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1.
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
2.
Int J Mol Sci ; 22(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34445423

RESUMO

Low-magnitude high-frequency vibration (LMHFV) has previously been reported to modulate the acute inflammatory response of ovariectomy-induced osteoporotic fracture healing. However, the underlying mechanisms are not clear. In the present study, we investigated the effect of LMHFV on the inflammatory response and the role of the p38 MAPK mechanical signaling pathway in macrophages during the healing process. A closed femoral fracture SD rat model was used. In vivo results showed that LMHFV enhanced activation of the p38 MAPK pathway at the fracture site. The acute inflammatory response, expression of inflammatory cytokines, and callus formation were suppressed in vivo by p38 MAPK inhibition. However, LMHFV did not show direct in vitro enhancement effects on the polarization of RAW264.7 macrophage from the M1 to M2 phenotype, but instead promoted macrophage enlargement and transformation to dendritic monocytes. The present study demonstrated that p38 MAPK modulated the enhancement effects of mechanical stimulation in vivo only. LMHFV may not have exerted its enhancement effects directly on macrophage, but the exact mechanism may have taken a different pathway that requires further investigation in the various subsets of immune cells.


Assuntos
Citocinas/sangue , Consolidação da Fratura , Fraturas por Osteoporose/terapia , Vibração/uso terapêutico , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Fenômenos Biomecânicos , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Humanos , Sistema de Sinalização das MAP Quinases , Camundongos , Fraturas por Osteoporose/sangue , Fraturas por Osteoporose/imunologia , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento , Microtomografia por Raio-X
3.
Isr Med Assoc J ; 23(8): 497-500, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34392625

RESUMO

BACKGROUND: The incidence of fragility hip fractures, intracapsular and extracapsular, has been increasing worldwide. Fracture stability is important for treatment decision-making and is related to the expected rate of complications. It is unclear whether metabolic therapy explains the increased incidence of unstable fractures. OBJECTIVES: To investigate the possible association between treatment with bisphosphonates and the various patterns encountered with intertrochanteric hip fractures. METHODS: Patients with fragility hip fractures who were treated in our department between 2013 and 2014 were included in this study. They were classified into three groups: group 1 had a stable extracapsular fracture, group 2 had an unstable extracapsular fracture, and group 3 had an intracapsular fracture. Collated data included: osteoporosis preventive therapy and duration, fracture-type, history of previous fractures, and vitamin D levels. RESULTS: Of 370 patients, 87 were previously treated with bisphosphonates (18.3% prior to fracture in group 1, 38.3% in group 2, and 13.8% in group 3). Of those treated with bisphosphonates, 56.3% had an unstable fracture, 21.8% had a stable fracture, and the rest an intracapsular fracture. In contrast, only 27.9% of patients who were not treated with bisphosphonates had an unstable fracture and 30.0% had stable fractures. CONCLUSIONS: Our findings show a higher proportion of complex and unstable fractures among patients with fragility hip-fractures who were treated with bisphosphonates than among those who did not receive this treatment. The risk for complex and unstable fracture may affect the preferred surgical treatment, its complexity, length of surgery, and rehabilitation.


Assuntos
Difosfonatos/uso terapêutico , Fraturas do Quadril , Efeitos Adversos de Longa Duração/epidemiologia , Osteoporose , Fraturas por Osteoporose , Complicações Pós-Operatórias , Idoso , Conservadores da Densidade Óssea/uso terapêutico , Duração da Terapia , Feminino , Fraturas do Quadril/classificação , Fraturas do Quadril/diagnóstico , Fraturas do Quadril/fisiopatologia , Fraturas do Quadril/cirurgia , Humanos , Incidência , Israel/epidemiologia , Masculino , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Fraturas por Osteoporose/sangue , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/prevenção & controle , Avaliação de Resultados em Cuidados de Saúde , Seleção de Pacientes , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Medição de Risco , Vitamina D/sangue
4.
Nutrients ; 13(4)2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33920153

RESUMO

Despite the adverse metabolic and functional consequences of obesity, caloric restriction- (CR) induced weight loss is often contra-indicated in older adults with obesity due to the accompanying loss of areal bone mineral density (aBMD) and subsequent increased risk of fracture. Several studies show a positive effect of exercise on aBMD among weight-stable older adults; however, data on the ability of exercise to mitigate bone loss secondary to CR are surprisingly equivocal. The purpose of this review is to provide a focused update of the randomized controlled trial literature assessing the efficacy of exercise as a countermeasure to CR-induced bone loss among older adults. Secondarily, we present data demonstrating the occurrence of exercise-induced changes in bone biomarkers, offering insight into why exercise is not more effective than observed in mitigating CR-induced bone loss.


Assuntos
Restrição Calórica/efeitos adversos , Terapia por Exercício/métodos , Obesidade/terapia , Osteoporose/epidemiologia , Fraturas por Osteoporose/epidemiologia , Biomarcadores/sangue , Densidade Óssea/fisiologia , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Humanos , Osteoporose/sangue , Osteoporose/etiologia , Osteoporose/prevenção & controle , Fraturas por Osteoporose/sangue , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Resultado do Tratamento , Perda de Peso/fisiologia
5.
Sci Rep ; 10(1): 22090, 2020 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-33328494

RESUMO

Pentosidine (PEN) and carboxymethyl-lysine (CML) are well-recognized advanced glycation end products (AGEs). However, how these AGEs affect the pathophysiology of osteoporosis and osteoporotic fractures remains controversial. This cross-sectional study aimed to investigate the associations of PEN and CML with bone markers, bone mineral density (BMD), and osteoporotic fractures in postmenopausal women from the Nagano Cohort Study. A total of 444 Japanese postmenopausal outpatients (mean ± standard deviation age: 69.8 ± 10.2 years) were enrolled after the exclusion of patients with acute or severe illness or secondary osteoporosis. The relationships among urinary PEN and serum CML levels, various bone markers, lumbar and hip BMD, and prevalent vertebral and long-bone fractures were evaluated. PEN associated significantly with prevalent vertebral fracture after adjustment for other confounders (odds ratio [OR] 1.59, 95% confidence interval [CI] 1.22-2.07; P < 0.001), but not with lumbar BMD. In contrast, a significant negative correlation was found between CML and lumbar BMD (r = - 0.180; P < 0.001), and this relationship was significant after adjustment for confounders (OR 0.84, 95% CI 0.76-0.93; P < 0.01). Although patients with prevalent vertebral fracture had significantly higher CML levels, the association between CML and prevalent vertebral fracture did not reach significance in the multivariate regression model. Both PEN and CML may play important roles in bone health for postmenopausal women, possibly via different mechanisms.


Assuntos
Arginina/análogos & derivados , Lisina/análogos & derivados , Osteoporose Pós-Menopausa/sangue , Fraturas por Osteoporose/sangue , Idoso , Idoso de 80 Anos ou mais , Arginina/urina , Densidade Óssea/genética , Estudos de Coortes , Feminino , Produtos Finais de Glicação Avançada/genética , Humanos , Japão/epidemiologia , Vértebras Lombares/fisiopatologia , Lisina/sangue , Lisina/urina , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/patologia , Osteoporose Pós-Menopausa/urina , Fraturas por Osteoporose/patologia , Fraturas por Osteoporose/urina , Pós-Menopausa
6.
Int J Mol Sci ; 21(18)2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32967246

RESUMO

Osteoporosis is a multifactorial skeletal disease that is associated with both bone mass decline and microstructure damage. The fragility fractures-especially those affecting the femur-that embody the clinical manifestation of this pathology continue to be a great medical and socioeconomic challenge worldwide. The currently available diagnostic tools, such as dual energy X-ray absorptiometry, Fracture Risk Assessment Tool (FRAX) score, and bone turnover markers, show limited specificity and sensitivity; therefore, the identification of alternative approaches is necessary. As a result of their advantageous features, such as non-invasiveness, biofluid stability, and easy detection, circulating cell-free miRs are promising new potential biomarkers for the diagnosis of osteoporosis and low-traumatic fracture risk assessment. However, due to the absence of both standardized pre-analytical, analytical, and post-analytical protocols for their measurement and universally accepted guidelines for diagnostic use, their clinical utility is limited. The aim of this review was to record all the data currently available in the literature concerning the use of circulating microRNAs as both potential biomarkers for osteoporosis diagnosis and fragility fracture risk evaluation, and group them according to the experimental designs, in order to support a more conscious choice of miRs for future research in this field.


Assuntos
Densidade Óssea , MicroRNA Circulante/sangue , Osteoporose/sangue , Osteoporose/diagnóstico , Fraturas por Osteoporose/sangue , Fraturas por Osteoporose/diagnóstico , Biomarcadores/sangue , Humanos , Medição de Risco
7.
Int J Mol Sci ; 21(18)2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32967315

RESUMO

Osteoporosis (OP) is a multifactorial disorder in which environmental factors along with genetic variants and epigenetic mechanisms have been implicated. Long non-coding RNAs (lncRNAs) have recently emerged as important regulators of bone metabolism and OP aetiology. In this study, we analyzed the expression level and the genetic association of lncRNA GAS5 in OP patients compared to controls. Quantitative RT-PCR analysis of GAS5 was performed on the serum of 56 OP patients and 28 healthy individuals. OP subjects were divided into three groups of analysis: 29 with fragility fractures of lumbar spine (OP_VF), 14 with fragility fractures of femoral neck (OP_FF) and 13 without fractures (OP_WF). Genotyping of the rs145204276 insertion/deletion polymorphism has also been performed by Restriction fragment length polymorphism (RFLP) and direct sequencing analyses. Expression of circulating GAS5 is significantly increased in OP patients compared to controls (p < 0.01), with a statistically higher significance in fractured OP individuals vs. healthy subjects (p < 0.001). No statistically significant change was found in female OP patients; conversely, GAS5 is upregulated in the subgroup of fractured OP women sera (p < 0.01) and in all OP males (p < 0.05). Furthermore, a direct correlation between GAS5 expression level and parathyroid hormone (PTH) concentration was found in OP patients (r = 0.2930; p = 0.0389). Genetic analysis of rs145204276 revealed that the deletion allele was correlated with a higher expression of GAS5 in OP patients (0.22 ± 0.02 vs. 0.15 ± 0.01, ** p < 0.01). Our results suggest circulating GAS5 as a putative biomarker for the diagnosis and prognosis of OP and OP-related fractures.


Assuntos
Ácidos Nucleicos Livres/sangue , Regulação da Expressão Gênica , Osteoporose/sangue , Fraturas por Osteoporose/sangue , RNA Longo não Codificante/sangue , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
8.
Artigo em Inglês | MEDLINE | ID: mdl-32903642

RESUMO

Introduction: Serum phosphate plays an important role in bone mineralization and might be a risk factor for many bone diseases. Patients with T2D usually have low serum phosphate level due to diet control, osmotic diuresis, and insulin stimulation. Current studies have discussed the linear association between serum phosphate and bone mineral density (BMD). Objective: We aimed to analyze both the linear and non-linear correlations between serum phosphate and BMD in patients with type 2 diabetes (T2D). Methods: We included 1,469 patients with T2D and obtained their basic information, laboratory measurements, and BMD data. Multivariate adjusted linear regression was used to analyze the linear associations, and we applied a two-piecewise linear regression model using a smoothing function to examine the non-linear association. Results: No linear correlation was found between serum phosphate and BMD in patients with T2D. In women with T2D, we found a non-linear correlation between serum phosphate level and femur neck or total hip BMD. When serum phosphate was <1.3 mmol/L, it was positively associated with femur neck and total hip BMD, whereas when phosphate was >1.3 mmol/L, it was negatively associated with femur neck BMD. Conclusions: In men with T2D, serum phosphate level was not associated with BMD. However, in women with T2D, we found a non-linear correlation between serum phosphate and femur neck or total hip BMD.


Assuntos
Densidade Óssea , Diabetes Mellitus Tipo 2/fisiopatologia , Fraturas por Osteoporose/fisiopatologia , Fosfatos/sangue , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/sangue , Fraturas por Osteoporose/etiologia , Estudos Retrospectivos , Fatores de Risco
9.
Panminerva Med ; 62(2): 83-92, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32515572

RESUMO

BACKGROUND: Obesity has been regarded to be protective against fracture in spite of its association with low levels of vitamin D. Vitamin D is the key regulator of bone metabolism and its deficiency contributes to higher level of parathyroid hormone (PTH), leading to the activation of bone turnover. METHODS: We studied 161 subjects of which 65 were young healthy subjects and 96 were elderly subjects. We measured creatinine, 25(OH)D, 1,25(OH)2D, PTH, albumin, and calcium plasma levels, we evaluated physical activity, and we calculated BMI. A sub-cohort of elderly subjects also underwent DXA scans. RESULTS: Overweight and obese subjects, as well as underweight ones, had lower levels of vitamin D but normal serum concentrations of 1,25(OH)2D and PTH was higher in underweight and obese subjects. Moreover, we found a nonlinear relationship between body mass index (BMI) and PTH with a significant U-shaped exponential regression. Regardless of BMI, 25(OH)D mean levels were higher in subjects who practice physical activity. CONCLUSIONS: These findings suggest that physical activity and BMI had a significant effect on the metabolism of bone and vitamin D, but the effect of BMI was different in underweight, normal weight or obese subjects. In obesity the real vitamin D deficiency could be estimate by serum 1,25(OH)2D concentrations whose lower levels contribute to the higher PTH production and consequently to bone loss and to a greater fracture risk.


Assuntos
Exercício Físico , Obesidade/sangue , Fraturas por Osteoporose/sangue , Deficiência de Vitamina D/sangue , Vitamina D/análogos & derivados , Adiposidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Índice de Massa Corporal , Densidade Óssea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/epidemiologia , Obesidade/fisiopatologia , Fraturas por Osteoporose/diagnóstico , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/fisiopatologia , Prevalência , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Cidade de Roma/epidemiologia , Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/fisiopatologia
10.
Aging (Albany NY) ; 12(11): 10633-10641, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32482913

RESUMO

The study evaluates the serum levels of Trimethylamine N-Oxide (TMAO), a gut microbial metabolite, in 286 postmenopausal women with hip fracture. From January 1, 2018 to December 31, 2018, eligible patients were included. Same women without fracture mated age were enrolled. TMAO serum levels were tested by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The serum levels of TMAO were significantly higher in patients with hip fracture than in those controls (P<0.001). The serum levels of TMAO were also higher in patients with hip fracture only than in those who also had upper limb fracture (P=0.001). High level of TMAO was proved a predictor of both hip fracture and had upper limb fracture combined hip fracture, after the adjustment of other existing risk factors [e.g., for each 1 uM increase of TMAO, odd ratio 1.16 (95% CI, 1.07-1.25), P < 0.001; and 1.12 (95% CI, 1.03-1.26), P=0.008, respectively]. In summary, increased TMAO serum levels associated with high risk of hip fracture, suggesting that increase TMAO may contribute to osteoporosis and fracture in postmenopausal women.


Assuntos
Microbioma Gastrointestinal/fisiologia , Fraturas do Quadril/epidemiologia , Metilaminas/sangue , Fraturas por Osteoporose/epidemiologia , Pós-Menopausa/sangue , Idoso , Estudos de Casos e Controles , Feminino , Fraturas do Quadril/sangue , Humanos , Metilaminas/metabolismo , Pessoa de Meia-Idade , Fraturas por Osteoporose/sangue , Fatores de Risco , Espectrometria de Massas em Tandem
11.
Biomolecules ; 10(6)2020 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-32570976

RESUMO

Osteoporosis, one of the leading causes of bone fractures, is characterized by low bone mass and structural deterioration of bone tissue, which are associated with a consequent increase in bone fragility and predisposition to fracture. Current screening tools are limited in estimating the proper assessment of fracture risk, highlighting the need to discover novel more suitable biomarkers. Genetic and environmental factors are both implicated in this disease. Increasing evidence suggests that epigenetics and, in particular, miRNAs, may represent a link between these factors and an increase of fracture risk. miRNAs are a class of small noncoding RNAs that negatively regulate gene expression. In the last decade, several miRNAs have been associated with the development of osteoporosis and bone fracture risk, opening up new possibilities in precision medicine. Recently, these molecules have been identified in several biological fluids, and the possible existence of a circulating miRNA (c-miRNA) signature years before the fracture occurrence is suggested. The aim of this review is to provide an overview of the c-miRNAs suggested as promising biomarkers for osteoporosis up until now, which could be helpful for early diagnosis and monitoring of treatment response, as well as fracture risk assessment, in osteoporotic patients.


Assuntos
MicroRNAs/sangue , Osteoporose/sangue , Fraturas por Osteoporose/sangue , Biomarcadores/sangue , Densidade Óssea , Epigênese Genética/genética , Humanos , MicroRNAs/genética , Osteoporose/diagnóstico , Osteoporose/genética , Fraturas por Osteoporose/diagnóstico , Fraturas por Osteoporose/genética
12.
Injury ; 51 Suppl 1: S30-S36, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32360086

RESUMO

Osteoporotic hip fracture (OHF) is an increasingly frequent age-related pathology, which results in high rates of functional loss and mortality within the first year after surgery. This study assessed whether preoperative levels of brain natriuretic peptide (NT-proBNP) and troponin I were related to early occurrence (30d) of major adverse cardio-vascular events (MACE) after OHF repair surgery. During a 6-month period, perioperative clinical and analytical data from consecutive patients, without known history of cardiovascular disease and undergoing surgery for OHF repair at a single centre, were prospectively collected. MACE was defined as acute myocardial ischaemia or infarction, acute heart failure or cardiovascular death. amongst the 140 patients included, 23 (16.4%) developed postoperative MACE (MACE group) and 117 did not (Control group). Compared to those from control group, patients from MACE group were older, had poorer physical status (ASA III-IV), received preoperative red blood cell transfusion (RBCT) more frequently, presented with lower haemoglobin concentrations and higher NT-proBNP, creatinine and troponin I concentrations. Overall, RBCT requirements and 30d mortality rate were also higher in MACE group. However, in multivariate analysis, only preoperative RBCT, creatinine >1 mg/dL and NT-proBNP >450 pg/mL remained as independent preoperative risks factors for postoperative MACE, while 95% confidence intervals of odds ratios were wide. Though our findings require confirmation in a larger multicentre cohort, identifying risk factors for early postoperative MACE after OHF repair surgery, might facilitate assessing patients' risk prior to and following surgery, and targeting them the appropriate preventive and/or therapeutic interventions.


Assuntos
Fraturas do Quadril/cirurgia , Peptídeo Natriurético Encefálico/sangue , Fraturas por Osteoporose/cirurgia , Fragmentos de Peptídeos/sangue , Troponina I/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Doenças Cardiovasculares/etiologia , Transfusão de Eritrócitos , Feminino , Fraturas do Quadril/sangue , Fraturas do Quadril/mortalidade , Humanos , Modelos Logísticos , Masculino , Análise Multivariada , Fraturas por Osteoporose/sangue , Fraturas por Osteoporose/mortalidade , Complicações Pós-Operatórias , Valor Preditivo dos Testes , Cuidados Pré-Operatórios/métodos , Estudos Prospectivos , Curva ROC , Medição de Risco , Fatores de Risco , Fatores de Tempo
13.
Clin Chem ; 66(5): 676-685, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32255480

RESUMO

BACKGROUND: Whether low plasma 25-hydroxyvitamin D concentrations cause osteoporotic fractures is unclear. We tested the hypothesis that low plasma 25-hydroxyvitamin D concentrations are associated with increased risk of osteoporotic fractures using a Mendelian randomization analysis. METHODS: We genotyped 116 335 randomly chosen white Danish persons aged 20-100 years in 2 population-based cohort studies for plasma 25-hydroxyvitamin D decreasing genotypes in CYP2R1 (rs117913124 and rs12794714), DHCR7 (rs7944926 and rs11234027), GEMIN2 (rs2277458), and HAL (rs3819817); 35 833 had information on plasma 25-hydroxyvitamin D. We assessed risk of total, osteoporotic, and anatomically localized fractures from 1981 through 2017. Information on fractures and vital status was obtained from nationwide registries. RESULTS: During up to 36 years of follow-up, we observed 17 820 total fractures, 10 861 osteoporotic fractures, and 3472 fractures of hip or femur. Compared with individuals with 25-hydroxyvitamin D ≥ 50nmol/L, multivariable adjusted hazard ratios (95% CIs) for total fractures were 1.03 (0.97-1.09) for individuals with 25-49.9 nmol/L, 1.19 (1.10-1.28) for individuals with 12.5-24.9 nmol/L, and 1.39 (1.21-1.60) for individuals with 25-hydroxyvitamin D < 12.5 nmol/L. Corresponding hazard ratios were 1.07 (1.00-1.15), 1.25 (1.13-1.37), and 1.49 (1.25-1.77) for osteoporotic fractures and 1.09 (0.98-1.22), 1.37 (1.18-1.57), and 1.41 (1.09-1.81) for fractures of hip or femur, respectively. Hazard ratios per 1 increase in vitamin D allele score, corresponding to 3.0% (approximately 1.6 nmol/L) lower 25-hydroxyvitamin D concentrations, were 0.99 (0.98-1.00) for total fractures, 0.99 (0.97-1.00) for osteoporotic fractures, and 0.98 (0.95-1.00) for fractures of hip or femur. CONCLUSIONS: Low plasma 25-hydroxyvitamin D concentrations were associated with osteoporotic fractures; however, Mendelian randomization analysis provided no evidence supporting a causal role for vitamin D in the risk for osteoporotic fractures.


Assuntos
Fraturas por Osteoporose/etiologia , Fatores de Risco , Deficiência de Vitamina D/complicações , Vitamina D/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Variação Genética , Humanos , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Fraturas por Osteoporose/sangue , Fraturas por Osteoporose/genética , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Adulto Jovem
14.
J Clin Endocrinol Metab ; 105(5)2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32155267

RESUMO

PURPOSE: Whether androgens, distinct from estrogen, maintain bone health during male aging has implications for understanding osteoporosis. We assessed associations of different sex hormones with incidence of any bone fracture or hip fracture in older men. PARTICIPANTS AND METHODS: Analysis of 3307 community-dwelling men aged 76.8 ± 3.5 years, median follow-up period of 10.6 years. Plasma testosterone (T), dihydrotestosterone (DHT), and estradiol (E2) assayed by mass spectrometry, sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) using immunoassay. Incident fractures determined via data linkage. We analyzed probability of fracture and performed Cox regression adjusted for age, medical comorbidities, and frailty. RESULTS: Incident fractures occurred in 330 men, including 144 hip fractures. Probability plots suggested nonlinear relationships between hormones and risk of any fracture and hip fracture, with higher risk at lower and higher plasma T, lower E2, higher SHBG, and higher LH. In fully adjusted models, there was a U-shaped association of plasma T with incidence of any fracture (Quartile 2 [Q2] versus Q1: fully adjusted hazard ratio [HR] = 0.69, 95% confidence interval [CI] 0.51-0.94, P = .020; Q3: HR 0.59, 95% CI 0.42-0.83, P = .002) and hip fracture (Q2 versus Q1: HR 0.60, 95% CI 0.37-0.93, P = .043; Q3: HR 0.52, 95% CI 0.31-0.88, P = .015). DHT, E2, and LH were not associated with fracture. Higher SHBG was associated with hip fracture (Q4 versus Q1: HR 1.76, 95% CI 1.05-2.96, P = .033). CONCLUSIONS: Midrange plasma T was associated with lower incidence of any fracture and hip fracture, and higher SHBG with increased risk of hip fracture. Circulating androgen rather than estrogen represents a biomarker for hormone effects on bone driving fracture risk.


Assuntos
Estradiol/sangue , Fraturas Ósseas/epidemiologia , Testosterona/sangue , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Densidade Óssea , Seguimentos , Fraturas Ósseas/sangue , Fraturas do Quadril/sangue , Fraturas do Quadril/epidemiologia , Humanos , Incidência , Vida Independente , Masculino , Osteoporose/sangue , Osteoporose/epidemiologia , Fraturas por Osteoporose/sangue , Fraturas por Osteoporose/epidemiologia , Fatores de Risco , Fatores Sexuais , Globulina de Ligação a Hormônio Sexual/análise , Austrália Ocidental/epidemiologia
15.
BMC Musculoskelet Disord ; 21(1): 164, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32164704

RESUMO

BACKGROUND: Vitamin D deficiency has long been studied as a risk factor for osteoporosis. However, the association between serum vitamin D status, bone mineral density (BMD) and the incidence of vertebral fractures (OVFs) remain controversial. It is believed that free portion of the circulating vitamin D carries the metabolic activities of vitamin D. Therefore, the aim of the present study is to analyse if free vitamin D correlates with BMD and osteoporotic fragile vertebral fractures in the elderly population. METHODS: A total of 90 consecutive patients, including 81 female and 9 male patients, aged > 48 years, were included in this cross sectional study between March and July of 2018. Total vitamin D (total 25(OH)D), free vitamin D (free 25(OH)D), calcium and phosphorus were measured. BMD was measured using dual energy X-ray absorptiometry (DEXA) and osteoporotic vertebral fracture was assessed using plain radiograph. Multiple linear regression was performed to find out the association between total vitamin D, free vitamin D and BMD at various sites. To evaluate the association with osteoporotic vertebral multivariate logistic regression model was used. RESULTS: The mean total vitamin D and free vitamin D were 25.1 ± 10.2 and 6.1 ± 1.7 respectively. Free vitamin D had a linear correlation with total vitamin D (R2 = 0.69). While free vitamin D had a positive correlation with lumbar BMD roles (p < 0.05), total vitamin D didn't have any association with BMD at any site. Of the total patients, 62 patients (68.9%) had thoracolumbar junction OVFs. Free vitamin D level correlated with the prevalence of OVFs as well as lumbar osteoporosis (p < 0.05). However, there was no statistical correlation between serum vitamin D status and the OVFs. CONCLUSIONS: Free vitamin D was significantly related to the occurrence of thoracolumbar junction OVFs and lumbar BMD, which assumed to be a positive predictor for fracture and osteoporosis prevention. However, total serum vitamin D levels did not have any association with BMD at different sites as well as fragile vertebral fracture. TRIAL REGISTRATION: The study is registered at clinicaltrials.gov NCT03605173.


Assuntos
Fraturas por Osteoporose/etiologia , Deficiência de Vitamina D/fisiopatologia , Vitamina D/análise , Absorciometria de Fóton , Idoso , Densidade Óssea , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Vértebras Lombares/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fraturas por Osteoporose/sangue , Fraturas da Coluna Vertebral/etiologia , Vértebras Torácicas/patologia , Vitamina D/sangue , Deficiência de Vitamina D/sangue
16.
Ann Med ; 52(3-4): 94-108, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32212941

RESUMO

Aim of the study: To assess serum sclerostin in transfusion-dependent beta-thalassaemia patients versus healthy controls and to examine its associations with bone mineral density, bone metabolism markers and beta thalassaemia alterations.Material and methods: Sixty-two transfusion-dependent beta-thalassaemia (TDßT) patients and 30 healthy controls were evaluated for serum sclerostin, osteocalcin, beta-cross laps, osteoprotegerin and serum level of receptor activator of nuclear factor kappa-Β ligand (sRANKL). Bone mineral density was measured at the lumbar spine and femoral neck. Thalassaemia characteristics were collected from the patients' medical records.Results: A significantly higher sclerostin level (median 565.50 pmol/L) was observed in the transfusion-dependent beta-thalassaemia patients vs. the healthy controls (median 48.65 pmol/L, p < .001). Sclerostin showed significant associations with the Z-scores at the lumbar spine and femoral neck, osteocalcin, beta-cross laps, osteoprotegerin, sRANKL, pretransfusion haemoglobin, liver iron concentration and female gonadal state. Significantly higher levels of sclerostin were observed in splenectomized TDßT patients and in those with fragility fractures. Age, sex, body mass index, disease severity, serum ferritin, cardiac T2* and male gonadal state did not show significant associations with sclerostin.Conclusion: Sclerostin may play a role in the bone pathophysiology of beta-thalassaemia patients and could serve as a marker of severe osteoporosis.KEY MЕSSAGESSerum sclerostin is more than 10-fold higher in adult patients with transfusion-dependent beta-thalassaemia compared to healthy controls.Serum sclerostin is negatively associated with bone mineral density and the bone synthesis markers and positively with the bone resorption indices.Serum sclerostin is significantly associated with pre-transfusion haemoglobin, liver iron concentration, splenectomy status and fragility fracture events in adult patients with transfusion-dependent beta-thalassaemia.Serum sclerostin could serve as a marker of severe osteoporosis in beta-thalassaemia patients.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/sangue , Densidade Óssea , Talassemia beta/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/sangue , Osteoporose/diagnóstico , Osteoporose/etiologia , Fraturas por Osteoporose/sangue , Fraturas por Osteoporose/etiologia , Talassemia beta/complicações
17.
J Orthop Surg Res ; 15(1): 81, 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32103764

RESUMO

BACKGROUND: The incidence of osteoporotic fractures has increased rapidly, and because of the poor prognosis and high mortality associated with osteoporotic fractures, they remain a prospective research area globally. One way to reduce their incidence is to investigate their intervention risk factors in the elderly. Hence, this study explores the correlation between serum 25-hydroxyvitamin D [25(OH)D] levels and osteoporotic fractures in elderly patients through a meta-analysis. METHODS: We conducted our literature search mainly in PubMed and Embase for identifying studies that investigated the relationship between serum 25(OH)D levels and the risk for osteoporotic fractures. We performed categorical analysis, heterogeneity checks, publication bias analysis, and subgroup analyses. RESULTS: In total, 20 studies were included, of which 4 were case-cohort studies and 16 were cohort studies. A total of 41,738 patients from 20 studies were included in the meta-analysis, of which 5916 had fractures, including 3237 hip fractures. By combining the lowest and highest categories of relative risks (RRs) and 95% confidence intervals (CIs), it was suggested that lower serum 25-hydroxyvitamin D levels may be a risk factor for fractures. RR (95% CI) for total and hip fractures were 1.11 (0.99, 1.24) and 0.89 (0.80, 0.98) after adjustments. CONCLUSIONS: Our study showed that compared to low serum 25(OH)D levels, high serum 25(OH)D levels reduce the risk of hip fractures in the patients aged 60 years or older. In contrast, serum 25(OH)D has no significant relationship with total fracture risk.


Assuntos
Fraturas do Quadril/sangue , Fraturas do Quadril/epidemiologia , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Coortes , Feminino , Fraturas do Quadril/diagnóstico , Humanos , Masculino , Fraturas por Osteoporose/sangue , Fraturas por Osteoporose/diagnóstico , Fraturas por Osteoporose/epidemiologia , Fatores de Risco , Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico
18.
Surgery ; 167(1): 144-148, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31582307

RESUMO

BACKGROUND: Parathyroidectomy (PTX) increases bone mineral density and decreases fracture risk in patients with primary hyperparathyroidism. This study examined the effect of adding bisphosphonates either before or after PTX on skeletal outcomes. METHODS: A retrospective cohort study of bisphosphonate-naïve patients (1995-2016) with osteoporosis and primary hyperparathyroidism (calcium >10.5 mg/dL; PTH >65) was performed. Time-varying Cox regression was used to estimate an adjusted risk of any fracture in 5 comparison groups: observation, bisphosphonates alone, PTX alone, bisphosphonates then PTX, and PTX then bisphosphonates. The secondary outcome was change in bone mineral density of the hip. RESULTS: The cohort comprised 1,737 patients, of whom 303 underwent PTX (17%), 433 received bisphosphonates only (25%), 125 had bisphosphonates then PTX (7%), and 69 had PTX then bisphosphonates (4%). PTX was associated with a decrease in fracture risk (HR 0.55, 95% CI 0.35-0.84), as was bisphosphonates then PTX (HR 0.46, 95% CI 0.25-0.83). In contrast, the fracture risks associated with PTX then bisphosphonates (HR 1.09, 95% CI 0.65-1.81) and bisphosphonates alone (HR 0.82, 95% CI 0.62-1.08) were similar to observation. Hip bone mineral density increased after both PTX (5.50%, 95% CI 3.39-7.61) and PTX then bisphosphonates (6.30%, 95% CI 2.53-10.07). CONCLUSION: Bisphosphonate initiation after PTX may interfere with the beneficial effects of PTX on fracture risk in osteoporotic patients with primary hyperparathyroidism.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Hiperparatireoidismo Primário/terapia , Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/epidemiologia , Paratireoidectomia , Absorciometria de Fóton , Idoso , Densidade Óssea/efeitos dos fármacos , Cálcio/sangue , Terapia Combinada/métodos , Difosfonatos/administração & dosagem , Feminino , Humanos , Hiperparatireoidismo Primário/sangue , Hiperparatireoidismo Primário/complicações , Masculino , Pessoa de Meia-Idade , Osteoporose/sangue , Osteoporose/etiologia , Osteoporose/prevenção & controle , Fraturas por Osteoporose/sangue , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/prevenção & controle , Hormônio Paratireóideo/sangue , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Resultado do Tratamento
19.
J Clin Endocrinol Metab ; 105(5)2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31872255

RESUMO

CONTEXT: Osteoporosis is a degenerative bone disease in aging men and women. MiRNAs associated with progressive bone loss in osteoporosis had not been clearly demonstrated. OBJECTIVE: The evaluation of the differentially expressed miRNAs in the bone tissue and serum of osteoporotic women with aging. METHODS: MiRNAs GeneChip and real-time PCR were used to screen differently expressed miRNAs in bone tissues of 21 osteoporotic women ages 60-69 years and 80-89 years. Identified miRNAs were detected in the serum of the validation cohort, which consisted of 14 healthy premenopausal women and 86 postmenopausal women with osteopenia or osteoporosis. MiR-181c-5p and miR-497-5p expression were validated in aging and OVX mice models, and osteoblasts. Their role in osteogenesis was validated in vitro. RESULTS: Twenty-four miRNAs showed the highest differential expression in bone tissues of osteoporotic women in initial screening. Among them, four miRNAs were identified both in the bone tissue and serum in the validation cohort. The levels of miR-181c-5p and miR-497-5p were decreased in the serum of postmenopausal women with osteopenia or osteoporosis, but increased in subjects treated with bisphosphonate plus calcitriol. MiR-181c-5p and miR-497-5p were significantly downregulated in the bone tissue of aging and OVX mice models, and upregulated during the osteogenic differentiation of hFOB1.19 and MC3T3-E1 cells. Overexpression of miR-181c-5p and miR-497-5p promoted the differentiation and mineralization of osteoblasts. CONCLUSIONS: MiR-181c-5p and miR-497-5p are involved in bone metabolism and associated with progressive bone loss of due to osteoporosis, suggesting that circulating miR-181c-5p and miR-497-5p might act as potential biomarkers for monitoring the effects of antiosteoporotic therapies or the diagnostic approach.


Assuntos
MicroRNAs/sangue , Osteoporose/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores/sangue , Estudos de Casos e Controles , Células Cultivadas , Estudos de Coortes , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Osteoporose/sangue , Osteoporose/genética , Osteoporose Pós-Menopausa/sangue , Osteoporose Pós-Menopausa/diagnóstico , Osteoporose Pós-Menopausa/genética , Fraturas por Osteoporose/sangue , Fraturas por Osteoporose/diagnóstico , Fraturas por Osteoporose/genética , Valor Preditivo dos Testes , Prognóstico , Células RAW 264.7
20.
Medicine (Baltimore) ; 98(45): e17774, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702629

RESUMO

The impact of magnesium on risk of knee osteoarthritis (KOE) is still under investigation. This meta-analysis evaluated the relationship between magnesium and risk of KOE.A comprehensive search was performed to identify retrospective cohort study or cross-sectional study of the association between magnesium and KOE from the Cochrane library, PubMed, and Embase. The search time limit was from the establishment of the database to December 2018. Two evaluators selected the literature, extracted the data, and evaluated the quality of the literature according to the inclusion and exclusion criteria, independently. Meta-analysis was performed using RevMan 5.3 software and publication bias was assessed using Begg and Egger test and funnel plot.Finally, 6 studies were included with a total of 15,715 participants. Although higher daily intake of magnesium was associated with a significantly reduced risk of fracture in patients with KOE (OR = 0.66, 95%CI: 0.56, 0.78; P < .00001), it was not significant for lowering the risk of KOE (OR = 0.80; 95% CI: 0.61, 1.04; P = .1). Meta-analysis also showed that population with higher serum magnesium levels had significantly lower risk of KOE (odds ratio (OR) = 0.84; 95% confidence interval (CI): 0.72, 0.98; P = .03). Further subgroup analysis showed that the relationship between serum magnesium level and KOE risk was significantly affected by serum magnesium level (P = .006 for quartiles 4 vs 1).Higher level of magnesium intake was not associated with lower risk of KOE. However, higher daily intake of magnesium may be inversely associated with risk of fracture in KOE patients.


Assuntos
Magnésio/uso terapêutico , Osteoartrite do Joelho/epidemiologia , Fraturas por Osteoporose/epidemiologia , Idoso , Estudos Transversais , Feminino , Humanos , Magnésio/sangue , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/sangue , Osteoartrite do Joelho/complicações , Fraturas por Osteoporose/sangue , Estudos Retrospectivos
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