VALERIA DE FALCO CAPARBO
Projetos de Pesquisa
Unidades Organizacionais
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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- Assessment of Bone Microarchitecture in Patients with Systemic Mastocytosis and its Association with Clinical and Biochemical Parameters of the Disease(2023) FRANCO, Andre S.; MURAI, Igor H.; TAKAYAMA, Liliam; CAPARBO, Valeria F.; MARCHI, Luan L.; VELLOSO, Elvira D. R. P.; PEREIRA, Rosa M. R.Patients with systemic mastocytosis (SM) are at high risk of bone deterioration. However, the evaluation of bone microarchitecture in this disease remains unclear. We aimed to assess bone microarchitecture in patients with SM. This was a cross-sectional study of 21 adult patients with SM conducted in a quaternary referral hospital in Sao Paulo, Brazil. A healthy, age-, weight-, and sex-matched cohort of 63 participants was used to provide reference values for bone microarchitecture, assessed by high resolution peripheral quantitative computed tomography (HR-pQCT). Total volumetric bone mineral density (vBMD), cortical vBMD, and cortical thickness at the radius were significantly lower in the control group compared with the SM group (all P < 0.001). Patients with aggressive SM had significantly lower trabecular number (Tb.N) (P = 0.035) and estimated failure load (F.load) (P = 0.032) at the tibia compared with those with indolent SM. Handgrip strength was significantly higher in patients who had more Tb.N at the radius (rho, 0.46; P = 0.036) and tibia (rho, 0.49; P = 0.002), and lower who had more trabecular separation at the radius (rho, -0.46; P = 0.035) and tibia (rho, -0.52; P = 0.016). Strong and positive associations between F.load (rho, 0.75; P < 0.001) and stiffness (rho, 0.70; P < 0.001) at the radius, and between F.load at the tibia (rho, 0.45; P = 0.038) were observed with handgrip strength. In this cross-sectional study, aggressive SM was more susceptible to bone deterioration compared with indolent SM. In addition, the findings demonstrated that handgrip strength was associated with bone microarchitecture and bone strength.
- Bone density, microarchitecture and estimated strength in stone formers: a cross-sectional HR-pQCT study(2023) ESPER, Priscila Ligeiro Goncalves; RODRIGUES, Fernanda Guedes; MELO, Thalita Lima; ORMANJI, Milene Subtil; CAMPOS, Carlos M.; ALVARENGA, Jackeline Couto; CAPARBO, Valeria de Falco; CARVALHO, Aluizio Barbosa; PEREIRA, Rosa Maria Rodrigues; HEILBERG, Ita PfefermanBackground Low areal bone mineral density (BMD), increased fracture risk and altered bone remodeling have been described among stone formers (SFs), but the magnitude of these findings differs by age, sex, menopausal status and urinary calcium (uCa). This study aimed to investigate volumetric BMD (vBMD), bone microarchitecture and biomechanical properties by high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA) in young SFs, irrespective of calciuria, further distinguishing trabecular from cortical compartments. Methods HR-pQCT/FEA was performed at the distal tibia (DT) and distal radius (DR) in 106 SFs (57 males and 49 premenopausal females; median age 37 years) and compared with 106 non-SFs (NSFs) retrieved from an existing database, matched for age, sex and body mass index (BMI). Biochemical/hormonal serum and urinary parameters were obtained from SFs. Results SFs exhibited significantly lower trabecular number (TbN) and higher trabecular separation (TbSp) than NSFs at both anatomical sites and lower cortical porosity in the DR. In a subgroup analysis separated by sex, female SFs presented significantly lower TbvBMD, relative bone volume fraction (BV/TV) and TbN and higher TbSp than NSFs at both sites, while male SFs showed significantly lower stiffness and failure load. Multivariate analysis showed TbN to be independently associated with sex and BMI at both sites and with uCa at the DR. Conclusions The present findings suggest that bone disease represents an early event among SFs, associated at least in part with calcium excretion and mainly characterized by trabecular bone microarchitecture impairment, especially among women, but with reduced bone strength parameters in men.
- Risk factors for bone loss in juvenile-onset systemic lupus erythematosus: a prospective study(2019) SOUSA, L. F. A. de; PAUPITZ, J. A.; AIKAWA, N. E.; TAKAYAMA, L.; CAPARBO, V. F.; PEREIRA, R. M. R.Objective Juvenile-onset systemic lupus erythematosus (JoSLE) is associated with low bone mass for age and fractures; nevertheless, risk factors for bone impairment are poorly understood. The aim of this study was to evaluate risk factors for bone mass loss in JoSLE patients. Methods Forty-nine female JoSLE patients were evaluated at baseline and after a 3.5-year follow-up regarding clinical, laboratory (including bone turnover markers), areal bone mineral density (aBMD) and bone microarchitecture parameters using high-resolution peripheral quantitative computed tomography (HR-pQCT). Based on the difference between final and baseline aBMD value, the patients were divided into three groups: aBMD gain (BG), aBMD loss (BL) and aBMD no change (NC). Results The mean patient age was 18.7 +/- 3.3 years. Sixty-one percent of patients presented with aBMD gain, 18.4% aBMD loss, and 20.4% remained stable during this follow-up period. Comparing the BL with the BG group, there was a higher frequency of alcohol consumption (p = 0.009), a higher frequency of inadequate calcium intake (p = 0.047) and lower levels of baseline procollagen type 1 amino-terminal propeptide (P1NP) (p = 0.036) in the BL group. Moreover, worsening of HR-pQCT parameters trabecular volumetric density (p = 0.003) and cortical thickness (p = 0.009) was observed in the BL group. In addition, a higher frequency of renal activity was observed comparing the BL + NC with the BG group (p = 0.036). Conclusions This is the first longitudinal study that has analyzed the risk factors of bone loss in JoSLE patients. The authors emphasize the importance of evaluating lifestyle habits and renal disease activity in these young women. Furthermore, this study suggests that trabecular and cortical compartments deteriorated, and low levels of P1NP may be a predictor of bone impairment in JoSLE.
- No deleterious effect of low dose methotrexate on titanium implant osseointegration in a rabbit model(2011) CARVAS, Janaina Badin; PEREIRA, Rosa Maria Rodrigues; BONFA, Eloisa; SILVEIRA, Celey Aparecida; LIMA, Luiz Lapa; CAPARBO, Valeria de Falco; MELLO, Suzana Beatriz Verissimo deOBJECTIVE: To evaluate the effect of low dose methotrexate alone or in combination with glucocorticoid treatment on titanium implant osseointegration. METHODS: Groups of 6-8 adult New Zealand White rabbits were treated for 18 weeks with saline (control), methotrexate, glucocorticoid, or methotrexate plus glucocorticoid. The animals received a titanium implant in the tibia at week 6. Lumbar spine and tibia bone mineral densities were analyzed before and after treatment. Histomorphometric analysis of bone cortical thickness, total bone area around the implant, and % of bone to implant contact was performed. RESULTS: After 18 weeks, the change in the bone mineral density in the lumbar spines and tibias in the methotrexate group was comparable to the control group (0.035 vs. 0.055 g/cm(2) and 0.021 vs. 0.041 g/cm(2), respectively). In contrast, both the glucocorticoid group and glucocorticoid plus methotrexate group had significant reductions at both sites. Histomorphometric analysis of the tibia in the control and methotrexate groups revealed no significant changes in cortical thickness (133 vs. 126 mu m), total bone area around the implant (33 vs. 30%), or bone to implant contact (40 vs. 38%). In contrast, glucocorticoid group had significant reductions compared to controls in tibia cortical thickness (99 vs. 133 mu m), total bone area around the implant (24 vs. 33%), and bone to implant contact (27 vs. 40%). Similar reductions were observed in the glucocorticoid plus methotrexate group. CONCLUSIONS: Our results demonstrate that low dose methotrexate treatment does not affect titanium implant osseointegration, suggesting that this therapy is safe for surgical procedures requiring a titanium implant.
- Bone Metabolism Impairment in Heart Transplant: Results From a Prospective Cohort Study(2020) SEGURO, Luis F. B. C.; PEREIRA, Rosa M. R.; SEGURO, Luciana P. C.; CAPARBO, Valeria F.; AVILA, Monica S.; MANGINI, Sandrigo; CAMPOS, Iascara W.; GAIOTTO, Fabio A.; MARCONDES-BRAGA, Fabiana G.; BACAL, FernandoBackground. Data on the prevention of fractures after heart transplant (HTx) are controversial in the literature. Understanding the effects of HTx on bone may guide appropriate treatments in this high-risk population. Methods. Seventy adult HTx patients were followed for 12 months. Clinical and laboratory parameters, bone mineral density, microarchitecture, and vertebral fractures were assessed at baseline (after intensive care unit discharge) and at 6 and 12 months. Patients received recommendations regarding calcium intake and vitamin D supplementation after HTx. Results. At baseline, 27% of patients had osteoporosis, associated with the length of hospitalization before HTx (P = 0.001). Bone mineral density decreased in the first 6 months, with partial recovery later. Bone microarchitecture deteriorated, mainly in the trabecular bone in the first 6 months and cortical bone in the subsequent 6 months. At baseline, 92.9% of patients had vitamin D levels <30 ng/mL and 20.0% <10 ng/mL. Patients also had calcium at the lower limit of normal, high alkaline phosphatase, and high bone resorption biomarker. These abnormalities were suggestive of impaired bone mineralization and normalized at 6 months with correction of vitamin D deficiency. The majority of vertebral fractures were identified at baseline (23% of patients). After multivariate analyses, only a lower fat mass persisted as a risk factor for vertebral fractures (odds ratio, 1.23; 95% confidence interval, 1.04-1.47; P = 0.012). Conclusions. High frequencies of densitometric osteoporosis, vitamin D deficiency, bone markers abnormalities, and vertebral fractures were observed shortly after HTx. Calcium and vitamin D supplementation should be the first step in correcting bone mineralization impairment before specific osteoporosis treatment.
- 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.
- Association of Bone Erosions and Osteophytes With Systemic Bone Involvement on High-Resolution Peripheral Quantitative Computed Tomography in Premenopausal Women With Longstanding Rheumatoid Arthritis(2022) PEREZ, Mariana O.; FIGUEIREDO, Camille P.; SALES, Lucas P.; MEDEIROS-RIBEIRO, Ana Cristina; TAKAYAMA, Liliam; DOMICIANO, Diogo S.; BONFIGLIOLI, Karina; CAPARBO, Valeria F.; PEREIRA, Rosa M. R.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/cm(3) versus 1,021 +/- 47 mg HA/cm(3) [P = 0.03]; at the distal tibia, 979 +/- 47 mg HA/cm(3) versus 1,003 +/- 34 mg HA/cm(3) [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.
- Vertebral Fracture Assessment by Dual X-Ray Absorptiometry: A Valid Tool to Detect Vertebral Fractures in Community-Dwelling Older Adults in a Population-Based Survey(2013) DOMICIANO, Diogo S.; FIGUEIREDO, Camille P.; LOPES, Jaqueline B.; KUROISHI, Marcia E.; TAKAYAMA, Liliam; CAPARBO, Valeria F.; FULLER, Priscila; MENEZES, Paulo F.; SCAZUFCA, Marcia; BONFA, Eloisa; PEREIRA, Rosa M. R.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 T4T6. 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 ( = 0.74) was observed, and the exclusion of grade 1 resulted in even better agreement ( = 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.
- Assessing bone impairment in ankylosing spondylitis (AS) using the trabecular bone score (TBS) and high-resolution peripheral quantitative computed tomography (HR-pQCT)(2019) CAPARBO, Valeria F.; FURLAM, Pedro; SAAD, Carla G. S.; ALVARENGA, Jackeline C.; AUBRY-ROZIER, Berengere; HANS, Didier; BRUM-FERNANDES, Artur J. de; PEREIRA, Rosa M. R.Objectives: To compare bone quality using the trabecular bone score (TBS) and bone microarchitecture in the distal tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT) in ankylosing spondylitis (AS) patients and healthy controls (HC). Methods: Areal bone mineral density (aBMD) and TBS (TBS iNsight software) were evaluated using DXA (Hologic, QDR 4500); while volumetric bone mineral density (vBMD) and bone microarchitecture were analyzed in the distal tibia using HR-pQCT (Scanco) in 73 male patients with AS and 52 age-matched HC. Results: AS patients were a mean 41.6 +/- 7.9 years old and had a mean disease duration of 16.4 +/- 8.6 y, with a mean mSASSS 25.6 +/- 16.4. No difference was observed in lumbar spine aBMD in AS patients and HC (p = 0.112), but total hip BMD (p = 0.011) and TBS (p < 0.001) were lower in AS patients. In the distal tibia, reduced trabecular volumetric density [Tb.vBMD (p < 0.006)] and structural alterations - trabecular thickness (Tb.Th), p = 0.044 and trabecular separation (Tb.Sp), p = 0.039 - were observed in AS patients relative to controls. Further analysis comparing TBS < 1.310 and TBS >= 1.310 in AS patients revealed a higher mean body mass index [BMI] (p = 0.010), lower tibia cortical vBMD [Ct.vBMD] (p = 0.007), lower tibia cortical thickness [Ct.Th] : (p = 0.048) in the former group. On logistic regression analysis, BMI (OR = 1.27; 95%IC = 1.08-1.50, p = 0.005), (VF 4.65; 1.13-19.1, p = 0.033) and tibial Ct.vBMD (0.98; 0.97-1.00, p = 0.007) were associated with a lower TBS ( < 1.310). Conclusions: The present study demonstrates that TBS and HR-pQCT imaging are important technologies evaluating bone impairment in AS patients. Moreover, in these patients vertebral fractures were associated with lower TBS.
- 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.