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1.
Medicine (Baltimore) ; 98(47): e18067, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31764838

RESUMO

Osteoporosis is a complication of type 2 diabetes mellitus (T2DM). Blockade of receptor activator of nuclear factor kappa-B ligand (RANKL) improves osteoporosis, but might also improve glucose tolerance through reduction of hepatic insulin resistance. However, the effect of denosumab (a human monoclonal antibody of RANKL) upon glycemic and metabolic parameters is controversial. We revealed the effect of denosumab upon glycemic and metabolic parameters for 52 weeks. We evaluated 20 individuals diagnosed with both osteoporosis (male and female: postmenopausal) and T2DM. We measured glycemic and metabolic parameters before and 26/52 weeks after administration of denosumab (60 mg per 26 weeks) without changing any other medication each patient was taking. All patients completed the study without complications and the T-score (lumbar spine and femoral neck) improved significantly from baseline to 52 weeks after denosumab administration (P < .001, .001, respectively). None of the glycemic parameters changed significantly from baseline to 26 weeks after denosumab administration, but levels of glycated hemoglobin and homeostasis model assessment of insulin resistance improved significantly from baseline to 52 weeks after administration (P = .019, .008, respectively). The levels of liver enzymes did not change significantly from baseline to 26 weeks after denosumab administration, but levels of aspartate transaminase and alanine aminotransferase improved significantly from baseline to 52 weeks after administration (P = .014, .004, respectively). None of the markers of lipid metabolism and body mass index changed significantly from baseline to 26/52 weeks after denosumab administration. These data demonstrated that denosumab is useful for T2DM patients with osteoporosis for glycemic control via improvement of insulin resistance. Also, the effect of denosumab might be due to improvement of hepatic function.


Assuntos
Glicemia/efeitos dos fármacos , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico , Denosumab/farmacologia , Denosumab/uso terapêutico , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Osteoporose/metabolismo , Idoso , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Masculino , Osteoporose/etiologia , Ligante RANK/imunologia
2.
Artigo em Inglês | MEDLINE | ID: mdl-31505801

RESUMO

A positive association between metabolic syndrome (MetS) and osteoporosis has been demonstrated in previous animal studies. The mechanisms of MetS in orchestrating the bone remodelling process have traditionally focused on the interactions between mature osteoblasts and osteoclasts, while the role of osteocytes is unexplored. Our earlier studies demonstrated the bone-promoting effects of tocotrienol using a rat model of osteoporosis induced by MetS. This study aimed to investigate the expression of osteocyte-derived peptides in the bone of rats with MetS-induced osteoporosis treated with tocotrienol. Age-matched male Wistar rats (12-week-old; n = 42) were divided into seven experimental groups. Two groups served as the baseline and normal group, respectively. The other five groups were fed with a high-carbohydrate high-fat (HCHF) diet to induce MetS. The five groups of HCHF animals were treated with tocopherol-stripped corn oil (vehicle), annatto tocotrienol (60 and 100 mg/kg), and palm tocotrienol (60 and 100 mg/kg) starting from week 8. At the end of the study, the rats were sacrificed and their right tibias were harvested. Protein was extracted from the metaphyseal region of the proximal right tibia and levels of bone peptides, including osteoprotegerin (OPG), soluble receptor activator of nuclear factor-kappa B ligand (sRANKL), sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH), were measured. The vehicle-treated animals displayed higher levels of sRANKL, SOST, DKK-1, FGF-23, and PTH as compared to the normal animals. Oral supplementation of annatto and palm tocotrienol (60 and 100 mg/kg) reduced the levels of sRANKL and FGF-23 in the HCHF animals. Only 100 mg/kg annatto and palm tocotrienol lowered SOST and DKK-1 levels in the HCHF animals. In conclusion, tocotrienol exerts potential skeletal-promoting benefit by modulating the levels of osteocytes-derived bone-related peptides.


Assuntos
Síndrome Metabólica/metabolismo , Osteoporose/metabolismo , Tíbia/efeitos dos fármacos , Tocotrienóis/farmacologia , Animais , Bixaceae , Proteínas Morfogenéticas Ósseas/metabolismo , Carotenoides , Modelos Animais de Doenças , Fatores de Crescimento de Fibroblastos/metabolismo , Marcadores Genéticos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Síndrome Metabólica/complicações , Osteócitos/efeitos dos fármacos , Osteócitos/metabolismo , Osteoporose/etiologia , Osteoprotegerina/metabolismo , Hormônio Paratireóideo/metabolismo , Extratos Vegetais , Ligante RANK/metabolismo , Ratos Wistar , Tíbia/metabolismo
3.
Maturitas ; 128: 70-80, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31561827

RESUMO

BACKGROUND: Osteoporosis is a key concern of women with premature ovarian insufficiency (POI) but there are gaps in clinicians' knowledge of bone health. OBJECTIVES: 1) To systematically evaluate the quality of clinical practice guidelines (CPGs) related to POI and bone health; 2) to formulate a management algorithm. METHODS: Systematic search for English-language clinical practice guidelines (CPGs) from August 2012 to August 2017 (PROSPERO registration number CRD42017075143). Four reviewers independently evaluated the methodological quality of included CPGs using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument (comprising 23 items across 6 domains) using the My AGREE PLUS platform. Inter-rater reliability was assessed using the intraclass correlation coefficient (ICC). Individual domain and total percentage scores were calculated for each CPG. Data from high-scoring CPGs were extracted and summarised to develop the algorithm, with subsequent refinement via expert and end-user clinician feedback. RESULTS: The systematic search yielded 16 CPGs for appraisal. ICC values were 0.71 (good) to 0.95 (very good). The quality of the CPGs was appraised as "high" in 4 cases, "average" in 8 and "low" in 4. High-quality CPGs had mean total scores of 82-96%. Recommendations from high-quality CPGs were summarised into 6 categories: screening; risk factors; initial assessment; diagnosis; subsequent assessment; and management. Only "management" had recommendations (moderate-quality to low-quality evidence) from all four high-quality CPGs. Limitations are reflected in the algorithm. CONCLUSIONS: Most CPGs regarding bone health and POI are of average to poor quality. High-quality CPGs have evidence limitations and recommendation gaps indicating the need for further research.


Assuntos
Densidade Óssea/fisiologia , Menopausa Precoce , Osteoporose/terapia , Guias de Prática Clínica como Assunto , Insuficiência Ovariana Primária/complicações , Adulto , Algoritmos , Feminino , Humanos , Osteoporose/etiologia , Reprodutibilidade dos Testes
4.
Eur J Endocrinol ; 181(5): 509-517, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31484162

RESUMO

Introduction: The role of vitamin D on bone microarchitecture and fragility is not clear. Objective: To investigate whether vitamin D deficiency (25(OH)D <20 ng/mL) increases cortical bone loss and the severity of fractures. Design: Cross-sectional study of 287 elderly women with at least one prevalent low-impact fracture. Methods: Biochemistry, X-rays to identify vertebral fractures (VFs) and to confirm non-vertebral fractures (NonVFs), and high-resolution peripheral quantitative computed tomography (HR-pQCT) to evaluate bone microstructure. Results: Serum 25(OH)D levels were associated with body mass index (BMI: r = -0.161, P = 0.006), PTH (r = -0.165; P = 0.005), CTX (r = -0.119; P = 0.043) and vBMD at cortical bone (Dcomp: r = 0.132; P = 0.033) and entire bone (D100: r = 0.162 P = 0.009) at the distal radius, but not at the tibia. Age and PTH levels were potential confounding variables, but in the multiple linear regressions only BMI (95% CI: 0.11-4.16; P < 0.01), 25(OH)D (95% CI: -0.007 to 1.70; P = 0.05) and CTX (95% CI: -149.04 to 21.80; P < 0.01) predicted Dcomp, while BMI (95% CI: 1.13-4.18; P < 0.01) and 25(OH)D (95% CI: 0.24-1.52; P < 0.01) predicted D100. NonVFs predominated in patients with 25(OH)D <20 ng/mL (P = 0.013). Logistic regression analysis showed a decrease in the likelihood of presenting grade 2-3 VFs/NonVFs for every increase in 25(OH)D (OR = 0.962, 95% CI: 0.940-0.984; P = 0.001), BMI (OR = 0.932, 95% CI: 0.885-0.981; P = 0.007) and D100 at radius (OR = 0.994, 95% CI: 0.990-0.998; P = 0.005). Conclusion: In elderly patients with prevalent fractures, vitamin D deficiency was associated with cortical bone loss and severity of fractures.


Assuntos
Fraturas Ósseas/epidemiologia , Fraturas Ósseas/etiologia , Osteoporose/epidemiologia , Osteoporose/etiologia , Deficiência de Vitamina D/complicações , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Hormônio Paratireóideo/sangue , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia
5.
Evid. actual. práct. ambul ; 22(2): e001112, sept. 2019.
Artigo em Espanhol | LILACS | ID: biblio-1046678

RESUMO

La osteopenia, una disminución de la densidad mineral ósea de menor severidad que la osteoporosis, definida por valores de T-score entre -1,0 y -2,5 en la densitometría ósea , podría asociarse con un mayor riesgo de fracturas. Motivado por el pedido de una paciente con osteopenia que solicita a su médico algún medicamento que le ayude a disminuir su riesgo de fracturas, el autor se pregunta si los bifosfonatos podrían ser beneficiosos para las pacientes con este factor de riesgo. Luego de realizar una búsqueda bibliográfica y seleccionar la evidencia más reciente y de mejor calidad, se concluye que estos fármacos podrían ser útiles para prevenir fracturas en mujeres mayores de 65 años con elevado riesgo de fractura,independientemente del resultado de la densitometría. (AU)


Osteopenia, a minor decrease in bone mineral density, defined by T-score values between -1.0 and -2.5 in a bone densitometry, is associated with an increased risk of fractures. Moved by the request of a patient with osteopenia who asks her doctor for any medication that may help her reduce his risk of fractures, the author wonders if bisphosphonates could be beneficial for patients with this condition. After conducting a bibliographic search and selecting the most recent and best quality evidence, he concluded that these drugs could be useful to prevent fractures in women older than 65 years with ahigh risk of fracture, regardless of densitometry results. (AU)


Assuntos
Humanos , Feminino , Idoso , Osteoporose/tratamento farmacológico , Doenças Ósseas Metabólicas/tratamento farmacológico , Difosfonatos/uso terapêutico , Fraturas por Osteoporose/prevenção & controle , Osteoporose/etiologia , Doenças Ósseas Metabólicas/complicações , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/diagnóstico por imagem , Fatores de Risco , Fraturas por Osteoporose/fisiopatologia , Fraturas por Osteoporose/tratamento farmacológico
6.
Lupus ; 28(10): 1233-1242, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31403902

RESUMO

BACKGROUND: Systemic lupus erythematosus (SLE) patients have lower bone mineral density (BMD) compared with healthy individuals because of general, genetic, disease and medication-related factors. The disturbance of the receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) ratio has been reported to be associated with low BMD in many disorders in adults and children alike. OBJECTIVES: The objectives of this study were (i) to assess serum OPG, RANKL and RANKL/OPG ratio levels in SLE children and controls, (ii) to determine whether the cumulative glucocorticoid (CGCS) dose had any effect on the concentration of serum RANKL, OPG and RANKL/OPG ratio, and (iii) to determine the relation of these parameters to BMD. METHODS: We evaluated 50 SLE children and 50 age- and sex-matched healthy controls. RANKL and OPG were assessed in serum and compared between patients and controls. For SLE patients, a univariate followed by multivariable analysis were carried out to detect the possible predictors of the changes in RANKL, OPG and RANKL/OPG ratio levels. Lumbar BMD for all patients was assessed by dual-energy X-ray absorptiometry (DXA) scan and then correlated to different probable correlated factors. RESULTS: RANKL, OPG and RANKL/OPG ratio were significantly higher in SLE patients (p ≤ 0.001). Univariate analysis showed significant correlations of RANKL with CGCS (p ≤ 0.001) and with DXA scan z-score (p = 0.007): OPG was significantly correlated to Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score (p = 0.001) and anti-double-stranded DNA (p = 0.001), whereas RANKL/OPG was significantly correlated to duration of illness and DXA z-score (p = 0.002). The multivariable analysis showed that DXA z-score was an independent predictor of RANKL and RANKL/OPG ratio (p = 0.019 and 0.008, respectively), whereas SLEDAI score was an independent predictor of OPG levels. BMD was negatively correlated to disease duration (p = 0.008) and CGCS dose (p = 0.015), but no significant correlation has been found between BMD and cumulative SLEDAI score (p = 0.29). CONCLUSIONS: Serum RANKL/OPG ratio is elevated in Egyptian children with SLE and is considered a risk factor for reduced bone mass in these children. Other risk factors for low BMD include high CGCS dose and disease duration, supporting that osteoporosis in SLE is multifactorial.


Assuntos
Densidade Óssea/fisiologia , Lúpus Eritematoso Sistêmico/sangue , Osteoprotegerina/sangue , Ligante RANK/sangue , Absorciometria de Fóton , Adolescente , Estudos de Casos e Controles , Criança , Relação Dose-Resposta a Droga , Egito , Feminino , Glucocorticoides/administração & dosagem , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Osteoporose/etiologia , Fatores de Risco , Índice de Gravidade de Doença
7.
Rev Med Suisse ; 15(659): 1458-1460, 2019 Aug 21.
Artigo em Francês | MEDLINE | ID: mdl-31436062

RESUMO

The number of bariatric surgery interventions has increased over the past 10 years. The effectiveness of bariatric surgery is currently well demonstrated. However, the need to organize a careful medical follow-up of these patients is essential to ensure a positive evolution over the long term. In fact, weight change may be highly variable : excessive weight loss, early stabilization, progressive weight recovery in the middle or long term, all events that often require a multidisciplinary approach. The risk of osteoporosis, dumping syndrome and micronutrient deficiencies requires long-term medical monitoring. In absence of adequate management, such complications may hinder the success of surgery. This article describes the most important points of long-term medical follow-up of patients who underwent bariatric surgery.


Assuntos
Cirurgia Bariátrica , Cirurgia Bariátrica/efeitos adversos , Síndrome de Esvaziamento Rápido/etiologia , Humanos , Osteoporose/etiologia , Tempo , Perda de Peso
8.
Eur J Pediatr ; 178(9): 1433-1441, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31352546

RESUMO

Bone quality in children is generally measured with dual-energy X-ray absorptiometry (DXA). Digital X-ray radiogrammetry (DXR) uses BoneXpert to measure cortical bone quality on hand radiographs. This prospective study compared DXR and DXA results in children with high probability of secondary low bone quality, defined as DXA of the lumbar spine (DXALS) Z-score ≤ - 2.0. One hundred one children underwent both DXA and DXR assessment. DXALSZ-scores were also adjusted for bone age. DXR Z-scores were compared with both DXALSZ-scores, using Pearson correlations, Bland-Altman analysis, and sensitivity-specificity analysis. Mean bone age, DXR, and both DXA Z-scores were significantly impaired. Pearson correlation coefficients were significant between DXR Z-scores and both DXALSZ-scores 0.507-0.564 (p < 0.001). Bland-Altman analysis showed a mean difference of 0.05-0.48 between DXR and both DXA Z-scores and showed more than 90% similarity for both DXALSZ-scores ≤ - 2.0. DXR had a sensitivity of 67-71% and specificity of 77-83% compared to both DXALSZ-scores.Conclusion: DXR correlates well with as well DXALS as bone age-adjusted DXALSZ-scores and shows good agreement with as well DXALS as bone age-adjusted DXALSZ-scores ≤ - 2.0. DXR shows best results when compared with DXALSZ-scores. What is Known: • Digital X-ray radiogrammetry (DXR) may correlate well with dual-energy X-ray absorptiometry (DXA) in pediatric, adolescent, and adult patients. • DXR is a feasible method for assessment of bone quality in children. What is New: • This is the first prospective study in children with suspected secondary low bone quality that illustrates correlation between DXR and bone age-adjusted DXA Z-scores and that shows good agreement between DXR and DXA as bone age-adjusted DXA Z-scores ≤ -2.0. • Our results suggest DXR to be a good alternative for DXA for determining low bone quality.


Assuntos
Absorciometria de Fóton , Osteoporose/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Osteoporose/etiologia , Estudos Prospectivos , Sensibilidade e Especificidade
9.
Medicine (Baltimore) ; 98(29): e16499, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335717

RESUMO

RATIONALE: Anorexia nervosa is a chronic psychiatric disease defined by severe weight loss, due to fear of obesity, and self-imposed semi-starvation. Of the many complications following anorexia nervosa, low bone mineral density (BMD) is a significant risk factor for fractures. Anorexia nervosa is associated with higher risk of incident fracture in females across all age groups, and in males >40 years old. Sites at highest risk of fracture include the hip/femur and pelvis in females, and vertebrae in males with anorexia nervosa. PATIENT CONCERNS: A 29-year-old woman known to have suffered from anorexia nervosa 15 years ago visited the emergency department due to right hip pain after falling while getting out of a taxi. During the period of anorexia nervosa, she had a body mass index (BMI) of 14.06 kg/m (weight, 36 kg; height, 1.60 m) and suffered from amenorrhea. At the time of presentation, she had a BMI of 19.53 kg/m (weight, 50 kg; height, 1.60 m) and had regular menstrual periods, indicating clinical recovery from anorexia nervosa. DIAGNOSES: Plain radiography, computed tomography, and bone scintigraphy revealed AO 31-A2.2 type right hip proximal femur intertrochanteric fracture. The BMD showed a T score of -3.9 in the hip and -3.6 at the lumbar level, indicating severe osteoporosis. INTERVENTIONS: Osteosynthesis was performed with proximal femoral nail antirotation (PFNA) and wiring. OUTCOMES: There were no specific symptoms, such as trauma or infection, during postoperative rehabilitation and postoperative management, and she was discharged after 2 weeks. After 1 year of follow-up at our outpatient clinic, she had no complications. LESSONS: Here, we describe an unusual case of unilateral femoral intertrochanteric fracture that occurred after clinical recovery from anorexia nervosa. This case indicated that the risk of fracture remains even after recovery of BMI. We propose that women who have clinically recovered from anorexia nervosa should be advised to undergo annual osteodensitometric analyses after consulting with specialists in other areas (psychiatry, endocrinology, eating disorders).


Assuntos
Acidentes por Quedas , Anorexia Nervosa/complicações , Fraturas do Quadril/etiologia , Osteoporose/complicações , Adulto , Índice de Massa Corporal , Pinos Ortopédicos , Fios Ortopédicos , Feminino , Fixação Interna de Fraturas/métodos , Fraturas do Quadril/cirurgia , Humanos , Osteoporose/etiologia , Fatores de Tempo
10.
Pan Afr Med J ; 32: 169, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31303938

RESUMO

A 61-year old female patient who was referred to the endocrine clinic for evaluation of an elevated alkaline phosphatase. She was originally referred to gastroenterology (GI), however no GI causes of elevated alkaline phosphatase was found. Upon fractionation, it was noted that she had elevation in bone specific alkaline phosphatase. Past history was significant for hypertension, atrial fibrillation and menopause 6 years ago. She was also noted to have multiple drug allergies manifesting as urticaria and flushing. Review of the past records revealed a persistently elevated alkaline phosphatase over the last two years. She had no history of falls or fractures. Computed tomography (CT) abdomen done to rule out biliary pathology, revealed osteosclerotic and osteolytic lesion in the pelvis concerning neoplastic disease. Bone marrow biopsy however, was negative for cancer but consistent with systemic mastocytosis (SM). Dual Energy X-ray absorbimetery (DEXA) scan revealed osteoporosis Serum tryptase levels were elevated; further genetic analysis showed a positive CKIT D816 mutation. She was started on bisphosphonates (initially alendronate and then ibandronate). Upon follow up at two years she had not experienced any fractures and her bone mineral density also had improved significantly.


Assuntos
Fosfatase Alcalina/metabolismo , Mastocitose Sistêmica/diagnóstico , Osteoporose/etiologia , Absorciometria de Fóton/métodos , Densidade Óssea , Difosfonatos/administração & dosagem , Feminino , Humanos , Mastocitose Sistêmica/complicações , Pessoa de Meia-Idade , Osteoporose/diagnóstico , Osteoporose/tratamento farmacológico
11.
Cell Mol Biol (Noisy-le-grand) ; 65(5): 24-31, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31304902

RESUMO

This study was carried out to evaluate the preventive and curative effects of Pilose antler against osteoporosis due to kidney deficiency, and investigate its potential mechanism of action. A model of osteoporosis due to kidney deficiency was established in rats using bilateral ovariectomy. Pilose antler polypeptide (PAP), Pilose antler polysaccharide (PAP'), and their mixture (PAP+PAP') were separately administered to the rats for 12 weeks, with progynova and xianlingubao tablets (XLGB) as the positive control groups. We determined the bone mineral density (BMD) and uterus Index of the rats. Osteoblastic bone metabolism-related indices in serum and bone tissue were measured with ELISA. Western blotting and RT-PCR were used to investigate the protein and mRNA expressions of Bmp-2, Smad1, Smad5, Runx2 in bone tissue. The morphology of bone tissue was determined using immunohistochemical methods. Compared with control group, PAP, PAP', PAP+PAP' increased BMD and regulated bone metabolism indices in serum and bone tissue. Treatment with Pilose antler up-regulated the mNRA and protein expressions of Bmp-2, Smad1, Smad5 and Runx2. Immunohistochemical staining showed that Bmp-2, Smad1, Smad5 and Runx2 were stained brown, indicating that all of them were positive. There were abnormal changes in the protein expressions of Bmp-2, Smad1, Smad5 and Runx2 in bone tissue, which may be an important mechanism underlying the development of kidney deficiency osteoporosis. Moreover, PAP, PAP' and PAP+PAP' had some preventive effects on osteoporosis, probably via the activation of the Bmp-2/Smad1 and Smad5/Runx2 signaling pathways through induction of high expressions of their mRNAs and proteins.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Osteoporose/etiologia , Peptídeos/farmacologia , Substâncias Protetoras/farmacologia , Insuficiência Renal/complicações , Animais , Densidade Óssea , Proteína Morfogenética Óssea 2/metabolismo , Osso e Ossos/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Osteoporose/prevenção & controle , Ovariectomia/efeitos adversos , Peptídeos/administração & dosagem , Peptídeos/uso terapêutico , Polissacarídeos/administração & dosagem , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/uso terapêutico , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Proteína Smad1/metabolismo , Proteína Smad5/metabolismo , Útero/patologia
12.
Environ Health Prev Med ; 24(1): 48, 2019 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-31301734

RESUMO

AIMS: To investigate the association of four single-nucleotide polymorphisms (SNPs) of the IL-6 gene with osteoporosis (OST) susceptibility. METHODS: PCR restriction fragment length polymorphism (PCR-RFLP) was carried out for SNPs detection. Generalized multifactor dimensionality reduction (GMDR) model and logistic regression model were used to examine the interaction between SNP and obesity on OST. RESULTS: Logistic regression model revealed that G allele of rs1800796 and the T allele of rs2069849 were associated with increased OST risk, compared to those with wild genotype. However, no significant correlations were found when analyzing the association of rs1800795 and rs1554606 with OST risk. GMDR analysis suggested that the interaction model composed of the rs1800796 and obesity was the best model with statistical significance (P value from sign test [Psign] = 0.012), indicating a potential gene-environment interaction between rs1800796 and obesity. Overall, the two-locus models had a cross-validation consistency of 10/10 and had the testing accuracy of 0.641. We also conducted stratified analysis for rs1800796 genotype and obesity, and found that obese subjects with CG or GG genotype have the highest OST risk, compared to subjects with CC genotype, and normal BMI OR (95% CI) = 2.21 (1.52-3.49), after adjustment for age, smoke, and alcohol consumption status. CONCLUSIONS: Our results suggested that the C allele of rs1800796 and the C allele of rs2069849 of IL-6 gene interaction between rs1800796 and abdominal obesity were all associated with increased OST risk.


Assuntos
Interleucina-6/genética , Obesidade/genética , Osteoporose/epidemiologia , Polimorfismo de Nucleotídeo Único , Pós-Menopausa/fisiologia , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Interação Gene-Ambiente , Humanos , Interleucina-6/metabolismo , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/etiologia , Osteoporose/etiologia , Osteoporose/genética , Pós-Menopausa/genética , Fatores de Risco
13.
Clin Appl Thromb Hemost ; 25: 1076029619861689, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31282181

RESUMO

Increased number of patients with hemophilia have been identified to have osteoporosis at early ages. Low bone mineral density in the setting of hemophilia has been associated with decreased mobility, sedentary life style, on demand treatment or delayed prophylaxis, low body weight and viral infections. The aim of this study was to investigate the impact of hemophilia on bone health of adult patients living in a middle income country. A total of 61 adult patients with hemophilia who were followed at the Hematology Department of Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa were consecutively included in this study. Bone health of the patients was assessed using the bone mineral density (BMD) and vitamin D levels. Z and t scores are used for evaluation of BMD in patients with hemophilia aged < 50 and ≥ 50 years, respectively. Information on treatment and co-morbidities including viral diseases were obtained from the medical files of the recruited patients. Bone mineral density was found normal in 30, and low in 29 patients. Vitamin D levels were below 20 ng/ml in 46 patients. No significant relationship was found between the severity of hemophilia and bone density. Vitamin D levels were significantly lower in patients who had a history of joint intervention. Neither annual bleeding rate nor the treatment modality (on demand versus prophylaxis) were associated with the bone mineral density and vitamin D levels. Annual factor consumption was higher in patients whose bone mineral densities was low both in femoral and lumbar regions. The results of this study depicting the situation of adult hemophilia population from a middle income country show that bone mineral density and vitamin D levels were decreased in a considerable amount of patients at early ages.


Assuntos
Hemofilia A/complicações , Hemofilia B/complicações , Osteoporose/etiologia , Adulto , Fatores Etários , Densidade Óssea , Comorbidade , Desenvolvimento Econômico , Humanos , Masculino , Osteoporose/diagnóstico , Osteoporose/epidemiologia , Fatores de Risco , Turquia/epidemiologia , Vitamina D/sangue , Adulto Jovem
14.
Diabetes Res Clin Pract ; 155: 107790, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31325536

RESUMO

AIMS: Trabecular bone score (TBS) is a surrogate indicator of bone microarchitecture. The present study sought to examine the association between type 2 diabetes (T2D) and trabecular bone score (TBS) in adult Vietnamese men and women. METHODS: The study was part of the Vietnam Osteoporosis Study, in which 2702 women and 1398 men aged ≥30 years were recruited from the general community in Ho Chi Minh City. HbA1c levels were measured by the ADAMS™ A1c HA-8160 (Arkray, Kyoto, Japan), and classified into 3 groups: normal if HbA1c < 5.7%; pre-diabetes (5.7-6.4%); and diabetes (>6.4%). TBS was evaluated by iNsight Software, version 2.1 (Medimaps, Merignac, France) on lumbar spine BMD scan (Hologic Horizon). Differences in TBS between diabetic status were analyzed by the multivariable regression model with adjustment for age and body mass index. RESULTS: The prevalence of pre-diabetes and diabetes in men and women was 30.2% and 8.3%, respectively. In women, TBS was lower in pre-diabetes (-0.02; P < 0.001) and diabetes (-0.02; P < 0.001) compared with normal individuals. In men, there was no statistically significant difference in TBS between diabetic status. Moreover, TBS was significantly inversely correlated with HbA1c levels in women (P = 0.01), but not in men (P = 0.89). CONCLUSION: Women, but not men, with type 2 diabetes and pre-diabetes have lower TBS than individuals without diabetes. These data suggest that diabetes and prediabetes are associated with deterioration of bone microarchitecture.


Assuntos
Índice de Massa Corporal , Osso Esponjoso/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Osteoporose/etiologia , Estado Pré-Diabético/complicações , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/diagnóstico , Osteoporose/epidemiologia , Prevalência , Prognóstico , Fatores de Risco , Vietnã/epidemiologia , Adulto Jovem
15.
Food Chem Toxicol ; 132: 110668, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31299293

RESUMO

Ruscus aculeatus is a source of steroidal saponins that could mimic sex hormones and could help alleviate the risk of fracture in osteoporotic patients. The aim of the present study was to evaluate the in vitro effects of an extract from R. aculeatus (ERA) on the proliferation of human osteoblast-like SaOS-2 cell line and to investigate the effects of the ERA administered orally for 10 weeks at three doses (50, 100 and 200 mg/kg) on the bone structure of rats with estrogen deficiency induced by bilateral ovariectomy. Bone turnover markers, hormones, histopathological and radiological disturbances were evidenced in the ovariectomized rats. ERA recovered most of the affected parameters in a dose-dependent manner similar to diosgenin and alendronate used as positive comparators. The main active compounds of ERA (ruscogenin and neoruscogenin) were docked into the Vit. D receptor and oestrogen receptors alpha and beta, and stable complexes were found with binding scores equal to those of estradiol and diosgenin. The findings of this study provide for the first time an insight into the effects of ERA on bone structure and suggest that ERA could be developed as a potential candidate for the prevention of postmenopausal osteoporotic complications.


Assuntos
Osteoporose/prevenção & controle , Ovariectomia/efeitos adversos , Extratos Vegetais/uso terapêutico , Ruscus/química , Animais , Remodelação Óssea , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Cálcio/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Glutationa/metabolismo , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoporose/etiologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar
16.
Planta Med ; 85(9-10): 766-773, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31167297

RESUMO

Osteoporosis is a clinical condition characterized by low bone strength that leads to an increased risk of fracture. Strategies for the treatment of osteoporosis involve inhibition of bone resorption by osteoclasts and an increase of bone formation by osteoblasts. Here, we identified the extract derived from the stem part of Edgeworthia papyrifera that enhanced differentiation of MC3T3-E1 cells to osteoblast-like cells and inhibited osteoclast differentiation of RAW 264.7 cells in vitro. In support of our observation, rutin and daphnoretin, which were previously reported to inhibit osteoclast differentiation, were identified in E. papyrifera extract. In an animal model of osteoporosis, the ovariectomy-induced increases in bone resorption biomarkers such as pyridinoline and tartrate-resistant acid phosphatase were significantly reduced by E. papyrifera extract administration at 25.6 and 48.1%, respectively. Furthermore, the ovariectomy-induced bone loss in animal models of osteoporosis was significantly prevented by the administration of E. papyrifera in our study. Taking these observations into account, we suggest that E. papyrifera is an interesting candidate for further exploration as an anti-osteoporotic agent.


Assuntos
Osteoblastos/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Extratos Vegetais/farmacologia , Thymelaeaceae/química , Fosfatase Alcalina/metabolismo , Aminoácidos/urina , Animais , Biomarcadores/sangue , Biomarcadores/urina , Reabsorção Óssea/tratamento farmacológico , Diferenciação Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Camundongos , Camundongos Endogâmicos , Modelos Animais , Osteoporose/etiologia , Extratos Vegetais/análise , Células RAW 264.7 , Ratos Sprague-Dawley
17.
Int J Mol Sci ; 20(11)2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31174394

RESUMO

Osteoporosis is an abnormal bone remodeling condition characterized by decreased bone density, which leads to high risks of fracture. Previous study has demonstrated that Lycii Radicis Cortex (LRC) extract inhibits bone loss in ovariectomized (OVX) mice by enhancing osteoblast differentiation. A bioactive compound, kukoamine B (KB), was identified from fractionation of an LRC extract as a candidate component responsible for an anti-osteoporotic effect. This study investigated the anti-osteoporotic effects of KB using in vitro and in vivo osteoporosis models. KB treatment significantly increased the osteoblastic differentiation and mineralized nodule formation of osteoblastic MC3T3-E1 cells, while it significantly decreased the osteoclast differentiation of primary-cultured monocytes derived from mouse bone marrow. The effects of KB on osteoblastic and osteoclastic differentiations under more physiological conditions were also examined. In the co-culture of MC3T3-E1 cells and monocytes, KB promoted osteoblast differentiation but did not affect osteoclast differentiation. In vivo experiments revealed that KB significantly inhibited OVX-induced bone mineral density loss and restored the impaired bone structural properties in osteoporosis model mice. These results suggest that KB may be a potential therapeutic candidate for the treatment of osteoporosis.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Ácidos Cafeicos/uso terapêutico , Osteoblastos/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Espermina/análogos & derivados , Animais , Conservadores da Densidade Óssea/farmacologia , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Ácidos Cafeicos/farmacologia , Diferenciação Celular , Linhagem Celular , Células Cultivadas , Medicamentos de Ervas Chinesas/química , Feminino , Camundongos , Osteoblastos/citologia , Osteoclastos/citologia , Osteoporose/etiologia , Ovariectomia/efeitos adversos , Espermina/farmacologia , Espermina/uso terapêutico
18.
J Orthop Surg Res ; 14(1): 177, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31196133

RESUMO

BACKGROUND: To provide a low-toxicity and high-efficacy clinical treatment for osteoporosis via a novel combination of LiCl and LY294002. METHODS: The protein levels of p-AKT, AKT, p-GSK3ß, GSK3ß, ß-catenin, p-ß-catenin, and NFATC1 were measured in osteoblasts and osteoclasts by Western blot. ALP activity and TRACP activity were measured using the corresponding kit. The levels of BALP, PINP, CTX, and TRACP-5b were determined in accordance with the requirements of the ELISA kits. Microstructural analysis was performed on the left distal femur using microcomputed tomography. RESULTS: Treatment with the combination of LiCl and LY294002 led to a markedly increased osteoblast activity but significantly decreased osteoclast differentiation and bone absorption capacity compared with the treatment with LiCl or LY294002 alone (P < 0.01). In serum, the low-dose combination of LiCl and LY294002 significantly enhanced BALP levels (P < 0.01) and significantly decreased PINP, TRACP-5b, and CTX levels (P < 0.01) compared with the application of either drug alone. CONCLUSIONS: This study indicates that drug combinations directed at multiple targets could be used for osteoporosis treatment by promoting osteoblast proliferation and inhibiting differentiation with high efficiency.


Assuntos
Cromonas/administração & dosagem , Cloreto de Lítio/administração & dosagem , Morfolinas/administração & dosagem , Osteoporose/tratamento farmacológico , Ovariectomia/efeitos adversos , Animais , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Imagem Tridimensional/métodos , Osteoporose/diagnóstico por imagem , Osteoporose/etiologia , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento
19.
Int J Mol Sci ; 20(12)2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31216684

RESUMO

Acteoside, an active phenylethanoid glycoside compound isolated from herbs of Cistanche, was chosen for the investigation of anti-osteoporotic effect on postmenopausal osteoporosis by using an ovariectomized (OVX) mice model. The results from in vivo experiments showed that after daily oral administration of acteoside (20, 40, and 80 mg/kg body weight/day) for 12 weeks, bone mineral density and bone biomechanical properties of OVX mice were greatly enhanced, with significant improvement in bone microarchitecture. Furthermore, biochemical parameters of bone resorption markers as well as bone formation index, including tartrate-resistant acid phosphatase, cathepsin K, deoxypyridinoline, alkaline phosphatase, and bone gla-protein, were ameliorated by acteoside treatment, whereas the body, uterus, and vagina wet weights were seemingly not impacted by acteoside administration. Acteoside significantly affected osteoclastogenesis by attenuating nuclear factor kappa B (NF-κB) and stimulating phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signal pathways through down-regulated levels of tumor-necrosis factor receptor-associated factor 6 (TRAF6), receptor activator of nuclear factor kappa B ligand (RANKL), RANK, NFKBIA, IκB kinase ß, nuclear factor of activated T-cells c2 (NFAT2), and up-regulated expressions of PI3K, AKT, and c-Fos. Accordingly, the current research validated our hypothesis that acteoside possesses potent anti-osteoporotic properties and may be a promising agent for the prevention of osteoporosis in the future.


Assuntos
Glucosídeos/farmacologia , Osteoporose/etiologia , Osteoporose/metabolismo , Ovariectomia/efeitos adversos , Fenóis/farmacologia , Substâncias Protetoras/farmacologia , Animais , Biomarcadores , Peso Corporal , Densidade Óssea/efeitos dos fármacos , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/genética , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Modelos Animais de Doenças , Feminino , Camundongos , Modelos Biológicos , Tamanho do Órgão , Osteoporose/tratamento farmacológico , Osteoporose/patologia , Ligante RANK/metabolismo , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo
20.
Pediatr Rev ; 40(5): 259-261, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31043448
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