VALERIA DE FALCO CAPARBO
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Departamento de Clínica Médica, Faculdade de Medicina
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
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- Risk Factors for Low Muscle Mass in a Population-based Prospective Cohort of Brazilian Community-dwelling Older Women: The Sao Paulo Ageing & Health (SPAH) Study(2020) MACHADO, Ketty L. L. L.; DOMICIANO, Diogo S.; MACHADO, Luana G.; LOPES, Jaqueline B.; FIGUEIREDO, Camille P.; CAPARBO, Valeria F.; TAKAYAMA, Liliam; MENEZES, Paulo R.; PEREIRA, Rosa M. R.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 Sao 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 (p = 0.11). Mean BMI was 30.6 +/- 5.2 kg/m(2) in the LMM group and 28.1 +/- 4.7 kg/m(2) in the normal group (p < 0.001). In multivariate analyses, predictors of LMM were: falls (OR = 1.14, p = 0.016), TSH levels (OR = 1.08, p = 0.018, per 1 mu UI/L-increase), serum creatinine levels (OR =11.11, p < 0.001, per 1 mg/dL-decrease), and visceral adipose tissue (VAT) mass (OR = 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.
- KLOTHO polymorphisms and age-related outcomes in community-dwelling older subjects: The SAo Paulo Ageing & Health (SPAH) Study(2020) PEREIRA, Rosa Maria R.; FREITAS, Thiago Quadrante; FRANCO, Andre Silva; TAKAYAMA, Liliam; CAPARBO, Valeria F.; DOMICIANO, Diogo S.; MACHADO, Luana G.; FIGUEIREDO, Camille P.; MENEZES, Paulo R.; ONUCHIC, Luiz Fernando; CASTRO, Isac deDefective 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.
- Overexpression of SNTG2, TRAF3IP2, and ITGA6 transcripts is associated with osteoporotic vertebral fracture in elderly women from community(2020) JALES NETO, Levi H.; WICIK, Zofia; TORRES, Georgea H. F.; TAKAYAMA, Liliam; CAPARBO, Valeria F.; LOPES, Neuza H. M.; PEREIRA, Alexandre C.; PEREIRA, Rosa M. R.Background: Vertebral fractures (VFs) are the most common clinical manifestation of osteoporosis associated with high morbimortality. A personal/familiar history of fractures increases the risk of fractures. The purpose of this study is to identify possible molecular markers associated with osteoporotic VFs in elderly women from community. Methods: Transcriptomic analysis using Affymetrix HTA2 microarray was performed using whole blood samples of 240 subjects from a population-based survey (Sao Paulo Ageing & Health [SPAR] study). Only elderly women with osteoporosis diagnosis by densitometry were analyzed, and divided in two groups: VF: women with osteoporosis and VFs versus no vertebral fracture (NVF): women with osteoporosis and NVFs. They were matched for age, chronic disease, medication use, and bone mineral density (BMD). The logistic regression model adjusted for age was applied for transcriptome data analysis. SYBR green-based quantitative polymerase chain reaction (qPCR) was used to validate the most significant expression changes obtained in the microarray experiment. Results: Microarray analysis identified 142 differentially expressed genes (DEGs, p < .01), 57 upregulated and 85 downregulated, compared VF versus NVF groups. The DEG with the greatest expression difference was the Gamma2-Syntrophin (SNTG2) (beta = 31.88, p = .005). Validation by qPCR confirmed increased expression in VF group of Syntrophin (SNTG2, fold change = 2.79, p = .009), TRAF3 Interacting Protein2 (TRAF3IP2, told change = 2.79, p = .020), and Integrin Subunit Alpha 6 (ITGA6, fold change = 2.86, p = .038). Conclusion: Our data identified and validated the association of SNTG2 (608715), TRAF3IP2 (607043), and ITGA6 (147556) with osteoporotic VF in elderly women, independently of BMD. These results suggest that these transcripts have potential clinical significance and may help to explain the molecular mechanisms and biological functions of vertebral fracture.
- Prevalence and risk factors of radiographic vertebral fracture in Brazilian community-dwelling elderly(2011) LOPES, J. B.; DANILEVICIUS, C. F.; TAKAYAMA, L.; CAPARBO, V. F.; MENEZES, P. R.; SCAZUFCA, M.; KUROISHI, M. E.; PEREIRA, R. M. R.The prevalence and risk factors of radiographic vertebral fracture were determined among Brazilian community-dwelling elderly. Vertebral fractures were a common condition in this elderly population, and lower hip bone mineral density was a significant risk factor for vertebral fractures in both genders. The aim of the study was to estimate the prevalence of radiographic vertebral fracture and investigate factors associated with this condition in Brazilian community-dwelling elderly. This cross-sectional study included 943 elderly subjects (561 women and 382 men) living in So Paulo, Brazil. Thoracic and lumbar spine radiographs were obtained, and vertebral fractures were evaluated using Genant's semiquantitative method. Bone mineral density (BMD) was measured by dual X-ray absorptiometry, and bone biochemical markers were also evaluated. Female and male subjects were analyzed independently, and each gender was divided into two groups based on whether vertebral fractures were present. The prevalence of vertebral fracture was 27.5% (95% CI 23.8-31.1) in women and 31.8% in men (95% CI 27.1-36.5) (P = 0.116). Cox regression analyses using variables that were significant in the univariate analysis showed that age (prevalence ratio = 1.03, 95% CI 1.01-1.06; p = 0.019) and total femur BMD (PR = 0.27, 95% CI 0.08-0.98; p = 0.048) were independent factors in predicting vertebral fracture for the female group. In the male group, Cox regression analyses demonstrated that femoral neck BMD (PR = 0.26, 95% CI 0.07-0.98; p = 0.046) was an independent parameter in predicting vertebral fractures. Our results suggest that radiographic vertebral fractures are common in Brazilian community-dwelling elderly and that a low hip BMD was an important risk factor for this condition in both genders. Age was also significantly correlated with the presence of vertebral fractures in women.
- Associations between OPG and RANKL polymorphisms, vertebral fractures, and abdominal aortic calcification in community-dwelling older subjects: the Sao Paulo Ageing & Health Study (SPAH)(2016) PEREIRA, R. M. R.; FIGUEIREDO, C. P.; CHA, C. C.; CAPARBO, V. F.; OLIVEIRA, R. M.; FRANCO, A. S.; MENEZES, P. R.; CASTRO, I. de; ONUCHIC, L. F.This is the first study analyzing concomitantly osteoprotegerin (OPG)/receptor activator of nuclear factor kappa B ligand (RANKL) polymorphisms and OPG/RANKL serum levels and their association with bone mineral density (BMD), vertebral fractures, and vascular aortic calcification in a cohort of 800 subjects in community-dwelling older individuals. Introduction Osteoprotegerin (OPG) and RANKL play an important role in osteoclast activation and differentiation as well as in vascular calcification. At present, there are no studies of OPG or RANKL gene polymorphisms in Brazilian older populations. The aim of this study was to evaluate OPG/RANKL polymorphism and their association with vertebral fractures (VFs) and aortic calcification. Methods Eight hundred subjects (497 women/303 men) were genotyped for the OPG 1181G>C (rs2073618), 163C>T (rs3102735), 245T>G (rs3134069), and 209G>A (rs3134070) and RANKL A>G (rs2277438) single-nucleotide polymorphisms (SNPs). VFs were evaluated by spine radiography (Genant's method). Aortic calcification was quantified using Kauppila's method. Results The isolated genotype analyses and single-allele frequency data showed association of OPG 163C, 245G, and 209A alleles with presence of VFs (P < 0.05). Multiple logistic regression of subjects with absence of VFs vs. those with VFs (grades II/III) revealed only OPG 209A homozygosity as a risk factor for higher-grade VFs (odds ratio (OR) = 4.17, 95 % CI 1.03-16.93, P = 0.046). Regarding aortic calcification, the isolated genotype analysis frequency data revealed a significant association of OPG 1181G, 163C, 245G, and 209A alleles with absent aortic calcification (P < 0.05). Multiple logistic regression data confirmed that the OPG 209A allele was protective for aortic calcification (OR = 0.63, 95 % CI 0.45-0.88, P = 0.007) and the OPG 1181C allele was a risk factor for aortic calcification (OR = 1.26, 95 % CI 1.00-1.58, P = 0.046). Conclusion This study showed that the OPG 209AA genotype was a risk factor for higher-grade VFs, the OPG 209A allele was protective for aortic calcification, and the OPG 1181C was a risk factor for aortic calcification, supporting the involvement of OPG polymorphisms in the analyzed phenotypes and the concept that the related pathogenesis is multifactorial.
- Incidence and risk factors for osteoporotic vertebral fracture in low-income community-dwelling elderly: a population-based prospective cohort study in Brazil. The Sao Paulo Ageing & Health (SPAH) Study(2014) DOMICIANO, D. S.; MACHADO, L. G.; LOPES, J. B.; FIGUEIREDO, C. P.; CAPARBO, V. F.; TAKAYAMA, L.; OLIVEIRA, R. M.; MENEZES, P. R.; PEREIRA, R. M. R.We ascertained the incidence and predictors of radiographic vertebral fracture in a Brazilian elderly cohort, since no data in this field have been reported in low-income countries. This is the first population-based study to demonstrate the high frequency of vertebral fracture in elderly Latin Americans. Age, prior fracture, BMD, and bone turnover were predictors of fracture. Vertebral fractures are associated with increased future fracture risk and mortality. No data on incidence of osteoporotic vertebral fracture have been reported in low-income countries where the population's aging has been faster. Thus, we sought to describe the incidence and risk factors for radiographic vertebral fracture in a longitudinal prospective Brazilian population-based elderly cohort. 707 older adults (449 women and 258 men) were evaluated with spinal radiographs obtained at baseline and after a mean follow-up of 4.3 +/- 0.8 years. New vertebral fracture was defined as distinct alteration in the morphology of vertebrae resulting in higher grade of deformity on the second radiograph when compared to the baseline radiograph. Clinical questionnaire, bone mineral density (BMD), and laboratory tests were performed at baseline. Multivariate Poisson regression models were used to identify independent predictors of fracture. The age-standardized incidence of vertebral fracture was 40.3/1,000 person-years in women and 30.6/1,000 in men. In women, three models of risk factors for fracture were fitted: (1) age (relative risks (RR) 2.46, 95 % confidence interval (CI) 1.66-3.65), previous osteoporotic fracture (RR 1.65, 95 % CI 1.00-2.71), and lumbar spine BMD (RR 1.21, 95 % CI 1.03-1.41); (2) age (RR 2.25, 95 % CI 1.52-3.34) and femoral neck BMD (RR 1.42, 95 % CI 1.11-1.81); (3) age (RR 2.11, 95 % CI 1.41-3.15) and total hip BMD (RR 1.56, 95 % CI 1.21-2.0). In men, the highest quartile of cross-linked C-telopeptide (CTx) (RR 1.96, 95 % CI 0.98-3.91) and prior fracture (RR 2.10, 95 % CI 1.00-4.39) were predictors of new vertebral fracture. This is the first population-based study to ascertain the incidence of vertebral fracture in elderly Latin Americans, confirming the high frequency of the disorder. Age, prior fracture, BMD, and bone turnover were predictors of the short-term incidence of vertebral fracture.
- Osteoporotic Fractures in the Brazilian Community-Dwelling Elderly: Prevalence and Risk Factors(2011) LOPES, Jaqueline B.; FIGUEIREDO, Camille P.; CAPARBO, Valeria F.; TAKAYAMA, Liliam; MENEZES, Paulo R.; SCAZUFCA, Marcia; PEREIRA, Rosa M. R.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 Sao 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.
- Monocytes from male patients with ankylosing spondylitis display decreased osteoclastogenesis and decreased RANKL/OPG ratio(2018) CAPARBO, V. F.; SAAD, C. G. S.; MORAES, J. C.; BRUM-FERNANDES, A. J. de; PEREIRA, R. M. R.aSummaryThe present study investigates the osteoclastogenic capacity of peripheral blood mononuclear cells (PBMCs) in male patients with ankylosing spondylitis (AS). We demonstrated that monocytes from these patients display a lower capacity to generate osteoclasts compared to cells from healthy controls, and osteoclastogenesis was negatively correlated with disease duration.IntroductionAnkylosing spondylitis (AS) is a disease characterized by new bone growth that leads to syndesmophyte formation but AS patients frequently present with low bone mineral density/fractures. Osteoclastogenesis in AS patients is poorly studied and controversial. The aim of this study is to determine if the osteoclastogenic capacity of PBMCs is different in AS patients compared to controls and the relationship between osteoclastogenesis and clinical/laboratory parameters.MethodsPBMCs from 85 male AS patients and 59 controls were tested for CD16+ cells and induced to differentiate into osteoclasts over 3weeks in vitro. Serum levels of RANKL, osteoprotegerin (OPG), C-terminal telopeptide of type I collagen (CTX), and amino-terminal pro-peptide of type I collagen (P1NP) were also evaluated.ResultsPBMCs from AS patients had fewer CD16+ cells and produced fewer osteoclasts compared to controls. Apoptosis occurred less frequently in osteoclasts obtained from AS patients than in osteoclasts from the controls. A lower RANKL/OPG and CTX/P1NP were observed in AS patients compared to controls. AS patients taking NSAIDs presented no difference regarding the number of OCs produced and the percentage of CD16+ cells compared to controls. However, patients taking TNF inhibitors (TNFi) presented lower OC numbers than controls. A negative correlation was demonstrated between the number of osteoclasts generated from PBMCs of AS patients and disease duration.ConclusionMonocytes from male AS patients display a lower capacity to generate osteoclasts in vitro compared to cells from controls. Osteoclastogenesis was negatively correlated with disease duration. This finding supports the idea that osteoclasts play a role in the physiopathology of bone disease in AS patients.
- Discriminating sarcopenia in community-dwelling older women with high frequency of overweight/obesity: the So Paulo Ageing & Health Study (SPAH)(2013) DOMICIANO, D. S.; FIGUEIREDO, C. P.; LOPES, J. B.; CAPARBO, V. F.; TAKAYAMA, L.; MENEZES, P. R.; BONFA, E.; PEREIRA, R. M. R.The criteria most used for the definition of sarcopenia, those based on the ratio between the appendicular skeletal muscle mass (ASM) and the square of the height (h(2)) underestimate prevalence in overweight/obese people whereas another criteria consider ASM adjusted for total fat mass. We have shown that ASM adjusted for fat seems to be more appropriate for sarcopenia diagnosis. Since the prevalence of overweight and obesity is a growing public health issue, the aim of this study was to evaluate the prevalence and risk factors associated with sarcopenia, based on these two criteria, among older women. Six hundred eleven community-dwelling women were evaluated by specific questionnaire including clinical data. Body composition and bone mineral density were evaluated by dual X-ray absorptiometry. Logistic regression models were used to identify factors independently related to sarcopenia by ASM/h(2) and ASM adjusted for total fat mass criteria. The prevalence of overweight/obesity was high (74.3 %). The frequency of sarcopenia was lower using the criteria of ASM/h(2) (3.7 %) than ASM adjusted for fat (19.9 %) (P < 0.0001). We also note that less than 5 %(1/23) of sarcopenic women, according to ASM/h(2), had overweight/obesity, whereas 60 % (74/122) of sarcopenic women by ASM adjusted for fat had this complication. Using ASM/h(2), the associated factors observed in regression models were femoral neck T-score (OR = 1.90; 95 % CI 1.06-3.41; P = 0.03) and current alcohol intake (OR = 4.13, 95 % CI 1.18-14.45, P = 0.03). In contrast, we have identified that creatinine (OR = 0.21; 95 % CI 0.07-0.63; P = 0.005) and the White race (OR = 1.81; 95 % CI 1.15-2.84; P = 0.01) showed a significant association with sarcopenia using ASM adjusted for fat. In women with overweight/obesity, ASM adjusted for fat seems to be the more appropriate criteria for sarcopenia diagnosis. This finding has relevant public health implications, considering the high prevalence of overweight/obesity in older women.