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We ascertained the fracture risk factors stratified by vertebral and non-vertebral sites in rheumatoid arthritis (RA) females. Bone/muscle features, but not disease activity, were the main markers for fractures in this long-standing RA population: low trabecular bone score (TBS) for vertebral fracture and decreased appendicular muscle mass for non-vertebral fracture. PURPOSE: To assess risk factors for fractures, including clinical, laboratory and dual energy X-ray absorptiometry (DXA) parameters (bone mass, trabecular bone score-TBS, muscle mass) in women with established rheumatoid arthritis (RA). METHODS: Three hundred females with RA (ACR, 2010) were studied. Clinical data were obtained by questionnaire and disease activity by composite indices (DAS28, CDAI, SDAI), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Bone mineral density (BMD), TBS, body composition and Vertebral Fracture Assessment (VFA) were performed by DXA. Logistic regression models were constructed to identify factors independently associated with vertebral (VF) and non-vertebral fractures (NVF), separately. RESULTS: Through rigorous eligibility criteria, a total of 265 women were yielded for final data analysis (median age, 55 [22-86] years; mean disease duration, 16.2 years). Prevalence of VF and NVF were 30.6% and 17.4%, respectively. In multivariate analyzes, TBS (OR = 1.6, 95%CI = 1.09-2.36, p = 0.017), CRP (OR = 1.54, 95%CI = 1.15-2.08, p = 0.004), and parathormone (OR = 1.24, 95%CI = 1.05-1.45, p = 0.009) were risk factors for VF, whereas low appendicular muscle mass (OR = 2.71; 95%CI = 1.01-7,28; p = 0.048), body mass index (BMI) (OR = 0.90, 95%CI = 0.82-0.99; p = 0.025), ESR (OR = 1.18, 95%CI = 1.01-1,38, p = 0,038) and hip BMD (OR = 1.82, 95%CI = 1.10-3.03, p = 0.02) were associated with NVF. CONCLUSION: In women with long-term RA, markers of fractures differed between distinct skeletal sites (vertebral and non-vertebral). The magnitude of association of bone/muscle parameters with fracture (TBS for VF and appendicular muscle mass for NVF) was greater than that of the association between RA activity and fracture. TBS seems to have greater discriminative power than BMD to identify subjects with VF in long-standing RA.
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Artrite Reumatoide , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Humanos , Feminino , Pessoa de Meia-Idade , Fraturas da Coluna Vertebral/epidemiologia , Osso Esponjoso/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Densidade Óssea/fisiologia , Absorciometria de Fóton , Fatores de Risco , Artrite Reumatoide/complicações , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/complicaçõesRESUMO
BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease depicted by synovial inflammation leading to local and systemic bone loss. The aim of this study was to evaluate by a HR-pQCT (High Resolution Peripheral Quantitative Computed Tomography) study which parameters are associated with volume of bone erosions including bone mineral density (BMD) around erosions (VOI 1 to 4 = volume of interest), BMD of metacarpophalangeal (MCP) head, BMD of radius, presence of osteophytes and joint space width (JSW). METHODS: Fifty female RA patients (18-50 years) were enrolled in this study. Demographic and disease-specific data, laboratory inflammatory parameters and handgrip test were performed. All patients underwent HR-pQCT of 2nd and 3rd MCP joints and distal radius, according to established protocols. The volume of bone erosions was evaluated by MIAF (Medical Image Analysis Framework) software. Osteophytes were analyzed by manual method. RESULTS: The mean of age and disease duration were 40.0 ± 6.0 yrs. and 10.8 ± 4.8 yrs., respectively. According to DAS-28 (Disease Activity Score), 54% (27) of the sample were in remission. However, when SDAI (Simplified Disease Activity Index) was used, only 18% (9) were under remission. The mean of HAQ (Health Assessment Questionnaire), ESR (Erythrocyte sedimentation rate) and CRP (C reactive protein) were 0.9 ± 0.7, 13.9 ± 12.2 mm and 5.6 ± 7.5 mg/mL, respectively. Forty-six bone erosions (0.9 ± 1.2 erosion/patient) and 14 osteophytes (0.3 ± 0.7 osteophyte/patient) were found in 2nd MCP head. The median (IQR-Interquartile range) of volume of erosion and volume of osteophytes were 14.9 (5.7;35.9)mm3 and 3.1 (2.1, 4.3)mm3, respectively. The mean of JSW was 80.5 ± 34.2 mm3. The volume of bone erosions was negatively correlated with BMD of 2nd MCP head, VOI-4 and JSW; and it was positively correlated with osteophytes number. Regarding absence or presence of erosion in 2nd MCP head, a significant difference was found between BMD of MCP head, osteophyte number and JSW. Multiple linear regression analysis showed that only BMD of 2nd MCP head was independently associated with volume of bone erosions. CONCLUSION: BMD of MCP head was independently associated with volume of bone erosion, suggesting that this parameter should be used to analyze and monitoring bone destruction, as well as to evaluate treatment response in RA patients.
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Artrite Reumatoide , Densidade Óssea , Artrite Reumatoide/diagnóstico por imagem , Feminino , Força da Mão , Humanos , Articulação Metacarpofalângica/diagnóstico por imagem , Articulação do PunhoRESUMO
Imaging is essential for the assessment of bone and inflammatory joint diseases. There are several imaging techniques available that differ regarding resolution, radiation exposure, time expending, precision, cost, availability or ability to predict disease progression. High-resolution peripheral quantitative computed tomography (HR-pQCT) that was introduced in 2004 allows the in vivo evaluation of peripheral bone microarchitecture and demonstrated high precision in assessing bone changes in inflammatory musculoskeletal diseases. This review summarizes the use of HR-pQCT for the evaluation of the hand skeleton in inflammatory joint diseases. We conducted a review of the literature regarding the protocols that involve hand joints assessment and evaluation of bone changes as erosions and osteophytes in chronic inflammatory diseases. Apart from measuring bone density and structure of the radius and the tibia, HR-pQCT has contributed to assessment of bone erosions and osteophytes, considered the hallmark of diseases as rheumatoid arthritis and psoriatic arthritis, respectively. In this way, there are some conventions recently established by rheumatic study groups that we just summarized here in order to standardize HR-pQCT measurements.
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Artrite Reumatoide/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Artrite Reumatoide/tratamento farmacológico , Densidade Óssea , Osso e Ossos/diagnóstico por imagem , Humanos , Tomografia Computadorizada por Raios X/normasRESUMO
INTRODUCTION: Sarcopenia is characterized by progressive loss of skeletal muscle mass, which results in decreased muscle strength, functional impairment, and increased risk of death. Few studies have performed a concomitant evaluation of clinical, laboratory, and body composition variables to accurately determine the contribution of each parameter to low muscle mass (LMM) in older subjects. This study aimed to identify risk factors (clinical, laboratory parameters, BMD, and body composition by DXA including visceral fat) for LMM in a prospective cohort of older Brazilian women. METHODS: A total of 408 women aged ≥65 yr from the São Paulo Ageing & Health study were evaluated with clinical data, laboratory bone tests, BMD, and body composition by DXA using Hologic QDR 4500A equipment. Risk factors were measured at baseline (2005-2007). After a follow-up of 4.3 ± 0.8 yr, subjects were classified according to the LMM definition of the Foundation for the National Institutes of Health criteria. LMM was defined when appendicular lean mass divided by body mass index was less than 0.512. Multivariate logistic regression models were used to identify independent risk factors for LMM. RESULTS: At the end of follow-up, 116 women (28.4%) had LMM. Age averages were 73.3 ± 4.9 yr in the LMM group and 72.5 ± 4.5 yr in the normal group (pâ¯=â¯0.11). Mean BMI was 30.6 ± 5.2 kg/m2 in the LMM group and 28.1 ± 4.7 kg/m2 in the normal group (p < 0.001). In multivariate analyses, predictors of LMM were: falls (ORâ¯=â¯1.14, pâ¯=â¯0.016), TSH levels (ORâ¯=â¯1.08, pâ¯=â¯0.018, per 1 µUI/L-increase), serum creatinine levels (ORâ¯=â¯11.11, p < 0.001, per 1 mg/dL-decrease), and visceral adipose tissue (VAT) mass (ORâ¯=â¯1.17, p < 0.001, per 100 g increase). CONCLUSIONS: Falls, high TSH, low creatinine, and high VAT were risk factors for LMM in older women. More attention should be paid to these factors, since they are potentially reversible with adequate intervention.
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Acidentes por Quedas/estatística & dados numéricos , Creatinina/sangue , Gordura Intra-Abdominal , Sarcopenia/epidemiologia , Tireotropina/sangue , Idoso , Composição Corporal , Índice de Massa Corporal , Brasil/epidemiologia , Estudos de Coortes , Feminino , Humanos , Vida Independente , Modelos Logísticos , Análise Multivariada , Estudos Prospectivos , Fatores de RiscoRESUMO
OBJECTIVE: To perform a detailed analysis of the autoantibody response against post-translationally modified proteins in patients with rheumatoid arthritis (RA) in sustained remission and to explore whether its composition influences the risk for disease relapse when tapering disease modifying antirheumatic drug (DMARD) therapy. METHODS: Immune responses against 10 citrullinated, homocitrullinated/carbamylated and acetylated peptides, as well as unmodified vimentin (control) and cyclic citrullinated peptide 2 (CCP2) were tested in baseline serum samples from 94 patients of the RETRO study. Patients were classified according to the number of autoantibody reactivities (0-1/10, 2-5/10 and >5/10) or specificity groups (citrullination, carbamylation and acetylation; 0-3) and tested for their risk to develop relapses after DMARD tapering. Demographic and disease-specific parameters were included in multivariate logistic regression analysis for defining the role of autoantibodies in predicting relapse. RESULTS: Patients varied in their antimodified protein antibody response with the extremes from recognition of no (0/10) to all antigens (10/10). Antibodies against citrullinated vimentin (51%), acetylated ornithine (46%) and acetylated lysine (37%) were the most frequently observed subspecificities. Relapse risk significantly (p=0.011) increased from 18% (0-1/10 reactivities) to 34% (2-5/10) and 55% (>5/10). With respect to specificity groups (0-3), relapse risk significantly (p=0.021) increased from 18% (no reactivity) to 28%, 36% and finally to 52% with one, two or three antibody specificity groups, respectively. CONCLUSIONS: The data suggest that the pattern of antimodified protein antibody response determines the risk of disease relapse in patients with RA tapering DMARD therapy. TRIAL REGISTRATION NUMBER: 2009-015740-42; Results.
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Antirreumáticos/administração & dosagem , Artrite Reumatoide/imunologia , Autoanticorpos/imunologia , Acetatos/imunologia , Acetilação , Artrite Reumatoide/tratamento farmacológico , Carbamatos/imunologia , Citrulina/análogos & derivados , Citrulina/imunologia , Humanos , Modelos Logísticos , Lisina/imunologia , Análise Multivariada , Ornitina/imunologia , Peptídeos/imunologia , Peptídeos Cíclicos/imunologia , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Vimentina/imunologiaRESUMO
Introduction: Polyarticular juvenile idiopathic arthritis (pJIA) is a childhood-onset autoimmune disease. Immune cells contribute to persistent inflammation observed in pJIA. Despite the crucial role of monocytes in arthritis, the precise involvement of classical monocytes in the pathogenesis of pJIA remains uncertain. Here, we aimed to uncover the transcriptomic patterns of classical monocytes in pJIA, focusing on their involvement in disease mechanism and heterogeneity. Methods: A total of 17 healthy subjects and 18 premenopausal women with pJIA according to ILAR criteria were included. Classical monocytes were isolated, and RNA sequencing was performed. Differential expression analysis was used to compare pJIA patients and healthy control group. Differentially expressed genes (DEGs) were identified, and gene set enrichment analysis (GSEA) was performed. Using unsupervised learning approach, patients were clustered in two groups based on their similarities at transcriptomic level. Subsequently, these clusters underwent a comparative analysis to reveal differences at the transcriptomic level. Results: We identified 440 DEGs in pJIA patients of which 360 were upregulated and 80 downregulated. GSEA highlighted TNF-α and IFN-γ response. Importantly, this analysis not only detected genes targeted by pJIA therapy but also identified new modulators of immuno-inflammation. PLAUR, IL1B, IL6, CDKN1A, PIM1, and ICAM1 were pointed as drivers of chronic hyperinflammation. Unsupervised learning approach revealed two clusters within pJIA, each exhibiting varying inflammation levels. Conclusion: These findings indicate the pivotal role of immuno-inflammation driven by classical monocytes in pJIA and reveals the existence of two subclusters within pJIA, regardless the positivity of rheumatoid factor and anti-CCP, paving the way to precision medicine.
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Artrite Juvenil , Monócitos , Transcriptoma , Humanos , Artrite Juvenil/genética , Artrite Juvenil/imunologia , Feminino , Monócitos/imunologia , Monócitos/metabolismo , Perfilação da Expressão Gênica , Adolescente , Adulto , Criança , Masculino , Inflamação/genética , Inflamação/imunologiaRESUMO
OBJECTIVES: To analyze longstanding polyarticular juvenile idiopathic arthritis (pJIA) for possible associations between localized bone damage (erosions), and systemic bone loss. Besides, to compare the systemic bone mass of pJIA with healthy controls. METHODS: Thirty-four pJIA women and 99 healthy controls (HC) were included. Radius and tibia of all subjects were scanned by HR-pQCT. Volumetric bone mineral density (vBMD), bone microarchitecture, and -finite element parameters were analyzed. Patients underwent HR-pQCT of 2nd and 3rd metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of the dominant hand, for bone erosions quantification. RESULTS: The mean age of patients was 31.5 ± 7.4yrs with a mean disease duration of 21.7 ± 9.2yrs. Bone erosions were detectable in 79% of patients. The number of bone erosions was positively correlated with cortical porosity (Ct.Po) at tibia (r = 0.575, p = 0.001), and radius (r = 0.423, p = 0.018); and negatively correlated with cortical vBMD at tibia (r=-0.420, p = 0.015). In a logistic regression analysis, adjusted for anti-CCP, the presence of bone erosions was independently associated with Ct.Po at radius (p = 0.018) and cortical vBMD at tibia (p = 0.020). Moreover, cortical and trabecular vBMD, trabecular number, and µ-finite element parameters were decreased in patients compared to HC (p < 0.05). CONCLUSION: Bone erosions in longstanding pJIA women were associated with decreased cortical bone parameters, and these patients showed systemic bone impairment at peripheral sites compared with healthy controls.
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Artrite Juvenil , Osteoporose , Humanos , Feminino , Adulto Jovem , Adulto , Artrite Juvenil/complicações , Artrite Juvenil/diagnóstico por imagem , Densidade Óssea , Rádio (Anatomia) , Tomografia Computadorizada por Raios X , Tíbia/diagnóstico por imagem , Absorciometria de FótonRESUMO
OBJECTIVE: To evaluate premenopausal women with longstanding rheumatoid arthritis (RA) for potential associations between parameters of localized bone involvement and parameters of systemic bone involvement in the affected joints. METHODS: Eighty consecutively evaluated premenopausal women with RA were included in the study, along with 160 healthy female control subjects who were matched to the patients by age and body mass index. Volumetric bone mineral density (vBMD), bone microarchitecture, and finite elements of biomechanical bone strength (bone stiffness and estimated failure load) at the distal radius and distal tibia were analyzed by high-resolution peripheral quantitative computed tomography (HR-pQCT) in patients with RA compared to healthy controls. In addition, in patients with RA, localized bone involvement in the metacarpophalangeal and proximal interphalangeal joints was analyzed by HR-pQCT, to identify bone erosions and osteophytes. RESULTS: Among the 80 premenopausal women with longstanding RA, the mean ± SD age was 39.4 ± 6.7 years and mean ± SD disease duration was 9.8 ± 5.3 years. Trabecular and cortical bone parameters and bone strength at the distal radius and distal tibia were all impaired in patients with RA compared to healthy controls (each P < 0.05). In total, 75% of RA patients had evidence of bone erosions, and 41.3% of RA patients had detectable osteophytes on HR-pQCT. RA patients with bone erosions, as compared to RA patients without bone erosions, had lower cortical vBMD (at the distal radius, mean ± SD 980 ± 72 mg HA/cm3 versus 1,021 ± 47 mg HA/cm3 [P = 0.03]; at the distal tibia, 979 ± 47 mg HA/cm3 versus 1,003 ± 34 mg HA/cm3 [P = 0.04]) and higher cortical bone porosity (at the distal radius, mean ± SD 2.8 ± 2.5% versus 1.8 ± 1.6% [P = 0.04]; at the distal tibia, 3.7 ± 1.6% versus 2.7 ± 1.6% [P = 0.01]). In patients with RA, osteophyte volume at the distal radius was positively correlated with trabecular vBMD (r = 0.392, P = 0.02), trabecular number (r = 0.381, P = 0.03), and trabecular stiffness (r = 0.411, P = 0.02), and negatively correlated with trabecular separation (r = -0.364, P = 0.04), as determined by Pearson's or Spearman's correlation test. CONCLUSION: The findings show that premenopausal women with longstanding RA have systemic bone fragility at peripheral joint sites. Moreover, the presence of bone erosions is mainly associated with cortical bone fragility at the distal radius and tibia, and presence of osteophytes is associated with repair of trabecular bone at the distal radius.
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Artrite Reumatoide/diagnóstico por imagem , Densidade Óssea/fisiologia , Osteófito/diagnóstico por imagem , Rádio (Anatomia)/diagnóstico por imagem , Tíbia/diagnóstico por imagem , Adulto , Osso Esponjoso/diagnóstico por imagem , Osso Cortical/diagnóstico por imagem , Feminino , Humanos , Pessoa de Meia-Idade , Pré-Menopausa , Tomografia Computadorizada por Raios XRESUMO
The risk of osteoporotic fractures is known to vary among populations. There are no studies analyzing concomitantly clinical, densitometric, and lab risk factors in miscigenated community-dwelling population of Brazil. A total of 1007 elderly subjects (600 women and 407 men) from São Paulo, were evaluated using a questionnaire that included risk factors for osteoporotic fractures. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at the hip and lumbar spine. Laboratory blood tests were also obtained. The prevalence of osteoporotic fractures was 13.2% (133 subjects), and the main fracture sites were distal forearm (6.0%), humerus (2.3%), femur (1.3%), and ribs (1.1%). Women had a higher prevalence (17.5%; 95% confidence interval [CI]: 14.6-20.6) than men (6.9%; 95% CI: 4.4-9.3) (p<0.001). After adjusting for significant variables, logistic regression revealed that female gender (odds ratio [OR]=2.7; 95% CI; 1.6-4.5; p<0.001), current smoking (OR=1.9; 95% CI: 1.2-3.3; p=0.013), and the femoral neck T-score (OR=0.7; 95% CI: 0.5-0.9; p=0.001) remain significant risk factors for osteoporotic fractures in the community-dwelling elderly. Our findings identified that female gender, current smoking, and low hip BMD are independent risk factors for osteoporotic fractures.
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Fraturas por Osteoporose/epidemiologia , Absorciometria de Fóton , Idoso , Idoso de 80 Anos ou mais , Antropometria , Densidade Óssea , Brasil/epidemiologia , Feminino , Colo do Fêmur , Articulação do Quadril , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Prevalência , Fatores de Risco , Fumar/efeitos adversosRESUMO
BACKGROUND: Owing to increasing remission rates, the management of patients with rheumatoid arthritis in sustained remission is of growing interest. The Rheumatoid Arthritis in Ongoing Remission (RETRO) study investigated tapering and withdrawal of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis in stable remission to test whether remission could be retained without the need to take DMARD therapy despite an absence of symptoms. METHODS: RETRO was an investigator-initiated, multicentre, prospective, randomised, controlled, open-label, parallel-group phase 3 trial in patients aged at least 18 years with rheumatoid arthritis for at least 12 months before randomisation who were in sustained Disease Activity Score using 28 joints with erythrocyte sedimentation rate (ESR) remission (score <2·6 units). Eligible patients were recruited consecutively from 14 German hospitals or rheumatology practices and randomly assigned (1:1:1) without stratification and regardless of baseline treatment, using a sequence that was computer-generated by the study statistician, to continue 100% dose DMARD (continue group), taper to 50% dose DMARD (taper group), or 50% dose DMARD for 6 months before stopping DMARDs (stop group). Neither patients nor investigators were masked to the treatment assignment. Patients were assessed every 3 months and screened for disease activity and relapse. The primary endpoint was the proportion of patients in sustained DAS28-ESR remission without relapse at 12 months, analysed using a log-rank test of trend and Cox regression. Analysis by a trained statistician of the primary outcome and safety was done in a modified intention-to-treat population that included participants with non-missing baseline data. This study is completed and closed to new participants and is registered with ClinicalTrials.gov (NCT02779114). FINDINGS: Between May 26, 2010, and May 29, 2018, 303 patients were enrolled and allocated to continue (n=100), taper (n=102), or stop DMARDs (n=101). 282 (93%) of 303 patients were analysed (93 [93%] of 100 for continue, 93 [91%] of 102 for taper, and 96 [95%] of 101 for stop). Remission was maintained at 12 months by 81·2% (95% CI 73·3-90·0) in the continue group, 58·6% (49·2-70·0) in the taper group, and 43·3% (34·6-55·5) in the stop group (p=0·0005 with log-rank test for trend). Hazard ratios for relapse were 3·02 (1·69-5·40; p=0.0003) for the taper group and 4·34 (2·48-7·60; p<0.0001)) for the stop group, in comparison with the continue group. The majority of patients who relapsed regained remission after reintroduction of 100% dose DMARDs. Serious adverse events occurred in ten of 93 (11%) patients in the continue group, seven of 93 (8%) patients in taper group, and 13 of 96 (14%) patients in the stop group. None were considered to be related to the intervention. The most frequent type of serious adverse event was injuries or procedural complications (n=9). INTERPRETATION: Reducing antirheumatic drugs in patients with rheumatoid arthritis in stable remission is feasible, with maintenance of remission occurring in about half of the patients. Because relapse rates were significantly higher in patients who tapered or stopped antirheumatic drugs than in patients who continued with a 100% dose, such approaches will require tight monitoring of disease activity. However, remission was regained after reintroduction of antirheumatic treatments in most of those who relapsed in this study. These results might help to prevent overtreatment in a substantial number of patients with rheumatoid arthritis. FUNDING: None.
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Defective KLOTHO gene expression in mice led to a syndrome resembling human ageing. This study evaluated three KLOTHO polymorphisms, namely G395A, C1818T, and C370S, in an elderly population (mean age of 73 years) and their associations with ageing-related outcomes (cardiovascular events, kidney function, osteoporosis, sarcopenia) and mortality. Estimated glomerular filtration rates (eGFR) was lower in subjects with 1818TT (P = 0.047) and 370SS (P = 0.046) genotypes. The 1818TT genotype (P = 0.006) and 1818T allele were associated with higher frequency of myocardial infarction (MI) (CC:1.7% vs. CT + TT:7.0%; P = 0.002). The 370SS genotype was associated with lower stroke frequency (P = 0.001). MI (OR 3.35 [95% CI: 1.29-8.74]) and stroke (OR 3.64 [95% CI: 1.48-8.97]) were associated with mortality. Regarding MI, logistic regression showed 1818T allele was a risk factor for death-related MI (OR 4.29 [95% CI: 1.60-11.52]; P = 0.003), while 370C was protective (OR 0.03 [95% CI: 0.01-0.08]; P < 0.001). Regarding stroke, the 395A and 370C alleles were protective factors (respectively: OR 0.28 [95% CI: 0.20-0.80]; P = 0.018; OR 0.10 [95% CI: 0.05-0.18]; P < 0.001). This is the first study to determine potential associations between common ageing-related outcomes/mortality and KLOTHO polymorphisms. The 1818T allele was a risk factor for MI-related death. The 395A and 370C alleles were protective factors for stroke-related death in elderly from community.
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Envelhecimento/genética , Doenças Cardiovasculares/mortalidade , Glucuronidase/genética , Vida Independente/estatística & dados numéricos , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/mortalidade , Idoso , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/patologia , Humanos , Proteínas Klotho , Masculino , Prognóstico , Fatores de Risco , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/patologia , Taxa de SobrevidaRESUMO
Body composition changes as a result of ageing may impact the survival of older adults. However, its influence on mortality risk is uncertain. Currently, the best method for body composition analysis in clinical practice is DXA. Nonetheless, the few studies on body composition by DXA and mortality risk in the elderly have some limitations. We investigated the association between body composition by DXA and mortality in a cohort of elderly subjects. Eight hundred thirty-nine community-dwelling subjects (516 women, 323 men) ≥ 65 years of age were assessed by a questionnaire, clinical data, laboratory exams, and body composition by DXA at baseline. Total fat and its components (eg, visceral adipose tissue [VAT]) were estimated. Appendicular lean mass (ALM) adjusted for fat and ALM divided by height² was used to ascertain the presence of low muscle mass (LMM). Mortality was recorded during follow-up. Multivariate logistic regression was used to compute ORs for all-cause and cardiovascular mortality. Over a mean follow-up of 4.06 ± 1.07 years, there were 132 (15.7%) deaths. In men, after adjustment for relevant variables, the presence of LMM (OR, 11.36, 95% CI, 2.21 to 58.37, P = 0.004) and VAT (OR, 1.99, 95% CI, 1.38 to 2.87, P < 0.001, for each 100-g increase) significantly increased all-cause mortality risk, whereas total fat, measured by the fat mass index, was associated with decreased mortality risk (OR, 0.48, 95% CI, 0.33 to 0.71, P < 0.001). Similar results were observed for cardiovascular mortality. In women, only LMM was a predictor of all-cause (OR, 62.88, 95% CI, 22.59 to 175.0, P < 0.001) and cardiovascular death (OR, 74.54, 95% CI, 9.72 to 571.46, P < 0.001). LMM ascertained by ALM adjusted for fat and fat mass by itself are associated with all-cause and cardiovascular mortality risk in the elderly. Visceral and subcutaneous fat have opposite roles on mortality risk in elderly men. Thus, DXA is a promising tool to estimate risk of mortality in the elderly. © 2019 American Society for Bone and Mineral Research.
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Envelhecimento/fisiologia , Gordura Intra-Abdominal/patologia , Mortalidade , Gordura Subcutânea/patologia , Magreza/patologia , Idoso , Brasil/epidemiologia , Feminino , Humanos , Masculino , Análise Multivariada , Curva ROC , Análise de SobrevidaRESUMO
BACKGROUND: In the present study, we investigated bone geometry, microstructure, and volumetric bone mineral density (vBMD) in a cohort of patients with nonradiographic axial spondyloarthritis (nr-axSpA) in order to define the early bone changes occurring in axial spondyloarthritis (axSpA) and to define potential factors for deterioration of bone microstructure. METHODS: Patients with axSpA (n = 107) and healthy control subjects (n = 50) of similar age and sex were assessed for geometric, volumetric, and microstructural parameters of bone using high-resolution peripheral quantitative computed tomography (HR-pQCT) at the radius. Additionally, demographic and disease-specific characteristics of patients with axSpA were recorded. RESULTS: Patients with nr-axSpA and control subjects were comparable in age, sex, and body mass index. Geometric and microstructural analysis by HR-pQCT revealed a significantly reduced cortical area (p = 0.022) and cortical thickness (p = 0.006) in patients with nr-axSpA compared with control subjects. Total and cortical vBMD were significantly reduced in patients with nr-axSpA (p = 0.042 and p = 0.007, respectively), whereas there was no difference in trabecular vBMD. Patients with a short disease duration (< 2 years; n = 46) also showed significant reduction of cortical thickness and cortical area compared with control subjects. Patients with disease duration > 2 years (n = 55) additionally developed a decrease of cortical and total vBMD. Multiple regression models identified male sex to be associated with lower cortical vBMD and female sex to be associated with lower trabecular vBMD. CONCLUSIONS: Bone microstructure in patients with nr-axSpA is characterized primarily by deterioration of cortical bone. Cortical bone loss starts early and is evident within the first 2 years of the disease.
Assuntos
Vértebra Cervical Áxis/diagnóstico por imagem , Densidade Óssea/fisiologia , Osso Cortical/diagnóstico por imagem , Espondilartrite/diagnóstico por imagem , Adulto , Idoso , Vértebra Cervical Áxis/metabolismo , Estudos de Coortes , Osso Cortical/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espondilartrite/metabolismoRESUMO
OBJECTIVE: The comparison between different techniques to quantify the 3-dimensional size of inflammatory bone erosions in rheumatoid arthritis(RA) patients. METHODS: Anti-cyclic citrullinated peptide antibody(ACPA) positive RA patients received high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the metacarpophalangeal joints (MCP). Erosions were measured by three different segmentation techniques: (1) manual method with calculation by half-ellipsoid formula, (2) semi-automated modified Evaluation Script for Erosions (mESE), and (3) semi-automated Medical Image Analysis Framework (MIAF) software. Bland & Altman plots were used to describe agreement between methods. Furthermore, shape of erosions was classified as regular or irregular and then compared to the sphericity obtained by MIAF. RESULTS: A total of 76 erosions from 65 RA patients (46 females/19 males), median age 57 years, median disease duration 6.1 years and median disease activity score 28 of 2.8 units were analyzed. While mESE and MIAF showed good agreement in the measurement of erosion size, the manual method with calculation by half-ellipsoid formula underestimated erosions size, particularly with larger erosions. Accurate segmentation is particularly important in larger erosions, which are irregularly shaped. In all three segmentation techniques irregular erosions were larger in size than regular erosions (MIAF: 19.7 vs. 3.4mm3; mESE: 15.5 vs. 2.3mm3; manual = 7.2 vs. 1.52mm3; all p < 0.001). In accordance, sphericity of erosions measured by MIAF significantly decreased with their size (p < 0.001). CONCLUSION: MIAF and mESE allow segmentation of inflammatory bone erosions in RA patients with excellent inter reader reliability. They allow calculating erosion volume independent of erosion shape and therefore provide an attractive tool to quantify structural damage in individual joints of RA patients.
Assuntos
Anticorpos Antiproteína Citrulinada/sangue , Artrite Reumatoide/diagnóstico por imagem , Articulação Metacarpofalângica/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Idoso , Artrite Reumatoide/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: To study whether stable treatment with DMARDs affects anti-CCP2 antibody levels in patients with rheumatoid arthritis. METHODS: In this longitudinal observational study 100 RA patients were followed for anti-CCP2 IgG antibody (U/L) and total IgG level (mg/dL) every 6 months for a total period of 2.5 years. All patients received stable DMARD treatment during this period. Five groups comprising each 20 patients were analyzed as follows: (1) methotrexate (MTX) alone, (2) tumor necrosis factor inhibitors (TNFi), (3) tocilizumab (TCZ), (4) rituximab (RTX), and (5) abatacept (ABA). RESULTS: Baseline demographic and disease-specific characteristics were comparable between the 5 groups. Anti-CCP2 antibody levels did not show significant changes in patients treated with MTX (mean ± SEM: -24.1 ± 8.1%), TNFi (-14.0 ± 11.1%) or TCZ (-24.3 ± 11.3%) between baseline and the 2.5 years follow-up. In contrast, anti-CCP2 antibody levels significantly decreased during treatment with RTX (-75.6 ± 4.4%) and ABA (-82.5 ± 3.7%). With respect to total IgG levels, no significant changes were observed with MTX (-1.6 ± 3.5%), TNFi (2.5 ± 3.4%), TCZ (-4.4 ± 3.1%), or ABA (-2.4 ± 3.8%) over 2.5 years. In contrast, total IgG levels significantly decreased during treatment with RTX (-22.0 ± 3.7%). CONCLUSIONS: DMARDs targeting the adaptive immune response such as ABA and RTX significantly lowered anti-CCP2 IgG levels, while cytokine inhibitors and methotrexate had no significant effects on anti-CCP2 IgG levels. RTX is the only DMARD, which also lowers total IgG level.
Assuntos
Anticorpos Antiproteína Citrulinada/sangue , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Abatacepte/uso terapêutico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Reumatoide/sangue , Artrite Reumatoide/imunologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Rituximab/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
OBJECTIVE: To search for evidence of secondary osteoarthritis (OA) in patients with rheumatoid arthritis (RA) in a cross-sectional and longitudinal setting, and to relate osteophyte formation to functional outcome. METHODS: Anti-citrullinated protein antibody (ACPA)-positive RA patients underwent high-resolution peripheral quantitative computed tomography of the hand. Cross-sectional and longitudinal measurements were performed. The number and size (volume) of osteophytes as well as bone erosions were documented. The relationship of osteophytes to bone erosions and to demographic and disease-specific data was evaluated by multiple logistic regression models. RESULTS: A total of 202 ACPA-positive RA patients were enrolled in the cross-sectional part of the study, and a total of 77 ACPA-positive RA patients were enrolled in the longitudinal analysis (interval of 1.5 years between baseline and follow-up assessment). The mean ± SD number of osteophytes per patient was 1.3 ± 2.3, and the mean ± SD osteophyte volume per patient was 2.6 ± 4.9 mm(3) . The total number of erosions was significantly correlated with the total number of osteophytes (P < 0.001), and the total volume of erosions was significantly correlated with the total volume of osteophytes (P < 0.001). Moreover, the number of osteophytes was related to age (P < 0.001) and disease duration (P = 0.001), while the volume of osteophytes was related to age (P = 0.001), disease duration (P < 0.001), and function as measured by the Health Assessment Questionnaire (P = 0.013). Multivariate regression analyses showed an independent association between osteophytes and erosions. In the longitudinal analysis, the mean number (P = 0.033) and volume (P < 0.001) of osteophytes increased significantly in RA patients during their disease course. CONCLUSION: Age, disease duration, and bone erosions are associated with osteophytes, indicating development of secondary OA in patients with RA.
Assuntos
Artrite Reumatoide/complicações , Autoanticorpos/fisiologia , Osteoartrite/imunologia , Peptídeos Cíclicos/imunologia , Adulto , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Osteófito/imunologiaRESUMO
Previous studies have shown a relationship between osteoporosis and increased mortality risk. However, none of these studies performed a concomitant evaluation of the parathyroid hormone (PTH)-calcium-vitamin D axis and bone mass to accurately determine the contribution of each of these parameters to survival in older subjects. Thus, we sought to investigate the association between bone parameters and mortality in a longitudinal, prospective, population-based cohort of 839 elderly subjects. Clinical data (including history of fractures and cardiovascular events) were assessed using a specific questionnaire. Laboratory exams, including serum 25OHD and PTH, were also performed. Bone mineral density (BMD) at the lumbar spine and hip were evaluated using DXA. All analyses were performed at baseline (2005 to 2007). Mortality was recorded during follow-up. Multivariate Cox proportional regression was used to compute hazard ratios for all-cause and cardiovascular mortality. Over a mean 4.06 ± 1.07 years, there were 132 (15.7%) deaths. These individuals were compared to 707 subjects who were alive at the end of the coverage period for mortality data collection. In a multivariate Cox proportional hazards model, age (HR 1.32; 95% CI, 1.13 to 1.55; p = 0.001, for each 5-year increase), male gender (HR 1.90; 95% CI, 1.30 to 2.79; p = 0.001), recurrent falls (more than two in the previous year; HR 1.65; 95% CI, 1.06 to 2.56; p = 0.026), diabetes mellitus (HR 2.17; 95% CI, 1.46 to 3.21; p < 0.001), low physical activity score (HR 1.78; 95% CI, 1.14 to 2.79; p = 0.011), prior cardiovascular event (HR 1.76; 95% CI, 1.18 to 2.63; p = 0.006), total hip BMD (HR 1.41; 95% CI, 1.15 to 1.72; p = 0.001, per each 1 SD decrease), and intact PTH (iPTH) (HR 1.06; 95% CI, 1.04 to 1.08; p < 0.001, per each 10 pg/mL increase) were independently associated with all-cause mortality. The subjects in the highest quartile of PTH (>49 pg/mL) were at a higher risk of cardiovascular death (HR 3.09; 95% CI, 1.36 to 6.99; p = 0.007) compared with the subjects in the lowest quartile (<26 pg/mL). Low BMD and higher PTH were significantly associated with mortality in community-dwelling older adults. These findings support the notion that careful screening of these bone parameters might lead to better management of older patients and improve outcomes in this population. © 2016 American Society for Bone and Mineral Research.
Assuntos
Densidade Óssea , Mortalidade , Hormônio Paratireóideo/sangue , Acidentes por Quedas/mortalidade , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Feminino , Seguimentos , Humanos , Masculino , Vitamina D/sangueRESUMO
BACKGROUND AND AIMS: To investigate the macro- and microstructural changes of bone in patients with inflammatory bowel disease [IBD] and to define the factors associated with bone loss in IBD. METHODS: A total of 148 subjects, 59 with Crohn's disease [CD], 39 with ulcerative colitis [UC], and 50 healthy controls were assessed for the geometric, volumetric and microstructural properties of bone using high-resolution peripheral quantitative computed tomography. In addition, demographic and disease-specific characteristics of IBD patients were recorded. RESULTS: IBD patients and controls were comparable in age, sex, and body mass index. Total [p = 0.001], cortical [p < 0.001], and trabecular volumetric bone mineral density [BMD] [p = 0.03] were significantly reduced in IBD patients compared with healthy controls. Geometric and microstructural analysis revealed significantly lower cortical area [p = 0.001] and cortical thickness [p < 0.001] without differences in cortical porosity, pore volume, or pore diameter. CD showed a more severe bone phenotype than UC: cortical bone loss was observed in both diseases, but CD additionally showed profound trabecular bone loss with reduced trabecular BMD [p = 0.008], bone volume [p = 0.008], and trabecular thickness [p = 0.009]. Multivariate regression models identified the diagnosis of CD, female sex, lower body mass index, and the lack of remission as factors independently associated with bone loss in IBD. CONCLUSION: IBD patients develop significant cortical bone loss, impairing bone strength. Trabecular bone loss is limited to CD patients, who exhibit a more severe bone phenotype compared with UC patients.
Assuntos
Osso Esponjoso/diagnóstico por imagem , Colite Ulcerativa/complicações , Osso Cortical/diagnóstico por imagem , Doença de Crohn/complicações , Osteoporose/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Osso Esponjoso/patologia , Estudos de Casos e Controles , Colite Ulcerativa/patologia , Osso Cortical/patologia , Doença de Crohn/patologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Osteoporose/etiologia , Osteoporose/patologia , Estudos Prospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X/métodosRESUMO
OBJECTIVE: To evaluate the prevalence of 25-hydroxyvitamin D insufficiency (25OHD<20 ng/mL) and to develop a predictive model for this status. METHODS: This is a cross-sectional study including 908 community-dwelling older subjects, 18% (158) of which were randomly selected to be a "test" sample, with the remaining (750) composing a "development" sample. A radioimmunoassay technique was used to measure 25OHD levels. Anthropometrical data, information about lifestyle habits and co-morbidities were obtained. Multiple logistic regression models were created. An Index Risk of Vitamin D Insufficiency (IRVDI) was designed and subsequently validated. The performance of this tool was assessed through ROC analysis. RESULTS: The prevalence of 25OHD<20 ng/mL was of 58.0% (CI 95% 51.6-64.6). The clinical independent factors for 25OHD<20 ng/mL were female gender (OR=2.16; 95%CI 1.13-4.13; p=0.020), diabetes (OR=1.84; 95%CI 1.23-2.74; p=0.003) and season (winter/spring) (OR=3.63, 95%CI 2.62-4.88; p<0.001). After statistical adjustments, the IRVDI was able to identify older people at risk for vitamin D insufficiency with a sensitivity of 55.9%, specificity 72.3% and ROC area of 0.685 (p<0.001). CONCLUSIONS: Our results suggest that vitamin D insufficiency is common among Brazilian community-dwelling elderly. Female gender, diabetes and the season (winter/spring) were the important parameters that predicted this status. The clinical use of these parameters can be help to design and target appropriate public health interventions. The IRVDI is a convenient tool for the selection of older people at risk for vitamin D insufficiency.
Assuntos
Avaliação Geriátrica , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Vitaminas/sangue , Idoso , Brasil/epidemiologia , Estudos Transversais , Diabetes Mellitus/sangue , Feminino , Humanos , Estilo de Vida , Modelos Logísticos , Masculino , Modelos Biológicos , Razão de Chances , Prevalência , Curva ROC , Características de Residência , Medição de Risco , Estações do Ano , Fatores Sexuais , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/etiologiaRESUMO
OBJECTIVE: Vertebral fractures are associated with higher morbidity and mortality. Since 70% of vertebral fractures are clinically silent, a radiologic image of the spine has to be acquired for the diagnosis. The aim of this study was to compare the performance of Vertebral Fracture Assessment (VFA) by dual x-ray absorptiometry (DXA) with radiographs to identify vertebral fractures in community-dwelling older adults. METHODS: A total of 429 older adults (ages ≥65 years) were enrolled in this cohort. VFA by DXA measurements were evaluated by 2 expert rheumatologists by consensus, and spine radiographs were analyzed according to the semiquantitative method by an expert radiologist. The correlation between VFA and spine radiographs to identify vertebral fractures was analyzed by kappa scores. RESULTS: The prevalence of vertebral fractures in VFA and radiographs was 29.1% and 29.4%, respectively (P = 0.99). The frequency of unavailable vertebrae was significantly lower in spinal radiographs than in VFA (0.9% and 5.6%, respectively; P < 0.001), particularly in T4-T6. According to VFA, 5,013 vertebrae (96%) were identified as normal and 144 (2.7%) had grade 1, 58 (1.1%) had grade 2, and 12 (0.2%) had grade 3 fractures. The sensitivity of VFA was 72.9% and the specificity was 99.1% to identify vertebral fractures. The sensitivity increased to 92% and the specificity increased to 99.9% when excluding grade 1 deformities. A good correlation between VFA and radiographs (κ = 0.74) was observed, and the exclusion of grade 1 resulted in even better agreement (κ = 0.84). CONCLUSION: In community-dwelling older adults, VFA and radiographs had comparable performances in identifying vertebral fractures, particularly if mild deformities are excluded. Therefore, this methodology is a feasible and promising alternative to improve the management of patients with a high risk of osteoporotic fractures.