Power Doppler signal at the enthesis and bone erosions are the most discriminative OMERACT ultrasound lesions for SpA: results from the DEUS (Defining Enthesitis on Ultrasound in Spondyloarthritis) multicentre study.

OBJECTIVES: To assess, in spondyloarthritis (SpA), the discriminative value of the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and their associations with clinical features in this population. METHODS: In this multicentre study involving 20 rheumatology centres, clinical and ultrasound examinations of the lower limb large entheses were performed in 413 patients with SpA (axial SpA and psoriatic arthritis) and 282 disease controls (osteoarthritis and fibromyalgia). 'Active enthesitis' was defined as (1) power Doppler (PD) at the enthesis grade ≥1 plus entheseal thickening and/or hypoechoic areas, or (2) PD grade >1 (independent of the presence of entheseal thickening and/or hypoechoic areas). RESULTS: In the univariate analysis, all OMERACT lesions except enthesophytes/calcifications showed a significant association with SpA. PD (OR=8.77, 95% CI 4.40 to 19.20, p<0.001) and bone erosions (OR=4.75, 95% CI 2.43 to 10.10, p<0.001) retained this association in the multivariate analysis. Among the lower limb entheses, only the Achilles tendon was significantly associated with SpA (OR=1.93, 95% CI 1.30 to 2.88, p<0.001) in the multivariate analyses. Active enthesitis showed a significant association with SpA (OR=9.20, 95% CI 4.21 to 23.20, p<0.001), and unlike the individual OMERACT ultrasound lesions it was consistently associated with most clinical measures of SpA disease activity and severity in the regression analyses. CONCLUSIONS: This large multicentre study assessed the value of different ultrasound findings of enthesitis in SpA, identifying the most discriminative ultrasound lesions and entheseal sites for SpA. Ultrasound could differentiate between SpA-related enthesitis and other forms of entheseal pathology (ie, mechanical enthesitis), thus improving the assessment of entheseal involvement in SpA.

Elevated Serum Levels of Sclerostin are Associated with High Disease Activity and Functional Impairment in Patients with Axial Spondyloarthritis.

BACKGROUND: Recent research suggests that biomarkers may be useful in assessing disease activity, structural damage, and response to therapy in axial spondyloarthritis (axSpA). Our study aims at evaluating the relationship between inflammation and bone remodeling markers and variables assessing disease activity and functional disability in patients with axSpA. METHODS: Serum levels of sclerostin, matrix metalloproteinase-3 (MMP-3), interleukin-17 (IL-17), and IL-23 were measured in 60 patients with axSpA and 20 healthy controls. Disease activity was evaluated using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Functional status was assessed by Bath Ankylosing Spondylitis Function Index (BASFI) and measures of spinal mobility. RESULTS: Sclerostin levels were more elevated in axSpA patients with high disease activity than in those with low disease activity and in controls. They were significantly correlated with BASFI values (r = 0.29, p = 0.03) and measures of spinal mobility, but not with the classical markers of disease activity (BASDAI, ASDAS, CRP, and ESR). Although both MMP-3 and IL-17 levels were elevated in patients with active disease, they were not correlated with markers of disease activity or with functional disability. The levels of sclerostin, MMP-3, IL-17, and IL-23 were similar in axSpA patients and healthy controls. CONCLUSIONS: Elevated levels of sclerostin, MMP-3, and IL-17 were observed in axSpA patients with active disease, suggesting their potential role in assessing disease activity. In axSpA patients, sclerostin levels might be equally influenced by inflammation and level of physical activity. Further studies are required to confirm our findings in order to understand their clinical value.

Bone mineral density, vertebral fractures and body mass index in postmenopausal women with abdominal aortic calcification.

BACKGROUND: Evidence suggest that there are connections between osteoporosis and cardiovascular diseases. OBJECTIVES: The aim of the study was to analyze the relationship between radiological measurements of abdominal aorta calcifications (AAC) and bone mineral density (BMD) in postmenopausal women. METHODS: In this cross-sectional study were included 125 postmenopausal women 50-84 years of age. BMD of the spine and hip was measured by dual energy X-ray absorptiometry (DXA). AAC were assessed by lateral radiographs of lumbar spine (L1-L4), using the antero-posterior severity score (0-24). Vertebral fractures were evaluated from T4 to L4 using Genant's semiquantitative method. RESULTS: Forty-one (32.8%) patients had osteoporosis and 61 (48.8%) had AAC with a mean score of 3.1. Postmenopausal women with AAC were older and had significantly lower femoral neck and trochanteric BMD than subjects without AAC (all p < 0.01). There were no significant differences in the frequency of fractures between subjects with AAC and those without AAC (p > 0.05). In univariate analysis, age, height, weight, femoral and trochanter BMD were significantly associated with the severity of AAC score. In multiple regression analysis, femoral neck BMD, but not lumbar spine, trochanter BMD or age, was an independent predictor of AAC. CONCLUSIONS: Reduced femoral neck BMD is negatively associated with the presence of AAC in postmenopausal women. The association between BMD and AAC seems to be age-independent, which suggests a common pathogenesis for bone loss and vascular calcifications.

Nutrition in Spondyloarthritis and Related Immune-Mediated Disorders.

Recent research on the pathogenesis of spondyloarthritis and related immune-mediated diseases associated with human leukocyte antigen class I molecule B27 (HLA-B27) has led to significant progress in terms of management and prognosis, with multiple treatments being constantly evaluated and implemented. Correlations between the genetic background of spondyloarthritis and inflammatory bowel diseases and the inflammatory processes involving gut microbiota have been established. This knowledge has allowed progress in pharmacological therapy. The role of diet in the pathogenesis and treatment of diseases pertaining to the HLA-B27 spectrum is of great significance, considering possible future applications in individualized medicine. Diet impacts the composition of gut microbiota, representing a substrate for the synthesis of metabolites affecting the mucosal immune system. Certain pro-inflammatory mediators, such as emulsifiers and microparticles, induce a more profound cytokine response, promoting inflammation. Numerous diets, including the low-starch diet, the Mediterranean diet, diets with low contents of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (low-FODMAP diets), gluten-free diets and fasting, have been analysed and correlated with patients' symptomatology and dietary adherence. The aim of this review is to provide an extensive perspective on the diets available to patients with spondyloarthritis and related immune-mediated disorders.

Novel Concepts in Systemic Sclerosis Pathogenesis: Role for miRNAs.

Systemic sclerosis (SSc) is a rare connective tissue disease with heterogeneous clinical phenotypes. It is characterized by the pathogenic triad: microangiopathy, immune dysfunction, and fibrosis. Epigenetic mechanisms modulate gene expression without interfering with the DNA sequence. Epigenetic marks may be reversible and their differential response to external stimuli could explain the protean clinical manifestations of SSc while offering the opportunity of targeted drug development. Small, non-coding RNA sequences (miRNAs) have demonstrated complex interactions between vasculature, immune activation, and extracellular matrices. Distinct miRNA profiles were identified in SSc skin specimens and blood samples containing a wide variety of dysregulated miRNAs. Their target genes are mainly involved in profibrotic pathways, but new lines of evidence also confirm their participation in impaired angiogenesis and aberrant immune responses. Research approaches focusing on earlier stages of the disease and on differential miRNA expression in various tissues could bring novel insights into SSc pathogenesis and validate the clinical utility of miRNAs as biomarkers and therapeutic targets.

Identification of clinical phenotypes of peripheral involvement in patients with spondyloarthritis, including psoriatic arthritis: a cluster analysis in the worldwide ASAS-PerSpA study.

OBJECTIVE: To identify clusters of peripheral involvement according to the specific location of peripheral manifestations (ie, arthritis, enthesitis and dactylitis) in patients with spondyloarthritis (SpA) including psoriatic arthritis (PsA), and to evaluate whether these clusters correspond with the clinical diagnosis of a rheumatologist. METHODS: Cross-sectional study with 24 participating countries. Consecutive patients diagnosed by their rheumatologist as PsA, axial SpA or peripheral SpA were enrolled. Four different cluster analyses were conducted: one using information on the specific location from all the peripheral manifestations, and a cluster analysis for each peripheral manifestation, separately. Multiple correspondence analyses and k-means clustering methods were used. Distribution of peripheral manifestations and clinical characteristics were compared across the different clusters. RESULTS: The different cluster analyses performed in the 4465 patients clearly distinguished a predominantly axial phenotype (cluster 1) and a predominantly peripheral phenotype (cluster 2). In the predominantly axial phenotype, hip involvement and lower limb large joint arthritis, heel enthesitis and lack of dactylitis were more prevalent. In the predominantly peripheral phenotype, different subgroups were distinguished based on the type and location of peripheral involvement: a predominantly involvement of upper versus lower limbs joints, a predominantly axial enthesitis versus peripheral enthesitis, and predominantly finger versus toe involvement in dactylitis. A poor agreement between the clusters and the rheumatologist's diagnosis as well as with the classification criteria was found. CONCLUSION: These results suggest the presence of two main phenotypes (predominantly axial and predominantly peripheral) based on the presence and location of the peripheral manifestations.

Clinical and ultrasound findings in patients with calcium pyrophosphate dihydrate deposition disease.

AIM: To evaluate the presence and distribution of calcium pyrophosphate (CPP) deposits in joints commonly affected by CPP deposition (CPPD) disease (acromio-clavicular, gleno-humeral, wrists, hips, knees, ankles, and symphysis pubis joints) using ultrasound (US). MATERIAL AND METHODS: Thirty consecutive patients fulfilling McCarty diagnostic criteria for CPPD were consecutively enrolled in the study. The data registered using the US included the affected joints, the calcification site, and the pattern of calcification (thin hyperechoic bands, parallel to the surface of the hyaline cartilage, hyperechoic spots, and hyperechoic nodular or oval deposits). The presence of CPP crystals in knees was confirmed by polarized light microscopy examination of the synovial fluid and radiographs of the knees were performed in all patients. RESULTS: In 30 patients, 390 joints were scanned, (13 joints in every patient). The mean±standard deviation number of joints with US CPPD evidence per patient was 2.93±1.8 (range 1-9). The knee was the most common joint involved both clinically and using US examination. The second US pattern (with hyperechoic spots) was the most frequent. Fibrocartilage calcifications were more common than hyaline calcification. Using radiography as reference method, the sensitivity and specificity of US for diagnosis CPPD in knees was 79.31%, 95CI(66.65%-88.83%), and 14.29%, 95CI(1.78%-42.81%), respectively. CONCLUSIONS: The knee is the most frequent joint affected by CPPD. The second ultrasound pattern is the most common. CPPD affects the fibrocartilage to a greater extent than the hyaline cartilage.

Acroosteolysis in systemic sclerosis: An insight into hypoxia-related pathogenesis.

Acro-osteolysis, or bony resorption of the terminal digital tufts, is a well-recognized, but under-researched, feature of systemic sclerosis. The mechanisms that disturbs local homeostatic balance of bone formation and resorption in favor of osteoclast activation and pathological bone loss remain to be established. Vascular alterations and reduced capillary density impair tissue oxygenation in systemic sclerosis, and the resulting hypoxia might contribute directly to the disease progression. In this paper we summarize the current evidence for hypoxia as the common pathophysiological denominator of digital vasculopathy and enhanced osteoclastic activity in systemic sclerosis-associated acroosteolysis. The hypoxia-inducible transcription factor HIF-1α and VEGF signaling has a critical role in regulating osteoclastic bone-resorption and angiogenesis, and increased osteoclastogenesis and higher VEGF levels may contribute to acroosteolysis in systemic sclerosis. The cells of the osteoblast lineage also have important roles in angiogenic-osteogenic coupling. The research in this field might help limiting the disability associated with the disease.

The role of ultrasonography in assessing disease activity in patients with rheumatoid arthritis and associated fibromyalgia.

AIM: The purpose of this study is to compare and correlate US evaluation with clinical scores of the disease activity in patients with rheumatoid arthritis (RA) and concomitant fibromyalgia (FM). MATERIAL AND METHODS: Ten patients diagnosed with RA according to the 2010 ACR/EULAR classification criteria and associated FM based on the ACR 1990 classification criteria and two control groups, one with RA (10 patients) and one with FM (10 patients), were included. Clinical assessment was performed and the disease activity scores were calculated. Synovial/tenosynovial hypertrophy, fluid collections in grey scale (GS), and Power Doppler (PD) US assessed by US in the 28 joints included in the disease activity score 28 (DAS28). RESULTS: GS US score and PD US scores were correlated with DAS28 only in patients with RA (Pearson r coefficients 0.3 and 0.5). Mean DAS28 score was significantly higher in the RA/FM group, compared to RA and FM (5.6 versus 4.6 versus 4.5, respectively). Patients with RA/FM had similar median US scores to RA patients, while in FM group significantly lower median US scores were detected (16 versus 9.5 versus 0 for GS US and 3.5 versus 1.5 versus 0 for PD US, respectively). CONCLUSIONS: Disease activity scores should be interpreted with caution in patients with RA and FM. When available, US should be used to guide treatment decisions in patients with RA and FM.

Primary complement and antibody deficiencies in autoimmune rheumatologic diseases with juvenile onset: a prospective study at two centers.

BACKGROUND: Our aim was to investigate the prevalence and clinical relevance of inherited complement and antibody deficiency states in a large series of patients with various autoimmune rheumatologic diseases (ARD) with juvenile onset. METHODS: A total number of 117 consecutive patients from 2 tertiary referral hospitals were included in the study. All patients underwent genetic screening for type I C2 deficiency and C4 allotyping. Serum levels of immunoglobulin classes measured systematically throughout their regular medical care were recorded retrospectively. RESULTS: Our cohort of patients included 84 with juvenile idiopathic arthritis (JIA), 21 with systemic lupus erythematosus (SLE), 6 with systemic vasculitis, 2 with juvenile scleroderma, 2 with idiopathic uveitis, 1 with mixed connective tissue disease and 1 with SLE/scleroderma overlap syndrome. We have found 16 patients with evidence of primary immunodeficiency in our series (13.7%), including 7 with C4 deficiency, 5 with selective IgA deficiency, 3 with C2 deficiency and 2 with unclassified hypogammaglobulinemia (one also presented C4D). Of the 84 patients with JIA, 4 (4.8%) had a complement deficiency, which was less prevalent than in the SLE cohort (23.8%), but all of them have exhibited an aggressive disease. Most of our patients with primary antibody deficiencies showed a more complicated and severe disease course and even the co-occurrence of two associated autoimmune diseases (SLE/scleroderma overlap syndrome and SLE/autoimmune hepatitis type 1 overlap). CONCLUSIONS: Our findings among others demonstrate that complement and immunoglobulin immunodeficiencies need careful consideration in patients with ARD, as they are common and might contribute to a more severe clinical course of the disease.

The relationship between the metabolic syndrome and its components and bone status in postmenopausal women.

UNLABELLED: The association between metabolic syndrome (MS) and bone status remains controversial. We aimed to study the relationships between MS, bone mineral density (BMD), and bone metabolism in postmenopausal women. MATERIAL AND METHODS: MS was assessed in 218 white postmenopausal women. BMD (lumbar spine and hip) was measured by dual energy X-ray absorptiometry (DXA). Serum carboxyterminal cross-linked telopeptide of type 1 collagen (CTX), undercarboxylated osteocalcin (uOC), bone alkaline phosphate (BAP) and vitamin D were assayed. RESULTS: Postmenopausal women with MS had a significantly higher lumber spine BMD than women without MS (p < 0.05). A progressive increase of the BMD at both sites with the number of MS components was observed. Bone turnover markers and vitamin D levels were not significantly influenced by the presence of MS. BMD at both sites positively correlated with body mass index (BMI), waist circumference (WC) and glucose in unadjusted analysis. In multiple regression analysis, WC was independently associated with BMD at both sites, while hypertension was associated only with lumbar spine BMD. CONCLUSIONS: In postmenopausal women, MS is associated with increased lumbar spine BMD and this relation is explained mainly by the higher BMI and WC in the MS group.

The value of osteopontin in the assessment of bone mineral density status in postmenopausal women.

BACKGROUND: Osteopontin (OPN) has been implicated in bone remodeling by activating the resorption process. We aimed to study the relationship between OPN, bone mineral density (BMD), bone turnover markers, vitamin D, and osteoporotic vertebral fractures in postmenopausal women. MATERIALS AND METHODS: Serum levels of OPN, osteocalcin, collagen type 1 cross-linked C-telopeptide (CTX), bone alkaline phosphatase, and vitamin D were assessed in 214 postmenopausal women. Bone mineral density was assessed by dual-energy x-ray absorptiometry in lumbar spine and femoral neck, and osteoporotic vertebral fractures by radiographs. RESULTS: Osteopontin levels were significantly higher in osteoporosis group versus osteopenic and normal group (all P < 0.05). The cutoff values of OPN for osteoporosis diagnosis were of 9.47 µg/L at the lumbar spine (area under the curve, 0.67; 95% confidence interval, 0.58-0.75; P < 0.001) and 10.15 µg/L at the femoral neck (area under the curve, 0.69; 95% confidence interval, 0.624-0.77; P = 0.0001), respectively. Postmenopausal women with osteoporosis-related vertebral fractures had significantly higher levels of OPN than those without vertebral fractures (15.69 ± 13.26 vs 12.63 ± 12.46 µg/L; P = 0.02). Significant negative correlations were found between OPN and BMD, which persisted after the adjustment for age at the lumbar spine. Osteopontin levels were directly correlated with bone turnover markers (osteocalcin, bone alkaline phosphatase, and CTX). No significant correlation was found between OPN and vitamin D. Multiple regression analysis showed that age, waist circumference, and CTX were independent predictors of serum OPN levels. CONCLUSIONS: High levels of OPN in postmenopausal women are associated with low BMD, increased levels of bone turnover markers, and osteoporotic vertebral fractures. These findings suggest that OPN might play some role in the pathophysiology of postmenopausal osteoporosis and warrant further clinical investigations.

Relation between intima-media thickness and bone mineral density in postmenopausal women: a cross-sectional study.

CONTEXT AND OBJECTIVES: Controversy exists regarding the relationship between atherosclerosis and osteoporosis. The aim of this study was to determine the relationship between intima-media thickness (IMT) of the common carotid artery (CCA), presence of calcified atherosclerotic plaques and bone mineral density (BMD) evaluated by dual energy X-ray absorptiometry (DXA), in postmenopausal women. DESIGN AND SETTING: Cross-sectional study at Second Internal Medicine Clinic, Cluj-Napoca, Romania. METHODS: We studied the IMT (left and right CCA and mean IMT) and T-score (lumbar spine L2-L4, femoral neck and total hip) in 100 postmenopausal women (mean age 64.5 years). The presence of calcified atherosclerotic plaque and osteoporotic vertebral fractures was also noted. RESULTS: IMT in the left and right CCA and mean IMT were significantly associated with T-score measured for the lumbar spine L2-L4, femoral neck and total hip, with lower T-score, in the osteoporotic group than in the normal and osteopenic groups (P < 0.05). IMT had a significantly negative correlation with the lumbar spine T-score and femoral neck T-score; and mean IMT with lowest T-score. Mean IMT (P < 0.001), high blood pressure (P = 0.005) and osteoporotic vertebral fractures (P = 0.048) showed statistical significance regarding the likelihood of developing atherosclerotic plaque. CONCLUSIONS: In women referred for routine osteoporosis screening, the relationship between CCA, atherosclerosis and osteoporosis can be demonstrated using either cortical or trabecular BMD. Vertebral fractures may be considered to be a likelihood factor for atherosclerotic plaque development.

Relative value of the lumbar spine and hip bone mineral density and bone turnover markers in men with ankylosing spondylitis.

The purpose of this study is to evaluate bone mineral density (BMD) and bone turnover markers in men with ankylosing spondylitis (AS) and to determine their relationship with clinical features and disease activity. Serum carboxi terminal cross-linked telopeptide of type I collagen (CTX), osteocalcin (OC) levels, and BMD of lumbar spine and proximal femur were evaluated in 44 males with AS, 18-60 years of age, and compared with those of 39 age-matched healthy men. Men with AS had a significantly lower BMD at the femoral neck and total hip as compared to age-matched controls (all p < 0.01). Osteopaenia or osteoporosis was found in 59.5% AS patients at the lumbar spine and in 47.7% at the femoral neck. Mean serum levels of OC and CTX were similar in AS patients and controls. There were no significant differences in BMD and bone turnover markers when comparing subgroups stratified according to disease duration or presence of peripheral arthritis. No correlations were found between disease activity markers and BMD or OC and CTX. In a cohort of relatively young males with AS, we found a high incidence of osteopaenia and osteoporosis. Disease activity and duration did not show any significant influence on BMD or serum levels of OC and CTX.

Relation between intima-media thickness and bone mineral density in postmenopausal women: a cross-sectional study / La relación entre el espesor mío-intimal y la densidad mineral ósea en las mujeres posmenopáusicas: un estudio transversal

CONTEXT AND OBJECTIVES: Controversy exists regarding the relationship between atherosclerosis and osteoporosis. The aim of this study was to determine the relationship between intima-media thickness (IMT) of the common carotid artery (CCA), presence of calcified atherosclerotic plaques and bone mineral density (BMD) evaluated by dual energy X-ray absorptiometry (DXA), in postmenopausal women. DESIGN AND SETTING: Cross-sectional study at Second Internal Medicine Clinic, Cluj-Napoca, Romania. METHODS: We studied the IMT (left and right CCA and mean IMT) and T-score (lumbar spine L2-L4, femoral neck and total hip) in 100 postmenopausal women (mean age 64.5 years). The presence of calcified atherosclerotic plaque and osteoporotic vertebral fractures was also noted. RESULTS: IMT in the left and right CCA and mean IMT were significantly associated with T-score measured for the lumbar spine L2-L4, femoral neck and total hip, with lower T-score, in the osteoporotic group than in the normal and osteopenic groups (P < 0.05). IMT had a significantly negative correlation with the lumbar spine T-score and femoral neck T-score; and mean IMT with lowest T-score. Mean IMT (P < 0.001), high blood pressure (P = 0.005) and osteoporotic vertebral fractures (P = 0.048) showed statistical significance regarding the likelihood of developing atherosclerotic plaque. CONCLUSIONS: In women referred for routine osteoporosis screening, the relationship between CCA, atherosclerosis and osteoporosis can be demonstrated using either cortical or trabecular BMD. Vertebral fractures may be considered to be a likelihood factor for atherosclerotic plaque development.

CONTEXTO Y OBJETIVOS: Hay controversias en cuanto a la relación entre la arterioesclerosis y la osteoporosis. El objetivo del estudio fue determinar la relación entre el espesor mío-intimal (EMI) de la arteria carótida común (ACC), la presencia de placas arterioescleróticas calcificadas, y la densidad mineral ósea (DMO) evaluada a través de absorciometría de rayos X de energía dual (DEXA) en mujeres posmenopáusicas. DISEÑO Y ENTORNO: Estudio transversal en la Segunda Clínica de Medicina Interna, Cluj-Napoca, Rumania. MÉTODOS: Hemos estudiado el EMI (ACC izquierda y derecha y EMI promedio) y el T-score (espina lumbar L2-L4, cuello femoral y cadera total) en 100 mujeres posmenopáusicas (edad promedia 64.5 años). Se ha observado también la presencia de las placas arterioescleróticas calcificadas y de la fractura vertebral osteoporótica. RESULTADOS: El EMI en ACC izquierda y derecha, como también el EMI promedio se ha asociado sobre todo con el T-score medido en la espina lumbar L2-L4, cuello femoral y cadera total o el valor más bajo del T-score, en el grupo osteoporótico, en comparación con el grupo normal y el osteopénico (P < 0.05). Se ha registrado una correlación significativamente negativa entre el EMI y el T-score de espina lumbar, el T-score del cuello femoral, y el EMI promedio con el T-score más bajo. El EMI promedio (P < 0.001), la alta presión (P = 0.005), y las fracturas vertebrales osteoporóticas (P = 0.048) demostraron tener una importancia estadística con respecto a la probabilidad de formación de placas arterioescleróticas. CONCLUSIONES: En el caso de las mujeres sometidas a screening rutinario para la osteoporosis, la relación entre ACC, arterioesclerosis y osteoporosis se puede demostrar utilizando sea la DMO cortical o trabecular. Las fracturas vertebrales se pueden considerar como un factor de probabilidad para el desarrollo de las placas arterioescleróticas.