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1.
J Bone Miner Res ; 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34405441

RESUMO

The determinants of the susceptibility to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection and severe coronavirus disease 2019 (COVID-19) manifestations are yet not fully understood. Amino-bisphosphonates (N-BPs) have anti-inflammatory properties and have been shown to reduce the incidence of lower respiratory infections, cardiovascular events, and cancer. We conducted a population-based retrospective observational cohort study with the primary objective of determining if oral N-BPs treatment can play a role in the susceptibility to development of severe COVID-19. Administrative International Classification of Diseases, Ninth Revision, Clinical ModificationI (ICD-9-CM) and anatomical-therapeutic chemical (ATC) code data, representative of Italian population (9% sample of the overall population), were analyzed. Oral N-BPs (mainly alendronate and risedronate) were included in the analysis, zoledronic acid was excluded because of the low number of patients at risk. Incidence of COVID-19 hospitalization was 12.32 (95% confidence interval [CI], 9.61-15.04) and 11.55 (95% CI, 8.91-14.20), of intensive care unit (ICU) utilization because of COVID-19 was 1.25 (95% CI, 0.38-2.11) and 1.42 (95% CI, 0.49-2.36), and of all-cause death was 4.06 (95% CI, 2.50-5.61) and 3.96 (95% CI, 2.41-5.51) for oral N-BPs users and nonusers, respectively. Sensitivity analyses that excluded patients with prevalent vertebral or hip fragility fractures and without concomitant glucocorticoid treatment yielded similar results. In conclusion, we found that the incidence of COVID-19 hospitalization, intensive care unit (ICU) utilization, and COVID-19 potentially related mortality were similar in N-BPs-treated and nontreated subjects. Similar results were found in N-BPs versus other anti-osteoporotic drugs. We provide real-life data on the safety of oral N-BPs in terms of severe COVID-19 risk on a population-based cohort. Our results do not support the hypothesis that oral N-BPs can prevent COVID-19 infection and/or severe COVID-19; however, they do not seem to increase the risk. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

2.
Nutrients ; 13(7)2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34371803

RESUMO

Comparative pharmacodynamic (PD) analyses on different dosing schedules for cholecalciferol supplementation are limited. This was an open-label, randomized, parallel-group study involving 75 healthy individuals deficient in vitamin D (baseline 25OHD < 20 ng/mL) receiving oral cholecalciferol with three different dosing regimens: Group A: 10,000 IU/day for 8 weeks followed by 1000 IU/day for 4 weeks; Group B: 50,000 IU/week for 12 weeks and Group C: 100,000 IU every other week for 12 weeks. Regulators of calcium and phosphate homeostasis, bone turnover markers and Wnt inhibitors were measured at baseline, Day 28, 53, 84, and 112. The 1,25OH2D increased at each time point. The increase was greater (p < 0.05) for group A vs. B and C at Day 28, and vs. group B at Day 56. No significant difference among groups was observed for the other biomarkers. The 24,25OH2D remained stable over time. PTH decreased at Day 84 and FGF-23 increased at all time points. CTX-I and PINP increased slightly at Day 28. BALP decreased from Day 56 onward. Dkk-1 increased from Day 56 onward, while sclerostin did not show significant changes. In healthy individuals deficient in vitamin D, vitamin D supplementation exerted effects on multiple regulators of calcium, phosphate and bone metabolism, without marked differences using the three regimens.


Assuntos
Colecalciferol/administração & dosagem , Deficiência de Vitamina D/tratamento farmacológico , Vitaminas/administração & dosagem , Adulto , Biomarcadores/sangue , Remodelação Óssea/efeitos dos fármacos , Cálcio/sangue , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatos/sangue , Deficiência de Vitamina D/sangue
3.
Arthritis Res Ther ; 23(1): 158, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34082806

RESUMO

BACKGROUND: Aortic stiffness index (AoSI) has to be considered a proxy outcome measure in patients with rheumatoid arthritis (RA). The aim of this study was to comparatively describe AoSI progression in two groups of RA patients on long-term treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) with or without tumour necrosis factor inhibitors (TNFi). METHODS: AoSI was evaluated by Doppler echocardiography at the level of the aortic root, using a two-dimensional guided M-mode evaluation. Eligible participants were assessed at baseline and after 12 months. Changes in serum lipids, glucose and arterial blood pressure were assessed. All patients who did not change DMARD treatment during follow-up were consecutively selected for this study. RESULTS: We included 107 (64 TNFi and 43 csDMARDs) RA patients. Most patients (74%) were in remission or low disease activity and had some CVD risk factors (45.8% hypertension, 59.8% dyslipidaemia, 45.3% smoking). The two groups did not differ significantly for baseline AoSI (5.95±3.73% vs 6.08±4.20%, p=0.867). Follow-up AoSI was significantly increased from baseline in the csDMARDs group (+1.00%; p<0.0001) but not in the TNFi group (+0.15%, p=0.477). Patients on TNFi had significantly lower follow-up AoSI from baseline than the csDMARDs group (-1.02%, p<0.001; ANCOVA corrected for baseline AoSI, age and systolic blood pressure). Furthermore, follow-up AoSI was significantly lower in TNFi than in csDMARDs users with an increasing number of CVD risk factors. CONCLUSION: Long-term treatment with TNFi was associated with reduced aortic stiffness progression in patients with established RA and several CVD risk factors.


Assuntos
Antirreumáticos , Artrite Reumatoide , Rigidez Vascular , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Humanos , Fatores de Risco , Inibidores do Fator de Necrose Tumoral , Fator de Necrose Tumoral alfa
4.
Front Endocrinol (Lausanne) ; 12: 620920, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093428

RESUMO

The relationship between endocrine hormones and the spectrum of rheumatic conditions has long been discussed in the literature, focusing primarily on sexual hormones, such as estrogens, androgens, prolactin (PRL). Estrogens are indeed involved in the pathogenesis of the main inflammatory arthritis thanks to their effects on the immune system, both stimulatory and inhibitory. The PRL system has been discovered in synovial tissue of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), patients and has been propose as a new potential therapeutic target. Besides sexual hormones, in the last years scientific interest about the crosstalk of immune system with other class of hormones has grown. Hormones acting on the bone tissue (i.e. parathyroid hormone, vitamin D) and modulators of the Wnt pathway (i.e. Dickkopf-1) have been demonstrated to play active role in inflammatory arthritis course, defining a new field of research named osteoimmunology. PTH, which is one of the main determinants of Dkkopf-1, plays a crucial role in bone erosions in RA and a correlation between PTH, Trabecular Bone Score (TBS) and disease activity has been found in ankylosing spondylitis (AS). In PSA is under studying the interaction among IL-17 and bone metabolism. The purpose of this review is to discuss and summarize the recent data about the interaction between endocrine hormone and immune system in the main rheumatic disorders, covering in particular the role of bone-related hormones and cytokines. We will describe this relationship from a biochemical, diagnostic and therapeutic perspective, with a particular focus on RA, PsA and AS.

5.
ACR Open Rheumatol ; 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34060251

RESUMO

BACKGROUND: There is increasing evidence that environmental air pollution is associated with the development of chronic inflammatory arthritides (CIA). The role of air pollutants on the biological treatment (biological disease-modifying antirheumatic drugs [bDMARDs]) response of CIA is still unclear. METHODS: We retrieved longitudinal data on patients affected by CIA on biological therapies and on the daily concentration of air pollutants in the Verona area. We designed a case-crossover study to compare the exposure to pollutants in the 60-day period preceding a drug switch or swap due to disease progression referent to the 60-day period preceding a visit with stable treatment for at least 6 months. RESULTS: A total of 1257 patients with CIA (863 with rheumatoid arthritis, 256 with psoriatic arthritis, and 138 with ankylosing spondylitis) with 5454 follow-up visits were included in the study (median follow-up 2.09 years [interquartile range: 0.82-2.58 years]). A total of 282 patients were included in the case-crossover study. We retrieved 13 636 daily air pollution records. We found that air pollutants' concentrations were higher in the 60-day period before a failure of bDMARD response and prior to a switch or swap compared with the period preceding a visit with stable bDMARD therapy for at least 6 months. CONCLUSION: We found that environmental air pollution was a determinant of poor response to bDMARDs in a cohort of patients with CIA followed over a 5-year period. An intervention aimed at decreasing fossil combustion emissions might have beneficial effects on biologic persistence rates of patients with CIA and economic expenditures related to switches and swaps.

6.
Arch Osteoporos ; 16(1): 56, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33723677

RESUMO

In the present observational cohort study in 4902 men and 9804 women, we found that the factors associated with osteoporosis care utilization in men were comorbidities, adjuvant hormonal therapy for prostate cancer, vertebral or hip fractures, and glucocorticoid treatment. INTRODUCTION: Male osteoporosis is associated with an important clinical and economic burden worldwide; nevertheless, undertreatment of men with osteoporosis is common. Understanding the factors associated with referral to bone specialists may help to define future interventions to improve access to osteoporosis care for male patients. METHODS: We conducted a retrospective analysis of a nationwide cohort (DeFRACalc79 database). DeFRACalc79 is a tool that estimates the fracture risk by considering clinical and densitometric risk factors, including the presence of prior hip or vertebral and non-vertebral or non-hip fractures. We compared the clinical characteristics of male individuals with an age-matched cohort of women. Propensity score generation with a 2:1 female-to-male ratio was performed using a logistic regression model to age-match the cohorts. RESULTS: We analyzed a sample of 4902 men at high risk for osteoporosis. We found that the factors associated with osteoporosis care utilization in men were the presence of comorbidities (OR 1.939, 95% CI 1.799-2.090), adjuvant hormonal therapy for prostate cancer (OR 1.482, 95% CI 1.315-1.670), the presence of vertebral or hip fractures (OR 1.490, 95% CI 1.378-1.611), and glucocorticoid treatment (OR 2.573, 95% CI 2.274-2.832). CONCLUSIONS: Men are more commonly referred to the bone specialist with a prevalent fragility fracture and/or diagnosis of secondary osteoporosis as compared with women. Our study suggests that there is a lack of screening for the primary prevention of osteoporosis in men as compared with that in women.


Assuntos
Fraturas do Quadril , Osteoporose , Fraturas da Coluna Vertebral , Densidade Óssea , Feminino , Humanos , Masculino , Osteoporose/epidemiologia , Encaminhamento e Consulta , Estudos Retrospectivos
7.
Arthritis Res Ther ; 23(1): 89, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33741041

RESUMO

BACKGROUND: Several studies on community populations found that metabolic syndrome (MetS) is associated with higher risk for total incident cancer with a predisposition for specific types of cancer. These findings have never been analyzed in patients with chronic inflammatory rheumatic and musculoskeletal diseases (RMD). We assessed prevalence/incidence and factors related to the development of cancer in a large cohort of these patients and evaluate whether MetS and its components were associated with cancer independent of traditional markers of inflammation. METHODS: Between March 2014 and April 2016, 474 patients with RMD involved in a cardiovascular primary prevention program were consecutively recruited into this ambispective (combination of retrospective/prospective) study. They underwent clinical, laboratory, and echocardiographic evaluations. MetS was diagnosed according to the ATPIII criteria. RESULTS: Duration of follow-up was 42 [18-60] months. Patients with a diagnosis of cancer (made before recruitment or during follow-up) were 46 (9.7%). Cancer was diagnosed in 22/76 patients (29%) with MetS and in 24/398 patients (6%, p < 0.001) without MetS; nearly two thirds of malignancies belonged to those traditionally related to MetS. MetS was the strongest cancer risk factor. Cancer was positively associated with the number of MetS components identified in each patient. Beyond MetS, cancer was associated to older age and increased inflammatory disease activity; this information allowed to build a simple performance indicator highly sensitive for cancer development. CONCLUSION: In light of our results, an increasingly accurate assessment of MetS would be required in patients with RMD as potential measure of clinical outcomes including the risk of cancer.


Assuntos
Síndrome Metabólica , Neoplasias , Doenças Reumáticas , Idoso , Humanos , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Neoplasias/epidemiologia , Prevalência , Estudos Prospectivos , Estudos Retrospectivos , Doenças Reumáticas/diagnóstico , Doenças Reumáticas/epidemiologia , Fatores de Risco
8.
Int J Rheum Dis ; 24(4): 510-518, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33719195

RESUMO

INTRODUCTION: Patients with rheumatoid arthritis (RA) develop early changes in left ventricular (LV) geometry and experience cardiovascular events in excess than in the general population. This study was designed to assess prevalence, predictors and prognostic role of LV hypertrophy (LVH) in a selected group of RA patients with normal blood pressure and glycemia who should be at low risk for LVH. METHODS: We prospectively analyzed 241 normotensive normoglycemic RA patients (mean age 53 ± 12 years, 61% women) involved in a primary prevention program for cardiovascular diseases who were followed-up for 40 (24-56) months. LVH was detected by echocardiography and defined as LV mass ≥49.2 g/m2.7 for men and ≥46.7 g/m2.7 for women. Primary outcome was a composite of cardiovascular death/hospitalization. RESULTS: LVH was detected in 39 patients (16%). Older age (>53 years), greater body mass index (BMI > 25 kg/m2 ), longer duration of RA disease, anti-cyclic citrullinated peptide antibody (ACPA) positivity and concentric LV geometry were the variables associated with LVH. During the follow-up, a cardiovascular event occurred in 12 of 39 (31%) patients with LVH and in 22 of 202 (11%; P < .001) patients without LVH. LVH independently predicted cardiovascular events (hazards ratio 3.28 [95% CI 1.03-9.20], P = .03) at Cox regression analysis together with C-reactive protein and ACPA positivity. CONCLUSIONS: Nearly one-sixth of normotensive normoglycemic RA patients analyzed in a primary prevention program for cardiovascular diseases has LVH which is associated with obesity and older age, and strongly predicts cardiovascular event in these subjects.

9.
Rheumatology (Oxford) ; 60(10): 4591-4597, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33470401

RESUMO

OBJECTIVES: Environmental air pollution has been linked to the pathogenesis of RA. Nevertheless, evidence linking higher concentrations of air pollutants with the risk of RA reactivations is missing. The objective of the present study was to determine the association between RA flares and air pollution. METHODS: We collected longitudinal data of patients affected by RA and of the daily concentration of air pollutants in the Verona area. We designed a case-crossover study. We compared the exposure to pollutants in the 30-day and 60-day periods preceding an arthritic flare referent to the 30-day and 60-day preceding a low-disease activity visit. RESULTS: The study included 888 patients with RA with 3396 follow-up visits; 13 636 daily air pollution records were retrieved. We found an exposure-response relationship between the concentration of air pollutants and the risk of having abnormal CRP levels. Patients exposed to greater concentrations of air pollutants were at higher risk of having CRP levels ≥5 mg/l. Concentrations of CO, NO, NO2, NOx, PM10, PM2.5 and O3 were higher in the 60-day period preceding a flare. CONCLUSIONS: We found a striking association between air pollution and RA disease severity and reactivations in a cohort of patients followed over a 5-year period. The exposure to high levels of air pollutants was associated with increased CRP levels and a higher risk of experiencing a flare of arthritis. This excessive risk was evident at very low levels of exposure.

10.
Intern Emerg Med ; 16(1): 73-81, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32221774

RESUMO

Inflammatory arthritis, including rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), are associated with both cancer and cardiovascular (CV) adverse events. Cancer and CV abnormalities have coincident etiologic and pathophysiologic pathways in RA/PsA/AS patients. However, a comprehensive evaluation of CV system has never been performed in these patients in relation to the presence of cancer. This study was designed to assess the possible relationships between CV abnormalities and cancer among RA/PsA/AS patients. Between March 2014 and March 2015, 414 patients (214 RA, 125 PsA, and 75 SA) in sinus rhythm without known cardiac disease underwent clinical and color Doppler echocardiographic evaluation and were prospectively followed up. Patients had a mean age of 58 ± 12 years, 64% women. Forty-two patients (10.1%) had a diagnosis of cancer (made before enrollment in 24 cases and in 18 cases during the 36 months of follow-up). Skin cancer was the most frequent malignancy found, followed by thyroid, colon, pancreas, and breast cancer. Patients who had cancer were older with higher systolic blood pressure, more frequent hypertension and moderate/high disease activity, left ventricular (LV) hypertrophy, diastolic dysfunction, and higher ascending aortic stiffness index (AOSI) than those who had not. At multivariate logistic regression analysis, LV diastolic dysfunction and abnormally high AOSI emerged as conditions associated with cancer together with older age and hypertension. Cancer in RA/PsA/AS adults without history of CV disease is closely associated with specific asymptomatic CV abnormalities, such as LV diastolic dysfunction and reduced vascular elasticity, which are independent of age and hypertension.

11.
Intern Emerg Med ; 16(4): 863-874, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33083946

RESUMO

Systemic chronic inflammation may favor the onset of metabolic syndrome (MetS) which represents a risk factor for CV events. Rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are disorders with high prevalence of MetS. We assessed the factors associated with MetS and its prognostic role in non-selected RA/AS/PsA patients. Between March 2014 and April 2016, 458 patients (228 RA, 134 PsA, 96 AS) selected for a primary prevention program for cardiovascular diseases were analyzed. Primary and co-primary end points were a composite of all-cause death/all-cause hospitalization and CV death/CV hospitalization, respectively. MetS was diagnosed according to the IDF Task Force on Epidemiology and Prevention. Patients were divided into MetS + (73 = 16%) and MetS - (385 = 84%). At multivariate logistic analysis, cancer, moderate/high disease activity, higher LV mass (LVM) and degree of LV diastolic dysfunction were independently associated with MetS. At 36-month follow-up, the event rate for primary/co-primary end point was 52/15% in MetS + vs 23/7% in MetS - (both p < 0.001). At multivariate Cox regression analysis, MetS was related to primary end point (HR 1.52 [CI 1.01-2.47], p = 0.04) together with higher LVM, disease duration and higher prevalence of biologic DMARDs refractoriness, and to co-primary end point (HR 2.05 [CI 1.16-3.60], p = 0.01) together with older age and higher LVM. The RA/AS/PsA phenotype MetS + is a subject with moderate/high disease activity, LV structural and functional abnormalities at increased risk for cancer. MetS + identifies RA/AS/PsA patients at higher risk for CV and non-CV events, independently of traditional CV risk factors analyzed individually and traditional indexes of inflammation.

12.
Calcif Tissue Int ; 108(2): 231-239, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33047242

RESUMO

We performed a cross-sectional study to investigate the prevalence of Diffuse Idiopathic Skeletal Hyperostosis (DISH) through Dual-Energy X-ray absorptiometry (DXA) Vertebral Fracture Assessment (VFA) in a group of post-menopausal women with Type 2 Diabetes Mellitus (T2DM). We also explored several biomarkers of bone turnover metabolism, including Wnt pathway modulators. DXA-VFA was performed to detect the presence of DISH. Serum samples were collected from all patients at the time of study recruitment. 16 different serum biomarkers were tested between the two subgroups. Given the exploratory nature of the study, we did not adjust for multiplicity. At VFA analysis, among 96 individuals enrolled in the study 20 (20.8%) showed features of DISH. No statistically significant difference was found for BMD values, between the DISH and NO-DISH subgroups. Concerning blood biomarkers, DISH patients showed a significant difference only in the sclerostin serum levels (32 vs 35.5 pmol/L, for the DISH and NO-DISH subgroup, respectively; p = 0.010). After adjustment for confounding factors, sclerostin serum levels remained significantly lower in DISH group (p = 0.002). We demonstrated a non-negligible prevalence of DISH in a population of post-menopausal women affected by T2DM and suggested low serum sclerostin as a possible key feature associated with DISH presence. In addition, we propose DXA-VFA analysis, whose radiation dose is considerably lower than conventional radiography, as a viable diagnostic and prognostic mean to obtain data not only on bone health, but also for the screening for DISH in subjects at risk.

13.
J Hypertens ; 39(1): 53-61, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33186315

RESUMO

OBJECTIVE: To assess the variables associated with the status of low myocardial mechano-energetic efficiency (MEE) [the ratio between myocardial left ventricular (LV) work and magnitude of myocardial oxygen consumption] and whether low-MEE is a prognosticator of adverse cardiovascular outcome in patients with chronic inflammatory arthritis. METHODS: A total of 432 outpatients with established chronic inflammatory arthritis without overt cardiac disease were recruited from March 2014-March 2016; 216 participants were used as comparison group. Low-MEE status was a priori identified by standard echocardiography at rest as less than 0.32 ml/s per g (5th percentile of MEE calculated in 145 healthy individuals). The pre-specified primary end-point of the study was a composite of cardiovascular death/hospitalization. Follow-up ended September 2019. RESULTS: MEE was significantly lower in chronic inflammatory arthritis patients than controls (0.35 ±â€Š0.11 vs. 0.45 ±â€Š0.10 ml/s per g; P < 0.001). Low-MEE was detected in 164 patients (38%). Independent predictors of low-MEE were older age, higher SBP, diabetes mellitus, LV concentric geometry and lower LV systolic function. During a follow-up of 36 (21-48) months, a primary end-point occurred in 37 patients (8.6%): 22/164 patients with low-MEE (13.4%) and 15/268 (5.6%) without low-MEE (P = 0.004). Low-MEE predicted primary end-points in multivariate Cox regression analysis [heart rate 2.23 (confidence interval 1.13-4.38), P = 0.02] together with older age, lower renal function and higher LV mass. CONCLUSION: Low-MEE is detectable in more than one-third of patients with chronic inflammatory arthritis and is associated with traditional cardiovascular risk factors and abnormalities in LV geometry and systolic function. In these patients low-MEE is a powerful prognosticator of adverse cardiovascular events.

14.
Front Med (Lausanne) ; 7: 551684, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33195301

RESUMO

Psoriatic arthritis (PsA) is an inflammatory condition characterized by a strong heterogeneity and multifaceted behavior. PsA manifests in two types-axial and peripheral-which may be present at the same time. Peripheral manifestations can be further divided into the articular (arthritis) and extra-articular (i.e., enthesitis and dactylitis) subgroups. In such a complex disease, imaging is often required to characterize the type of involvement and to evaluate the radiological damage and progression of PsA. In addition, imaging plays a pivotal role in clinical practice; that is, for axial involvement. Conventional radiology has been the main standard of reference for many years. However, in recent years, there has been growing interest in different imaging modalities, such as ultrasonography (US) and magnetic resonance imaging (MRI). All these techniques play a role in the diagnosis and follow-up of patients with PsA and cover all the types of the disease. US and MRI have good sensitivities and specificities for detecting synovitis, and this may be helpful for differential diagnosis with other musculoskeletal diseases and useful in the early or preclinical phases of the disease. However, US is not useful in the diagnosis of axial PsA. In addition, other modalities have been investigated in the field of PsA imaging. Computed tomography (CT), in particular, dual energy-CT and high-resolution peripheral CT (HRpQ-CT) might play an important role in the assessment of bone damage, erosions, and new bone formation. Regarding advanced functional imaging, FDG PET/CT is another interesting technique for exploring disease activity.

15.
Front Med (Lausanne) ; 7: 551, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33015101

RESUMO

Background: In polymyalgia rheumatica (PMR), data on bone turnover markers (BTM), on Wnt inhibitors (Dkk-1, sclerostin) and their changes induced by glucocorticoids (GC) are lacking. The aims of our study were to compare the baseline levels of Wnt inhibitors and BTM in PMR patients with healthy controls (HC) and to study their changes over the first 4 weeks of GC treatment. Materials and Methods: We enrolled 17 treatment-naïve patients affected by PMR and 17 age and sex-matched healthy controls (HC) from retired hospital personnel. PMR patients were administered methylprednisolone 16 mg daily for 4 weeks. Blood samples were taken at baseline and at week 4 for the PMR group, a single sample was taken for HC. N-propeptide of type I collagen (PINP), C-terminal telopeptide of type I collagen (CTX-I), sclerostin, Dkk-1, and C-reactive protein (CRP) were dosed. Results: At baseline, Dkk-1 was significantly higher in the PMR group as compared to HC (p = 0.002) while PINP, CTX-I and sclerostin levels were comparable between PMR patients and HC, After 4 weeks of GC treatment we found in the PMR group a decrease of PINP (mean ± SD percentage decrement as compared to baseline -40 ± 18.6%, p < 0.001), CTX-I (-23.5 ± 41.3%, p = 0.032), Dkk-1 (-22.4 ± 39.6, p = 0.033), and sclerostin (-32.49 ± 20.47, p < 0.001) as compared to baseline levels. Conclusions: In treatment-naïve PMR, systemic inflammation is associated with a dysregulation of the Wnt system (increased Dkk-1). Within the 1st month, treatment with GC showed noteworthy effects on bone resorption, formation, and on Wnt pathway modulators.

18.
Nutrients ; 12(6)2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32471106

RESUMO

BACKGROUND: the aim of this study was to investigate the pharmacokinetic (PK) and safety profile of high-dose vitamin D supplementation, comparing different schedules (daily, weekly, or bi-weekly) in an otherwise healthy vitamin D-deficient population. Methods: single-center, open-label study on healthy subjects deficient in vitamin D (25 (OH)D < 20 ng/mL), randomized to receive cholecalciferol (DIBASE®, Abiogen Pharma, Italy) using three different schedules: Group A: 10,000 IU/day for eight weeks followed by 1000 IU/day for four weeks; Group B: 50,000 IU/week for 12 weeks, Group C: 100,000 IU/every other week for 12 weeks. Total cumulative doses were: 588,000 IU, 600,000 IU, 600,000 IU. The treatment regimens corresponded to the highest doses allowed for cholecalciferol for the correction of vitamin D deficiency in adults in Italy. RESULTS: mean 25 (OH)D plasma levels significantly increased from baseline 13.5 ± 3.7 ng/mL to peak values of 81.0 ± 15.0 ng/mL in Group A, 63.6 ± 7.9 ng/mL in Group B and 59.4 ± 12 ng/mL in Group C. On day 28, all subjects showed 25 (OH)D levels ≥ 20 ng/mL and 93.1% had 25 (OH)D levels ≥ 30 ng/mL. On day 56 and 84, all subjects had 25 (OH)D levels ≥ 30 ng/mL. No serious adverse events occurred during the study. CONCLUSIONS: normalization of 25 (OH)D serum levels was quickly attained with all the studied regimens. A more refracted schedule provided a higher systemic 25 (OH)D exposure.


Assuntos
Colecalciferol/administração & dosagem , Colecalciferol/farmacocinética , Deficiência de Vitamina D/tratamento farmacológico , Adolescente , Adulto , Cálcio/sangue , Suplementos Nutricionais , Feminino , Voluntários Saudáveis , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Osteomalacia/tratamento farmacológico , Osteoporose/tratamento farmacológico , Fosfatos/sangue , Albumina Sérica , Vitamina D/sangue , Adulto Jovem
19.
ACR Open Rheumatol ; 2(4): 232-241, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32267101

RESUMO

OBJECTIVE: This prospective study was designed to analyze the incidence and the factors associated with impairment in left ventricular systolic function (LVSF) overtime in patients with rheumatoid arthritis (RA) without overt cardiac disease. In particular, we verified the hypothesis that a relationship between worsening of LVSF and markers of RA disease activity exists. METHODS: One hundred forty outpatients with RA without overt heart disease underwent clinical, laboratory, and echocardiographic evaluation at baseline and after 35 (interquartile range [IQR] 23-47) months of follow-up. A clinical Disease Activity Index (CDAI) score greater than 10 indicated the presence of moderate-high RA disease activity; data on anticitrullinated peptide antibody (ACPA) positivity were recorded at baseline. Stress-corrected midwall fractional shortening (sc-MFS) was used as a measure of LVSF and was considered impaired if less than 86.5%. RESULTS: At 36 (IQR 23-47) months follow-up, impaired sc-MFS was detected in 60 of 140 (43%) patients, compared with 80 patients with normal sc-MFS. Disease duration and activity, ACPA positivity, inflammatory markers, cardiovascular and antirheumatic therapies, and sc-MFS were similar between the two groups at baseline. A multiple logistic regression analysis showed ACPA positivity, moderate-high disease activity (CDAI greater than 10), and disease duration as independent predictors of impaired sc-MFS at follow-up. Finally, a simple clinical score to predict worsening of LVSF at midterm was built (area under the curve of 0.80, with a sensibility and specificity of 78% and 82%, respectively). CONCLUSION: Disease duration, ACPA positivity, and moderate-high disease activity are independent prognosticators of LVSF impairment in RA. Adverse changes in heart function could be prevented by good control of inflammation and modulation of autoimmunity.

20.
Calcif Tissue Int ; 106(4): 371-377, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31897527

RESUMO

Tumor Necrosis Factor (TNF)-α and Interleukin (IL)-6 play a fundamental role in bone loss in rheumatoid arthritis (RA), partly due to the inhibition of the Wnt canonical pathway. The aim of our study was to investigate the short-term effects of three different treatments on Wnt inhibitors (Dkk-1 and sclerostin) and on bone turnover markers (BTMs): N-propeptide of type I collagen (PINP) and C-terminal telopeptide of type I collagen (ß-CTX-I). We performed a retrospective analysis of prospectively collected data. We enrolled women affected by early RA (< 12 months) with active disease (DAS28 ≥ 2.6) despite a 6-month treatment with methotrexate (10-15 mg/week), who then started certolizumab pegol, tocilizumab, or methyl-prednisolone (8 mg/daily). Patients were divided into three groups according to the treatment. Blood samples were collected at baseline, week 1, and week 4. We selected 14 patients treated with certolizumab pegol, 14 patients with tocilizumab, and 20 patients with methyl-prednisolone. No difference between any of the tested parameters was found at baseline. ß-CTX-I, Dkk-1, and sclerostin decreased after 1 week of treatment with certolizumab pegol (- 27% ± 21.5, - 50% ± 13.2, and - 30% ± 30.4, respectively, p < 0.05). Methyl-prednisolone induced similar changes, albeit less marked, on ß-CTX-I and Wnt inhibitors, with a decrease in PINP (- 16.1% ± 16.5, p < 0.05). Tocilizumab did not significantly affect BTMs or Wnt inhibitors. No significant changes were found for PTH and 25OHD. In the first four weeks of treatment, TNFα inhibition showed strong effects on BTMs and Wnt inhibitors, differently from IL-6 blockade. Glucocorticoids induced similar changes; nonetheless, they showed undesired effects on bone formation.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Remodelação Óssea/efeitos dos fármacos , Glucocorticoides/farmacologia , Receptores de Interleucina-6/antagonistas & inibidores , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Anticorpos Monoclonais/farmacologia , Densidade Óssea/efeitos dos fármacos , Colágeno Tipo I/sangue , Humanos , Metotrexato/farmacologia , Projetos Piloto , Estudos Retrospectivos
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