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1.
Med Sci Monit ; 27: e930513, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33859156

RESUMO

BACKGROUND Regional citrate anticoagulation (RCA) is a recommended anticoagulation alternative for patients at high risk of bleeding while undergoing intermittent hemodialysis. Previous reports implied the risk of citrate application on bone metabolism. It is unclear whether long-term use of RCA is safe for maintenance hemodialysis patients in terms of bone metabolism. MATERIAL AND METHODS Seven patients with cerebral hemorrhage were included in the study. Blood samples were collected at baseline and 4 and 8 weeks after treatment. Spent dialysate samples were collected during each mid-week dialysis session, using the partial dialysate collection method. All patients were treated with RCA for 4 to 8 weeks, according to their clinical condition. We assessed bone metabolism-associated parameters, bone turnover markers, and magnesium loss at each dialysis session. RESULTS Serum magnesium levels were 1.24±0.13 mmol/L at baseline and significantly decreased to 1.16±0.14 mmol/L after 4 weeks of RCA treatment (P=0.025). Most patients had negative magnesium balance during citrate hemodialysis. Serum total calcium levels did not change significantly after treatment. One bone marker, N-terminal propeptide of type I procollagen (PINP), significantly decreased from 146.07±130.12 mmol/L to 92.42±79.01 mmol/L after citrate treatment (P=0.018). No significant changes were detected in other bone turnover markers. CONCLUSIONS Relatively long-term RCA treatment may decrease serum magnesium levels due to negative magnesium balance. Bone formation marker PINP seemed to decrease after treatment, while other bone turnover markers did not change significantly. Further investigation is needed to verify the effect of RCA on bone remodeling.


Assuntos
Anticoagulantes/uso terapêutico , Hemorragia Cerebral/terapia , Ácido Cítrico/uso terapêutico , Diálise Renal/métodos , Idoso , Idoso de 80 Anos ou mais , Remodelação Óssea , Cálcio/sangue , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteogênese , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue
2.
Clin Drug Investig ; 41(3): 277-285, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33638863

RESUMO

BACKGROUND AND OBJECTIVE: Abaloparatide, an anabolic osteoporosis treatment administered by subcutaneous (SC) injection, increases bone mineral density (BMD) and reduces fracture risk in postmenopausal women with osteoporosis. The abaloparatide-solid Microstructured Transdermal System [abaloparatide-sMTS (Kindeva, St Paul, MN, USA)], which delivers abaloparatide intradermally, is in development to provide an alternative method for abaloparatide delivery. The objective of this study was to evaluate the ability of subjects to self-administer abaloparatide-sMTS, based on pharmacokinetic and pharmacodynamic markers. METHODS: In this single-arm, open-label, Phase 1b study, 22 healthy postmenopausal women aged 50-85 years with low BMD were trained to self-administer abaloparatide-sMTS 300 µg once daily to the thigh for 5 min for 29 days. The primary endpoint was systemic exposure to abaloparatide. Secondary endpoints included percent change from baseline in serum procollagen type I N-terminal propeptide (s-PINP), patient experience, and safety. RESULTS: All 22 subjects completed the study. At baseline, mean age was 65.2 years, mean total hip T-score was - 1.32, and mean lumbar spine T-score was - 1.98. On Day 1, the median time to reach maximum concentration (Tmax) for abaloparatide-sMTS was 0.33 h and geometric mean (CV %) maximum concentration (Cmax) and area under the concentration-time curve from time 0 to the time of the last quantifiable concentration (AUC0-t) were 447 (38.0) pg/mL and 678 (45.3) pg·h/mL, respectively; the pharmacokinetic profile was similar on Days 15 and 29. Median percentage change in s-PINP was 45.4% and 64.4% at Days 15 and 29, respectively. The most common adverse events (AEs) were application site erythema, pain, and swelling, which were mostly of mild or moderate severity. No AEs led to study drug withdrawal and no serious AEs were reported. The success rate for self-administration at first application was 99.7%, and subject acceptability was high (~ 4.5 on a 5-point Likert Scale). CONCLUSIONS: Subjects successfully self-administered abaloparatide-sMTS, which provided a consistent pharmacokinetic profile over 29 days and produced s-PINP increases from baseline similar to that observed in the pivotal trial with abaloparatide-SC. Observed patient experience along with the clinical data support continued clinical development of abaloparatide-sMTS. TRIAL REGISTRATION NUMBER: NCT04366726, Date of registration 04/29/2020, retrospectively registered.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Osteoporose Pós-Menopausa/tratamento farmacológico , Proteína Relacionada ao Hormônio Paratireóideo/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Injeções Subcutâneas , Vértebras Lombares/efeitos dos fármacos , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue
3.
Medicine (Baltimore) ; 100(3): e24259, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33546047

RESUMO

BACKGROUND: Osteoporosis (OP) results in an increased risk of fragility fractures, representing a major public health problem. In preventing OP, complementary and alternative medicine, such as acupuncture, was recommended because of the low efficiency and side effects of medications. Recently, there is insufficient evidence on electroacupuncture as an effective therapy for OP management. Hence, we evaluated the effectiveness of electroacupuncture for OP treatment. METHODS: We conducted a systematic review and meta-analysis of clinical studies on patients with OP. Five databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Wanfang) were searched from the earliest publication date to March 12, 2020. Randomized controlled trials (RCTs) were included if electroacupuncture was applied as the sole treatment or as an adjunct to other treatments compared with medications in patients with OP. The measurement outcomes included serum aminoterminal propeptide of type I procollagen (PINP) and C-telopeptide of type I collagen (CTX) levels, bone mineral density (BMD) of lumbar, and visual analog scale scores for OP-related pain. Acupoints were extracted when available. RESULTS: In total, 11 RCTs involving 731 participants were included for further meta-analysis. The meta-analysis showed that the use of electroacupuncture as a sole treatment or as an adjunct to other treatments could relieve OP-related pain compared with medications [mean difference (MD) =  -0.58, 95% confidence interval (CI); MD =  -0.97 to -0.19, P = .003, I2 = 88%; MD =  -1.47, 95% CI = -2.14 to -0.79, P < .001, I2 = 96%). Meanwhile, the results showed a favorable effect of electroacupuncture on decreasing serum beta-CTX levels. However, there were no significant differences in serum PINP levels and BMD of lumbar. Shenshu (BL23) was the most frequent acupoint stimulation among these studies. CONCLUSIONS: The application of electroacupuncture as an independent therapy or as an adjunct to other treatments might attenuate OP-related pain and serum beta-CTX levels. However, to overcome the methodological shortcomings of the existing evidence, due to a small size of samples and high risk of bias in these included RCTs, further rigorous studies are required.


Assuntos
Eletroacupuntura , Osteoporose/terapia , Dor nas Costas/terapia , Densidade Óssea , Colágeno Tipo I/sangue , Humanos , Osteoporose/sangue , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Pró-Colágeno/sangue
4.
Aging (Albany NY) ; 13(1): 194-203, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431713

RESUMO

The aim of the study were to evaluate the prognostic potential of serum level of N-terminal propeptide procollagen type III (PIIINP) and heart parameters for predicting heart cardiac fibrosis 1 year after ST-segment elevation myocardial infarction (STEMI) with preserved left ventricular ejection fraction (LVEF). 68 patients with STEMI and preserved LVEF with acute heart failure of the I-III degree according to the Killip classification were examined. Echocardiography was performed and PIIINP levels were measured on days 1 and 12, as well as 1 year after STEMI. A year after STEMI, was performed contrast magnetic resonance imaging and patients were assigned into four groups depending on the severity of cardiac fibrosis: cardiac fibrosis 0% (n=49, 57% of 86 patients); ≤5% (n=18, 20.9%); 6-15% (n=10, 11.6%); ≥16% (n=9, 10.5%). Direct correlations between the severity of cardiac fibrosis, PIIINP level and indicators of diastolic function were established. The risk of cardiac fibrosis increases at the level of PIIINP ≥381.4 ng / ml on the 12th day after STEMI with preserved LVEF (p=0.048). Thus, measuring the level of PIIINP in the inpatient period can allow timely identification of patients with a high risk of cardiac fibrosis 1 year after STEMI with preserved LVEF.


Assuntos
Biomarcadores/sangue , Infarto do Miocárdio/patologia , Miocárdio/patologia , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Feminino , Fibrose/etiologia , Fibrose/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Prognóstico , Volume Sistólico
5.
J Toxicol Sci ; 45(10): 611-617, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33012729

RESUMO

Acute paraquat poisoning (APP) is a serious public health problem with a high mortality rate and there is no specific antidote for APP in clinical. Early haemoperfusion (HP) treatment is effective in APP rescue. In this study, we compared the influence of routine HP and continuous HP on the survival rate and the treatment of pulmonary fibrosis in mild and moderate APP patients. Eighty-two cases of mild and moderate APP patients who were admitted to our hospital from January of 2017 to December of 2018 were selected. All patients were randomly divided into a routine haemoperfusion (HP) group (n = 40) and a continuous haemoperfusion (CHP) group (n = 42). Compared with the HP group, the 28-day survival rate of mild and moderate APP patients was elevated in the CHP group. Blood N-terminal procollagen Ш propeptide (PIIINP) levels in APP patients were positively related with paraquat (PQ) concentration (r = 0.309, P = 0.000). There were statistically significant differences in the levels of PIIINP, Collage TypeIV (CIV), transforming growth factor-beta 1 (TGF-ß1), malondialdehyde (MDA), superoxide dismutase (SOD) activity and sequential organ failure assessment (SOFA) score between the two groups both on the third and seventh days after treatment, and the treatment effect of the CHP group on pulmonary fibrosis in APP patients was better than that of the HP group. In conclusion, CHP treatment had a significant therapeutic effect on mild and moderate APP patients, which could effectively improve the survival rate and relieve pulmonary fibrosis.


Assuntos
Hemoperfusão/métodos , Paraquat/envenenamento , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/terapia , Adolescente , Adulto , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Fibrose Pulmonar/diagnóstico , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
6.
Folia Med Cracov ; 60(1): 61-74, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32658213

RESUMO

BACKGROUND AND STUDY AIMS: The aim of the study was to assess the usefulness of serum concentrations of YKL-40/ CHI3L1 (a 40-kilodalton glycoprotein also referred to as chitinase 3 like- 1 - CHI3L1) and PIIINP (N-terminal propeptide of type III procollagen), markers of fibrosis, in the monitoring of inflammatory processes and fibrosis in children with inflammatory bowel disease (IBD). PATIENTS AND METHODS: In 60 patients (41 with Crohn's disease (CD), 19 with ulcerative colitis (UC)) concentrations of investigated parameters were measured at baseline (day 0), after 3 and after 6-8 weeks of pharmacological treatment. RESULTS: PIIINP concentrations were significantly higher in CD patients compared to UC (baseline results: median concentrations 1013.73 vs 78.30 ng/mL; P = 0.06 for the Kruskall-Wallis test; results at 6-8 weeks: 1076.48 vs 53.10 ng/mL, P = 0.01). Fibrosis was clearly present in patients with CD and its severity increased (reflected by both YKL-40/ CHI3L1 and PIIINP concentrations) in 6-8 weeks of follow up, regardless of the treatment used during that time. In patients with UC the levels of YKL-40/CHI3L1 and PIIINP were lower at baseline and further decreased after 6-8 weeks (median concentrations were respectively: 39.5 ng/mL vs 24.7 ng/mL and 78.3 ng/mL vs 53.1 ng/mL). CONCLUSION: Fibrosis was more severe in CD than in UC patients. The marker that more accurately reflected these differences was PIIINP.


Assuntos
Colite Ulcerativa/sangue , Colite Ulcerativa/diagnóstico , Doença de Crohn/sangue , Doença de Crohn/diagnóstico , Fibrose/sangue , Fibrose/diagnóstico , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Adolescente , Biomarcadores/sangue , Criança , Pré-Escolar , Feminino , Humanos , Masculino
7.
Curr Cardiol Rep ; 22(6): 41, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32430626

RESUMO

PURPOSE OF REVIEW: Biomarkers of cardiac fibrosis closely track the disease state that gives rise to heart failure. The purpose of this review is to highlight recent data on the use of soluble ST2, galectin-3, and procollagen, three markers of cardiac fibrosis, for aiding with prognostication, and to explore the use of these biomarkers for guiding therapy. RECENT FINDINGS: Soluble ST2, galectin-3, and procollagen are prognostic in both acute and chronic heart failure, and data are emerging as to their potential uses for guiding therapies. Mortality benefit from exercise, cardiac resynchronization therapy, statin use, as well as anti-fibrotic therapies such as aldosterone antagonism may vary based upon levels of these fibrosis markers. Soluble ST2, galectin-3, and procollagen provide independent prognostic information for heart failure morbidity and mortality. Markers of cardiac fibrosis may also help identify the subsets of patients who are most likely to benefit from various therapies. However, further studies are needed prior to formalizing individual patient care algorithms guided by fibrosis biomarkers.


Assuntos
Fibrose/diagnóstico , Galectina 3/sangue , Insuficiência Cardíaca/diagnóstico , Proteína 1 Semelhante a Receptor de Interleucina-1/sangue , Pró-Colágeno/sangue , Biomarcadores/sangue , Fibrose/sangue , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/etiologia , Humanos , Valor Preditivo dos Testes , Prognóstico
8.
Open Heart ; 7(1): e001041, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32341786

RESUMO

Objective: This study aims to investigate the time-dependent prognostic utility of two fibrosis markers representing organ fibrogenesis (N-terminal propeptide of procollagen III (PIIINP) and type IV collagen 7S (P4NP 7S)) in patients with acute heart failure (HF). Methods: 390 patients with acute HF were dichotomised based on the median value of fibrosis markers at discharge. The primary outcome measure was a composite of cardiac death and HF hospitalisation. Results: P4NP 7S significantly declined during hospitalisation, whereas PIIINP did not. The cumulative 90-day and 365-day incidence of the primary outcome measure was 16.6% vs 16.0% (p=0.42) and 33.3% vs 28.4% (p=0.34) in the patients with high versus low PIIINP; 19.9% vs 13.0% (p=0.04) and 32.3% vs 29.0% (p=0.34) in the patients with high and low P4NP 7S, respectively. After adjusting for confounders, high P4NP 7S correlated with significant excess risk relative to low P4NP 7S for both 90-day and 365-day primary outcome measure (adjusted HR, 1.50; 95% CI, 1.02 to 2.21; p=0.04 and adjusted HR, 1.89; 95% CI, 1.11 to 3.26; p=0.02, respectively), which was driven by significant association of high P4NP 7S with higher incidence of HF hospitalisation. Furthermore, P4NP 7S exhibited an additive value to conventional prognostic factors for predicting 90-day outcome (p=0.038 for net reclassification improvement; p=0.0068 for integrated discrimination improvement). High PIIINP did not correlate with significant excess risk for both 90-day and 365-day outcome. Conclusions: This study suggests a possible role of P4NP 7S in the risk stratification of patients with acute HF.


Assuntos
Colágeno Tipo IV/sangue , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/diagnóstico , Miocárdio/metabolismo , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Causas de Morte , Feminino , Fibrose , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Hospitalização , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo
9.
J Bone Miner Metab ; 38(4): 501-510, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32140785

RESUMO

INTRODUCTION: High-turnover bone disease is a major consequence of SHPT and may explain the high risk for fracture in patients with advanced chronic kidney disease (CKD). Bisphosphonates suppress bone turnover and improve bone strength, but their effects have not been fully characterized in advanced CKD with severe SHPT. Bisphosphonates also increase 1,25-dihydroxyvitamin D levels in normal and uremic rats, but the underlying mechanism remains to be determined. MATERIALS AND METHODS: We investigated the skeletal and mineral metabolic effects of RIS, a pyridinyl bisphosphonate, in rats with severe SHPT induced by 5/6 nephrectomy plus a high phosphate diet. RESULTS: Nephrectomized rats developed severe SHPT, along with hyperphosphatemia, low 1,25-dihydroxyvitamin D, and markedly increased FGF23. Moreover, these rats exhibited characteristic features of high-turnover renal osteodystrophy, including increased indices of trabecular bone turnover, decreased cortical bone thickness, inferior cortical biomechanical properties, and a prominent increase in peritrabecular fibrosis. RIS treatment increased bone volume and partially attenuated trabecular bone remodeling, cortical bone loss, and mechanical properties, whereas it produced a marked improvement in peritrabecular fibrosis along with a corresponding decrease in osteogenic gene markers. RIS treatment also suppressed the elevation of FGF23, which was associated with increased 1,25-dihydroxyvitamin D. CONCLUSIONS: In a rat model of severe SHPT, treatment with RIS partially attenuated histological manifestations of high-turnover bone disease. RIS treatment also suppressed the elevation of FGF23, which may explain the increased 1,25-dihydroxyvitamin D production during the treatment.


Assuntos
Remodelação Óssea , Osso e Ossos/patologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/tratamento farmacológico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/fisiopatologia , Minerais/metabolismo , Ácido Risedrônico/uso terapêutico , Animais , Fenômenos Biomecânicos , Nitrogênio da Ureia Sanguínea , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/fisiopatologia , Cálcio/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Creatinina/sangue , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Nefrectomia , Fragmentos de Peptídeos/sangue , Fósforo/sangue , Pró-Colágeno/sangue , Ratos Sprague-Dawley , Ácido Risedrônico/farmacologia
10.
J Cardiovasc Magn Reson ; 22(1): 13, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-32036784

RESUMO

BACKGROUND: Using cardiovascular magnetic resonance imaging (CMR), it is possible to detect diffuse fibrosis of the left ventricle (LV) in patients with atrial fibrillation (AF), which may be independently associated with recurrence of AF after ablation. By conducting CMR, clinical, electrophysiology and biomarker assessment we planned to investigate LV myocardial fibrosis in patients undergoing AF ablation. METHODS: LV fibrosis was assessed by T1 mapping in 31 patients undergoing percutaneous ablation for AF. Galectin-3, coronary sinus type I collagen C terminal telopeptide (ICTP), and type III procollagen N terminal peptide were measured with ELISA. Comparison was made between groups above and below the median for LV extracellular volume fraction (ECV), followed by regression analysis. RESULTS: On linear regression analysis LV ECV had significant associations with invasive left atrial pressure (Beta 0.49, P = 0.008) and coronary sinus ICTP (Beta 0.75, P < 0.001), which remained significant on multivariable regression. CONCLUSION: LV fibrosis in patients with AF is associated with left atrial pressure and invasively measured levels of ICTP turnover biomarker.


Assuntos
Fibrilação Atrial/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Função Ventricular Esquerda , Remodelação Ventricular , Adulto , Idoso , Fibrilação Atrial/sangue , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/cirurgia , Função do Átrio Esquerdo , Pressão Atrial , Biomarcadores/sangue , Ablação por Cateter , Colágeno Tipo I/sangue , Técnicas Eletrofisiológicas Cardíacas , Feminino , Fibrose , Galectina 3/sangue , Ventrículos do Coração/metabolismo , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Valor Preditivo dos Testes , Pró-Colágeno/sangue
11.
J Cardiovasc Pharmacol ; 75(3): 250-258, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31895871

RESUMO

Heart failure (HF) is highly prevalent and a major cause of death in the United States. The effect of HF medications on survival has been predicted by validated models studied in populations predominantly of European descent. This study aimed to identify medications associated with survival in a racially diverse HF population. Patients with HF were recruited and followed from 2001 to 2015. Data were collected from electronic health records and the Social Security Death Index. The primary analysis tested the association between medication dose and all-cause mortality, with a secondary analysis assessing the composite outcome of death or cardiac-related hospitalization. Circulating concentration of the fibrotic marker procollagen type III N-terminal peptide (PIIINP) was also compared with medication doses in patients with concentrations available. The study population consisted of 337 patients, of which 25.2% died and 46% were hospitalized. Increased beta-blocker (BB) dose was significantly associated with survival in the base model [hazard ratio (HR) = 0.71, P = 0.017] and marginally associated in the comprehensive model (HR = 0.75, P = 0.068). BB dose was also associated with decreased risk of the composite end point in the base model (HR = 0.80, P = 0.029) and to a lesser extent in the comprehensive model (HR = 0.83, P = 0.085). Furthermore, increased BB dose was inversely associated with circulating PIIINP concentration (P = 0.041). In conclusion, our study highlights the importance of BB dose escalation for survival and decreased hospitalization in patients with HF, regardless of race or HF type. It also suggests that benefits observed with high-dose BBs could be mediated, at least in part, by decreased cardiac fibrosis.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Antagonistas Adrenérgicos beta/efeitos adversos , Idoso , Biomarcadores/sangue , Causas de Morte , Chicago/epidemiologia , Feminino , Fibrose , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etnologia , Insuficiência Cardíaca/mortalidade , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Prevalência , Pró-Colágeno/sangue , Fatores de Proteção , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
12.
Maturitas ; 132: 24-29, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31883659

RESUMO

OBJECTIVE: To evaluate trabecular bone score (TBS) in Spanish postmenopausal women from our area. To analyze its relationship with bone mineral density (BMD), bone quantitative ultrasound (QUS) and serum concentrations of 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone (PTH) and bone turnover markers. STUDY DESIGN: A total of 1450 postmenopausal women aged 44-94 (62 ± 10) participated in this cross-sectional study nested in a population-based cohort. BMD and TBS were assessed by DXA. QUS measurements were performed using a Sahara Clinical Sonometer. Serum 25(OH)D, PTH, P1NP, ß-CTX were determined by electrochemiluminescence. RESULTS: Mean TBS of postmenopausal women in our region was 1.341 ± 0.111. Nearly 50 % of them had normal values. Only 11 % had scores compatible with a clearly degraded microarchitecture. TBS decreased with age, correlated negatively with BMI and was lower in current smokers than in non-smokers. An association was observed between TBS and QUS, although the association was weak and lower than that found between TBS and BMD or QUS and BMD. No association was found between TBS and 25(OH)D, PTH or bone turnover markers. CONCLUSIONS: Half of postmenopausal women in our region have TBS values that indicate a preserved microarchitecture. Only about 10 % have scores compatible with a clearly degraded microarchitecture. A weak association was observed between TBS and QUS, suggesting that the two techniques capture different aspects of bone microarchitecture. The absence of association with 25(OH)D, PTH, and bone turnover markers may be due to the fact that TBS assesses a specific (mostly trabecular) part of the skeleton, whilst the three serum factors are related to the whole skeleton.


Assuntos
Densidade Óssea , Osso Esponjoso/diagnóstico por imagem , Pós-Menopausa , Absorciometria de Fóton , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Colágeno Tipo I/sangue , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Pós-Menopausa/sangue , Pró-Colágeno/sangue , Espanha , Ultrassonografia , Vitamina D/análogos & derivados , Vitamina D/sangue
13.
Appl Physiol Nutr Metab ; 45(1): 91-100, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31652407

RESUMO

Exercise combined with protein and calcium has been shown to benefit bone turnover and bone metabolism. Greek yogurt (GY) contains important nutrients that support bone but has yet to be studied with exercise for this purpose. Thirty untrained, university-aged, males were randomized to 2 groups (n = 15/group): GY (20 g protein, 208 mg calcium/dose) or placebo pudding (PP; 0 g protein, 0 g calcium/dose) consumed 3×/day on training days and 2×/day on nontraining days. Both groups underwent a resistance/plyometric training program for 12 weeks. Blood was obtained at weeks 0, 1, and 12 to measure procollagen-type-I-N-terminal-propeptide (P1NP) and C-terminal-telopeptide (CTX). After outlier treatment, P1NP increased more over time in GY versus PP (p = 0.002; interaction). Both groups decreased CTX over time (p = 0.046; time effect). Following 1 week of training, there was a trend towards a significant increase in CTX in PP with no change in GY (p = 0.062; interaction). P1NP changed more in GY than PP (baseline to week 12; p = 0.029) as did the P1NP/CTX ratio (p = 0.015) indicating a greater increase in formation with GY. Thus, GY added to a high-load, high-impact exercise program positively shifted bone turnover towards increased formation while attenuating resorption. GY could be a plausible postexercise food to support bone health in young adult males. Novelty Greek yogurt, with exercise, increased bone formation in young adult males over 12 weeks. After 1 week of an osteogenic exercise program, Greek yogurt tended to blunt a rise in bone resorption seen with the placebo. Greek yogurt is a plausible postexercise food that supports bone.


Assuntos
Remodelação Óssea/fisiologia , Dieta , Exercício Físico/fisiologia , Iogurte , Adolescente , Adulto , Biomarcadores/sangue , Terapia por Exercício , Humanos , Masculino , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Treinamento de Força , Adulto Jovem
14.
J Orthop Res ; 38(1): 82-91, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31441073

RESUMO

To evaluate the effect of local parathyroid hormone (PTH) administration on rotator cuff tendon-to-bone healing in a rat model compared with systemic PTH injection and untreated controls. PTH-alginate scaffold was prepared and sustained release of PTH was confirmed. Bilateral supraspinatus tendon repairs were performed in 39 rats (group 1, supraspinatus repair only; group 2, supraspinatus repair with systemic PTH injection; group 3, supraspinatus repair with local PTH administration via an absorbable scaffold; n = 13 each). Biomechanical (cross-sectional area, mode of failure, load to failure, and ultimate stress: right side) and histological analyses (hematoxylin and eosin stain, Masson's Trichrome stain Picrosirius red stain, Immunohistochemistry for BMP2, PTH1R, ColI, and ColIII: Left side) were performed to evaluate tendon-to-bone healing quality at 8 weeks after repair, and blood test (osteocalcin and procollagen type I N-terminal pro-peptide [PINP] levels) was performed in all rats. There was no intergroup difference in the healing failure rate (p = 0.910) or failure mode (p = 0.585). Biomechanically, subjects in groups 2 and 3 exhibited significantly larger cross-sectional areas and higher ultimate failure loads and ultimate stress than those in group 1 (all p < 0.05); however, no differences were noted between groups 2 and 3 (all p > 0.05). Histologically, groups 2 and 3 exhibited more organized tendon-to-bone interface structures with higher density, parallel orientation, and collagen fiber continuity than group 1 (all p < 0.05 except collagen fiber continuity in group 1 vs. 2); however, no differences in histological parameters between groups 2 and 3 (all p > 0.05). The protein levels of bone morphogenic protein 2, PTH 1 receptor, and collagen I and III and the serum level of PINP were increased in groups 2 and 3 versus group 1 (all p < 0.05) without showing differences between groups 2 and 3 (all p > 0.05). Local PTH administration using an absorbable scaffold improved the biomechanical and histological outcomes of rotator cuff tendon-to-bone healing comparable with systemic PTH injection at 8 weeks after repair in a rat model. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:82-91, 2020.


Assuntos
Osso e Ossos/fisiopatologia , Hormônio Paratireóideo/administração & dosagem , Lesões do Manguito Rotador/cirurgia , Manguito Rotador/fisiopatologia , Tendões/fisiopatologia , Cicatrização/efeitos dos fármacos , Animais , Fenômenos Biomecânicos , Osso e Ossos/patologia , Imuno-Histoquímica , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Ratos , Ratos Sprague-Dawley , Lesões do Manguito Rotador/tratamento farmacológico , Lesões do Manguito Rotador/patologia , Lesões do Manguito Rotador/fisiopatologia , Tendões/patologia
15.
AIDS Care ; 32(8): 984-993, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-31137948

RESUMO

There are limited studies regarding bone health among people living with HIV (PLHIV) in Asia. We compared bone mineral density (BMD), serum 25-hydroxyvitamin D (25(OH)D) status and bone turnover markers (serum procollagen type1 N-terminal propeptide (P1NP), osteocalcin (OC) and C-terminal cross-linking telopeptide of type1 collagen) among 302 antiretroviral therapy (ART) naive PLHIV compared to 269 HIV-uninfected controls from Thailand. People aged ≥30 years, with and without HIV infection (free of diabetes, hypertension, and active opportunistic infection) were enrolled. BMD at the lumbar spine, total hip, and femoral neck were measured using Hologic DXA at baseline and at 5 years. We analyzed BMD, serum 25(OH)D levels, and bone turnover markers at the patients' baseline visit. PLHIV were 1.5 years younger and had lower BMI. PLHIV had higher mean serum 25(OH)D level and similar BMD to the controls. Interestingly, PLHIV had significantly lower bone formation (serum P1NP and OC), particularly those with low CD4 count. Only a few participants had low bone mass. ARV naïve middle-aged PLHIV did not have lower BMD or lower vitamin D levels compared to the controls. However, PLHIV had lower bone formation markers, particularly those with low CD4 count. This finding supports the benefit of early ART.


Assuntos
Biomarcadores/sangue , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Infecções por HIV/diagnóstico , Osteogênese/efeitos dos fármacos , Vitamina D/análogos & derivados , Absorciometria de Fóton , Adulto , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais , Estudos de Casos e Controles , Colágeno Tipo I/sangue , Feminino , Colo do Fêmur/diagnóstico por imagem , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Articulação do Quadril/diagnóstico por imagem , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Osteocalcina/sangue , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Pró-Colágeno/sangue , Estudos Prospectivos , Tailândia/epidemiologia , Vitamina D/sangue
16.
Clin Res Cardiol ; 109(2): 194-204, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31250134

RESUMO

INTRODUCTION: After myocardial infarction complicated by heart failure or diabetes, eplerenone (compared to placebo) significantly decreases amino-terminal propeptide of type III procollagen (PIIINP). Determining the subset of patients who are more prone to have a decrease in PIIINP and those who may respond better to the anti-fibrotic effects of mineralocorticoid receptor antagonists (MRA) therapy may be relevant for a personalized treatment approach. The aim of this study is to identify predictors of a PIIINP decrease and assess potential subgroups of "responders" to eplerenone. METHODS: Clinical factors and biomarkers were evaluated as predictors of a PIIINP decrease from randomization to month 9 in 323 patients from the biomarker substudy of Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Additionally, the association between PIIINP decrease and the composite of cardiovascular (CV) death or CV hospitalization were also explored. External validation was performed in the REMINDER trial. RESULTS: Female sex, eplerenone, reperfusion therapy, potassium < 4 mmol/L, circulating levels of PIIINP ≥ 3.6 ng/mL and PINP ≥ 27 ng/mL predicted a PIIINP decrease (AUC = 0.75). Randomization PIIINP showed a significant interaction with the treatment allocation: patients with PIIINP ≥ 3.6 ng/mL had a better response (decrease in PIIINP) to eplerenone (OR for PIIINP ≥ 3.6 = 2.9, 95% CI 1.46-5.89, p = 0.003) and OR for PIIINP < 3.6 = 1.09, 95% CI 0.55-2.2, p = 0.8; interactionp = 0.026). These findings were internally robust using another statistical approach (LOESS). External validation showed good discrimination (AUC = 0.70). There was a tendency toward a lower rate of CV death/CV hospitalizations in patients with decreased PIIINP (adjusted HR = 0.52, 95% CI 0.26-1.02, p = 0.058). CONCLUSION: In patients who had a myocardial infarction, clinical factors used in combination and treatment with eplerenone were associated with a PIIINP decrease. Interestingly, higher randomization PIIINP levels might help in identifying patients more prone to have an "anti-fibrotic response" when treated with MRAs. Predictors of an antifibrotic response after MI complicated by HF. Several clinical factors and biomarkers predicted a PIIINP decrease after an MI complicated by HF. There was a significant interaction between baseline PIIINP levels and eplerenone treatment: patients with baseline PIIINP ≥ 3.6 mmol/L treated with eplerenone had the best response (PIIINP decrease).


Assuntos
Eplerenona/uso terapêutico , Insuficiência Cardíaca/prevenção & controle , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Miocárdio/patologia , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Remodelação Ventricular/efeitos dos fármacos , Idoso , Biomarcadores/sangue , Tomada de Decisão Clínica , Eplerenona/efeitos adversos , Feminino , Fibrose , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Seleção de Pacientes , Fragmentos de Peptídeos/sangue , Valor Preditivo dos Testes , Pró-Colágeno/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Infarto do Miocárdio com Supradesnível do Segmento ST/patologia , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
17.
Nutr J ; 18(1): 82, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791333

RESUMO

BACKGROUND: Deficient and insufficient vitamin D status (defined as serum 25(OH)D < 30 nmol/L and > 50 nmol/L) is prevalent worldwide and associated with decreased muscle strength and poor bone health. We aimed to investigate the effect of vitamin D fortification on bone markers and muscle strength among younger adult women at risk of vitamin D deficiency. METHODS: A 12-week randomised double-blinded placebo-controlled winter intervention trial, providing 30 µg vitamin D3/day through fortified yoghurt, cheese, eggs and crisp-bread or similar placebo products. Participants were 143 women of Danish and Pakistani origin 18-50 years of age, living in Denmark, randomised into four groups stratified by ethnicity. Serum 25-hydroxyvitamin D (25(OH)D) by LC-MS/MS and the secondary endpoints: four specific bone markers (osteocalcin (OC), Bone specific Alkaline Phosphatase (BALP), Procollagen type 1 amino-terminal propeptide (P1NP), C-terminal crosslinked telopeptide of type 1 collagen (CTX)) and three muscle strength measures (handgrip, knee extension strength, chair-standing), were assessed using one-way ANOVA, Tukey HSD and subsequent linear ANCOVA models, adjusted for relevant covariates. RESULTS: Significantly increased serum 25(OH)D concentration from 53.3 (17) to 77.8 (14) nmol/L and from 44.5 (21) to 54.7 (18) nmol/L among Danish and Pakistani women in the fortified groups, respectively (P <  0.05). The bone turnover markers OC, BALP, P1NP and CTX did not change significantly. Muscle strength by handgrip, knee extension and chair-standing test did not change significantly following the intervention. CONCLUSIONS: Consumption of vitamin D fortified foods for 12 weeks did not result in significant changes of the bone turnover markers OC, BALP, P1NP and CTX. Muscle strength measured as hand grip strength, knee extension strength and chair-standing did not change significantly following the intervention.


Assuntos
Fosfatase Alcalina/sangue , Colágeno Tipo I/sangue , Alimentos Fortificados , Força Muscular , Osteocalcina/sangue , Vitamina D/administração & dosagem , Vitamina D/sangue , Adolescente , Adulto , Biomarcadores/sangue , Remodelação Óssea , Dinamarca , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Paquistão , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Vitaminas/administração & dosagem , Vitaminas/sangue , Adulto Jovem
18.
Artigo em Inglês | MEDLINE | ID: mdl-31877849

RESUMO

Introduction: The purpose of this study was to analyze the relationship between the parameters of bone turnover and the levels of hormonal parameters, such as total testosterone (TT), bioavailable and free testosterone (FT), and estradiol (E2) in men. Material and methods: The study group included 63 men with testosterone deficiency syndrome (TDS). The control group consisted of 112 patients without TDS. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of osteocalcin (OC), parathyroid hormone (PTH), E2, sex hormone binding globulin (SHBG), dehydroepiandrosterone sulphate (DHEAS), insulin (I), Serum CrossLaps (CtX-I), human procollagen I N-terminal peptide (PINP), and TT. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Results: The groups with TSD and without TDS differed in terms of the following parameters: body weight (p = 0.001), BMI (p = 0.003), TT (p = 0.001), FT (p = 0.004), bioavailable testosterone (p = 0.001), E2 (p = 0.003), SHBG (p = 0.003), and PINP (p = 0.004). In the group without TDS, higher PINP levels were accompanied by higher levels of E2 (beta = 0.360, p = 0.002) and TT (beta = 0.389, p = 0.001). In the group without TDS, PINP was positively correlated with E2 (beta = 0.726, p <0.001). Patients with TDS had significantly lower PINP levels (p < 0.004). Conclusions: Analysis of sex hormones and biochemical bone markers in reflecting the quality of the bone tissue in men may suggest a relationship between these parameters. Nevertheless, further research based on a larger sample size is necessary to better describe this relationship.


Assuntos
Androgênios/sangue , Remodelação Óssea , Osso e Ossos/metabolismo , Absorciometria de Fóton , Idoso , Envelhecimento/metabolismo , Biomarcadores/sangue , Densidade Óssea , Colágeno Tipo I , Sulfato de Desidroepiandrosterona/sangue , Estradiol/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fragmentos de Peptídeos/sangue , Peptídeos , Pró-Colágeno/sangue , Globulina de Ligação a Hormônio Sexual/metabolismo , Testosterona/sangue
19.
PLoS One ; 14(11): e0225539, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31765401

RESUMO

The balance between bone resorption and formation may be assessed by measurement of bone turnover markers (BTMs), like carboxyl-terminal cross-linked telopeptide of type 1 collagen (CTX-1) and procollagen type 1 amino-terminal propeptide (P1NP). Smoking has been shown to influence bone turnover and to reduce bone mass density (BMD), the exact mechanism for this is, however, not settled. In this post-hoc study including 406 subjects (mean age 51.9 years), we aimed to study the impact of smoking on bone turnover. Moreover, we wanted to assess the inter-correlation between substances regulating bone metabolism and BTMs, as well as tracking over time. BMD measurements and serum analyses of CTX-1, P1NP, osteoprotegerin (OPG), receptor activator of nuclear factor ĸB ligand (RANKL), Dickkopf-1 (DKK1), sclerostin, tumor necrosis factor-α (TNF-α), and leptin were performed. Repeated serum measurements were made in 195 subjects after four months. Adjustments were made for sex, age, body mass index (BMI), smoking status, insulin resistance, serum calcium, parathyroid hormone, 25-hydroxyvitamin D and creatinine. Smokers had higher levels of DKK1 and OPG, and lower levels of RANKL, as reflected in lower BTMs and BMD compared to non-smokers. There were strong and predominantly positive inter-correlations between BTMs and the other substances, and there was a high degree of tracking with Spearman's rho from 0.72 to 0.92 (P < 0.001) between measurements four months apart. In conclusion, smokers exhibited higher levels of DKK1 and OPG and a lower bone turnover than did non-smokers. The strong inter-correlations between the serum parameters illustrate the coupling between bone resorption and formation and crosstalk between cells.


Assuntos
Remodelação Óssea , Fumar , Adulto , Biomarcadores/sangue , Densidade Óssea , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Masculino , Pessoa de Meia-Idade , Osteoprotegerina/sangue , Hormônio Paratireóideo/sangue , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Ligante RANK/sangue , Vitamina D/análogos & derivados , Vitamina D/sangue
20.
Yonsei Med J ; 60(12): 1174-1180, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31769248

RESUMO

PURPOSE: Bone markers can be useful for the diagnosis and treatment of skeletal diseases in children and adolescents. Owing to high skeletal growth velocity and rapid bone turnover, children and adolescents have higher bone marker levels than adults. Thus, a valid age- and sex-specific reference should be established for pediatric populations living in similar environments. We aimed to assess the associations of procollagen type I N-terminal propeptide (P1NP) and osteocalcin with age and sex in a group of healthy Korean children and adolescents. MATERIALS AND METHODS: The participants (290 boys and 290 girls, age range 0-18 years) were Korean outpatients. Serum P1NP and osteocalcin levels were measured in control materials and patient samples by electrochemiluminescence immunoassay using an automated Cobas e411 analyzer. RESULTS: Significant age-dependent variations in bone marker levels were observed in both sexes (p<0.001). The highest P1NP levels were observed during the first year of life; thereafter, levels decreased until puberty. There was no postnatal peak for osteocalcin; however, its levels remained higher than the adult reference range throughout childhood. Significant differences were observed between boys and girls (p<0.05), especially between the ages of 12 and 17 years. Cobas e411 results for P1NP showed satisfactory precision and linearity. CONCLUSION: We established reference data for P1NP and osteocalcin levels in healthy Korean children and adolescents, as the first and only study of these parameters in pre-adulthood in Korea. Cobas e411-quantified bone markers may be useful for determining bone metabolism indices.


Assuntos
Osteocalcina/sangue , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Adolescente , Adulto , Biomarcadores/sangue , Remodelação Óssea , Osso e Ossos/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Valores de Referência , República da Coreia , Adulto Jovem
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