Performance of the Brazilian Fracture Assessment Risk Tool (FRAX) model and the age-dependent intervention thresholds according to National Osteoporosis Guideline Group (NOGG) guidelines on fracture prediction in community-dwelling older adults: the São Paulo Ageing and Health (SPAH) Study.

The SPAH study is a population-based prospective cohort of Brazilian community-dwelling elderlies with higher fracture risk than observed in the studies used to construct the Brazilian FRAX model. In this study, the FRAX tool was a good fracture predictor within this high-risk elderly cohort, especially when calculated without bone density. PURPOSE: To determine the performances of FRAX and age-dependent intervention thresholds according to National Osteoporosis Guideline Group (NOGG) guidelines with and without bone mineral density (BMD) regarding fracture prediction in community-dwelling elderly Brazilians. METHODS: Seven hundred and five older adults (447 women; 258 men) were followed for 4.3 ± 0.8 years. FRAX risk for hip and major osteoporotic fractures with and without BMD was calculated at baseline. The bivariate analysis investigated the associations between the absolute probability of fracture (FRAX), as well as the age-dependent intervention thresholds (NOGG), and the incidence of vertebral fracture (VF), non-vertebral fracture (NVF), and major osteoporotic fractures (MOF), segregated by sex. Age-adjusted Poisson's multiple regression and ROC curves were constructed to determine FRAX and NOGG's accuracies as fracture predictors. RESULTS: Fractures occurred in 22% of women and 15% of men. FRAX with and without BMD was higher in women with all types of fractures (p < 0.001). Only NOGG risk classification without BMD was associated with NVF (p = 0.047) and MOF (p = 0.024). FRAX was associated with NVF in the multiple regression, regardless of BMD. ROC curves of FRAX with and without BMD had AUCs of 0.74, 0.64, and 0.61 for NVF, VF, and MOF, respectively. The most accurate risk cutoffs for FRAX were 8% for MOF and 3% for hip fractures. No statistically significant associations were found in men. CONCLUSION: FRAX predicted NVF more accurately than VF or MOF in elderlies, regardless of BMD. These results reiterate that FRAX may be used without BMD, even considering that Brazilian elderlies have known higher fracture risk.

Transcriptomic characterization of classical monocytes highlights the involvement of immuno-inflammation in bone erosion in Rheumatoid Arthritis.

Introduction: Evidence-based data suggest that under inflammatory conditions, classical monocytes are the main source of osteoclasts and might be involved in bone erosion pathophysiology. Here, we analyze the transcriptomic profile of classical monocytes in erosive and non-erosive rheumatoid arthritis patients in order to better understand their contribution to bone erosion. Methods: Thirty-nine premenopausal RA patients were consecutively enrolled and divided into two groups based on the presence of bone erosions on hand joints. Classical monocytes were isolated from peripheral blood through negative selection, and RNA-seq was performed using a poly-A enrichment kit and Illumina® platform. Classical monocytes transcriptome from healthy age-matched women were also included to identify differentially expressed genes (DEGs). Therefore, gene sets analysis was performed to identify the enriched biological pathways. Results: RNA-seq analysis resulted in the identification of 1,140 DEGs of which 89 were up-regulated and 1,051 down-regulated in RA patients with bone erosion compared to those without bone erosions. Among up-regulated genes, there was a highlighted expression of IL18RAP and KLF14 related to the production of pro-inflammatory cytokines, innate and adaptive immune response. Genes related to collagen metabolism (LARP6) and bone formation process (PAPPA) were down-regulated in RA patients with erosions. Enriched pathways in patients with erosions were associated with greater activation of immune activation, and inflammation. Interestingly, pathways associated with osteoblast differentiation and regulation of Wnt signaling were less activated in RA patients with erosions. Conclusion: These findings suggest that alterations in expression of monocyte genes related to the inflammatory process and impairment of bone formation might have an important role in the pathophysiology of bone erosions in RA patients.

A rare giant geode of humeral head in an uncontrolled rheumatoid arthritis: a case report.

INTRODUCTION: Rheumatoid Arthritis (RA) is a chronic inflammatory disease depicted by peripheral bone erosive damage leading to joint destruction, deformity and functional impairment. Shoulder involvement is less frequent than hands, wrists and feet, and relevant joint damage may be underdiagnosed if a lower threshold for careful analysis of this joint is not settled, especially in uncontrolled disease. CASE REPORT: A 70-year-old male with a difficult-to-manage RA since 2010, presenting severe shoulder arthritis with MRI showing a striking giant geode in the left humeral head. CONCLUSION: An impressive MRI image showing a giant geode in poorly controlled RA should alert rheumatologists to raise suspicion of shoulder involvement for early investigation and treatment.

Lower hand grip in rheumatoid arthritis patients is associated with low finite element analysis using high resolution peripheral quantitative computed tomography scan of the 2nd metacarpophalangeal joint.

AIM: To evaluate hand function by hand grip test in rheumatoid arthritis (RA) patients, and its association with bone erosions and the estimated bone strength (finite element - FE analysis) through the analysis of the 2nd metacarpal head of the dominant hand using high resolution peripheral quantitative computed tomography (HR-pQCT). METHOD: Eighty-two female RA patients between 18-50 years old were selected. Demographic data, Health Questionnaire Assessment Disability Index (HAQ), Disease Activity Score of 28 joints (DAS)-28, simplified disease activity index (SDAI) and the hand grip test were set. The HR-pQCT scans of 2nd metacarpophalangeal joints of the dominant hand of all patients were performed according to SPECTRA group protocols. The images were used to assess bone erosions and FE analysis. The hand grip test was categorized in 2 groups and separately compared (< 18 vs ≥18 kgf). A logistic regression was performed using hand grip test <18 kgf as a dependent variable. RESULTS: A significant difference was found between the 2 groups regarding HAQ, inflammatory markers (erythrocyte sedimentation rate, C-reactive protein), DAS-28, SDAI, total volume of erosion and bone strength parameter (FE analysis - Failure Load [F.Load]). The logistic regression analysis showed that the risk factors associated with hand grip test <18 kgf were higher SDAI (odds ratio [OR] 0.912; 95% CI 0.837-0.993) and lower values of bone strength parameter (F.Load) (OR 1.007; 95% CI 1.002-1.012). CONCLUSION: Lower values of hand grip test were associated with higher disease activity score-SDAI and lower bone strength of 2nd metacarpal bone head of the dominant hand evaluated here through a FE analysis using HR-pQCT scan.

Evaluation of bone erosion in rheumatoid arthritis patients by high-resolution peripheral quantitative computed tomography scans: Comparison between two semi-automated programs in a three-dimensional setting.

AIM: The aim of this study was to compare OsiriX software with the previous published Medical Image Analysis Framework (MIAF) method to assess the volume of erosion in patients with rheumatoid arthritis (RA). METHODS: Forty RA patients underwent high-resolution peripheral quantitative computed tomography scans of the second and third metacarpophalangeal joints, and thirty-four patients with any bone erosion were enrolled. Two techniques were applied to erosion evaluation: (a) semi-automated MIAF software, and (b) semi-automated segmentation by free open-source Digital Imaging and Communications in Medicine viewer, OsiriX software. MIAF has been published before, but this is the first time that OsiriX has been used in this way in rheumatology. Bland & Altman plots described agreement between methods. RESULTS: Forty-eight erosions from 34 patients were analyzed. Mean age was 40.74 ± 5.32 years and mean disease duration was 10.68 ± 4.96 years. Both methods demonstrated a strong correlation regarding erosion volume (r = 0.96, P < 0.001). Median (interquartile range) of erosion volume was 12.14 (4.5-36.07) when MIAF was considered, and 11.80 (3.45-29.42) when the OsiriX tool was used (P = 0.139). MIAF and OsiriX showed good agreement when the Bland & Altman plot was performed. Evaluation by MIAF took 22.69 ± 6.71 minutes, whereas OsiriX took only 2.62 ± 1.09 minutes (P < 0.001). CONCLUSION: The three-dimensional segmentation of bone erosions can be done by both MIAF and OsiriX software with good agreement. However, because OsiriX is a widespread tool and faster, its method seems to be more feasible for evaluating peripheral bone damage, especially bone erosions.

Comparison of the effects of tocilizumab monotherapy and adalimumab in combination with methotrexate on bone erosion repair in rheumatoid arthritis.

OBJECTIVE: To compare the effects of interleukin-6 (IL-6) receptor and tumour necrosis factor inhibition on inducing repair of existing bone erosions in patients with very early rheumatoid arthritis (RA). METHODS: Prospective non-randomised observational study in patients with active erosive RA with inadequate response to methotrexate (MTX) receiving either tocilizumab (TOC) monotherapy or adalimumab (ADA) with MTX for 52 weeks. Erosion volumes were assessed in metacarpal heads (MCH) and the radius by high-resolution peripheral quantitative CT at baseline and after 52 weeks. Clinical response was monitored using Clinical Disease Activity Index, Simple Disease Activity Index and Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) scores every 12 weeks. RESULTS: TOC (N=33) and ADA/MTX (N=33) treatment groups were balanced for age, sex, body mass index, comorbidities, disease and activity, functional state, autoantibody status, baseline bone damage and baseline bone biomarkers. Both TOC (DAS28-ESR: baseline: 6.2±0.5; 52 weeks: 2.3±1.0) and ADA/MTX (6.3±0.6; 2.8±1.2) significantly reduced disease activity. Erosion volumes significantly decreased in the MCH and radius of patients with RA treated with TOC (p<0.001) but not in patients treated with ADA/MTX (p=0.77), where they remained stable in size. Mean decrease in erosion volume in TOC-treated patients was -1.0±1.1 mm3 and -3.3±5.9 mm3 in the MCH and radius of TOC-treated patients, respectively, and -0.05±0.9 mm3 and -0.08±4.1 mm3 in patients treated with ADA/MTX. CONCLUSIONS: The REBONE study shows that TOC monotherapy achieves more pronounced repair of existing bone erosions than ADA/MTX. Hence, IL-6 is a central factor for the disturbed bone homeostasis in the joints of patients with RA.

Avaliação de calcificação vascular e osteoporose em uma população de indivíduos com 65 anos ou mais na área do Butantã / Assessment of vascular calcification and osteoporosis in a population of individuals aged 65 years or more in Butantã

O objetivo deste trabalho foi avaliar a associação de calcificação da aorta abdominal (CAA) com marcadores do metabolismo ósseo: densidade mineral óssea (DMO), dados laboratoriais (cálcio, fósforo, 25OH-vitamina D, PTH) e clínicos em uma população brasileira de idosos. Este foi um estudo de corte transversal onde foram incluídos 815 indivíduos com idade igual ou superior a 65 anos. Os dados demográficos e de estilo de vida, bem como os parâmetros clínicos que identificam os fatores de risco para osteoporose e calcificação vascular foram obtidos por um questionário padronizado. Densidade mineral óssea (DMO) e parâmetros laboratoriais foram avaliados em todos os indivíduos. Foram realizadas radiografias de coluna lombar para a análise de calcificação da aorta abdominal nos segmentos correspondentes às vértebras L1 a L4. Para cada segmento lombar foi dada uma pontuação de 0-3 para as paredes anterior e posterior, com um escore máximo de 24 pontos (Kaupilla et al., 1997). Resultados: 63,2% dos idosos apresentavam algum grau de CAA, com um escore médio de 4,68 5,88. Analisando as variáveis contínuas observamos que o escore de CAA foi correlacionado diretamente à idade, fósforo sérico, LDL-colesterol (LDL-C), triglicérides e inversamente ao índice de massa corpórea (IMC), DMO do colo do fêmur e DMO do fêmur total (p<0,05). Em relação às variáveis binárias o escore de CAA foi associado à história de fraturas prévias por fragilidade, baixa atividade física, quedas no último ano, tabagismo atual e hipertensão arterial (p<0,05). A análise de regressão linear múltipla demonstrou que o escore de CAA foi diretamente relacionado à idade (p<0,001), tabagismo atual (p<0,001), hipertensão arterial (p=0,002), LDL-C (p=0,05), triglicérides (p=0,002), fósforo sérico (p=0,005) e inversamente associado à DMO de fêmur total (p<0,001). Um aumento no escore de CAA foi observado com a elevação dos níveis séricos de fósforo [ 2,4mg/dL: escore de CAA = 1,9 (DP: 3,9); 2,5-3,5mg/dL...

The aim of this study was to analyze abdominal aortic calcification (AAC) and its possible association with bone mineral density (BMD) as well as the clinical and laboratory data. This was a cross-sectional study conducted between 2005 to 2007, with a population-based sample of older men and women living in Brazil. Eight hundred and fifteen subjects 65 years old were studied. The risk factors for osteoporosis and cardiovascular disease, demographic data and lifestyle characteristics were collected using a standardized questionnaire. BMD was measured by DXA. Kauppilas method was used to quantify the AAC score (AACS) by spine X-rays. Laboratory analyses were also performed. AAC was observed in 63.2% of subjects with a mean AACS of 4.68 (5.88). AACS was directly correlated with age, phosphorus, LDL-cholesterol, triglycerides, and inversely correlated with body mass index, femoral neck BMD and total femur BMD (p<0.05). Regarding binary variables, the AACS was associated with previous fragility fractures, current smoking, low physical activity, falls and arterial hypertension (p<0.05). Multiple linear regression analysis demonstrated that the AACS was positively associated with age (p<0.001), current smoking (p<0.001), arterial hypertension (p=0.002), LDL-C (p=0.05), triglycerides (p=0.002), phosphate (p=0.005) and negatively associated with total femur BMD (p<0.001). An increased of AACS was observed with the elevation of serum phosphorus levels [ 2.4mg/dL: AACS=1.9 (SD:3.9); 2.5-3.5mg/dL: AACS=4.5 (SD:5.6) and > 3.5mg/dL: AACS=5.3 (SD:6.3), p=0.003]. Our study identified serum phosphate and hip BMD as additional players in the complex process of vascular calcification outside the setting of kidney failure in community-dwelling older population and extended the previous observations of well-known risk factors for cardiovascular disease.

Síndrome de Sjõgren primária com vasculite cutânea manifestada por úlceras em membro inferior / Primary Sjõgren's syndrome with cutaneous vasculitis manifested as leg ulcerations

A síndrome de Sjõgren (SS) primária é uma doença autoimune cujo espectro de manifestação clínica estende-se desde um acometimento órgão-específico (exocrinopatia auto-imune) até um processo sistêmico. O envolvimento da pele é bastante comum, e a freqüência de doença vascular inflamatória é estimada entre 20 por cento e 30 por cento. Duas formas clínicas específicas de vasculite cutânea, a púrpura palpável e urticária crônica são predominantes, mas eritema multiforme, eritema perstans, eritema nodoso, mácula eritematosa e nódulo subcutâneo também já foram descritos. Os autores descrevem o caso de uma paciente de 46 anos, que desenvolveu quadro de síndrome de Sjõgren primária, com manifestações oculares, orais, articulares e alterações laboratoriais (FAN, anti-Ro, fator reumatóide positivos, e hipergamaglobulinemia). Após dez anos do diagnóstico, apresentou úlcera em membro inferior, cuja biópsia confirmou tratar-se de lesão tipo vasculítica, com excelente resposta ao tratamento com ciclofosmida endovenosa. Foram descritos na literatura apenas dois relatos de caso de pacientes com úlceras em membros inferiores, como acometimento cutâneo da SS. Os autores ressaltam a importância do diferencial de úlceras em membros inferiores como acometimento cutâneo da SS primária.

[Primary Sjögren's syndrome with cutaneous vasculitis manifested as leg ulcerations]. / Síndrome de Sjögren primária com vasculite cutânea manifestada por úlceras em membro inferior.

Primary Sjögren's Syndrome (pSS) is an autoimmune disease with a large spectrum of clinical manifestations extending from an organ-specific involvement to a systemic process. The skin is affected quite commonly and the estimated frequency of inflammatory vascular lesions is from 20% to 30%. Two specific, clinically recognizable forms of cutaneous vasculitis predominate, palpable purpura and chronic urticaria, but erythema multiforme, erythema perstans, erythema nodosum, erithematous macules and subcutaneous nodules have also been described. The authors report the case of a 46-year-old female patient, diagnosed as primary SS, who presented ocular and oral symptoms, poliarthritis and laboratory alterations (with a positive ANA, anti-SSA, rheumatoid factor, and hypergammaglobulinemia). Ten years after the diagnosis, she presented leg ulcers. The biopsy confirmed the presence of vasculitic process, and the ulcers improved rapidly after the treatment with endovenous cyclophosphamide. There are only two reports of chronic ulceration of the legs as cutaneous manifestation of SS. The authors stress the importance of considering ulcers in the differential diagnosis of cutaneous involvement of primary SS.

Vasculite mesentérica como única manifestação de atividade lúpica: a importância de um diagnóstico precoce / Mesenteric vasculitis as the only manifestation of lupic activity: the importance of a premature diagnosis

A vasculite mesentérica é uma grave complicação do lúpus eritematoso sistêmico (LES), pois é considerada uma importante causa de morbidade e mortalidade nesta doença. Na verdade, ela é também uma preocupação diagnóstica e terapêutica, e seu reconhecimento e intervenção precoce afetam diretamente o prognóstico. Este relato descreve uma paciente de 28 anos com diagnóstico de lúpus eritematoso sistêmico, que subitamente apresentou forte dor abdominal na ausência de outras manifestações de atividade de doença. Os procedimentos diagnósticos são discutidos e revisados. Os autores também enfatizam a necessidade de estabalecer um diagnóstico precoce dessa entidade para evitar complicações e uma pior evolução.

Uso de medicamentos durante a gravidez: enfoque dermatológico

Os autores apresentam breve revisão sobre os principais medicamentos usados pelo dermatologista, com seus prováveis efeitos teratogênicos, demonstrando que a prescrição durante a gravidez deve ser segura e sempre respaldada por concimento científico específico