-inflammatory cytokine production on cartilage integrity. However, the strong association between cartilage damage and BME observed in RA was not identified in gout. This emphasizes differences in the underlying pathophysiology of joint damage in these two conditions., (© 2015 The Royal Australian and New Zealand College of Radiologists.)

Objectives: The aim of this work was to examine the relationship between joint damage and monosodium urate (MSU) crystal deposition in gout., Methods: Plain radiographs and dual-energy CT (DECT) scans of the feet were prospectively obtained from 92 people with tophaceous gout. Subcutaneous tophus count was recorded. The ten metatarsophalangeal joints were scored on plain radiography for Sharp-van der Heijde erosion and joint space narrowing (JSN) scores, and presence of spur, osteophyte, periosteal new bone and sclerosis (920 total joints). DECT scans were analysed for the presence of MSU crystal deposition at the same joints., Results: DECT MSU crystal deposition was more frequently observed in joints with erosion (OR (95% CI) 8.5 (5.5 to 13.1)), JSN (4.2 (2.7 to 6.7%)), spur (7.9 (4.9 to 12.8)), osteophyte (3.9 (2.5 to 6.0)), periosteal new bone (7.0 (4.0 to 12.2)) and sclerosis (6.9 (4.6 to 10.2)), p<0.0001 for all. A strong linear relationship was observed in the frequency of joints affected by MSU crystals with radiographic erosion score (p<0.0001). The number of joints at each site with MSU crystal deposition correlated with all features of radiographic joint damage (r>0.88, p<0.05 for all). In linear regression models, the relationship between MSU crystal deposition and all radiographic changes except JSN and osteophytes persisted after adjusting for subcutaneous tophus count, serum urate concentration and disease duration., Conclusions: MSU crystals are frequently present in joints affected by radiographic damage in gout. These findings support the concept that MSU crystals interact with articular tissues to influence the development of structural joint damage in this disease., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: The aim of this study was to compare the frequency and volume of dual energy CT (DECT) urate deposits in people with asymptomatic hyperuricaemia and symptomatic gout., Methods: We analysed DECT scans of the feet from asymptomatic individuals with serum urate ≥540 µmol/L (n=25) and those with crystal proven gout without clinically apparent tophi (n=33)., Results: DECT urate deposits were observed in 6/25 (24%) participants with asymptomatic hyperuricaemia, 11/14 (79%) with early gout (predefined as disease duration ≤3 years) and 16/19 (84%) with late gout (p<0.001). DECT urate deposition was observed in both joints and tendons in the asymptomatic hyperuricaemia group, but significantly less frequently than in those with gout (p≤0.001 for both joint and tendon sites). The volume of urate deposition was also significantly lower in those with asymptomatic hyperuricaemia, compared with the early and the late gout groups (p<0.01 for both comparisons). Similar urate volumes were observed in the early and late gout groups., Conclusions: Although subclinical urate deposition can occur in people with asymptomatic hyperuricaemia, these deposits occur more frequently and at higher volumes in those with symptomatic gout. These data suggest that a threshold of urate crystal volume may be required before symptomatic disease occurs., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objectives: The osteoclast has been implicated in development of bone erosion in gout. The aim of this study was to determine whether zoledronate, a potent antiosteoclast drug, influences bone erosion in people with tophaceous gout., Methods: This was a 2-year, randomised, double-blind, placebo-controlled trial of 100 people with tophaceous gout. Participants were randomised to annual administration of 5 mg intravenous zoledronate or placebo. The primary endpoint was change in the foot CT bone erosion score from baseline. Secondary endpoint was change in plain radiographic damage scores. Other endpoints were change in bone mineral density (BMD), bone turnover markers and the OMERACT-endorsed core domains for chronic gout studies., Results: There was no change in CT erosion scores over 2 years, and no difference between the two treatment groups at Year 1 or 2 (p(treat)=0.10, p(time)=0.47, p(treat*time)=0.23). Similarly, there was no change in plain radiographic scores over 2 years, and no difference between the two groups at Year 1 or 2. By contrast, zoledronate increased spine, neck of femur, total hip and total body BMD. Zoledronate therapy also reduced the bone turnover markers P1NP and β-CTX compared with placebo. There was no difference between treatment groups in OMERACT-endorsed core domains., Conclusions: Despite improvements in BMD and suppression of bone turnover markers, antiosteoclast therapy with zoledronate did not influence bone erosion in people with tophaceous gout. These findings suggest a disconnect between responses in the healthy skeleton and at sites of focal bone erosion in tophaceous gout.

Imaging in the crystal arthropathies has undergone great advances in the past decade, with newer techniques having additional benefits for assisting diagnosis, predicting prognosis, and monitoring the treatment of these conditions. Three-dimensional digitized modalities such as computed tomography, dual-energy computed tomography, and magnetic resonance imaging (MRI) offer a multislice view of any anatomic region. Both ultrasonography and MRI reveal features of inflammation and joint damage in all crystal arthropathies, and can be used to monitor the inflammatory response to therapy. The type of imaging used needs to be adapted to the clinical question of relevance., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: Tophi are strongly associated with structural damage in gout, and urate-lowering therapy reduces tophus size. Pegloticase leads to dramatic reductions in serum urate and subcutaneous tophi in treatment responders. The aim of this analysis was to examine whether profound urate lowering can alter radiographic findings in gout., Methods: Serial plain radiographs of the hands and feet were obtained from 8 patients with tophaceous gout treated with pegloticase. Radiographs were scored for erosion and joint space narrowing (JSN) according to the gout-modified Sharp/van der Heijde method. Scorers were blinded to each other's scores and to the clinical characteristics of the patients (including the clinical response to pegloticase). A detailed qualitative site-by-site analysis was undertaken to define additional changes observed from baseline., Results: All patients experienced a profound urate-lowering response (serum urate level <1 mg/dl) during pegloticase treatment. For the entire group, the median total radiographic scores reduced from 69.25 (range 1.5-138) at baseline to 57.25 (range 1.5-110) at 12 months (P = 0.02). Median erosion scores reduced over 1 year (P = 0.008), but JSN scores did not change (P = 0.50). Further reductions were observed in total scores and erosion scores in 5 patients with 24-month followup films (one-way analysis of variance P = 0.009 for total score, 0.02 for erosion, and 0.95 for JSN). Qualitative site-by-site analysis identified regression of soft tissue masses, increased sclerosis, and filling in of erosions in the followup films., Conclusion: This exploratory study suggests that profound urate lowering can lead to improvement in structural damage, particularly bone erosion, in patients with tophaceous gout., (Copyright © 2014 by the American College of Rheumatology.)

Introduction: Dual-energy computed tomography (DECT) has potential for monitoring urate deposition in patients with gout. The aim of this prospective longitudinal study was to analyse measurement error of DECT urate volume measurement in clinically stable patients with tophaceous gout., Methods: Seventy-three patients with tophaceous gout on stable therapy attended study visits at baseline and twelve months. All patients had a comprehensive clinical assessment including serum urate testing and DECT scanning of both feet. Two readers analysed the DECT scans for the total urate volume in both feet. Analysis included inter-reader intraclass correlation coefficients (ICCs) and limits of agreement, and calculation of the smallest detectable change., Results: Mean (standard deviation) serum urate concentration over the study period was 0.38 (0.09) mmol/L. Urate-lowering therapy was prescribed in 70 (96%) patients. The median (interquartile range) baseline DECT urate volume was 0.49 (0.16, 2.18) cm(3), and change in DECT urate volume was -0.01 (-0.40, 0.28) cm(3). Inter-reader ICCs were 1.00 for baseline DECT volumes and 0.93 for change values. Inter-reader bias (standard deviation) for baseline volumes was -0.18 (0.63) cm(3) and for change was -0.10 (0.93) cm(3). The smallest detectable change was 0.91 cm3. There were 47 (64%) patients with baseline DECT urate volumes <0.91 cm(3). Higher serum urate concentrations were observed in patients with increased DECT urate volumes above the smallest detectable change (P = 0.006). However, a relationship between changes in DECT urate volumes and serum urate concentrations was not observed in the entire group., Conclusions: In patients with tophaceous gout on stable conventional urate-lowering therapy the measurement error for DECT urate volume assessment is substantially greater than the median baseline DECT volume. Analysis of patients commencing or intensifying urate-lowering therapy should clarify the optimal use of DECT as a potential outcome measure in studies of chronic gout.

Objectives: To examine the frequency and patterns of monosodium urate (MSU) crystal deposition in tendons and ligaments in patients with gout using dual-energy CT (DECT)., Methods: Ninety-two patients with tophaceous gout had DECT scanning of both feet. Two readers scored the DECT scans for MSU crystal deposition at 20 tendon/ligament sites and 42 bone sites (total 1840 tendon/ligament sites and 3864 bone sites)., Results: MSU crystal deposition was observed by both readers in 199/1840 (10.8%) tendon/ligament sites and in 399/3864 (10.3%) bone sites (p=0.60). The Achilles tendon was the most commonly involved tendon/ligament site (39.1% of all Achilles tendons), followed by the peroneal tendons (18.1%). Tibialis anterior and the extensor tendons were involved less commonly (7.6-10.3%), and the other flexor tendons, plantar fascia and deltoid ligaments were rarely involved (<5%) (p<0.0001 between sites). Involvement of the enthesis alone was more common in the Achilles tendon (OR (95% CI) 74.5 (4.4 to 1264), p<0.0001), as was any involvement of the enthesis (OR (95% CI) 6.8 (3.6 to 13.0), p<0.0001)., Conclusions: Tendons are commonly affected by MSU crystal deposition in patients with tophaceous gout. The patterns of MSU crystal deposition suggest that biomechanical strain or other local factors may contribute to deposition of MSU crystals.

The diverse clinical states and sites of pathology in gout provide challenges when considering the features apparent on imaging. Ideally, an imaging modality should capture all aspects of disease including monosodium urate crystal deposition, acute inflammation, tophus, tissue remodelling and complications of disease. The modalities used in gout include conventional radiography, ultrasonography, magnetic resonance imaging, computed tomography and dual-energy computed tomography. This review discusses the role of each of these imaging modalities in gout, focussing on the imaging characteristics, role in gout diagnosis and role for disease monitoring. Ultrasonography and dual-energy computed tomography are particularly promising methods for both non-invasive diagnosis and monitoring of disease. The observation that ultrasonographic appearances of monosodium urate crystal deposition can be observed in patients with hyperuricaemia but no other clinical features of gout raises important questions about disease definitions., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

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.

Purpose of Review: Imaging has the potential to assess various pathological manifestations of gout, including monosodium urate (MSU) crystal deposition, tophus formation and cartilage, soft tissue, and bone pathology. This review discusses recent research examining the role of imaging to assess the manifestations of disease., Recent Findings: Various imaging techniques are used in the assessment of gout, including plain radiography, ultrasonography, conventional computed tomography (CT), dual energy computed tomography (DECT), and MRI. Potential roles for ultrasonography are MSU crystal detection, measurement of tophi, and assessment of disease complications. Ultrasonography may allow detection of MSU crystals in patients with hyperuricaemia, prior to development of clinically apparent gout. Conventional CT allows excellent visualization of tophi and bone erosion. DECT is a promising method of noninvasive MSU crystal detection. MRI allows assessment of tophi, synovial and soft tissue disease, and bone pathology. The relative absence of MRI bone marrow oedema in gout suggests that the mechanisms of bone erosion in gout are quite different from those in other erosive arthropathies., Summary: Imaging modalities have provided important insights into the pathology of gout. The role of various imaging techniques in gout diagnosis, monitoring, and prediction of outcome is rapidly developing.

Background: Dual-energy computed tomography (DECT) has recently been described as a sensitive method to detect urate deposits in patients with gout., Objectives: The aim of this study was to compare the reproducibility of DECT with various physical measurement methods of tophus size assessment., Methods: Sixty-four tophi from 25 patients were analyzed. Each tophus was assessed by 2 independent observers using Vernier calipers and tape measure. All patients proceeded to DECT scanning of both feet. Urate volume within index tophi was assessed by 2 independent observers using automated DECT volume assessment software (n = 55 tophi). Five patients returned within 1 week for repeat physical assessment of tophus size. Dual-energy computed tomography scans from the returning patients were scored twice by both observers. Intraobserver and interobserver reproducibility was assessed by intraclass correlation coefficient (ICC) and limits-of-agreement analysis., Results: Overall, DECT was more reproducible than the physical methods with interobserver ICCs for DECT of 0.95, for calipers 0.78, and for tape measurement 0.88, and intraobserver ICCs for DECT of 1.00, for calipers 0.75, and for tape measurement 0.91. Vernier caliper and tape measurements correlated highly with each other (rs = 0.84, P < 0.0001) but less well with DECT (for index tophi, r(s) = 0.46, P = 0.004 for both). Large variation was observed in the amount of urate deposits documented by DECT in tophi of similar physical size., Conclusions: Dual-energy computed tomography scanning is a highly reproducible method for measuring urate deposits within tophi. This imaging modality reveals the composition of tophi that contain variable urate deposits embedded within soft tissue.

Objective: Magnetic resonance imaging (MRI) is commonly used in autoimmune inflammatory arthritis to define disease activity and damage, but its role in gout remains unclear. The aim of our study was to identify and describe the MRI features of gout., Methods: Over a 10-year period we identified patients with gout who underwent MRI scanning of the hands or feet. Scans were reviewed for erosions, synovitis, tenosynovitis, tendinosis, bone edema, and tophi by a musculoskeletal radiologist and 2 rheumatologists in a blinded manner. MRI features in patients with uncomplicated gout were compared with features where concomitant osteomyelitis was diagnosed., Results: A total of 47 patients with gout (51 scans) were included: 33 (70%) had uncomplicated gout and 14 (30%) had gout complicated by osteomyelitis. MRI features included tophi in 36 scans (71%), erosions in 35 (69%), bone edema in 27 (53%), synovitis in 15 (29%), tenosynovitis in 8 (16%), and tendinosis in 2 (4%). Uncomplicated gout and gout plus osteomyelitis did not differ for most MRI features. However, "severe bone marrow edema" was much more common in gout plus osteomyelitis, occurring in 14/15 scans (93%) compared with 3/36 scans (8%) in uncomplicated gout (OR 154.0, 95% CI 14.7-1612, p < 0.0001). Sensitivity and specificity of "severe bone edema" for concomitant osteomyelitis were 0.93 (95% CI 0.68-0.99) and 0.92 (95% CI 0.78-0.98), respectively., Conclusion: MRI reveals that gout affects the joints, bones, and tendons. Bone edema in patients with chronic tophaceous gout is frequently mild and this contrasts with the "severe bone edema" observed in patients with concomitant osteomyelitis.

Objective: To identify methods of tophus measurement for gout studies, summarise the properties of these methods and compile a detailed pictorial reference guide to demonstrate the methods., Methods: A systematic search strategy for methods of tophus measurement was formulated. For each method, papers were assessed by two reviewers to summarise information according to the specific components of the Outcomes Measures in Rheumatology (OMERACT) filter: feasibility, truth and discrimination. Detailed images were obtained to construct the reference guide., Results: Eight methods of tophus measurement were identified: counting the total number of tophi, physical measurement using tape measure, physical measurement using Vernier callipers, digital photography, ultrasonography (US), MRI, CT and dual energy CT. Feasibility aspects of the methods are well documented. Physical measurement techniques are more feasible than advanced imaging methods, but do not allow for assessment of intra-articular tophi or for data storage and central reading. The truth aspect of the filter has been documented for many methods, particularly Vernier callipers, US, MRI and CT. Reliability of most methods has been reported as very good or excellent. Sensitivity to change has been reported for all methods except MRI and CT., Conclusion: A variety of methods of tophus assessment have been described for use in clinical trials of chronic gout. Physical measurement techniques (particularly the Vernier calliper method) and US measurement of tophus size appear to meet most aspects of the OMERACT filter.

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.

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.

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.

Objective: Computed tomography (CT) has high accuracy for tophus detection. This study assessed reliability of CT measurement of tophus volume and compared reproducibility of CT with physical measurement of tophus size., Methods: Forty-seven hand tophi were analyzed in 20 patients with gout. The longest tophus diameter was recorded by 2 independent observers. All patients proceeded to CT scanning of the hands on a Philips Brilliance scanner (0.8-mm slices). Two independent observers measured tophus volume using the Surface Shaded Display 3-dimensional function on the Philips CT workstation. Five patients underwent repeat physical and CT assessments within 1 week (18 observations). Inter- and intraobserver reproducibility were analyzed by limits of agreement and coefficients of variation., Results: Of the 47 lesions identified as tophi on physical examination, 42 (89%) were also identified on CT. The mean (95% confidence interval [95% CI]) difference between observers for physical measurement was 0.45 mm (-4.07, 4.96) and for CT was 65.2 mm(3) (-293.0, 423.3). The mean (95% CI) difference between visits for physical measurement was -0.72 mm (-5.47, 4.03) and for CT was -13.1 mm(3) (-112.5, 86.3). There was no difference between coefficients of variation for inter- and intraobserver reproducibility for the 2 measurement techniques. For tophi identified by physical and CT assessment, there was good correlation between measurements (r = 0.91, P < 0.0001)., Conclusion: CT assessment of tophus volume is reliable and reproducible. However, physical measurement correlates well with CT and has equivalent reproducibility. These data support the use of physical measurement as a simple and reliable method to assess tophus size.

Introduction: The aim of this study was to assess the distribution of bone erosions in the feet of patients with gout using CT and thereby to test the hypothesis that gout is an asymmetric arthropathy. Methods: 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 1,100 bones) by two independent radiologists. Symmetry was assessed by two methods: (i) comparing right and left foot scores for each patient; and (ii) calculating the proportion of paired joints with or without erosions. Results: Observer agreement was excellent (intra-class correlation coefficient 0.92). In the group overall, the difference in scores between the feet was not significant (Student's t-test P = 0.8). In 17 of 25 patients, the difference in erosion scores between the two feet was less than the inter-observer difference. In 24 of 25 patients, the proportion of paired joints was greater than 0.5, indicating symmetric disease. Conclusions: Erosive disease from gout is, in fact, a symmetric process in our patient group. This finding is contrary to the established view of gout as an asymmetric arthritis and lends new insight into the behaviour of this common disease. [ABSTRACT FROM AUTHOR]

Objectives. Bone erosion has been linked with tophus deposition in gout but the roles of osteitis (MRI bone oedema) and synovitis remain uncertain. Our aims in this prospective 3 T MRI study were to investigate the frequency of these features in gout and determine their relation to one another.Methods. 3 T MRI scans of the wrist were obtained in 40 gout patients. Scans were scored independently by two radiologists for bone oedema, erosions, tophi and synovitis. Dual-energy CT (DECT) scans were scored for tophi in a subgroup of 10 patients.Results. Interreader reliability was high for erosions and tophi [intraclass correlation coefficients (ICCs) 0.77 (95% CI 0.71, 0.87) and 0.71 (95% CI 0.52, 0.83)] and moderate for bone oedema [ICC = 0.60 (95% CI 0.36, 0.77)]. Compared with DECT, MRI had a specificity of 0.98 (95% CI 0.93, 0.99) and sensitivity of 0.63 (95% CI 0.48, 0.76) for tophi. Erosions were detected in 63% of patients and were strongly associated with tophi [odds ratio (OR) = 13.0 (95% CI 1.5, 113)]. In contrast, no association was found between erosions and bone oedema. Using concordant data, bone oedema was scored at 6/548 (1%) sites in 5/40 patients (12.5%) and was very mild (median carpal score = 1, maximum = 45). In logistic regression analysis across all joints nested within individuals, tophus, but not synovitis, was independently associated with erosion [OR = 156.5 (21.2, >999.9), P < 0.0001].Conclusion. Erosions were strongly associated with tophi but not bone oedema or synovitis. MRI bone oedema was relatively uncommon and low grade. These findings highlight the unique nature of the osteopathology of gout. [ABSTRACT FROM PUBLISHER]