Taper versus discontinuation of tocilizumab in patients with giant cell arteritis: Real-world experience from a tertiary center.

INTRODUCTION: Following the approval of tocilizumab (TCZ) for giant cell arteritis (GCA), recent studies have shown a high relapse frequency after abrupt discontinuation of TCZ. However, a thorough exploration of TCZ tapering compared to abrupt discontinuation has never been undertaken. Likewise, adverse events have only been scarcely investigated in routine care. This study aimed to compare the incidence of relapses in GCA patients undergoing TCZ tapering compared to abrupt discontinuation. METHODS: We performed a single-center retrospective cohort study from 2012 to 2022. Data from GCA patients treated with TCZ was obtained from the Electronic Patients Record. Relapse-free survival is reported in Kaplan-Meier plots and tapering versus abrupt discontinuation were compared using a Wilcoxon-Brewlos-Gehan test. RESULTS: We included 155 patients receiving TCZ treatment for GCA, of which 104 discontinued TCZ. Among the 104 patients discontinuing TCZ, 42 (40 %) experienced a relapse within the first year. A total of 57 patients underwent taper with 6/38 (16 %) and 2/19 (11 %) relapsing while receiving TCZ every second or third week, respectively. In comparison, 59 patients underwent abrupt discontinuation with 27 (46 %) relapsing during follow-up. The patients undergoing abrupt TCZ discontinuation demonstrated a significantly shorter time to relapse compared to all tapered patients (p = 0.02) as well as patients tapered from weekly TCZ treatment to every second week (p < 0.01). Furthermore, 15 % of patients discontinued TCZ due to adverse events. CONCLUSION: This is the first study indicating that TCZ taper induced longer relapse-free survival than abrupt discontinuation, implying that taper may be favored over discontinuation in patients with GCA.

The DANIsh VASculitis cohort study: protocol for a national multicenter prospective study including incident and prevalent patients with giant cell arteritis and polymyalgia rheumatica.

The DANIsh VASculitis cohort study, DANIVAS, is an observational national multicenter study with the overall aim to prospectively collect protocolized clinical data and biobank material from patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) diagnosed and/or followed at Danish rheumatology departments. A long-term key objective is to investigate whether the use of new clinically implemented diagnostic imaging modalities facilitates disease stratification in the GCA-PMR disease spectrum. In particular, we aim to evaluate treatment requirements in GCA patients with and without large-vessel involvement, treatment needs in PMR patients with and without subclinical giant cell arteritis, and the prognostic role of imaging with respect to aneurysm development. Hence, in GCA and PMR, imaging stratification is hypothesized to be able to guide management strategies. With an established infrastructure within rheumatology for clinical studies in Denmark, the infrastructure of the Danish Rheumatologic Biobank, and the possibility to cross-link data with valid nationwide registries, the DANIVAS project holds an exceptional possibility to collect comprehensive real-world data on diagnosis, disease severity, disease duration, treatment effect, complications, and adverse events. In this paper, we present the research protocol for the DANIVAS study. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT05935709.

Association of Autoimmune Diseases With Coronary Atherosclerosis Severity and Ischemic Events.

BACKGROUND: Some autoimmune diseases carry elevated risk for atherosclerotic cardiovascular disease (ASCVD), yet the underlying mechanism and the influence of traditional risk factors remain unclear. OBJECTIVES: This study sought to determine whether autoimmune diseases independently correlate with coronary atherosclerosis and ASCVD risk and whether traditional cardiovascular risk factors modulate the risk. METHODS: The study included 85,512 patients from the Western Denmark Heart Registry undergoing coronary computed tomography angiography. A diagnosis of 1 of 18 autoimmune diseases was assessed. Adjusted OR (aOR) for any plaque, any coronary artery calcification (CAC), CAC of >90th percentile, and obstructive coronary artery disease as well as adjusted HR (aHR) for ASCVD were calculated. RESULTS: During 5.3 years (Q1-Q3: 2.8-8.2 years) of follow-up, 3,832 ASCVD events occurred. A total of 4,064 patients had a diagnosis of autoimmune disease, which was associated with both presence of any plaque (aOR: 1.29; 95% CI: 1.20-1.40), any CAC (aOR: 1.28; 95% CI: 1.19-1.37), and severe CAC of >90th percentile (aOR: 1.53; 95% CI: 1.39-1.68), but not with having obstructive coronary artery disease (aOR: 1.04; 95% CI: 0.91-1.17). Patients with autoimmune diseases had a 46% higher risk (aHR: 1.46; 95% CI: 1.29-1.65) for ASCVD. Traditional cardiovascular risk factors were strongly associated with future ASCVD events, and a favorable cardiovascular risk factor profile in autoimmune patients was associated with ∼54% lower risk compared to patients with presence of risk factors (aHR: 0.46; 95% CI: 0.27-0.81). CONCLUSIONS: Autoimmune diseases were independently associated with higher burden of coronary atherosclerosis and higher risk for future ASCVD events, with risk accentuated by traditional cardiovascular risk factors. These findings suggest that autoimmune diseases increase risk through accelerated atherogenesis and that cardiovascular risk factor control is key for improving prognosis in patients with autoimmune diseases.

COVID-19 Vaccination Before Initiating Rituximab Treatment Induces Strong Serological Response in Autoimmune Rheumatic Disease, Reducing Post-Pandemic Concerns About the Impact of Rituximab.

OBJECTIVE: Rituximab (RTX)-treated patients exhibit suboptimal responses to COVID-19 vaccines. However, existing research primarily involves patients already receiving RTX when vaccines were introduced, failing to account for the current landscape where patients are vaccinated before initiating RTX. Our objective was to compare the serological response to COVID-19 vaccines in patients vaccinated before or after RTX initiation. METHODS: We included 254 RTX-treated patients with autoimmune inflammatory rheumatic diseases (AIIRDs) and 113 blood donors (BDs) in a retrospective, observational cohort study. Patients were categorized based on the timing of RTX treatment relative to primary COVID-19 vaccination. Serological vaccine responses were assessed using three immunoassays, and logistic regression analysis was used to identify predictors of serological response. RESULTS: Patients vaccinated before initiating RTX treatment had significantly higher seroconversion rates of SARS-CoV-2 immunoglobulin G (87%) and neutralizing antibodies (91%) compared with those receiving RTX before and after vaccination (n = 132) (61% and 65%, respectively). In the logistic regression analysis, a positive serological response was associated with the number of vaccines administered >9 months after the last RTX treatment. Patients receiving the highest number of vaccines with >9 months after RTX showed a response comparable to that of the BDs. CONCLUSION: Vaccinating before RTX initiation yields a robust serological response in patients with AIIRDs. Furthermore, we highlight the reversibility of antibody impairment after RTX treatment cessation, provided that adequate vaccinations occur within a minimum of 9 months after RTX. Our findings offer essential insights for clinical decision-making regarding COVID-19 vaccination and RTX treatment, alleviating concerns about future RTX use.

Erosive Progression by High-Resolution Peripheral Quantitative Computed Tomography and Conventional Radiography in Rheumatoid Arthritis.

OBJECTIVES: To investigate the diagnostic accuracy of high-resolution peripheral quantitative computed tomography (HR-pQCT) to assess erosive progression during one year compared to conventional radiography (CR) in rheumatoid arthritis (RA). METHODS: This prospective study included 359 patients with RA (disease duration ≥ 5 years) between March 2018 and October 2020. HR-pQCT and CR were obtained at inclusion and after one year. Erosive assessment was performed at two metacarpophalangeal joints of the dominant hand using HR-pQCT and progression was defined as an increase in erosion number ≥ 1 or an increase in erosive volume > least significant change. CR of hands, wrists, and feet were evaluated using Sharp/van der Heijde scores and erosive progression was defined as a 1.1-point increase in erosion score according to the smallest detectable change. RESULTS: In paired analyses (n = 310), erosive progression was identified in 30 patients using CR and in 40 patients using HR-pQCT. In the 40 patients with erosive progression on HR-pQCT, progression was not identified by CR in 33 patients. Adding HR-pQCT to CR doubled the proportion of patients identified with progression from 30 (10%) to 63 (20%) patients. Using CR as the reference, the sensitivity (% (95% CI)) of HR-pQCT for identifying erosive progression was 23.3 (9.9-42.3) and the specificity was 88.2 (83.8-91.7). CONCLUSION: A substantial proportion of patients with erosive progression are overlooked using CR only to monitor erosive progression. Adding high-resolution peripheral CT to CR doubles the proportion of patients, who may benefit from individualised therapy targeting erosive progression in RA.

Cardiovascular safety of using non-steroidal anti-inflammatory drugs for gout: a Danish nationwide case-crossover study.

Gout attacks are treated with uric-lowering and anti-inflammatory drugs. In patients with gout, non-steroidal anti-inflammatory drugs (NSAIDs) could be both cardiovascular beneficial, due to their anti-inflammatory actions, and cardiovascular hazardous, due to their prothrombotic, hypertensive, and proarrhythmic side effects. We, therefore, examined the risk of cardiovascular events associated with NSAID use in patients with gout. We conducted a nationwide, population-based case-crossover study of all Danes ≥ 18 years of age with first-time gout during 1997-2020, who experienced a cardiovascular event (myocardial infarction, ischemic stroke, congestive heart failure, atrial fibrillation/flutter, or cardiovascular death) (n = 59,150). The exposure was use of NSAIDs, overall and according to type (ibuprofen, naproxen, or diclofenac). We used the dates 300, 240, 180, and 120 before the outcome date as reference dates. We used the Mantel-Haenszel method to calculate odds ratios (ORs) with 95% confidence intervals (CIs) of the association between NSAID use and cardiovascular events. NSAID use was overall associated with 12% decreased odds of a cardiovascular event (OR = 0.88, 95% CI: 0.85-0.91). This decreased odds ratio was observed for the use of ibuprofen (OR = 0.92, 95% CI: 0.88-0.97) and naproxen (OR = 0.85, 95% CI: 0.74-0.97), but not for the use of diclofenac (OR = 0.97, 95% CI: 0.90-1.05). Overall, use of NSAIDs was associated with decreased odds of all the individual components of the composite outcome. NSAIDs were not associated with an increased cardiovascular event rate when used in gout patients. Ibuprofen and naproxen appeared to have better cardiovascular risk profiles than diclofenac.

The effect of prednisolone and a short-term prednisolone discontinuation for the diagnostic accuracy of FDG-PET/CT in polymyalgia rheumatica-a prospective study of 101 patients.

PURPOSE: 2-[18F]Fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) has been suggested as an imaging modality to diagnose polymyalgia rheumatica (PMR). However, the applicability of FDG-PET/CT remains unclear, especially following glucocorticoid administration. This study aimed to investigate the diagnostic accuracy of FDG-PET/CT before and during prednisolone treatment, as well as following short-term prednisolone discontinuation. METHODS: Treatment naïve suspected PMR patients were clinically diagnosed at baseline and subsequently had an FDG-PET/CT performed. Patients diagnosed with PMR were administered prednisolone following the first FDG-PET/CT and had a second FDG-PET/CT performed after 8 weeks of treatment. Subsequently, prednisolone was tapered with short-term discontinuation at week 9 followed by a third FDG-PET/CT at week 10. An FDG-PET/CT classification of PMR/non-PMR was applied, utilizing both the validated Leuven score and a dichotomous PMR score. The final diagnosis was based on clinical follow-up after 1 year. RESULTS: A total of 68 and 27 patients received a final clinical diagnosis of PMR or non-PMR. A baseline FDG-PET/CT classified the patients as having PMR with a sensitivity/specificity of 86%/63% (Leuven score) and 82%/70% (dichotomous score). Comparing the subgroup of non-PMR with inflammatory diseases to the PMR group demonstrated a specificity of 39%/54% (Leuven/dichotomous score). After 8 weeks of prednisolone treatment, the sensitivity of FDG-PET/CT decreased to 36%/41% (Leuven/dichotomous score), while a short-term prednisolone discontinuation increased the sensitivity to 66%/60%. CONCLUSION: FDG-PET/CT has limited diagnostic accuracy for differentiating PMR from other inflammatory diseases. If FDG-PET/CT is intended for diagnostic purposes, prednisolone should be discontinued to enhance diagnostic accuracy. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04519580). Registered 17th of August 2020.

Effectiveness of a novel digital patient education programme to support self-management of early rheumatoid arthritis: a randomised controlled trial.

OBJECTIVES: To evaluate the effectiveness of a novel digital patient education (PE) programme in improving self-management in patients newly diagnosed with rheumatoid arthritis (RA). METHODS: This was a parallel, open-label, two arms, randomised controlled trial with superiority design. Patients from five rheumatology clinics were randomised into digital PE (intervention) or face-to-face PE (control). The primary outcome was self-efficacy, measured by average difference in the Rheumatoid Arthritis Self-Efficacy (RASE) score from baseline to month 12. Secondary outcomes were RA knowledge, health literacy, adherence, and quality of life. Healthcare utilisation data and digital PE programme usage were recorded. Self-efficacy, knowledge, and health literacy data were analysed using mixed-effects repeated measures modelling; adherence using logistic regression, and quality of life and healthcare utilization using descriptive statistics with the Wilcoxon rank-sum test. RESULTS: Of the 180 patients randomised (digital PE, n = 89; face-to-face PE, n = 91), 175 had data available for analysis. Median age was 59.0 years, and 61% were women. The average difference in self-efficacy between groups from baseline to month 12 was significant by a -4.34 difference in RASE score, favouring the intervention group (95%CI -8.17 to -0.51; p= 0.026). RA knowledge, health literacy, and quality of life showed minor improvements over time but no difference between groups, except out-patient clinic contacts which were fewer in the intervention group. CONCLUSIONS: The findings suggest that digital PE is effective in improving self-efficacy and therefore self-management in patients with early RA. This intervention has potential to lower healthcare costs by decreasing out-patient clinic contacts. TRIAL REGISTRATION NUMBER: clinicaltrials.gov, NCT04669340.

Long-term efficacy of a 2-year MRI treat-to-target strategy on disease activity and radiographic progression in patients with rheumatoid arthritis in clinical remission: 5-year follow-up of the IMAGINE-RA randomised trial.

OBJECTIVE: To investigate whether a 2-year MRI treat-to-target strategy targeting the absence of osteitis combined with clinical remission, compared with a conventional treat-to-target strategy targeting clinical remission only (IMAGINE-rheumatoid arthritis (RA) trial) improves clinical and radiographic outcomes over 5 years in patients with RA in clinical remission. METHODS: IMAGINE-more was an observational extension study of the original 2-year IMAGINE-RA randomised trial (NCT01656278). Clinical examinations and radiographs (hands and feet) were obtained yearly. Prespecified coprimary outcomes at year 5 were Disease Activity Score in 28 joints C reactive protein (DAS28-CRP) remission rate (DAS28-CRP<2.6) and no radiographic progression (van der Heijde-modified Sharp score (vdHSS) ≤0) from baseline. Secondary outcomes included 5-year changes in radiographic, MRI and clinical measures of disease activity and physical function. RESULTS: In total 131 patients, 86 women (67%), mean age 61.2, disease duration 9.5 years, median baseline DAS28-CRP 1.9 (IQR 1.6-2.2) and vdHSS 16.0 (IQR 7.0-36.0) were included in the study; 59 (59%) patients from the original MRI treat-to-target group and 72 (72%) from the conventional group. At year 5, 47 patients (80%) in the MRI treat-to-target group vs 54 patients (75%) in the conventional treat-to-target group were in DAS28-CRP remission (OR 2.00 (95% CI 0.76 to 5.28); p=0.16) while 14 patients (24%) vs 19 patients (26%) had no radiographic progression (OR 0.70, (95% CI 0.28 to 1.71); p=0.43). CONCLUSION: A 2-year combined MRI and clinical treat-to-target strategy, compared with a conventional clinical treat-to-target strategy alone, had no effect on the long-term probability of achieving DAS28-CRP remission and of avoiding radiographic progression.

Preoperative proximal tibial bone density, bone microarchitecture, and bone turnover are not associated with postoperative tibial component migration in cemented and cementless medial unicompartmental knee replacements: secondary analyses from a randomized controlled trial.

BACKGROUND AND PURPOSE: Cementless arthroplasty fixation relies on early bone ingrowth and may be poor in patients with low proximal tibial bone density or abnormal bone turnover. We aimed first to describe the baseline bone properties in patients undergoing medial unicompartmental knee replacement (UKR), and second to investigate its association with cemented and cementless tibial component migration until 2 years. METHODS: A subset investigation of 2 patient groups from a 3-armed randomized controlled trial was conducted. There were 26 cemented and 25 cementless medial UKRs with twin-pegged femoral components. Volumetric bone mineral density (vBMD) and microstructure of the excised medial tibial plateau were ascertained with µCT. Bone turnover was estimated using dynamic histomorphometry (eroded surface/bone surface = ES/BS, osteoid surface/bone surface = OS/BS, mineralizing surface/bone surface = MS/BS). Tibial component migration in 4 feature points was followed for 2 years with radiostereometry. RESULTS: At the 2-year follow-up, the cementless tibial components migrated 0.38 mm (95% confidence interval [CI] 0.14-0.62) total translation more than the cemented components at the posterior feature point. The greatest migration in the cementless group was subsidence at the posterior feature point of 0.66 mm (CI 0.48-0.84) until 6 weeks, and from 3 months the components were stable. Cemented tibial components subsided very little. Between 1- and 2-year follow-ups, no cementless but 4 cemented tibial components revealed continuous migration. OS/BS was half of the ES/BS. No µCT or histomorphometric parameters showed any clinically relevant correlation with tibial component migration at the posterior feature point for either cemented or cementless UKR at 6 weeks' or 2 years' follow-up after adjustment for age, BMI, and sex. CONCLUSION: Preoperative vBMD, bone turnover, and microstructure were not associated with postoperative tibial component migration of cemented and cementless medial UKR.

The one-year infection risk among patients diagnosed with giant cell arteritis: use of antibiotics and hospitalisations.

OBJECTIVES: Patients with giant cell arteritis (GCA) primarily have their infections managed by primary care providers and hospitalisation is rarely necessary. Existing studies in GCA focus on infection-related hospitalisations only, whereas the use of antibiotic prescriptions is largely unknown. This study aims to examine the one-year overall infection risk among patients with GCA. METHODS: This nationwide observational cohort study included patients aged ≥50 years with a first-time GCA diagnosis in the Danish National Patient Registry (1996-2022). Patients with GCA were matched 1:10 by sex and date of birth with general population individuals and followed from date of diagnosis. Overall infections were defined as redeemed antibiotic prescriptions or infection-related hospitalisations. Utilising a pseudo-observation approach, we assessed 1-year cumulative incidence proportions (CIP), risk differences (RD), and relative risks (RR) of infections. RESULTS: The study included 17 773 incident patients with GCA and 177 730 reference individuals. Patients with GCA had a 1-year CIP of 52.4% (95% CI: 51.7-53.2) for overall infections and 17.6% (95% CI: 17.1-18.2) for infection-related hospitalisations. Compared with the reference cohort, patients with GCA had a RR of 1.40 (95% CI: 1.38-1.42) for overall infections and 2.71 (95% CI: 2.61-2.82) for infection-related hospitalisations. Additionally, higher cumulative glucocorticoid doses, advanced age (≥70 years), and higher comorbidity were associated with an increased risk of infections among patients with GCA. CONCLUSIONS: The use of antibiotic prescriptions and infection-related hospitalisations in the first year after a GCA diagnosis is high compared with the background population. The cumulative glucocorticoid dose is associated with the infection risk.

Bony proliferations in rheumatoid arthritis, psoriatic arthritis and osteoarthritis using high-resolution peripheral quantitative computed tomography-A systematic literature review.

PURPOSE: Osteoarthritis (OA), rheumatoid arthritis (RA), and psoriatic arthritis (PsA) can all lead to the formation of bony proliferations (BP). This systematic review aimed to examine the characteristics of BPs in patients with RA, PsA, OA, and healthy controls (HC) using high-resolution peripheral quantitative computed tomography (HR-pQCT). Secondarily, we examined any treatment-related effect on BP number and size. METHODS: A systematic literature search was conducted in PubMed and Embase, and a total of 15 studies were included. RESULTS: Seven studies demonstrated a disease-specific variation in BP location. One study showed no difference in the number of BPs between patients with PsA and OA. The number of BPs was greater in patients with PsA compared to RA in one study, and to HC in another study, while one study documented no difference in the number of BPs between patients with RA and HC. Five studies showed larger BPs in patients with PsA compared to HC, and one study larger BPs in patients with PsA compared to RA. One study showed no difference in BP size between patients with PsA and OA. Secukinumab may have a potential effect on arresting BP progression. Otherwise, no other treatment was reported to influence BP size and progression. No standard definitions or measurement techniques for BPs using HR-pQCT have been identified. CONCLUSION: BPs showed disease-specific variations in location, size, and number. Results regarding treatment-related effects are sparse. An agreement on the definition and measurement technique for BPs using HR-pQCT is warranted for diagnostic accuracy, disease comparability, and monitoring potential.

High-resolution peripheral quantitative computed tomography for the assessment of acro-osteolysis and calcinosis in patients with systemic sclerosis.

OBJECTIVE: To assist the development of future treatments in systemic sclerosis (SSc), the development of reliable outcome measures is pivotal. We aimed to evaluate the use of high-resolution peripheral quantitative CT (HR-pQCT) for visualization and gradation of acro-osteolysis (AO) and calcinosis compared to conventional hand radiographs (CR) in patients with SSc. METHODS: HR-pQCT scans of the 2nd to 4th fingers, CR, nail fold capillaroscopy, and a clinical examination were conducted. Images were reviewed for the presence and degree of AO and calcinosis according to semiquantitative grading scales. RESULTS: Forty patients were included. Fourteen had AO according to CR, whereas HR-pQCT revealed AO in 18 patients. The sensitivity and specificity of classifying patients as having AO by HR-pQCT when CR was used as reference were 93% (95% CI: 66-99%) and 80% (95% CI: 59-93%), respectively. By CR and with HR-pQCT as reference, the sensitivity and specificity were 72% (95% CI: 47-90%) and 95% (95% CI: 76-99%). Patients with AO had more or larger calcifications than patients without AO according to the proposed HR-pQCT grading system, with a median grade of 2 (IQR: 1-3) versus 0 (IQR: 0-1) (P<0.01). Grade 3 changes were observed exclusively in patients with AO (n=6/14, 42.9%). Assessment of AO and calcinosis by HR-pQCT demonstrated moderate to excellent test-retest reliability. CONCLUSION: HR-pQCT allowed precise and reliable classification and grading of acro-osteolysis and acral calcinosis. The modality could prove helpful for detecting and monitoring these lesions as well as facilitating early diagnosis and guide treatment of these patients.

Revaccination of patients with systemic lupus erythematosus or rheumatoid arthritis without an initial COVID-19 vaccine response elicits seroconversion in half of the patients.

OBJECTIVES: To investigate the effect of COVID-19 mRNA revaccination (two doses) on the antibody response in patients with rheumatic diseases (RD) who were initial vaccine non-responders. Further, to examine if B-cell levels or T-cell responses before revaccination predicted seroconversion. METHODS: From a RD cohort vaccinated with the standard two-dose COVID-19 vaccinations, we enrolled cases without detectable antibody responses (n=17) and controls with detectable antibody response (n=29). Blood donors (n=32) were included as additional controls. Samples were collected before and six weeks after completed revaccination. Total antibodies and specific IgG, IgA, and IgM against SARS-CoV-2 spike protein, SARS-CoV-2 neutralising antibodies, and SARS-CoV-2 reacting CD4+ and CD8+ T-cells were measured before and after revaccination. B-cells (CD19+CD45+) were quantified before revaccination. RESULTS: Forty-seven percent of cases had detectable neutralising antibodies after revaccination. However, antibody levels were significantly lower than in controls and blood donors. Revaccination induced an antibody class switch in cases with a decrease in IgM and increase in IgG. No significant difference was observed in T-cell responses before and after revaccination between the three groups. Only 29% of cases had measurable B-cells compared to 100% of controls and blood donors. Fifty percent of revaccinated cases who seroconverted had measurable B-cells before revaccination. CONCLUSIONS: Forty-seven percent of initial non-responders seroconverted after two-dose revaccination but still had lower levels of SARS-CoV-2 antibodies compared with controls and blood donors. RD patients without a detectable serological response after the initial COVID-19 mRNA vaccine had a T-cell response similar to immunocompetent controls and blood donors.

Bone Mineral Density Derived from Cardiac CT Scans: Using Contrast Enhanced Scans for Opportunistic Screening.

PURPOSE: Osteoporosis is under-diagnosed and often co-exists with other diseases. Very low bone mineral density (BMD) indicates risk of osteoporosis and opportunistic screening for low BMD in CT-scans has been suggested. In a non-contrast enhanced thoracic CT scan, the scan-field-of-view includes vertebrae enabling BMD estimation. However, many CT scans are obtained by administration of contrast material. If the impact of contrast enhancement on BMD measurements could be quantified, considerably more patients are eligible for screening. METHODS: This study investigated the impact of intravenous contrast on thoracic BMD measurements in cardiac CT scans pre- and post-contrast, including different contrast trigger levels of 130 and 180 Hounsfield units (HU). BMD was measured using quantitative CT with asynchronous calibration. RESULTS: In 195 participants undergoing cardiac CT (mean age 57±9 years, 37 % females) contrast increased mean thoracic BMD from 116±33 mg/cm3 (non-enhanced CT) to 130±38 mg/cm3 (contrast-enhanced CT) (p<0.001). Using clinical cut-off values for very low (<80 mg/cm3) and low BMD (<120 mg/cm3) showed that 24 % (47/195 participants) were misclassified when BMD was measured on contrast-enhanced CT-scans. Of the misclassified patients, 6 % (12/195 participants) were categorized as having low BMD despite having very low BMD on the non-enhanced images. Contrast-CT using a higher contrast trigger level showed a significant increase in BMD compared to the lower trigger level (119±32 vs. 135±40 mg/cm3, p<0.01). CONCLUSION: For patients undergoing cardiac CT, using contrast-enhanced images to assess BMD entails substantial overestimation. Contrast protocol trigger levels also affect BMD measurements. Adjusting for these factors is needed before contrast-enhanced images can be used clinically. MINI ABSTRACT: Osteoporosis is under-diagnosed. Contrast-enhanced CT made to examine other diseases might be utilized simultaneously for bone mineral density (BMD) screening. These scans, however, likely entails overestimation of BMD due to the effect of contrast. Adjusting for this effect is needed before contrast-enhanced images can be implemented clinically for BMD screening.

Recommendations for early referral of individuals with suspected polymyalgia rheumatica: an initiative from the international giant cell arteritis and polymyalgia rheumatica study group.

OBJECTIVE: To develop international consensus-based recommendations for early referral of individuals with suspected polymyalgia rheumatica (PMR). METHODS: A task force including 29 rheumatologists/internists, 4 general practitioners, 4 patients and a healthcare professional emerged from the international giant cell arteritis and PMR study group. The task force supplied clinical questions, subsequently transformed into Population, Intervention, Comparator, Outcome format. A systematic literature review was conducted followed by online meetings to formulate and vote on final recommendations. Levels of evidence (LOE) (1-5 scale) and agreement (LOA) (0-10 scale) were evaluated. RESULTS: Two overarching principles and five recommendations were developed. LOE was 4-5 and LOA ranged between 8.5 and 9.7. The recommendations suggest that (1) each individual with suspected or recently diagnosed PMR should be considered for specialist evaluation, (2) before referring an individual with suspected PMR to specialist care, a thorough history and clinical examination should be performed and preferably complemented with urgent basic laboratory investigations, (3) individuals with suspected PMR with severe symptoms should be referred for specialist evaluation using rapid access strategies, (4) in individuals with suspected PMR who are referred via rapid access, the commencement of glucocorticoid therapy should be deferred until after specialist evaluation and (5) individuals diagnosed with PMR in specialist care with a good initial response to glucocorticoids and a low risk of glucocorticoid related adverse events can be managed in primary care. CONCLUSIONS: These are the first international recommendations for referral of individuals with suspected PMR, which complement the European Alliance of Associations for Rheumatology/American College of Rheumatology management guidelines for established PMR.

Transitory Activation and Improved Transition from Erosion to Formation within Intracortical Bone Remodeling in Hypoparathyroid Patients Treated with rhPTH(1-84).

In hypoparathyroidism, lack of parathyroid hormone (PTH) leads to low calcium levels and decreased bone remodeling. Treatment with recombinant human PTH (rhPTH) may normalize bone turnover. This study aimed to investigate whether rhPTH(1-84) continued to activate intracortical bone remodeling after 30 months and promoted the transition from erosion to formation and whether this effect was transitory when rhPTH(1-84) was discontinued. Cortical histomorphometry was performed on 60 bone biopsies from patients (aged 31 to 78 years) with chronic hypoparathyroidism randomized to either 100 µg rhPTH(1-84) a day (n = 21) (PTH) or similar placebo (n = 21) (PLB) for 6 months as add-on to conventional therapy. This was followed by an open-label extension, where patients extended their rhPTH(1-84) (PTH) (n = 5), continued conventional treatment (CON) (n = 5), or withdrew from rhPTH(1-84) and resumed conventional therapy (PTHw) for an additional 24 months (n = 8). Bone biopsies were collected at months 6 (n = 42) and 30 (n = 18). After 6 and 30 months, the overall cortical microarchitecture (cortical porosity, thickness, pore density, and mean pore diameter) in the PTH group did not differ from that of the PLB/CON and PTHw groups. Still, the PTH group had a significantly and persistently higher percentage of pores undergoing remodeling than the PLB/CON groups. A significantly higher percentage of these pores was undergoing bone formation in the PTH compared with the PLB/CON groups, whereas the percentage of pores with erosion only was not different. This resulted in a shift in the ratio between formative and eroded pores, reflecting a faster transition from erosion to formation in the PTH-treated patients. In the rhPTH(1-84) withdrawal group PTHw, the latter effects of PTH were completely reversed in comparison to those of the PLB/CON groups. In conclusion, rhPTH(1-84) replacement therapy in hypoparathyroidism patients promotes intracortical remodeling and its transition from erosion to formation without affecting the overall cortical microstructure. The effect persists for at least 30 months and is reversible when treatment is withdrawn. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Disturbed bone marrow adiposity in patients with Cushing's syndrome and glucocorticoid- and postmenopausal- induced osteoporosis.

Background: Skeletal stem/progenitor cells (SSPCs) in the bone marrow can differentiate into osteoblasts or adipocytes in response to microenvironmental signalling input, including hormonal signalling. Glucocorticoids (GC) are corticosteroid hormones that promote adipogenic differentiation and are endogenously increased in patients with Cushing´s syndrome (CS). Here, we investigate bone marrow adiposity changes in response to endogenous or exogenous GC increases. For that, we characterize bone biopsies from patients with CS and post-menopausal women with glucocorticoid-induced osteoporosis (GC-O), compared to age-matched controls, including postmenopausal osteoporotic patients (PM-O). Methods: Transiliac crest bone biopsies from CS patients and healthy controls, and from postmenopausal women with GC-O and matched controls were analysed; an additional cohort included biopsies from women with PM-O. Plastic-embedded biopsies were sectioned for histomorphometric characterization and quantification of adipocytes. The fraction of adipocyte area per tissue (Ad.Ar/T.Ar) and marrow area (Ad.Ar/Ma.Ar), mean adipocyte profile area (Ad.Pf.Ar) and adipocyte profile density (N.Ad.Pf/Ma.Ar) were determined and correlated to steroid levels. Furthermore, the spatial distribution of adipocytes in relation to trabecular bone was characterized and correlations between bone marrow adiposity and bone remodeling parameters investigated. Results: Biopsies from patients with CS and GC-O presented increased Ad.Ar/Ma.Ar, along with adipocyte hypertrophy and hyperplasia. In patients with CS, both Ad.Ar/Ma.Ar and Ad.Pf.Ar significantly correlated with serum cortisol levels. Spatial distribution analyses revealed that, in CS, the increase in Ad.Ar/Ma.Ar near to trabecular bone (<100 µm) was mediated by both adipocyte hypertrophy and hyperplasia, while N.Ad.Pf/Ma.Ar further into the marrow (>100 µm) remained unchanged. In contrast, patients with GC-O only presented increased Ad.Ar/Ma.Ar and mean Ad.Pf.Ar>100 µm from trabecular bone surface, highlighting the differential effect of increased endogenous steroid accumulation. Finally, the Ad.Ar/Ma.Ar and Ad.Ar/T.Ar correlated with the canopy coverage above remodeling events. Conclusion: Increased cortisol production in patients with CS induces increased bone marrow adiposity, primarily mediated by adipocyte hypertrophy. This adiposity is particularly evident near trabecular bone surfaces, where hyperplasia also occurs. The differential pattern of adiposity in patients with CS and GC-O highlights that bone marrow adipocytes and their progenitors may respond differently in these two GC-mediated bone diseases.

The WebRA study: Opportunities and challenges in digital patient education from the perspective of patients with rheumatoid arthritis: A qualitative study.

OBJECTIVE: To explore patients' perceptions of digital patient education (PE), and how this contributes to self-management of rheumatoid arthritis (RA). METHODS: Individual interviews based on 'interpretive description' methodology. The patients were purposively selected from a randomized controlled trial that investigated the effects of digital PE. The analysis included a descriptive section, followed by the interpretation and extraction of the main messages. RESULTS: Overall, participants had positive perceptions of the e-learning program. Advantages were flexibility, the possibility for repetition, entertainment, availability, and learning in familiar surroundings. Disadvantages were unmet relational support needs due to missing dialogue with health care providers (HCPs). For the majority, a need for insight into the condition led to an active approach to using e-learning. The e-learning program facilitated knowledge acquisition about RA, but relational support from HCPs and a positive attitude toward living with RA were also important for achieving self-management. CONCLUSION: Digital PE is useful for self-management support in RA, however different forms and combinations of PE must be offered in the future to accommodate various needs throughout the disease course. PRACTICE IMPLICATIONS: These results may inform future development and implementation of digital PE that adequately takes individual preferences for self-management support into account.