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1.
Artigo em Inglês | MEDLINE | ID: mdl-35228118

RESUMO

The pharmacological effects and therapeutic targets of naringin (NG) against osteoporosis (OP) is still unclear. Liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS) based non-targeted metabonomics has been used to explore the differentiated metabolites and potential biological pathways of NG in the pathological process of OP. Using network pharmacology analysis, the key protein targets of NG against OP were also screened. By the metabonomics analysis, a total of 33 differentiated metabolites in serum were discovered, of which 21 were significantly regulated by NG treatment. These metabolites majorly associated with to amino acid metabolism,polyunsaturated fatty acid metabolism, pyruvate metabolism and glycerophospholipidmetabolism. Using the network pharmacology prediction analysis, NG was related to the expression changes of 13 important protein targets. It showed that high-throughput metabonomics strategy integrated with network pharmacology could insight into molecular mechanisms of natural products.


Assuntos
Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão/métodos , Flavanonas/administração & dosagem , Metabolômica/métodos , Osteoporose/tratamento farmacológico , Espectrometria de Massas em Tandem/métodos , Aminoácidos/sangue , Animais , Glicerofosfolipídeos/sangue , Humanos , Masculino , Camundongos , Osteoporose/sangue
2.
J Endocrinol Invest ; 45(6): 1255-1263, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35237949

RESUMO

PURPOSE: Girls affected with Turner syndrome (TS) present with low bone mineral density (BMD) and osteopenia/osteoporosis. Thus, they have an increased risk to develop fractures compared to normal population. The aim of this study was to deepen the pathophysiology of skeletal fragility in TS subjects by evaluating the serum levels of Dickkopf-1 (DKK-1) and sclerostin, main regulators of bone mass, as well as the percentage of circulating osteoblast precursors (OCPs). METHODS: Thirty-four TS girls and 24 controls were recruited. All subjects underwent anthropometric measures (height, weight, body mass index-BMI). A peripheral venous blood sample was collected to determine serum levels of active intact parathyroid hormone (PTH), 25-OH vitamin D, calcium, phosphorus, bone alkaline phosphatase (bALP), osteocalcin, sclerostin, DKK-1, RANKL and OPG. OCPs were detected by flow cytometry. In TS subjects bone mineralization was measured at lumbar spine by dual energy X-ray absorptiometry (DXA). RESULTS: bALP, 25-OH Vitamin D, and osteocalcin levels were significant lower in TS subjects than in the controls. Statistically significant higher levels of sclerostin, DKK-1 and RANKL were measured in patients compared with the controls. The percentage of OCPs did not show significant differences between patients and controls. Sclerostin and DKK-1 levels were related with anthropometric parameters, bone metabolism markers, HRT, rhGH therapy, RANKL and lumbar BMAD-Z-score. CONCLUSION: TS patients showed higher levels of sclerostin and DKK-1 than controls which can be related to HRT, and to reduced bone formation markers as well as the increased bone resorption activity.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Peptídeos e Proteínas de Sinalização Intercelular , Osteoporose , Síndrome de Turner , Via de Sinalização Wnt , Proteínas Adaptadoras de Transdução de Sinal/sangue , Fosfatase Alcalina/sangue , Fosfatase Alcalina/metabolismo , Biomarcadores/metabolismo , Densidade Óssea , Feminino , Marcadores Genéticos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Masculino , Osteocalcina/metabolismo , Osteoporose/sangue , Osteoporose/metabolismo , Osteoporose/patologia , Síndrome de Turner/sangue , Síndrome de Turner/metabolismo , Síndrome de Turner/patologia , Vitamina D/sangue
3.
J Orthop Surg Res ; 17(1): 92, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-35168655

RESUMO

BACKGROUND: Serum lipids are highly inheritable and play a major role in bone health. However, the relationship between high-density lipoprotein cholesterol (HDL-C) and bone mineral density (BMD) remains uncertain. The goal of this study was to see if there was a link between HDL-C levels and BMD in persons aged 20-59. METHODS: Multivariate logistic regression models were used to determine the link between HDL-C and lumbar BMD using data from the National Health and Nutrition Examination Survey (NHANES) 2011-2018. Generalized additive models and fitted smoothing curves were also used. RESULTS: The analysis included a total of 10,635 adults. After controlling for various variables, we discovered that HDL-C was positively linked with lumbar BMD. The favorable connection of HDL-C with lumbar BMD was maintained in subgroup analyses stratified by sex and race in women, but not in men, and in blacks, but not in whites. The relationship between HDL-C and lumbar BMD in men and whites was a U-shaped curve with the same inflection point: 0.98 mmol/L. CONCLUSIONS: In people aged 20 to 59, our research discovered a positive relationship among HDL-C and lumbar BMD. Among males and whites, this relationship followed a U-shaped curve (inflection point: 0.98 mmol/L). HDL-C measurement might be used as a responsive biomarker for detecting osteoporosis early and guiding therapy.


Assuntos
Densidade Óssea , Doenças Ósseas Metabólicas/sangue , HDL-Colesterol/sangue , Osteoporose/sangue , Adulto , Densidade Óssea/fisiologia , Estudos Transversais , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Osteoporose/epidemiologia , Adulto Jovem
4.
Ann Clin Lab Sci ; 52(1): 48-59, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35181618

RESUMO

OBJECTIVE: Osteoporosis is likely becoming a new disease challenge with increasing aging population. Circ_0006873 dysregulation may serve as an event linked to osteoporosis. Thus, this study sought to evaluate the function and mechanism of circ_0006873 on osteoporosis. METHODS: Clinical serum samples collected from 30 osteoporosis patients were utilized to obtain circ_0006873 and miR-142-5p expression data. The link between circ_0006873, miR-142-5p, and phosphatase and tensin homolog (PTEN) was demonstrated via online tools (starBase, circinteractome), RNA Immunoprecipitation (RIP) and dual-Luciferase reporter assays. After knockdown or overexpression, cell counting kit-8 (CCK-8) assay measured cell viability. Alizarin red S (ARS) staining as well Alkaline phosphatase (ALP) staining detected osteoblastic differentiation levels. Quantitative real-time PCR (qRT-PCR) and western blot analyzed expression of RNAs and proteins after transfection or during osteoblastic differentiation. RESULTS: circ_0006873 was upregulated in osteoporosis patients and decreased during osteoblastic differentiation. Following experiments revealed that cell viability, proliferation-related factors, osteogenic marker genes (ALP, Runx2, Bglap) and osteoblastic differentiation degree were promoted after circ_0006873 knockdown but inhibited after overexpression. Circ_0006873 sponged miR-142-5p, which was downregulated in osteoporosis patients and became higher during osteoblastic differentiation. Rescue assay indicated miR-142-5p mimic could reverse the effects of circ_0006873 overexpression on cell viability and osteogenic markers, and also could activate Akt pathway. Furthermore, circ_0006873 can negatively target miR-142-5p via regulating PTEN to inhibit osteoblastic differentiation. CONCLUSION: Circ_0006873 sponges miR-142-5p thereby enhances PTEN expression to suppress osteoblastic differentiation via regulation of Akt signaling pathway, thus, may provide a treatment approach for osteoporosis.


Assuntos
Células-Tronco Mesenquimais , MicroRNAs , Osteoblastos , Osteoporose , PTEN Fosfo-Hidrolase , Proteínas Proto-Oncogênicas c-akt , RNA Circular , Idoso , Diferenciação Celular , Humanos , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Osteoblastos/metabolismo , Osteoblastos/patologia , Osteoporose/sangue , Osteoporose/genética , Osteoporose/metabolismo , Osteoporose/patologia , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Transdução de Sinais
5.
Nutrients ; 14(2)2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35057457

RESUMO

Osteoporosis is a major health concern in aging populations, where 54% of the U.S. population aged 50 and older have low bone mineral density (BMD). Increases in inflammation and oxidative stress play a major role in the development of osteoporosis. Men are at a greater risk of mortality due to osteoporosis-related fractures. Our earlier findings in rodent male and female models of osteoporosis, as well as postmenopausal women strongly suggest the efficacy of prunes (dried plum) in reducing inflammation and preventing/reversing bone loss. The objective of this study was to examine the effects of two doses of prunes, daily, on biomarkers of inflammation and bone metabolism in men with some degree of bone loss (BMD; t-score between -0.1 and -2.5 SD), for three months. Thirty-five men between the ages of 55 and 80 years were randomized into one of three groups: 100 g prunes, 50 g prunes, or control. Consumption of 100 g prunes led to a significant decrease in serum osteocalcin (p < 0.001). Consumption of 50 g prunes led to significant decreases in serum osteoprotegerin (OPG) (p = 0.003) and serum osteocalcin (p = 0.040), and an increase in the OPG:RANKL ratio (p = 0.041). Regular consumption of either 100 g or 50 g prunes for three months may positively affect bone turnover.


Assuntos
Densidade Óssea/fisiologia , Osso e Ossos/metabolismo , Osteoporose/sangue , Fitoterapia/métodos , Prunus domestica , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Composição Corporal , Remodelação Óssea , Exercício Físico , Humanos , Inflamação/sangue , Inflamação/prevenção & controle , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Osteocalcina/sangue , Osteoporose/prevenção & controle , Fraturas por Osteoporose/prevenção & controle , Osteoprotegerina/sangue , Ligante RANK/sangue
6.
J Endocrinol Invest ; 45(1): 125-137, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34213743

RESUMO

PURPOSE: The study aimed to define the clinical, biochemical and genetic features of adult patients with osteopenia/osteoporosis and/or bone fragility and low serum alkaline phosphatase (sALP). METHODS: Twenty-two patients with at least two sALP values below the reference range were retrospectively enrolled after exclusion of secondary causes. Data about clinical features, mineral and bone markers, serum pyridoxal-5'-phosphate (PLP), urine phosphoethanolamine (PEA), lumbar and femur bone densitometry, and column X-ray were collected. Peripheral blood DNA of each participant was analyzed to detect ALPL gene anomalies. RESULTS: Pathogenic ALPL variants (pALPL) occurred in 23% and benign variants in 36% of patients (bALPL), while nine patients harbored wild-type alleles (wtALPL). Fragility fractures and dental anomalies were more frequent in patients harboring pALPL and bALPL than in wtALPL patients. Of note, wtALPL patients comprised women treated with tamoxifen for hormone-sensitive breast cancer. Mineral and bone markers were similar in the three groups. Mean urine PEA levels were significantly higher in patients harboring pALPL than those detected in patients harboring bALPL and wtALPL; by contrast, serum PLP levels were similar in the three groups. A 6-points score, considering clinical and biochemical features, was predictive of pALPL detection [P = 0.060, OR 1.92 (95% CI 0.972, 3.794)], and more significantly of pALPL or bALPL [P = 0.025, OR 14.33 (95% CI 1.401, 14.605)]. CONCLUSION: In osteopenic/osteoporotic patients, single clinical or biochemical factors did not distinguish hypophosphatasemic patients harboring pALPL or bALPL from those harboring wtALPL. Occurrence of multiple clinical and biochemical features is predictive of ALPL anomalies, and, therefore, they should be carefully identified. Tamoxifen emerged as a hypophosphatasemic drug.


Assuntos
Fosfatase Alcalina/genética , Biomarcadores/análise , Hipofosfatemia , Fosfatase Alcalina/análise , Fosfatase Alcalina/sangue , Biomarcadores/sangue , Densidade Óssea , Doenças Ósseas Metabólicas/sangue , Doenças Ósseas Metabólicas/epidemiologia , Doenças Ósseas Metabólicas/genética , Doença Crônica , Estudos Transversais , Análise Mutacional de DNA , Feminino , Fraturas Ósseas/sangue , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/genética , Humanos , Hipofosfatemia/sangue , Hipofosfatemia/diagnóstico , Hipofosfatemia/epidemiologia , Hipofosfatemia/genética , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Osteoporose/sangue , Osteoporose/epidemiologia , Osteoporose/genética , Polimorfismo de Nucleotídeo Único , Fosfato de Piridoxal/análise , Fosfato de Piridoxal/sangue , Estudos Retrospectivos
7.
Front Endocrinol (Lausanne) ; 12: 763538, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858335

RESUMO

Background: This study aimed to explore the association between serum amino acids (AAs) levels and bone mineral density (BMD). Methods: We performed a two-sample Mendelian randomization (MR) analysis to analyze the associations between the levels of eight AAs and BMD values by using summary-level genome-wide association study (GWAS) data. We applied the MR Steiger filtering method and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) global test to check for and remove single nucleotide polymorphisms (SNPs) that were horizontally pleiotropic. The associations were estimated with the inverse variance weighted (IVW), MR-Egger, weighted median and MR Robust Adjusted Profile Score (MR.RAPS) methods. Results: Our study found that genetically increased isoleucine (Ile) [IVW: effect = 0.1601, 95% confidence interval (CI) = 0.0604 ~ 0.2597, p = 0.0016] and valine (Val) levels (IVW: effect = 0.0953, 95% CI = 0.0251 ~ 0.1655, p = 0.0078) were positively associated with total body BMD (TB-BMD). The results also revealed that genetically increased tyrosine (Tyr) levels were negatively associated with TB-BMD (IVW: effect = -0.1091, 95% CI = -0.1863 ~ -0.0320, p = 0.0055). Conclusions: In this study, associations between serum AA levels and BMD were established. These findings underscore the important role that serum AAs play in the development of osteoporosis and provide evidence that osteoporosis can be prevented and treated by the intake of certain AAs.


Assuntos
Aminoácidos/sangue , Aminoácidos/genética , Densidade Óssea/fisiologia , Estudo de Associação Genômica Ampla/métodos , Análise da Randomização Mendeliana/métodos , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/sangue , Osteoporose/diagnóstico , Osteoporose/genética
8.
Front Endocrinol (Lausanne) ; 12: 759843, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777254

RESUMO

Diabetic osteoporosis (DOP) belongs to secondary osteoporosis caused by diabetes; it has the characteristics of high morbidity and high disability. In the present study, we constructed a type 1 diabetic rat model and administered chondroitin sulfate (200 mg/kg) for 10 weeks to observe the preventive effect of chondroitin sulfate on the bone loss of diabetic rats. The results showed that chondroitin sulfate can reduce blood glucose and relieve symptoms of diabetic rats; in addition, it can significantly increase the bone mineral density, improve bone microstructure, and reduce bone marrow adipocyte number in diabetic rats; after 10 weeks of chondroitin sulfate administration, the SOD activity level was upregulated, as well as CAT levels, indicating that chondroitin sulfate can alleviate oxidative stress in diabetic rats. Chondroitin sulfate was also found to reduce the level of serum inflammatory cytokines (TNF-α, IL-1, IL-6, and MCP-1) and alleviate the inflammation in diabetic rats; bone metabolism marker detection results showed that chondroitin sulfate can reduce bone turnover in diabetic rats (decreased RANKL, CTX-1, ALP, and TRACP 5b levels were observed after 10 weeks of chondroitin sulfate administration). At the same time, the bone OPG and RUNX 2 expression levels were higher after chondroitin sulfate treatment, the bone RANKL expression was lowered, and the OPG/RANKL ratio was upregulated. All of the above indicated that chondroitin sulfate could prevent STZ-induced DOP and repair bone microstructure; the main mechanism was through anti-oxidation, anti-inflammatory, and regulating bone metabolism. Chondroitin sulfate could be used to develop anti-DOP functional foods and diet interventions for diabetes.


Assuntos
Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Sulfatos de Condroitina/uso terapêutico , Diabetes Mellitus Tipo 1/complicações , Osteoporose/tratamento farmacológico , Animais , Glicemia/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Medula Óssea/efeitos dos fármacos , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/metabolismo , Sulfatos de Condroitina/farmacologia , Citocinas/sangue , Avaliação Pré-Clínica de Medicamentos , Lipogênese/efeitos dos fármacos , Masculino , Osteoporose/sangue , Osteoporose/diagnóstico por imagem , Osteoporose/etiologia , Osteoprotegerina/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ligante RANK/metabolismo , Ratos , Microtomografia por Raio-X
9.
J Exp Med ; 218(12)2021 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-34698806

RESUMO

Osteoporosis is caused by an imbalance of osteoclasts and osteoblasts, occurring in close proximity to hematopoietic cells in the bone marrow. Recurrent somatic mutations that lead to an expanded population of mutant blood cells is termed clonal hematopoiesis of indeterminate potential (CHIP). Analyzing exome sequencing data from the UK Biobank, we found CHIP to be associated with increased incident osteoporosis diagnoses and decreased bone mineral density. In murine models, hematopoietic-specific mutations in Dnmt3a, the most commonly mutated gene in CHIP, decreased bone mass via increased osteoclastogenesis. Dnmt3a-/- demethylation opened chromatin and altered activity of inflammatory transcription factors. Bone loss was driven by proinflammatory cytokines, including Irf3-NF-κB-mediated IL-20 expression from Dnmt3a mutant macrophages. Increased osteoclastogenesis due to the Dnmt3a mutations was ameliorated by alendronate or IL-20 neutralization. These results demonstrate a novel source of osteoporosis-inducing inflammation.


Assuntos
Hematopoiese Clonal/genética , Osteoporose/genética , Adulto , Idoso , Alendronato/farmacologia , Animais , Anticorpos Neutralizantes/farmacologia , Diferenciação Celular/genética , Hematopoiese Clonal/fisiologia , Feminino , Humanos , Interleucinas/imunologia , Interleucinas/metabolismo , Masculino , Camundongos Knockout , Pessoa de Meia-Idade , Osteoclastos/patologia , Osteoporose/sangue , Osteoporose/tratamento farmacológico , Osteoporose/fisiopatologia
10.
Medicine (Baltimore) ; 100(40): e27442, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34622861

RESUMO

ABSTRACT: Ankle fractures are the most common intra-articular fractures. Osteoporosis is a common and frequent disease among the elderly with a poor prognosis and high risk of fractured ankles. However, the relationship between vitamin B6 and the incidence of fractured ankles in patients with osteoporosis is unclear.A total of 101 patients with osteoporosis were recruited. Clinical and followed-up information was recorded. And the vitamin B6, albumin, globulin, and hemoglobin in the blood were tested. Pearson's chi-squared and spearman test were performed to analyze the correlation between fractured ankles and relative parameters. Univariate and multivariate logistic regression, receiver operating characteristic curve analysis, univariate and multivariate Cox proportional hazards regression analysis, and Kaplan-Meier method were also performed.There exist strong relation between the expression level of vitamin B6 and fractured ankle (P < .001). The expression of vitamin B6 [Odd ratio (OR) = 12.071, 95% confidence interval (CI): 4.69-31.143, P < .001] has a clear correlation with whether the patients have fractured ankles via the univariate logistic regression analysis. In terms of multivariate logistic regression level, vitamin B6 (OR = 15.384, 95% CI:5.195-45.556, P < .001) was significantly associated with fractured ankle. In addition, expression level of vitamin B6 [hazard ratio (HR) = 11.684, 95% CI: 6.419-21.267, P < .001] was significantly associated with Maintenance time from recovery to recurrence (MRTT) of patients with osteoporosis.Enhanced vitamin B6 is significantly correlated with the poor prognosis of patients with osteoporosis and the increasing incidence of fractured ankles.


Assuntos
Fraturas do Tornozelo/sangue , Osteoporose/sangue , Vitamina B 6/sangue , Adulto , Idoso , Fraturas do Tornozelo/epidemiologia , Biomarcadores/sangue , Causalidade , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Osteoporose/epidemiologia , Estudos Prospectivos , Fatores de Risco
11.
Front Endocrinol (Lausanne) ; 12: 719920, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539572

RESUMO

Observational studies report some association between circulating bilirubin levels and osteoporosis, but it is unknown if this association is causal or confounded. In this two-sample Mendelian randomization (MR) study, we included a large genome-wide association study (GWAS) associated with total bilirubin levels among 317,639 people, a large meta-analysis to identify genetic variants associated with bone mineral density (BMD) estimated by heel quantitative ultrasound (eBMD) among 426,824 individuals and fracture among 1.2 million individuals. The results revealed that circulating bilirubin levels had no causal influence on eBMD (beta-estimate: 0.004, 95% confidence interval [CI]: -0.019 to 0.028, SE:0.012, P-value=0.705) or the risk of fracture (beta-estimate: -0.009, 95% CI: -0.035 to 0.017, SE:0.013, P-value=0.488), which were both confirmed by multiple sensitivity analyses. Our results confirm that circulating bilirubin levels have no causal role in eBMD or the incidence of fracture, indicating that circulating bilirubin levels is unlikely to be a causal risk factor for osteoporosis or fracture.


Assuntos
Bilirrubina/sangue , Fraturas Ósseas/sangue , Osteoporose/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea/genética , Causalidade , Feminino , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Osteoporose/epidemiologia , Osteoporose/genética , Polimorfismo de Nucleotídeo Único , Fatores de Risco
12.
Tissue Cell ; 73: 101645, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34509824

RESUMO

The current approach was designed to unearth the therapeutic potential of osteoblasts infusion, yielded from cultivating rat mesenchymal stem cells of bone marrow source in osteogenic differentiation media supplied with either hydroxyapatite nanoparticles (HA-NPs), chitosan/hydroxyapatite nanomaterials (C/HA-NPs), or chitosan nanoparticles, in the osteoporotic rats. The successful migration of the osteoblasts to the diseased bones of rats in C/HA-NPs and HA-NPs groups was evidenced by PCR screening of the Y-linked sex-determining gene (SRY) in the femoral bone tissue. Serum bone biomarker levels and gene expression patterns of cathepsin K, receptor activator of nuclear factor kappa B ligand (RANKL), and osteoprotegerin (OPG) were assessed. Additionally, histological examination of the femoral bone tissues of rats was performed. The current outcomes revealed that osteoblast implantation, resulted from C/HA-NPs or HA-NPs group, significantly lessened bone sialoprotein level. In Addition, it yielded a significant decline in the gene expression patterns of cathepsin K, RANKL, and RANKL/OPG proportion as well as up-regulation in BMP-2 and Runx-2 gene expression levels as opposed to the untreated ovariectomized animals. Moreover, it could restrain bone resorption and refine bone histoarchitecture. Conclusively, this study sheds light on the therapeutic significance of osteoblasts transplantation in alleviating the intensity of the bone remodeling cycle, consequently representing a hopeful therapeutic approach for primary osteoporosis.


Assuntos
Reabsorção Óssea/complicações , Diferenciação Celular , Células-Tronco Mesenquimais/citologia , Nanoestruturas/química , Osteoblastos/patologia , Osteoporose/complicações , Animais , Biomarcadores/sangue , Reabsorção Óssea/sangue , Reabsorção Óssea/genética , Feminino , Fêmur/patologia , Regulação da Expressão Gênica , Masculino , Osteoporose/sangue , Osteoporose/genética , Ovariectomia , Ratos Wistar
13.
Sci Rep ; 11(1): 19372, 2021 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-34588560

RESUMO

The rising incidence of bone pathologies such as osteoporosis and osteoarthritis is negatively affecting the functional status of millions of patients worldwide. The genetic component of these multifactorial pathologies is far from being fully understood, but in recent years several epigenetic mechanisms involved in the pathophysiology of these bone diseases have been identified. The aim of the present study was to compare the serum expression of four miRNAs in women with hip fragility fracture (OF group), osteoarthritis requiring hip replacement (OA group) and control women (Ctrl group). Serum expression of miR-497-5p, miR-155-5p, miR-423-5p and miR-365-3p was determined in a sample of 23 OA women, 25 OF women and 52 Ctrl women. Data shown that women with bone pathologies have higher expression of miR-497 and miR-423 and lower expression of miR-155 and miR-365 than control subjects. Most importantly, miR-497 was identified as an excellent discriminator between OA group and control group (AUC: 0.89, p < 0.000) and acceptable in distinguishing from the OF group (AUC: 0.76, p = 0.002). Our data suggest that circulating miR-497 may represent a significant biomarker of OA, a promising finding that could contribute towards future early-stage diagnosis of this disease. Further studies are required to establish the role of miR-155, miR-423 and miR-365 in bone pathologies.


Assuntos
MicroRNAs/sangue , Osteoartrite/sangue , Osteoporose/sangue , Fraturas por Osteoporose/sangue , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade
14.
Int J Mol Sci ; 22(18)2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34576172

RESUMO

Global data correlate severe vitamin D deficiency with COVID-19-associated coagulopathy, further suggesting the presence of a hypercoagulable state in severe COVID-19 patients, which could promote thrombosis in the lungs and in other organs. The feedback loop between COVID-19-associated coagulopathy and vitamin D also involves platelets (PLTs), since vitamin D deficiency stimulates PLT activation and aggregation and increases fibrinolysis and thrombosis. Vitamin D and PLTs share and play specific roles not only in coagulation and thrombosis but also during inflammation, endothelial dysfunction, and immune response. Additionally, another 'fil rouge' between vitamin D and PLTs is represented by their role in mineral metabolism and bone health, since vitamin D deficiency, low PLT count, and altered PLT-related parameters are linked to abnormal bone remodeling in certain pathological conditions, such as osteoporosis (OP). Hence, it is possible to speculate that severe COVID-19 patients are characterized by the presence of several predisposing factors to bone fragility and OP that may be monitored to avoid potential complications. Here, we hypothesize different pervasive actions of vitamin D and PLT association in COVID-19, also allowing for potential preliminary information on bone health status during COVID-19 infection.


Assuntos
Plaquetas/imunologia , COVID-19/complicações , Osteoporose/imunologia , Trombose/imunologia , Deficiência de Vitamina D/imunologia , Vitamina D/metabolismo , Plaquetas/metabolismo , Remodelação Óssea/imunologia , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/imunologia , Retroalimentação Fisiológica , Humanos , Osteoporose/sangue , Ativação Plaquetária/imunologia , Contagem de Plaquetas , SARS-CoV-2/imunologia , Índice de Gravidade de Doença , Trombose/sangue , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações
15.
Biomed Res Int ; 2021: 5567666, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497849

RESUMO

BACKGROUND: Fracture risk assessment tool (FRAX) index was developed for estimating of the 10-year risk of major or hip osteoporotic fracture. To date, there is insufficient information regarding the correlation between FRAX and serum bone turnover markers (BTMs), such as soluble ligand of receptor activator of nuclear factor-κB (sRANKL), osteoprotegerin (OPG), and other molecules related with secondary osteoporosis in rheumatoid arthritis (RA). Therefore, this study is aimed at assessing the correlation between the FRAX and serum levels of sRANKL, OPG, sRANKL/OPG ratio, Dickkopf-1 (DKK-1), and sclerostin (SOST) in RA. METHODS: Cross-sectional study included 156 postmenopausal women with RA. Bone mineral density (BMD) was measured at lumbar spine (L1-L4) and total hip using dual-energy X-ray absorptiometry (DXA). RA patients were divided into (A) RA + osteoporosis and (B) RA without osteoporosis. FRAX scores were calculated including the total hip BMD. Serum sRANKL, OPG, DKK-1, and SOST levels were measured by ELISA. Pearson tests were used for assessing the correlation between serum levels of these molecules and FRAX scores in RA. RESULTS: The RA + osteoporosis group had elevated sRANKL levels (p = 0.005), higher sRANKL/OPG ratio (p = 0.017), decreased DKK-1 (p = 0.028), and lower SOST levels (p < 0.001). Low total hip BMD correlated with high sRANKL (p = 0.001) and sRANKL/OPG ratio (p = 0.005). Total hip and lumbar spine BMD correlated with DKK-1 (p = 0.009 and p = 0.05, respectively) and SOST levels (p < 0.001 and p < 0.001, respectively). Higher sRANKL levels and sRANKL/OPG ratio correlated with estimated 10-year risk of a major osteoporotic fractures (p = 0.003 and p = 0.003, respectively) and hip fracture (p = 0.002 and p = 0.006, respectively). High serum SOST levels were associated with a low estimated 10-year risk of a major osteoporotic fracture (p = 0.003) and hip fracture (p = 0.009). CONCLUSION: High sRANKL levels and sRANKL/OPG ratio can be useful to detect a subgroup of RA patients who has an increased 10-year risk of major and hip osteoporotic fractures.


Assuntos
Artrite Reumatoide/sangue , Remodelação Óssea/fisiologia , Osteoporose/sangue , Fraturas por Osteoporose/diagnóstico , Osteoprotegerina/sangue , Ligante RANK/sangue , Artrite Reumatoide/complicações , Artrite Reumatoide/patologia , Biomarcadores/sangue , Densidade Óssea , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose/etiologia , Osteoporose/patologia , Fraturas por Osteoporose/sangue , Fraturas por Osteoporose/etiologia , Pós-Menopausa/sangue , Prognóstico
16.
Nutrients ; 13(8)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34445056

RESUMO

Musculoskeletal deficits are among the most commonly reported extra-intestinal manifestations and complications of inflammatory bowel disease (IBD), especially in those with Crohn's disease. The adverse effects of IBD on bone and muscle are multifactorial, including the direct effects of underlying inflammatory disease processes, nutritional deficits, and therapeutic effects. These factors also indirectly impact bone and muscle by interfering with regulatory pathways. Resultantly, individuals with IBD are at increased risk of osteoporosis and sarcopenia and associated musculoskeletal morbidity. In paediatric IBD, these factors may contribute to suboptimal bone and muscle accrual. This review evaluates the main pathogenic factors associated with musculoskeletal deficits in children and adults with IBD and summarises the current literature and understanding of the musculoskeletal phenotype in these patients.


Assuntos
Colite Ulcerativa/complicações , Doença de Crohn/complicações , Doenças Musculoesqueléticas/etiologia , Sarcopenia/etiologia , Fatores Etários , Composição Corporal , Remodelação Óssea , Colite Ulcerativa/sangue , Colite Ulcerativa/fisiopatologia , Doença de Crohn/sangue , Doença de Crohn/tratamento farmacológico , Doença de Crohn/fisiopatologia , Citocinas/sangue , Glucocorticoides/efeitos adversos , Humanos , Mediadores da Inflamação/sangue , Doenças Musculoesqueléticas/sangue , Doenças Musculoesqueléticas/fisiopatologia , Estado Nutricional , Osteoporose/sangue , Osteoporose/etiologia , Osteoporose/fisiopatologia , Medição de Risco , Fatores de Risco , Sarcopenia/sangue , Sarcopenia/fisiopatologia
17.
Isr Med Assoc J ; 23(8): 490-493, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34392623

RESUMO

BACKGROUND: Osteoporosis is a common medical condition in older ages. A devastating result of osteoporosis may be a hip fracture with up to 30% mortality rate in one year. The compliance rate of osteoporotic medication following a hip fracture is 20% in the western world. OBJECTIVES: To evaluate the impact of the fracture liaison service (FLS) model in the orthopedic department on patient compliance following hip fracture. METHODS: We performed a retrospective review of all patients with hip fracture who were involved with FLS. We collected data regarding kidney function, calcium levels, parathyroid hormone levels, and vitamin D levels at admission. We educated the patient and family, started vitamin D and calcium supplementation and recommended osteoporotic medical treatment. We phoned the patient 6-12 weeks following the fracture to ensure treatment initiation. RESULTS: From June 2018 to June 2019 we identified 166 patients with hip fracture who completed at least one year of follow-up. Over 75% of the patients had low vitamin D levels and 22% had low calcium levels at admission. Nine patients (5%) died at median of 109 days. Following our intervention, 161 patients (96%) were discharged with a specific osteoporotic treatment recommendation; 121 (73%) received medication for osteoporosis on average of < 3 months after surgery. We recommended on injectable medications; however, 51 (42%) were treated with oral biphsophonate. CONCLUSIONS: FLS improved the compliance rate of osteoporotic medical treatment and should be a clinical routine in every medical center.


Assuntos
Cálcio/administração & dosagem , Fraturas do Quadril , Osteoporose , Fraturas por Osteoporose , Período Pós-Operatório , Prevenção Secundária , Vitamina D/administração & dosagem , Idoso , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/classificação , Suplementos Nutricionais , Quimioterapia Combinada , Feminino , Fraturas do Quadril/mortalidade , Fraturas do Quadril/prevenção & controle , Fraturas do Quadril/cirurgia , Humanos , Israel/epidemiologia , Masculino , Mortalidade , Procedimentos Ortopédicos/estatística & dados numéricos , Osteoporose/sangue , Osteoporose/complicações , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Fraturas por Osteoporose/mortalidade , Fraturas por Osteoporose/prevenção & controle , Fraturas por Osteoporose/cirurgia , Estudos Retrospectivos , Prevenção Secundária/métodos , Prevenção Secundária/organização & administração , Vitamina D/sangue
18.
Molecules ; 26(16)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34443306

RESUMO

This study aimed to evaluate and compare the effects of co-treatment with purified annatto oil (PAO) or its granules (GRA, Chronic®) with that of testosterone on the orchiectomy-induced osteoporosis in Wistar rats. After surgery, rats were treated from day 7 until day 45 with testosterone only (TES, 7 mg/kg, IM) or TES + PAO or GRA (200 mg/kg, p.o.). The following parameters were evaluated: food/water intake, weight, HDL, LDL, glucose, triglycerides (TG), total cholesterol (TC), alkaline phosphatase levels, blood phosphorus and calcium contents, femur weight, structure (through scanning electron microscopy), and calcium content (through atomic absorption spectrophotometry). Our results show that orchiectomy could significantly change the blood lipid profile and decrease bone integrity parameters. Testosterone reposition alone could improve some endpoints, including LDL, TC, bone weight, and bone calcium concentration. However, other parameters were not significantly improved. Co-treatment with PAO or GRA improved the blood lipid profile and bone integrity more significantly and improved some endpoints not affected by testosterone reposition alone (such as TG levels and trabeculae sizes). The results suggest that co-treatment with annatto products improved the blood lipid profile and the anti-osteoporosis effects of testosterone. Overall, GRA had better results than PAO.


Assuntos
Bixaceae/química , Carotenoides/química , Fêmur/efeitos dos fármacos , Lipídeos/sangue , Orquiectomia , Osteoporose/sangue , Osteoporose/etiologia , Extratos Vegetais/química , Óleos Vegetais/farmacologia , Testosterona/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Comportamento de Ingestão de Líquido/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Fêmur/ultraestrutura , Masculino , Substâncias Protetoras/farmacologia , Ratos Wistar
19.
BMC Endocr Disord ; 21(1): 170, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34416890

RESUMO

BACKGROUND: The occurrence of hypomagnesemia in patients with primary hyperparathyroidism (PHPT) has been noted previously; however, the association of hypomagnesemia and severity of primary hyperparathyroidism remains unknown. The present study aimed to evaluate the association of hypomagnesemia with biochemical and clinical manifestations in patients with PHPT. METHODS: This was a retrospective study conducted at a tertiary hospital. We obtained data from 307 patients with PHPT from January 2010 through August 2020. Data on demographics, history, laboratory findings, bone densitometry findings, and clinical presentation and complications were collected and were compared in normal magnesium group vs hypomagnesemia group. RESULTS: Among the 307 patients with PHPT included in our study, 77 patients (33/102 [32.4%] males and 44/205 [21.5%] females) had hypomagnesemia. Mean hemoglobin levels in the hypomagnesemia group were significantly lower than those in the normal magnesium group in both males and females. In contrast, patients with hypomagnesemia had a higher mean serum calcium and parathyroid hormone than individuals with normal magnesium. The typical symptoms of PHPT, such as nephrolithiasis, bone pain/fractures, polyuria, or polydipsia, were more common in the hypomagnesemia group. In addition, patients with hypomagnesemia had a higher prevalence of osteoporosis, anemia, and hypercalcemic crisis. Even after adjusting for potential confounders, including age, sex, body mass index, estimated glomerular filtration rate, and parathyroid hormone levels, these associations remained essentially unchanged. CONCLUSION: Biochemical and clinical evidence indicates that patients with PHPT with hypomagnesemia have more severe hyperparathyroidism than those without hypomagnesemia. In addition, PHPT patients with hypomagnesemia had a higher prevalence of osteoporosis, anemia, and hypercalcemic crisis.


Assuntos
Biomarcadores/sangue , Densidade Óssea , Hipercalciúria/fisiopatologia , Hiperparatireoidismo Primário/patologia , Nefrocalcinose/fisiopatologia , Osteoporose/patologia , Erros Inatos do Transporte Tubular Renal/fisiopatologia , Cálcio/sangue , Estudos de Casos e Controles , China/epidemiologia , Feminino , Seguimentos , Humanos , Hipercalciúria/sangue , Hiperparatireoidismo Primário/sangue , Hiperparatireoidismo Primário/epidemiologia , Masculino , Pessoa de Meia-Idade , Nefrocalcinose/sangue , Osteoporose/sangue , Osteoporose/etiologia , Hormônio Paratireóideo/sangue , Prognóstico , Estudos Prospectivos , Erros Inatos do Transporte Tubular Renal/sangue
20.
BMC Endocr Disord ; 21(1): 156, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362364

RESUMO

BACKGROUND: Despite the increased fracture risk, bone mineral density (BMD) is variable in type 1 (T1D) and type 2 (T2D) diabetes mellitus. We aimed at comparing independent BMD predictors in T1D, T2D and control subjects, respectively. METHODS: Cross-sectional case-control study enrolling 30 T1D, 39 T2D and 69 age, sex and body mass index (BMI) - matched controls that underwent clinical examination, dual-energy X-ray absorptiometry (BMD at the lumbar spine and femoral neck) and serum determination of HbA1c and parameters of calcium and phosphate metabolism. RESULTS: T2D patients had similar BMD compared to T1D individuals (after adjusting for age, BMI and disease duration) and to matched controls, respectively. In multiple regression analysis, diabetes duration - but not HbA1c- negatively predicted femoral neck BMD in T1D (ß= -0.39, p = 0.014), while BMI was a positive predictor for lumbar spine (ß = 0.46, p = 0.006) and femoral neck BMD (ß = 0.44, p = 0.007) in T2D, besides gender influence. Age negatively predicted BMD in controls, but not in patients with diabetes. CONCLUSIONS: Long-standing diabetes and female gender particularly increase the risk for low bone mass in T1D. An increased body weight partially hinders BMD loss in T2D. The impact of age appears to be surpassed by that of other bone regulating factors in both T1D and T2D patients.


Assuntos
Biomarcadores/sangue , Densidade Óssea , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Fraturas Ósseas/diagnóstico , Osteoporose/diagnóstico , Adulto , Glicemia/análise , Índice de Massa Corporal , Estudos de Casos e Controles , Estudos Transversais , Feminino , Seguimentos , Fraturas Ósseas/sangue , Fraturas Ósseas/epidemiologia , Hemoglobina A Glicada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/sangue , Osteoporose/epidemiologia , Prognóstico , Romênia/epidemiologia
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