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1.
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
2.
Prague Med Rep ; 120(2-3): 84-94, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31586507

RESUMO

Ageing is associated with the accumulation of damage to all the macromolecules within and outside cells leading to progressively more cellular and tissue defects and resulting in age-related frailty, disability and disease. As a result of the aging process the bone deteriorates in composition, structure and function. Age-related musculoskeletal losses are a major public health burden because they can cause physical disability and increased mortality. We tried to find out on a small set of old women, without risk factors for osteoporosis, what caused them the loss of bone minerals. All 492 women had just only one risk factor - the old age. Laboratory findings have shown a decreased serum C telopeptide and low serum alkaline phosphatase circulating markers, used to quantify bone resorption and formation, and very low level of vitamin D. Very low level of vitamin D that disrupted calcium absorption through the intestine, and decreased calcemia increased parathyroid hormone levels with resulting bone effect. The manifestation of physiological aging is worsening eyesight, peripheral neuropathy, depression, worsening of physical condition, skin aging, sarcopenia and bone mineral loss. Senile osteoporosis, which is not caused by known risk factors for osteoporosis, does not appear to be a separate disease, but is part of the physiological process of aging. Treatment of senile osteoporosis should be focused on the control of secondary hyperparathyroidism by administration of vitamin D and calcium. The risk of fractures in the advanced age is determined by a large number of factors ranging from hazards in the home environment to frailty and poor balance.


Assuntos
Envelhecimento/sangue , Envelhecimento/patologia , Fosfatase Alcalina/sangue , Densidade Óssea , Cálcio/metabolismo , Colágeno Tipo I/sangue , Feminino , Humanos , Osteogênese , Osteoporose/sangue , Hormônio Paratireóideo/sangue , Peptídeos/sangue , Vitamina D/sangue
3.
Maturitas ; 129: 12-22, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31547908

RESUMO

OBJECTIVE: To systematically evaluate the effects of bone anabolic therapies (BATs) - specifically, drug therapy with teriparatide, abaloparatide or romosozumab - on fractures, bone mineral density (BMD), and bone metabolites in postmenopausal osteoporosis. METHODS: Six computerized engines were searched through to November 2018. We selected randomized controlled trials (RCTs) evaluating the effect of BATs on postmenopausal osteoporosis and with at least 6 months of follow-up. Controls were placebo, no treatment, or bisphosphonates. Primary outcomes were vertebral and non-vertebral fractures. Secondary outcomes were: BMD determined by dual energy X-ray absorptiometry at total hip, lumbar spine, and femoral neck; N-terminal propeptide of type I procollagen (PINP); C-terminal telopeptide of type I collagen (CTX); and severe adverse events (SAE). We followed the PRISMA guidelines for reporting, and used version 2 of the Cochrane risk-of-bias tool. Frequentist network meta-analyses were performed per outcome. Effects for dichotomous and continuous outcomes were expressed as relative risks and mean differences and their 95% confidence intervals. We used p-scores to rank best treatments per outcome. RESULTS: Sixteen RCTs (n = 18,940) were evaluated. Mean ages ranged between 61 and 74 years, and follow-up times between 6 and 30 months. Four RCTs (n = 971) excluded patients with previous fractures. In contrast to placebo/no treatment, all BATs significantly reduced the risk of vertebral fractures, but no intervention significantly reduced the risk of non-vertebral fractures; abaloparatide ranked better than other interventions for both fracture types (p-scores: 0.95, and 0.89, respectively). All BATs significantly increased BMD at all locations in comparison with placebo/no treatment; romosozumab consistently ranked better than other interventions at all BMD locations (p-scores >0.86). Teriparatide ranked better than other interventions for increasing PINP. No differences in SAE were observed among treatments. CONCLUSIONS: Abaloparatide, romosozumab, and teriparatide are the best treatments, respectively, to reduce vertebral/non-vertebral fractures, increase BMD, and increase bone formation.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Proteína Relacionada ao Hormônio Paratireóideo/uso terapêutico , Teriparatida/uso terapêutico , Anticorpos Monoclonais/farmacologia , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/farmacologia , Colágeno Tipo I/sangue , Feminino , Humanos , Metanálise em Rede , Osteoporose Pós-Menopausa/sangue , Proteína Relacionada ao Hormônio Paratireóideo/farmacologia , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Pró-Colágeno/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Teriparatida/farmacologia
4.
Nutrients ; 11(7)2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31261978

RESUMO

Type 2 diabetes increases bone fracture risk in postmenopausal women. Usual treatment with anti-resorptive bisphosphonate drugs has some undesirable side effects, which justified our interest in the osteogenic potential of nutrition and exercise. Since meal eating reduces bone resorption, downhill locomotion increases mechanical stress, and brief osteogenic responsiveness to mechanical stress is followed by several hours of refractoriness, we designed a study where 40-min of mechanical stress was manipulated by treadmill walking uphill or downhill. Exercise preceded or followed two daily meals by one hour, and the meals and exercise bouts were 7 hours apart. Fifteen subjects each performed two of five trials: No exercise (SED), uphill exercise before (UBM) or after meals (UAM), and downhill exercise before (DBM) or after meals (DAM). Relative to SED trial, osteogenic response, defined as the ratio of osteogenic C-terminal propeptide of type I collagen (CICP) over bone-resorptive C-terminal telopeptide of type-I collagen (CTX) markers, increased in exercise-after-meal trials, but not in exercise-before-meal trials. CICP/CTX response rose significantly after the first exercise-after-meal bout in DAM, and after the second one in UAM, due to a greater CICP rise, and not a decline in CTX. Post-meal exercise, but not the pre-meal exercise, also significantly lowered serum insulin response and homeostatic model (HOMA-IR) assessment of insulin resistance.


Assuntos
Remodelação Óssea , Diabetes Mellitus Tipo 2/terapia , Terapia por Exercício , Fraturas Ósseas/prevenção & controle , Refeições , Osteogênese , Idoso , Biomarcadores/sangue , Colágeno Tipo I/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Feminino , Fraturas Ósseas/sangue , Fraturas Ósseas/etiologia , Fraturas Ósseas/fisiopatologia , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/sangue , Resistência à Insulina , Pessoa de Meia-Idade , Valor Nutritivo , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Pós-Menopausa/sangue , Período Pós-Prandial , Pró-Colágeno/sangue , Fatores de Tempo , Resultado do Tratamento
5.
Artigo em Inglês | MEDLINE | ID: mdl-31337049

RESUMO

The purpose of this study was to analyze the influence of aqua fitness training in deep water on bone tissue. The study was performed with 18 postmenopausal women separated into two groups: training and control groups. Before and after the training program, the hip and spine areal bone mineral density were measured along with the biochemical parameters of serum concentration of osteocalcin (OC) and C-terminal telopeptide of type I collagen (CTX). The most significant effect was found in differences between the two groups of women in terms of femur strength index (p < 0.05) during the period of the training program. The study demonstrated that an aqua fitness training program caused favorable changes in femur strength index in postmenopausal women, and this kind of exercise could be a useful form of physical activity for postmenopausal women.


Assuntos
Densidade Óssea , Remodelação Óssea , Exercício Físico , Osteoporose Pós-Menopausa/sangue , Pós-Menopausa/sangue , Biomarcadores/sangue , Osso e Ossos/metabolismo , Colágeno Tipo I/sangue , Feminino , Fêmur , Humanos , Pessoa de Meia-Idade , Osteocalcina/sangue
6.
J Med Food ; 22(10): 982-992, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31194598

RESUMO

Osteoporosis and cardiovascular disease are global health burdens, with postmenopausal women being at great risk. Dried plums/prunes (DPs) have been reported to provide bone health benefits in animal models, which is consistent with in vitro models. Data from human studies suggest that DP intake can enhance lipid metabolism, anti-inflammatory, and oxidant defense systems, which can impact cardiovascular health. We tested the hypothesis that short-term consumption of low and reasonable levels of DPs augments bone resorption and vascular function. Twenty-seven healthy, postmenopausal women were randomly assigned to consume six DPs (∼42 g) or two DPs (∼14 g) per day for 2 weeks, then a 2-week washout period and then crossed over. Serum C-telopeptide, beta-crosslinked (CTX) was used as a measure of bone resorption. Peripheral artery tonometry (PAT) was used to assess microvascular function. The pattern of changes in CTX in the second 2-week period (no change or decline) differed significantly from the pattern in the first 2 weeks (increases in both groups; F = 9.26, P = .006), suggesting a trend in CTX reduction (i.e., a decrease in bone resorption) in those consuming six DPs per day in the second phase. No effects on vascular function were noted. A significant interaction was observed for the augmentation index, a measure of arterial stiffness, between treatment and years after menopause (P = .045). The results suggest a potentially favorable impact of DPs on bone health when assessed with a short-term, crossover study design in postmenopausal women. Given the novel assessments used in this study, follow-up studies are warranted.


Assuntos
Reabsorção Óssea , Colágeno Tipo I/sangue , Frutas , Peptídeos/sangue , Prunus domestica , Rigidez Vascular , Idoso , Glicemia/análise , Pressão Sanguínea , Estudos Cross-Over , Feminino , Humanos , Lipídeos/sangue , Manometria , Pessoa de Meia-Idade , Pós-Menopausa
7.
J Anim Sci ; 97(8): 3300-3312, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31231753

RESUMO

Previous research has determined that maintaining young animals in stalls is detrimental to their bone health, while the addition of 50 to 82-m sprints 5 d/week aids in counteracting the reduction of bone strength from confinement. The current research aims to determine if 1 or 3 d/week of sprinting affords the same benefits to bone as 5 d/week of sprinting compared to animals confined with no sprinting. Twenty-four Holstein bull calves were obtained from the Michigan State University Dairy Cattle Teaching and Research Center. At 9 wk of age, calves were randomly assigned to treatments of 1, 3, or 5 d/week of sprint exercise, or to the confined control group sprinted 0 d/week. Each treatment had 6 calves. Individual sprinting bouts included a single sprint down a 71-m concrete aisle. For the duration of the 6-wk study, calves were housed at the MSU Beef Cattle Teaching and Research Center in stalls which afforded calves room to stand, lay down, and turn around. Serum was collected weekly via jugular venipuncture to obtain concentrations of osteocalcin (OC) and C-telopeptide crosslaps of type I collagen (CTX-1)-markers of bone formation and degradation, respectively. Sprints were videotaped weekly to determine stride frequency and sprint velocity. On day 42, calves were humanely euthanized at the Michigan State University Meat Lab and both front limbs were immediately harvested. Computed tomography scans and mechanical testing were performed on the left fused third and fourth metacarpal bones. Serum OC concentration was greatest for calves sprinted 5 d/week (P < 0.001). Calves sprinted 5 d/week had both greater stride frequency (P < 0.05) and lower sprint velocity (P < 0.05). All exercise treatments experienced greater dorsal cortical widths compared to control animals (P < 0.01). Through mechanical testing, fracture forces of all sprinting treatments were determined to be greater than the control treatment (P < 0.02). Results from this study support that sprinting 1, 3, or 5 d/week during growth can increase bone health and cause favorable alterations in bone markers. While all exercise treatments had over a 20% increase to fracture force, calves sprinted 1 d/week sprinted only 426 m over the 6-wk study and still experienced over a 20% increase in bone strength compared to confined calves. This study demonstrates the remarkably few strides at speed needed to enhance bone strength and emphasizes the danger to skeletal strength if sprinting opportunities are not afforded.


Assuntos
Cavalos/fisiologia , Animais , Biomarcadores/sangue , Reabsorção Óssea/fisiopatologia , Osso e Ossos/fisiologia , Bovinos , Colágeno Tipo I/sangue , Masculino , Osteocalcina/sangue , Osteogênese/fisiologia , Condicionamento Físico Animal , Distribuição Aleatória
8.
Fertil Steril ; 112(2): 362-370, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31227287

RESUMO

OBJECTIVE: To study the effects of metformin treatment on bone turnover in women with polycystic ovary syndrome (PCOS), as measured by serum concentrations of bone turnover markers. DESIGN: Post hoc study of a previously conducted prospective multicenter, placebo-controlled, randomized study. SETTING: University clinic. PATIENT(S): The study cohort consisted of 74 non-obese women (body mass index < 27 kg/m2) and 44 obese women (body mass index ≥ 27 kg/m2) diagnosed with PCOS, with a mean age of 27.6 ± 4.0 (SD) years. INTERVENTION(S): Randomization to receive metformin or placebo for 3 months. MAIN OUTCOME MEASURE(S): Serum levels of bone formation marker procollagen type I amino-terminal propeptide (PINP) and bone resorption marker carboxy-terminal cross-linking telopeptide of type I collagen (CTX) at baseline and after metformin/placebo treatment. RESULT(S): Serum levels of PINP and CTX were similar between the metformin and placebo groups at baseline in the whole study population. Obese women, when compared with non-obese, had lower baseline levels of PINP and CTX. Levels of PINP and CTX were significantly reduced in the whole study population, as well as in both non-obese and obese women after 3 months of metformin treatment, whereas no significant changes were observed in the placebo group. CONCLUSION(S): Metformin treatment, when compared with placebo, was associated with reduced bone turnover, as suggested by reductions in markers of bone formation and resorption, leading to slower bone remodeling in premenopausal women with PCOS. CLINICAL TRIAL REGISTRATION NUMBER: NCT00994812.


Assuntos
Biomarcadores/sangue , Remodelação Óssea/efeitos dos fármacos , Metformina/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Adulto , Densidade Óssea/efeitos dos fármacos , Colágeno Tipo I/sangue , Feminino , Humanos , Metformina/farmacologia , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Placebos , Síndrome do Ovário Policístico/sangue , Pró-Colágeno/sangue , Estudos Retrospectivos , Adulto Jovem
9.
Osteoporos Int ; 30(9): 1755-1765, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31227885

RESUMO

The relationships of osteocalcin (OC) and C-telopeptide of type I collagen (CTX) with long-term incidence of hip fracture were examined in 1680 post-menopausal women from a population-based study. CTX, but not OC, levels were associated with incident hip fracture in these participants, a relationship characterized by an inverted U-shape. INTRODUCTION: We sought to investigate the relationships of OC, a marker of bone formation, and CTX, a marker of bone resorption, with long-term incidence of hip fracture in older women. METHODS: We included 1680 women from the population-based Cardiovascular Health Study (mean [SD] age 74.5 [5.0] years). The longitudinal association of both markers with incidence of hip fracture was examined using multivariable Cox models. RESULTS: During a median follow-up of 12.3 years, 288 incident hip fractures occurred. Linear spline analysis did not demonstrate an association between OC levels and incident hip fracture. By contrast, increasing levels of CTX up to the middle-upper range were associated with a significantly greater risk of hip fracture (HR = 1.52 per SD increment, 95% CI = 1.10-2.09), while further increases were associated with a marginally non-significant lower risk (HR = 0.80 per SD increment, 95% CI = 0.63-1.01), after full adjustment for potential confounders. In analyses of quartiles, CTX exhibited a similar inverted U-shaped relationship with incident fracture after adjustment, with a significant association observed only for the comparison of quartile 3 to quartile 1 (HR = 1.63, 95% CI = 1.10-2.43). In a subset with available measures, both OC and CTX were inversely associated with bone mineral density of the hip. CONCLUSION: CTX, but not OC, levels were associated with incident hip fracture in post-menopausal women, a relationship characterized by an inverted U-shape. These findings highlight the complex relationship of bone turnover markers with hip fracture risk.


Assuntos
Remodelação Óssea/fisiologia , Fraturas do Quadril/fisiopatologia , Osteoporose Pós-Menopausa/fisiopatologia , Fraturas por Osteoporose/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Densidade Óssea/fisiologia , Colágeno Tipo I/sangue , Feminino , Seguimentos , Fraturas do Quadril/sangue , Fraturas do Quadril/epidemiologia , Humanos , Incidência , Estilo de Vida , Osteocalcina/sangue , Osteoporose Pós-Menopausa/sangue , Osteoporose Pós-Menopausa/epidemiologia , Fraturas por Osteoporose/sangue , Fraturas por Osteoporose/epidemiologia , Peptídeos/sangue , Desempenho Físico Funcional , Medição de Risco/métodos , Estados Unidos/epidemiologia
10.
Nutrients ; 11(6)2019 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-31234587

RESUMO

The diurnal rhythm of bone remodeling suggests nocturnal dietary intervention to be most effective. This study investigated the effect of bedtime ingestion of a calcium-fortified, milk-derived protein matrix (MBPM) or maltodextrin (CON) on acute (0-4 h) blood and 24-h urinary change in biomarkers of bone remodeling in postmenopausal women with osteopenia. In CON, participants received 804 ± 52 mg calcium, 8.2 ± 3.2 µg vitamin D and 1.3 ± 0.2 g/kg BM protein per day. MBPM increased calcium intake to 1679 ± 196 mg, vitamin D to 9.2 ± 3.1 µg and protein to 1.6 ± 0.2 g/kg BM. Serum C-terminal cross-linked telopeptide of type I collagen (CTX) and procollagen type 1 amino-terminal propeptide (P1NP), and urinary N-telopeptide cross-links of type I collagen (NTX), pyridinoline (PYD) and deoxypyridinoline (DPD) was measured. Analyzed by AUC and compared to CON, a -32% lower CTX (p = 0.011, d = 0.83) and 24% (p = 0.52, d = 0.2) increase in P1NP was observed for MBPM. Mean total 24 h NTX excreted in MBPM was -10% (p = 0.035) lower than CON. Urinary PYD and DPD were unaffected by treatment. This study demonstrates the acute effects of bedtime ingestion of a calcium-fortified, milk-based protein matrix on bone remodeling.


Assuntos
Doenças Ósseas Metabólicas/dietoterapia , Remodelação Óssea , Cálcio na Dieta/administração & dosagem , Ritmo Circadiano , Suplementos Nutricionais , Alimentos Fortificados , Proteínas do Leite/administração & dosagem , Pós-Menopausa/sangue , Idoso , Biomarcadores/sangue , Doenças Ósseas Metabólicas/sangue , Doenças Ósseas Metabólicas/diagnóstico , Doenças Ósseas Metabólicas/fisiopatologia , Cálcio na Dieta/efeitos adversos , Colágeno Tipo I/sangue , Suplementos Nutricionais/efeitos adversos , Feminino , Alimentos Fortificados/efeitos adversos , Humanos , Irlanda , Pessoa de Meia-Idade , Proteínas do Leite/efeitos adversos , Hormônio Paratireóideo/sangue , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Pró-Colágeno/sangue , Fatores de Tempo , Resultado do Tratamento , Vitamina D/administração & dosagem
11.
Med Sci Sports Exerc ; 51(8): 1599-1605, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31083027

RESUMO

Endurance exercise can cause a decrease in serum ionized calcium (iCa) and increases in parathyroid hormone (PTH) and c-terminal telopeptide of type I collagen (CTX), which may be due to Ca loss in sweat. PURPOSE: This study aimed to determine whether exercise in a warm environment exaggerates the decrease in iCa and increases in PTH and CTX compared with a cool environment in older adults. METHODS: Twelve women and men 61-78 yr old performed two identical 60-min treadmill bouts at ~75% of maximal heart rate under warm and cool conditions. Serum iCa, PTH, and CTX were measured every 15 min starting 15 min before and continuing for 60 min after exercise. Sweat Ca loss was estimated from sweat volume and sweat Ca concentration. RESULTS: Sweat volume was low and variable; there were no differences in sweat volume or Ca concentration between conditions. iCa decreased after 15 min of exercise, and the change was similar in both conditions. Increases in PTH (warm: 16.4, 95% confidence interval [CI] = 6.2, 26.5 pg·mL; cool: 17.3, 95% CI = 8.1, 26.4 pg·mL) and CTX (warm: 0.08, 95% CI = 0.05, 0.11 ng·mL; cool: 0.08, 95% CI = 0.01, 0.16 ng·mL) from before to immediately after exercise were statistically significant and similar between conditions. Adjusting for plasma volume shifts did not change the results. CONCLUSION: The increases in PTH and CTX, despite the low sweat volume, suggest that dermal Ca loss is not a major factor in the decrease in iCa and increases in PTH and CTX observed during exercise in older adults.


Assuntos
Osso e Ossos/metabolismo , Cálcio/sangue , Colágeno Tipo I/sangue , Temperatura Alta , Hormônio Paratireóideo/sangue , Peptídeos/sangue , Caminhada/fisiologia , Idoso , Biomarcadores/sangue , Densidade Óssea , Temperatura Baixa , Colágeno Tipo I/urina , Feminino , Homeostase , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos/urina , Pele/metabolismo , Suor/metabolismo , Sudorese/fisiologia
12.
Nutrients ; 11(5)2019 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-31130694

RESUMO

The purpose of this work was to describe changes in metabolic activity in the bones of young male competitive cyclists (CYC) as compared with age-matched controls (CON) over a one-year period of study. Eight adolescent male cyclists aged between fourteen and twenty, and eight age-matched controls participated in this longitudinal study. Serum osteocalcin (OC), amino-terminal propeptide of type I procollagen (PINP), beta-isomerized C-telopeptides (ß-CTx) and plasma 25 hydroxyvitamin D [25(OH)D], were investigated by an electrogenerated chemiluminescence immunoassay. Analysis of variance revealed no significant differences in formation and resorption markers between cyclists and controls. Within the groups, both CYC and CON showed decreased OC at -30% and -24%, respectively, and PINP where the figures were -28% and -30% respectively (all p < 0.05). However, only the CYC group showed a decrease in [25(OH)D], lower by 11% (p < 0.05). The similarity in the concentrations of markers in cyclists and controls seems to indicate that cycling does not modify the process of bone remodeling. The decrease in vitamin D in cyclists might be detrimental to their future bone health.


Assuntos
Ciclismo/fisiologia , Remodelação Óssea , Reabsorção Óssea , Osso e Ossos/efeitos dos fármacos , Osteogênese , Adolescente , Atletas , Biomarcadores/sangue , Densidade Óssea , Osso e Ossos/metabolismo , Estudos de Casos e Controles , Colágeno Tipo I/sangue , Humanos , Estudos Longitudinais , Masculino , Osteocalcina/sangue , Osteoporose/sangue , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Vitamina D/análogos & derivados , Vitamina D/sangue
13.
Tumour Biol ; 41(5): 1010428319847081, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31122159

RESUMO

Type 1 collagen is an important part of the extracellular matrix and changes in its metabolism and distribution are essential in breast cancer induction and progression. Serum concentrations of type 1 collagen synthesis (aminoterminal propeptide (PINP)) and degradation markers (carboxyterminal telopeptide (ICTP)) have previously been studied in early and metastatic breast cancer, but no data are available on specific breast cancer subtypes. We assayed 662 preoperative serum samples for PINP and ICTP and 109 postoperative serum samples for ICTP. The results were linked to prospectively collected clinical data and the cases were divided into breast cancer subtypes for survival analyses. The concentrations of both pre- and postoperative ICTP serum levels increased linearly from ductal in situ carcinoma to stage I-II tumors, stage III tumors, and finally to those with concomitant primary metastases (preoperative ICTP, p = 0.009; postoperative ICTP, p = 0.016). High-preoperative ICTP levels were associated with better breast cancer-specific survival in connection with luminal-B-like (HER2-negative) tumors (p = 0.017), which was confirmed in Cox regression analysis (relative risk = 3.127; 95% confidence interval = 1.081-9.049, p = 0.035), when T-class (relative risk = 4.049; 95% confidence interval = 1.263-12.981; p = 0.019) and nodal status (relative risk = 3.896; 95% confidence interval = 1.088-13.959; p = 0.037) were included in the analysis. In patients with triple-negative breast cancer, a high-preoperative ICTP level was a significant predictor of local relapse-free survival in univariate (p = 0.0020) and multivariate analyses (relative risk = 13.04; 95% confidence interval = 1.354-125.5; p = 0.026; for T-class, relative risk = 2.128 and 95% confidence interval = 0.297-15.23; p = 0.452; for N-class, relative risk = 0.332 and 95% confidence interval = 0.033-3.307; p = 0.347). A preoperatively elevated serum ICTP level appears to be an important marker of better prognosis in triple-negative breast cancer and luminal-B-like (HER2-negative) subtypes.


Assuntos
Biomarcadores Tumorais/sangue , Colágeno Tipo I/sangue , Neoplasias de Mama Triplo Negativas/sangue , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Intervalo Livre de Doença , Matriz Extracelular/genética , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Período Pré-Operatório , Pró-Colágeno/sangue , Prognóstico , Modelos de Riscos Proporcionais , Receptor ErbB-2/genética , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia
14.
PLoS One ; 14(4): e0200968, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31039163

RESUMO

Adenosine (A) to inosine (I) RNA editing is a hydrolytic deamination reaction catalyzed by the adenosine deaminase (ADAR) enzyme acting on double-stranded RNA. This posttranscriptional process diversifies a plethora of transcripts, including coding and noncoding RNAs. Interestingly, few studies have been carried out to determine the role of RNA editing in vascular disease. The aim of this study was to determine the potential role of ADARs in congenital heart disease. Strong downregulation of ADAR2 and increase in ADAR1 expression was observed in blood samples from congenital heart disease (CHD) patients. The decrease in expression of ADAR2 was in line with its downregulation in ventricular tissues of dilated cardiomyopathy patients. To further decipher the plausible regulatory pathway of ADAR2 with respect to heart physiology, miRNA profiling of ADAR2 was performed on tissues from ADAR2-/- mouse hearts. Downregulation of miRNAs (miR-29b, miR-405, and miR-19) associated with cardiomyopathy and cardiac fibrosis was observed. Moreover, the upregulation of miR-29b targets COL1A2 and IGF1, indicated that ADAR2 might be involved in cardiac myopathy. The ADAR2 target vascular development associated protein-coding gene filamin B (FLNB) was selected. The editing levels of FLNB were dramatically reduced in ADAR2-/- mice; however, no observable changes in FLNB expression were noted in ADAR2-/- mice compared to wild-type mice. This study proposes that sufficient ADAR2 enzyme activity might play a vital role in preventing cardiovascular defects.


Assuntos
Adenosina Desaminase/biossíntese , Regulação Enzimológica da Expressão Gênica , Cardiopatias Congênitas/sangue , RNA Mensageiro/sangue , Proteínas de Ligação a RNA/biossíntese , Adenosina Desaminase/genética , Adolescente , Animais , Criança , Pré-Escolar , Colágeno Tipo I/sangue , Colágeno Tipo I/genética , Feminino , Filaminas/sangue , Filaminas/genética , Cardiopatias Congênitas/genética , Humanos , Fator de Crescimento Insulin-Like I/biossíntese , Fator de Crescimento Insulin-Like I/genética , Masculino , Camundongos , Camundongos Knockout , MicroRNAs/sangue , MicroRNAs/genética , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genética
15.
Mol Med Rep ; 19(6): 4603-4612, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30957178

RESUMO

As the incidence of osteoporosis (OP) and hypercholesterolaemia in men has increased, male OP has drawn more attention from clinicians worldwide. The present study sought to investigate the effects of cholesterol on male bone. Between July 2015 and October 2015, 216 men (aged ≥18 years) were recruited for this cross­sectional study. To test our clinical hypothesis, we designed two male animal models: Exogenous hypercholesterolaemia induced by a high­cholesterol diet (HCD) and endogenous hypercholesterolaemia induced by apolipoprotein E (ApoE) knockout. Finally, the direct effects of cholesterol on osteoblasts were observed in cell experiments. In our clinical studies, men with hypercholesterolaemia displayed a lower bone mineral density (BMD) and increased beta collagen cross­linking (beta­CTX) and type I anterior collagen amino terminal peptide (PINP) levels compared to those of the control subjects. Serum cholesterol levels were a significant independent predictor of BMD, beta­CTX and PINP and were negatively correlated with BMD and positively correlated with beta­CTX and PINP levels. Our animal experimental results validated our clinical results, as they also indicated that hypercholesterolaemia damages bone microstructure and reduces bone strength. Cholesterol directly increased osteoblast functional gene expression in vitro. Hypercholesterolaemia increases the risk of high­turnover osteoporosis in men at least in part by excessively promoting the activity of the remodelling pathway. In addition, hypercholesterolaemia damages the bone microstructure, resulting in osteopenia or OP and reduced bone strength, leading to a higher risk of fracture in men. We emphasize the importance of preventing and treating hypercholesterolaemia as well as monitoring bone metabolic markers and BMD in men with hypercholesterolemia for the effective prevention of bone loss and subsequent fracture. In addition, our findings provide a theoretical basis for the development of treatments for high cholesterol­induced osteoporosis in men.


Assuntos
Remodelação Óssea , Hipercolesterolemia/sangue , Osteoporose/sangue , Adulto , Animais , Biomarcadores/sangue , Reabsorção Óssea/sangue , Osso e Ossos/metabolismo , Colágeno Tipo I/sangue , Estudos Transversais , Modelos Animais de Doenças , Humanos , Hipercolesterolemia/complicações , Masculino , Pessoa de Meia-Idade , Osteoporose/etiologia , Fragmentos de Peptídeos/sangue , Ratos , Ratos Sprague-Dawley
16.
Psychiatry Res ; 276: 39-44, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31003023

RESUMO

Several preclinical and clinical studies show that selective serotonin reuptake inhibitors (SSRI's) are associated with bone loss and an increase in fracture risk, not many reports on their effect on bone turnover markers. This cross-sectional study evaluated the effect of SSRIs treatment on bone turnover markers in Indian population for the first time. Inclusion criteria were subjects of either sex and age 18-45 years undergoing treatment with an SSRI for at least 3 months, regardless of the indication. The results were compared with age-matched healthy controls. A total of 141 subjects were screened out of which 85 were enrolled, 44 in treatment and 41 in the control group. Serum Procollagen Type 1 Amino Terminal Propeptide (P1NP) levels were decreased in patients on SSRI treatment whereas no change was observed in the beta-C-terminal telopeptide (ß-CTX) and receptor activator of nuclear factor kappa-Β ligand (RANKL) levels suggesting that these drugs can reduce bone formation but not resorption. Patients on SSRI treatment also showed reduced pCREB levels indicating that reduced bone formation is possibly through the gut mediated pathway. Our study suggests that SSRIs treatment at therapeutic doses may have a deteriorating effect on bone requiring caution in patients with additional risk factors.


Assuntos
Densidade Óssea/efeitos dos fármacos , Osteoporose/sangue , Osteoporose/induzido quimicamente , Inibidores de Captação de Serotonina/efeitos adversos , Adulto , Biomarcadores/sangue , Densidade Óssea/fisiologia , Colágeno Tipo I/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/diagnóstico , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Inibidores de Captação de Serotonina/farmacologia , Inibidores de Captação de Serotonina/uso terapêutico
17.
J Am Coll Cardiol ; 73(12): 1398-1410, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30922470

RESUMO

BACKGROUND: A combination of circulating biomarkers associated with excessive myocardial collagen type-I cross-linking or CCL+ (i.e., decreased carboxy-terminal telopeptide of collagen type-I to matrix metalloproteinase-1 ratio) and with excessive myocardial collagen type-I deposition or CD+ (i.e., increased carboxy-terminal propeptide of procollagen type-I) has been described in heart failure (HF) patients and associates with poor outcomes. OBJECTIVES: The purpose of this study was to investigate whether the CCL+CD+ combination of biomarkers associates with atrial fibrillation (AF). METHODS: Biomarkers were analyzed in serum samples from 242 HF patients (study 1) and 150 patients referred for AF ablation (study 2). Patients were classified into 3 groups (CCL-CD-, CCL+CD- or CCL-CD+, and CCL+CD+) in accordance to biomarker threshold values. Left atrial electroanatomic high-density mapping was performed in 71 patients from study 2. RESULTS: In study 1, 53.7% patients had AF at baseline and 19.6% developed AF (median follow-up 5.5 years). Adjusted odds and hazard ratios associated with baseline and new-onset AF, respectively, were both ≥3.3 (p ≤ 0.050) in CCL+CD+ patients compared with CCL-CD- patients, with nonsignificant changes in the other group. In study 2, 29.3% patients had AF recurrence during 1-year post-ablation. The adjusted hazard ratio for AF recurrence was 3.4 (p = 0.008) in CCL+CD+ patients compared with CCL-CD- patients, with nonsignificant changes in the other group. The CCL+CD+ combination added incremental predictive value over relevant covariables. CCL+CD+ patients exhibited lower left atrial voltage than the remaining patients (p = 0.005). CONCLUSIONS: A combination of circulating biomarkers reflecting excessive myocardial collagen type-I cross-linking and deposition is associated with higher AF prevalence, incidence, and recurrence after ablation.


Assuntos
Fibrilação Atrial , Ablação por Cateter/efeitos adversos , Colágeno Tipo I , Metaloproteinase 1 da Matriz , Miocárdio , Fibrilação Atrial/sangue , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/terapia , Biomarcadores/sangue , Ablação por Cateter/métodos , Colágeno Tipo I/sangue , Colágeno Tipo I/metabolismo , Feminino , Fibrose , Humanos , Masculino , Metaloproteinase 1 da Matriz/sangue , Metaloproteinase 1 da Matriz/metabolismo , Pessoa de Meia-Idade , Miocárdio/metabolismo , Miocárdio/patologia , Valor Preditivo dos Testes , Prevalência , Recidiva
18.
Clin Interv Aging ; 14: 445-451, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30880926

RESUMO

Aim: The aim of this study was to determine the relationship between abnormal glucose metabolism and osteoporosis (OP) in Han Chinese men over the age of 50 years. Patients and methods: A cross-sectional study of 775 male patients aged over 50 years was performed at our hospital in 2011. The patients were divided into a normal glucose metabolism group, an impaired glucose regulation (IGR) group, and a type 2 diabetes mellitus (T2DM) group. Differences in their bone mineral densities (BMDs), OP detection rates, and indices of bone metabolism were assessed. Results: After adjusting for age and body mass index (BMI), there were no significant differences in lumbar spine, femoral neck, and total hip BMD values in the three groups (P>0.05) nor in OP detection rates (P=0.19). However, there were some significant differences in bone metabolism markers between the groups after adjusting for age, BMI, and serum creatinine (Cr): 25-hydroxyvitamin D (25(OH)D) was positively correlated with the presence of abnormal glycometabolism (r=0.08; P<0.01), while ß-carboxy-terminal cross-linking telopeptide of type I collagen (ß-CTX), bone gamma-carboxyglutamic acid protein (BGP; osteocalcin [OC]), and procollagen type 1 intact N-terminal propeptide (P1NP) were negatively correlated (r=-0.13, -0.21, -0.14, respectively; P<0.01). Logistic regression analysis of the data indicated that BGP was the only bone metabolism marker significantly influenced by abnormal glucose metabolism (OR =0.96). Conclusion: There were no significant differences in BMD or OP detection rates between the three glycometabolism groups after adjusting for age and BMI. However, the bone metabolism marker, BGP, was significantly negatively correlated with abnormal glucose metabolism.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Glucose/metabolismo , Osteoporose/sangue , Osteoporose/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático , Densidade Óssea , China , Colágeno Tipo I/sangue , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Colo do Fêmur/diagnóstico por imagem , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Osteocalcina/sangue , Osteoporose/complicações , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Pró-Colágeno/sangue , Vitamina D/análogos & derivados , Vitamina D/sangue
19.
Biosci Biotechnol Biochem ; 83(6): 1146-1156, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30739561

RESUMO

Collagen hydrolysate is a well-known nutritional supplement for the improvement of healthy skin. Here, collagen peptide NS (CPNS) from fish scale was prepared, and its physicochemical properties were investigated. Gly-Pro was revealed as a representative low molecular weight peptide of CPNS, by performing prep-HPLC and LC-MS/MS. CPNS treatment attenuated matrix metalloproteinase-1 production and increased the synthesis of type 1 procollagen in HDF cells. After orally administering CPNS to rats, the plasma concentrations of Gly-Pro and Pro-Hyp increased dramatically. To examine the protective effects of CPNS against ultraviolet B (UVB)-induced photoaging in vivo, the dorsal skins of hairless mice were exposed to UVB and supplemented with CPNS for 12 weeks. The CPNS consumption significantly attenuated UVB-induced wrinkle formation, transepidermal water loss, and epidermis thickness, and increased skin hydration. Collectively, these results suggest that bioactive peptides of CPNS, Gly-Pro and Pro-Hyp, exert beneficial effects on skin health.


Assuntos
Colágeno Tipo I/química , Dipeptídeos/farmacologia , Hidroxiprolina/química , Prolina/química , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/efeitos da radiação , Raios Ultravioleta , Administração Oral , Animais , Células Cultivadas , Cromatografia Líquida de Alta Pressão/métodos , Colágeno Tipo I/sangue , Dipeptídeos/administração & dosagem , Dipeptídeos/sangue , Dipeptídeos/química , Feminino , Humanos , Metaloproteinase 1 da Matriz/metabolismo , Camundongos , Camundongos Pelados , Peso Molecular , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem/métodos
20.
Osteoporos Int ; 30(3): 667-673, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30635696

RESUMO

Early PINP changes correlate with 18-month lumbar spine BMD changes and the correlation was greater with abaloparatide versus teriparatide. The uncoupling index was similar between the two agents. INTRODUCTION: We evaluated the relationship between early PINP changes and subsequent changes in spine BMD following abaloparatide and teriparatide treatments. We also explored the use of an "uncoupling index" (UI), the balance between bone formation and bone resorption, which we hypothesised would be similar in response to these treatment groups. METHODS: Blood samples were taken for measurement of bone turnover markers (BTMs) s-PINP and s-CTX at baseline, 1, 3, 6, 12, and 18 months from 189 abaloparatide patients and 227 teriparatide patients randomly selected from all participants who completed the study. BMD was measured by DXA at baseline, 6, 12, and 18 months. Correlations were calculated between log ratio of BTMs from baseline to 3 months and percent change from baseline in BMD at 18 months. A UI was calculated using log transformation and subtraction of the standard deviate for s-CTX from the standard deviate for s-PINP for each patient. RESULTS: Early BTM changes were associated with subsequent BMD changes for both treatments. Pearson correlations for the log ratio of PINP over baseline at 3 months and BMD percent change from baseline at 18 months were larger (P < 0.0001) with abaloparatide (r = 0.561) than teriparatide (r = 0.198). The mean UI at 1 month was greater for abaloparatide versus teriparatide (1.743 and 1.493, respectively; P = 0.03) but was similar at 3 months or later time points. CONCLUSIONS: Early s-PINP changes correlate with percentage change in lumbar spine BMD 18 months after treatment with both abaloparatide and teriparatide, though the correlation with abaloparatide was greater. The UI was similar between abaloparatide and teriparatide suggesting that the balance between formation and resorption markers was similar.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Remodelação Óssea/efeitos dos fármacos , Osteoporose Pós-Menopausa/fisiopatologia , Proteína Relacionada ao Hormônio Paratireóideo/farmacologia , Teriparatida/farmacologia , Idoso , Biomarcadores/sangue , Densidade Óssea/efeitos dos fármacos , Densidade Óssea/fisiologia , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea/fisiologia , Colágeno Tipo I/sangue , Método Duplo-Cego , Feminino , Humanos , Vértebras Lombares/fisiopatologia , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/sangue , Osteoporose Pós-Menopausa/tratamento farmacológico , Proteína Relacionada ao Hormônio Paratireóideo/uso terapêutico , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Pró-Colágeno/sangue , Teriparatida/uso terapêutico
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