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1.
Adv Exp Med Biol ; 1164: 153-160, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576547

RESUMO

Skeletal aging begins after peak bone mass is reached; progressive bone loss then occurs. Peak bone mass may occur at different ages in different skeletal sites and varies between sexes. Accelerated loss of bone occurs in the perimenopausal period in women, whereas more gradual but progressive loss of bone occurs in aging men. Changes in bone quality as well as bone quantity occur during growth and subsequent aging. These include changes in bone microarchitecture which may differ between cortical and trabecular compartments and in different sites, and may impact on bone size and geometry. Changes in material properties of bone matrix may also occur with aging. Loss of bone quantity and altered bone quality with aging may weaken bones and culminate in osteoporosis with an increased risk of fractures. Both genetic and epigenetic mechanisms may predispose to osteoporosis. Cellular and molecular events underlie the alterations in bone quantity and quality. Osteoclastic bone resorption and osteoblastic bone formation, tightly regulated by hormones, growth factors, and cytokines, are organized in coordinated activities resulting in remodeling and modeling. Malignancies, and anti-neoplastic therapies, may impact on the cellular and molecular events in the aging skeleton and produce focal or diffuse skeletal lesions and fractures.


Assuntos
Envelhecimento , Reabsorção Óssea , Osso e Ossos , Densidade Óssea , Osso e Ossos/fisiologia , Feminino , Humanos , Masculino , Osteoporose , Fatores Sexuais
2.
Braz Oral Res ; 33: e079, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31531565

RESUMO

Cell therapy associated with guided bone regeneration (GBR) can be used to treat bone defects under challenging conditions such as osteoporosis. This study aimed to evaluate the effect of mesenchymal stem cells (MSCs) in combination with a poly(vinylidene-trifluoroethylene)/barium titanate (PVDF-TrFE/BT) membrane on bone repair in osteoporotic rats. Osteoporosis was induced in female rats by bilateral removal of the ovaries (OVX) or sham surgery (SHAM), and the osteoporotic condition was characterized after 5 months by microtomographic and morphometric analyses. Calvarial defects were created in osteoporotic rats that immediately received the PVDF-TrFE/BT membrane. After 2 weeks, bone marrow-derived MSCs from healthy rats, characterized by the expression of surface markers using flow cytometry, or phosphate-buffered saline (PBS) (Control) were injected into the defects and bone formation was evaluated 4 weeks post-injection by microtomographic, morphometric, and histological analyses. A reduction in the amount of bone tissue in the femurs of OVX compared with SHAM rats confirmed the osteoporotic condition of the experimental model. More bone formation was observed when the defects were injected with MSCs compared to that with PBS. The modification that we are proposing in this study for the classical GBR approach where cells are locally injected after a membrane implantation may be a promising therapeutic strategy to increase bone formation under osteoporotic condition.


Assuntos
Compostos de Bário/farmacologia , Regeneração Tecidual Guiada/métodos , Células-Tronco Mesenquimais/fisiologia , Osteogênese/efeitos dos fármacos , Osteoporose/terapia , Polivinil/farmacologia , Titânio/farmacologia , Animais , Compostos de Bário/química , Densidade Óssea , Regeneração Óssea/efeitos dos fármacos , Regeneração Óssea/fisiologia , Feminino , Citometria de Fluxo , Imagem Tridimensional , Células-Tronco Mesenquimais/química , Osteogênese/fisiologia , Osteoporose/fisiopatologia , Ovariectomia , Polivinil/química , Distribuição Aleatória , Ratos Wistar , Reprodutibilidade dos Testes , Fatores de Tempo , Titânio/química , Resultado do Tratamento
3.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(8): 987-992, 2019 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-31511221

RESUMO

OBJECTIVE: To investigate the effects of risedronate on bone marrow adipogenesis and the expression of the receptor activator of nuclear factor κB ligand (RANKL) in adipocytes in the bone marrow micro-environment. METHODS: Primary cultured rat mesenchymal stem cells (BMSCs) with or without adipogenic induction for 14 days were treated with 1, 5, 10, and 25 µmol/L risedronate. The droplets of the differentiated adipocytes were analyzed, and Western blotting was performed to detect the expression level of RANKL. Female SD rats (24-week-old) were randomly divided into sham-operated group and ovariectomy (OVX) group, and 12 weeks after the operation, the OVX rats were further divided into control group and risedronate group (2.4 µg/kg, injected subcutaneously for 3 times a week). Eight weeks later, the bone mineral density (BMD) of the rats and bone marrow histopathology of the femurs was examined to evaluate the effect of risedronate on the fat fraction in the bone marrow. RESULTS: Risdronate significantly inhibited adipogenic differentiation of rat BMSCs and suppressed RANKL expression in the adipocytes derived from the BMSCs in a concentration-dependent manner. In OVX rats, risdronate treatment significantly increased the BMD and decreased the fat content in the bone marrow. CONCLUSIONS: Risdronate can effectively inhibit the adipogenic differentiation of rat BMSCs, decrease fat content in the bone marrow, and suppress the generation and function of osteoclasts by down-regulating the expression of RANKL, which can be an important mechanism underlying the therapeutic effect of risedronate against osteoporosis.


Assuntos
Adipogenia , Adipócitos , Animais , Densidade Óssea , Medula Óssea , Feminino , Ovariectomia , Ligante RANK , Ratos , Ratos Sprague-Dawley , Ácido Risedrônico
4.
Medicine (Baltimore) ; 98(31): e16628, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374030

RESUMO

To investigate the differences in bone mineral density between patients with liver cirrhosis and healthy control, and to analyze the risk factors of hepatic osteoporosis in patients with HBV related liver cirrhosis.A total of 189 patients with liver cirrhosis and 207 health controls were enrolled. The bone mineral density of lumbar spine and femoral neck was examined by dual energy X-ray absorptiometry. -2.0

Assuntos
Hepatite B/complicações , Cirrose Hepática/epidemiologia , Cirrose Hepática/etiologia , Osteoporose/epidemiologia , Absorciometria de Fóton , Adulto , Fatores Etários , Idoso , Peso Corporal , Densidade Óssea , Doenças Ósseas Metabólicas/epidemiologia , Fibrose , Humanos , Cirrose Hepática/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais
5.
Medicine (Baltimore) ; 98(32): e16770, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393399

RESUMO

BACKGROUND: Osteoporosis is a major side effect of aromatase inhibitors (AIs), which are greatly effective in the treatment of breast cancer. However, there are no satisfactory measures against osteoporosis. In this multicenter, randomized, comparative study, we evaluate the efficacy of denosumab for preventing loss of bone mineral density (BMD) induced by adjuvant therapy with AI s in breast cancer patients with normal BMD. PATIENTS AND METHODS: The bone loss-suppressing effect of denosumab will be comparatively evaluated in postmenopausal patients scheduled to receive letrozole or anastrozole as a postoperative endocrine therapy for stage I-IIIA hormone-sensitive breast cancer and a control group. Patients will be administered letrozole 2.5 mg or anastrozole 1 mg once a day, and the treatment will be continued for 5 years unless recurrence, secondary cancer, or unacceptable toxicity develops. Patients in the denosumab group will receive a subcutaneous injection of 60 mg of denosumab every 6 months. The primary endpoint is the rate of change in the lumbar spine (L1-L4) BMD, as determined by dual-energy X-ray absorptiometry (DXA), 12 months after the start of the injection. The secondary endpoints were ETHICS AND DISSEMINATION:: The protocol was approved by the institutional review boards of Kyoto Prefectural University of Medicine and all the participating faculties. Written informed consent was obtained from all patients before registration, in accordance with the Declaration of Helsinki. Results of the study will be disseminated via publications in peer-reviewed journals. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT03324932, Japan Registry of Clinical Trial (jRCT): CRB5180001.


Assuntos
Inibidores da Aromatase/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Denosumab/administração & dosagem , Osteoporose/induzido quimicamente , Osteoporose/prevenção & controle , Adulto , Inibidores da Aromatase/uso terapêutico , Biomarcadores , Osso e Ossos/metabolismo , Neoplasias da Mama/tratamento farmacológico , Intervalo Livre de Doença , Feminino , Fraturas Ósseas/epidemiologia , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Projetos de Pesquisa
6.
Medicine (Baltimore) ; 98(35): e16926, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464929

RESUMO

The femoral neck-preserving ratio is crucial in arthroplasty with a collum femoris-preserving (CFP) stem. The aim of our study was to analyze the relationships between the neck-preserving ratio and the short-term radiologic and clinical outcomes of patients who underwent total-hip arthroplasty (THA) with a CFP stem.The data of 325 hips from January 2015 to December 2016 were retrospectively reviewed. The demographic and radiologic data before and after surgery were obtained from patients. The neck-preserving ratio was defined as the ratio of the preserved femoral neck length to the preoperative femoral neck length. Correlations between the neck-preserving ratio and the radiologic and clinical outcomes of patients were analyzed.The mean neck-preserving ratio was 66.38 ±â€Š6.91% in the current study. We divided patients into 3 groups according to the neck-preserving ratio: group A (neck-preserving ratio ≤60.00%), group B (60.00% < neck-preserving ratio < 70.00%), group C (neck-preserving ratio ≥70.00%). Radiologic features, including the neck-shaft angle ratio (0.96 ±â€Š0.05), canal fill ratio (0.64 ±â€Š0.07), anterior-posterior offset ratio (1.04 ±â€Š0.10), and lateral offset ratio (2.55 ±â€Š1.56) (ratios of the postoperative values to the preoperative values), and the prevalence of complications was significantly different among the groups (χ = 21.173, P < .001). In the correlation analysis, we found a moderate negative correlation between the neck-preserving ratio and neck-shaft angle ratio (r = -0.308, P < .001) and a slight positive correlation of the neck-preserving ratio with the anterior-posterior offset ratio (r = 0.415, P < .001) and the lateral offset ratio (r = 0.164, P = .003). In the linear regression analyses, the neck-preserving ratio was significantly linearly correlated with the neck-shaft angle ratio (B = -0.232, 95% confidence interval [CI] = -0.311 to -0.154, P < .001), anterior-posterior offset ratio (B = 0.589, 95% CI = 0.447-0.730, P < .001), and lateral offset ratio (B = 3.693, 95% CI = 1.256-6.131, P = .003). However, there was no significant linear correlation between the neck-preserving ratio and the canal fill ratio (B = 0.073, 95% CI = -0.033 to 0.180, P = .174). Logistic regression analyses also showed that a sufficient neck-preserving ratio was a protective factor for periprosthetic femoral fractures (odds ratio [OR] = 0.924, 95% CI = 0.859-0.994, P = .035), dislocations (OR = 0.892, 95% CI = 0.796-0.999, P = .048), and thigh pain (OR = 0.886, 95% CI = 0.818-0.960, P = .003).For CFP stems, an insufficient neck-preserving ratio is significantly correlated with poor radiologic and clinical outcomes. Therefore, surgeons should be cognizant to preserve a sufficient femoral neck length during surgery to improve the outcomes for patients undergoing THA with CFP stems.


Assuntos
Artroplastia de Quadril/métodos , Colo do Fêmur/anatomia & histologia , Desenho de Prótese/métodos , Adulto , Fatores Etários , Idoso , Índice de Massa Corporal , Densidade Óssea , Comorbidade , Feminino , Colo do Fêmur/diagnóstico por imagem , Comportamentos Relacionados com a Saúde , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores Sexuais , Fatores Socioeconômicos
7.
Arch Endocrinol Metab ; 63(4): 394-401, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31365627

RESUMO

OBJECTIVE: To measure type 1 serum amino-terminal propeptide procollagen (P1NP) and type 1 cross-linked C-terminal telopeptide collagen (CTX) before parathyroidectomy (PTX) in PHPT patients, correlating these measurements with bone mineral density (BMD) changes. SUBJECTS AND METHODS: 31 primary hyperparathyroidism (HPTP) were followed from diagnosis up to 12-18 months after surgery. Serum levels of calcium, parathyroid hormone (PTH) vitamin D, CTX, P1NP, and BMD were measured before and 1 year after surgery. RESULTS: One year after PTX, the mean BMD increased by 8.6%, 5.5%, 5.5%, and 2.2% in the lumbar spine, femoral neck (FN), total hip (TH), and distal third of the nondominant radius (R33%), respectively. There was a significant correlation between BMD change 1 year after the PTX and CTX (L1-L4: r = 0.614, p < 0.0003; FN: r = 0.497, p < 0.0051; TH: r = 0.595, p < 0.0005; R33%: r = 0.364, p < 0.043) and P1NP (L1-L4: r = 0,687, p < 0,0001; FN: r = 0,533, p < 0,0024; TH: r = 0,642, p < 0,0001; R33%: r = 0,467, p < 0,0079) preoperative levels. The increase in 25(OH)D levels has no correlation with BMD increase (r = -0.135; p = 0.4816). On linear regression, a minimum preoperative CTX value of 0.331 ng/mL or P1NP of 37.9 ng/mL was associated with a minimum 4% increase in L1-L4 BMD. In TH, minimum preoperative values of 0.684 ng/mL for CTX and 76.0 ng/mL for P1NP were associated with a ≥ 4% increase in BMD. CONCLUSION: PHPT patients presented a significant correlation between preoperative levels of turnover markers and BMD improvement 1 year after PTX.


Assuntos
Densidade Óssea , Colágeno Tipo I/metabolismo , Hiperparatireoidismo Primário/metabolismo , Paratireoidectomia/reabilitação , Fragmentos de Peptídeos/metabolismo , Peptídeos/metabolismo , Pró-Colágeno/metabolismo , Idoso , Biomarcadores/sangue , Cálcio/sangue , Feminino , Humanos , Hiperparatireoidismo Primário/cirurgia , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fragmentos de Peptídeos/sangue , Período Pós-Operatório , Valor Preditivo dos Testes , Período Pré-Operatório , Pró-Colágeno/sangue , Estudos Retrospectivos , Vitamina D/sangue
8.
Pan Afr Med J ; 33: 37, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31384352

RESUMO

Introduction: Osteoporosis is characterized by low bone mass and density, as well as change in microarchitecture of bone tissue leading to decreased bone strength. In vitro research shows nicotine can increase osteoblast activity and proliferation, also suppress osteoclast activity. Therefore we explore nicotine anti-resorptive property by in vivo true experimental and randomized posttest only controlled group research that was conducted in 18-20 weeks old Rattus norvegicus. Methods: Twenty-five female rats were divided into five groups, with 5 rats per group. The first group represented normal rats (Sham), while the second to fifth group underwent bilateral ovariectomy. The second group serves as positive control group (ovariectomy-only/OVX). The third to fifth group serve as dose 1 (P1-0.25mg/kg), dose 2 (P2-0.5 mg/kg), and Dose 3 (P3-0.75 mg/kg) treatment group receiving daily per-oral nicotine for 28 days, started 3 weeks post- ovariectomy. After 28 days treatment, the serum was checked. Results: Nicotine has dose-dependent manner on serum osteocalcin and serum DPD level. Level of osteocalcin in P2 group was significantly lower (Mann-Whitney, p = 0.008) compared to OVX group (59.4% lower). Level of DPD in all group was not significantly different (ANOVA, p < 0.05) but shows lowest level in P2 group. For serum calcitonin level, there's no significant different between groups. Conclusion: Nicotine at right low-dose might be able to inhibit osteoclast activity, thus open a possibility of anti-resorptive property of nicotine.


Assuntos
Densidade Óssea/efeitos dos fármacos , Nicotina/farmacologia , Osteoclastos/efeitos dos fármacos , Osteoporose/prevenção & controle , Aminoácidos/sangue , Animais , Biomarcadores/metabolismo , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Nicotina/administração & dosagem , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteocalcina/sangue , Osteoclastos/metabolismo , Osteoporose/patologia , Ovariectomia , Ratos , Ratos Wistar
9.
Unfallchirurg ; 122(10): 750-754, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31440789

RESUMO

BACKGROUND: Osteoporosis is a common disease that affects both women and men. Due to a reduced bone mineral density and increasing age, the risk for atraumatic fractures increases. These fractures cause pain due to the fracture itself and also have far-reaching sequelae in nearly all areas of life of patients. OBJECTIVE: The aim of this article is to summarize the consequences of osteoporotic fractures from the patient's point of view and to highlight the consequences of osteoporosis for the patient. The necessity for timely diagnostics and treatment after a fracture event is explained. MATERIAL AND METHODS: For each term a literature search was performed using key topic-related terms and the results are presented as a narrative review. RESULTS: Various areas of importance for patients were identified. A direct assessment of the patient's point of view was not feasible using a literature search; however, studies with surveys of patients could be identified and therefore, the patient's point of view could be integrated. Areas of interest that could be identified in the literature were pain, psychological well-being, cognitive abilities, mortality and long-term need for nursing. CONCLUSION: The effects of osteoporosis and fractures are multifactorial and often severe for the patient. The measures for prevention of osteoporotic fractures should be consistently implemented in the daily clinical routine and the necessary diagnostics and treatment should be rapidly initiated.


Assuntos
Fraturas por Osteoporose , Densidade Óssea , Feminino , Humanos , Masculino , Osteoporose , Inquéritos e Questionários
10.
BMJ ; 366: l4410, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31371314

RESUMO

OBJECTIVE: To determine if genetically increased serum calcium levels are associated with improved bone mineral density and a reduction in osteoporotic fractures. DESIGN: Mendelian randomisation study. SETTING: Cohorts used included: the UK Biobank cohort, providing genotypic and estimated bone mineral density data; 25 cohorts from UK, USA, Europe, and China, providing genotypic and fracture data; and 17 cohorts from Europe, providing genotypic and serum calcium data (summary level statistics). PARTICIPANTS: A genome-wide association meta-analysis of serum calcium levels in up to 61 079 individuals was used to identify genetic determinants of serum calcium levels. The UK Biobank study was used to assess the association of genetic predisposition to increased serum calcium with estimated bone mineral density derived from heel ultrasound in 426 824 individuals who had, on average, calcium levels in the normal range. A fracture genome-wide association meta-analysis comprising 24 cohorts and the UK Biobank including a total of 76 549 cases and 470 164 controls, who, on average, also had calcium levels in the normal range was then performed. RESULTS: A standard deviation increase in genetically derived serum calcium (0.13 mmol/L or 0.51 mg/dL) was not associated with increased estimated bone mineral density (0.003 g/cm2, 95% confidence interval -0.059 to 0.066; P=0.92) or a reduced risk of fractures (odds ratio 1.01, 95% confidence interval 0.89 to 1.15; P=0.85) in inverse-variance weighted mendelian randomisation analyses. Sensitivity analyses did not provide evidence of pleiotropic effects. CONCLUSIONS: Genetic predisposition to increased serum calcium levels in individuals with normal calcium levels is not associated with an increase in estimated bone mineral density and does not provide clinically relevant protection against fracture. Whether such predisposition mimics the effect of short term calcium supplementation is not known. Given that the same genetically derived increase in serum calcium is associated with an increased risk of coronary artery disease, widespread calcium supplementation in the general population could provide more risk than benefit.


Assuntos
Densidade Óssea/genética , Cálcio/sangue , Predisposição Genética para Doença , Fraturas por Osteoporose/sangue , Fraturas por Osteoporose/genética , Adenosina Trifosfatases/genética , Diacilglicerol Quinase/genética , Feminino , Fator de Transcrição GATA3/genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Receptores de Detecção de Cálcio/genética , Medição de Risco , Vitamina D3 24-Hidroxilase/genética , Vitamina K Epóxido Redutases/genética
11.
Klin Lab Diagn ; 64(7): 417-423, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31408594

RESUMO

Recently, they increasingly began to pay attention to the role of a nonspecific immune-inflammatory vascular response as a link in general pathogenetic mechanisms with a change in the elastic properties of arteries and phenomena of destructive bone changes, which at the subclinical level is of great importance for the prevention of the development of socially significant diseases. A total of 104 patients were examined (mean age 57.45 years), which were divided into three groups. The first group included 39 healthy women, the second group included 30 patients with hypertension and osteopenia, and the third group included 35 women with hypertension and osteoporosis. The analysis of markers of the immune inflammatory response, endothelial dysfunction, hormonal and mineral-vitamin status parameters was conducted against the background of the study of parameters of daily monitoring of arterial pressure, study of parameters of vascular wall stiffness and densitometry to clarify the predictors of cardiovascular and degenerative bone changes in postmenopausal women. A significant increase in the concentration of HF-CRP, the level of homocystemine, IL-8, parathyroid hormone, against the background of a significant decrease in the level of estrogen, progesterone, testosterone, with a persistent tendency to increase in total cholesterol, atherogenic lipid fractions, myeloperoxidase, endothelin-1 and decrease was recorded calcitonin, total and ionized calcium, with a significantly minimal value of vitamin D in the 3rd group of patients. The risks of development and progression of bone destructive changes were calculated using the logistic regression method for the group of AH with osteopenia and osteoporosis. Thus, for patients with hypertension and osteopenia, a significantly significant parameter associated with the risk of developing osteoporosis was an indicator of the velocity of the pulse wave, an increase in the level of which exceeds 12.05 m/s is associated with an increased risk of developing osteoporosis by 3.8 times. Increased levels of pro-inflammatory parameters, IL-6 and 8, TNF-α, HB-SRB, parathyroid hormone and reduced levels of progesterone and IL10, took the most active part in aggravating the degree of available bone tissue destruction. Timely specialized multidirectional study of biochemical and instrumental parameters (in particular, the study of the speed of the pulse wave and densitometry) can be the basis for the development of personalized prevention and treatment tactics for women in order to prevent socially dangerous cardiovascular and bone complications.


Assuntos
Hipertensão/patologia , Inflamação/patologia , Osteoporose/patologia , Densidade Óssea , Doenças Ósseas Metabólicas/imunologia , Doenças Ósseas Metabólicas/patologia , Osso e Ossos , Estudos de Casos e Controles , Citocinas/sangue , Feminino , Hormônios/sangue , Humanos , Hipertensão/imunologia , Pessoa de Meia-Idade , Osteoporose/imunologia , Pós-Menopausa
12.
JAMA ; 322(8): 736-745, 2019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-31454046

RESUMO

Importance: Few studies have assessed the effects of daily vitamin D doses at or above the tolerable upper intake level for 12 months or greater, yet 3% of US adults report vitamin D intakes of at least 4000 IU per day. Objective: To assess the dose-dependent effect of vitamin D supplementation on volumetric bone mineral density (BMD) and strength. Design, Setting, and Participants: Three-year, double-blind, randomized clinical trial conducted in a single center in Calgary, Canada, from August 2013 to December 2017, including 311 community-dwelling healthy adults without osteoporosis, aged 55 to 70 years, with baseline levels of 25-hydroxyvitamin D (25[OH]D) of 30 to 125 nmol/L. Interventions: Daily doses of vitamin D3 for 3 years at 400 IU (n = 109), 4000 IU (n = 100), or 10 000 IU (n = 102). Calcium supplementation was provided to participants with dietary intake of less than 1200 mg per day. Main Outcomes and Measures: Co-primary outcomes were total volumetric BMD at radius and tibia, assessed with high resolution peripheral quantitative computed tomography, and bone strength (failure load) at radius and tibia estimated by finite element analysis. Results: Of 311 participants who were randomized (53% men; mean [SD] age, 62.2 [4.2] years), 287 (92%) completed the study. Baseline, 3-month, and 3-year levels of 25(OH)D were 76.3, 76.7, and 77.4 nmol/L for the 400-IU group; 81.3, 115.3, and 132.2 for the 4000-IU group; and 78.4, 188.0, and 144.4 for the 10 000-IU group. There were significant group × time interactions for volumetric BMD. At trial end, radial volumetric BMD was lower for the 4000 IU group (-3.9 mg HA/cm3 [95% CI, -6.5 to -1.3]) and 10 000 IU group (-7.5 mg HA/cm3 [95% CI, -10.1 to -5.0]) compared with the 400 IU group with mean percent change in volumetric BMD of -1.2% (400 IU group), -2.4% (4000 IU group), and -3.5% (10 000 IU group). Tibial volumetric BMD differences from the 400 IU group were -1.8 mg HA/cm3 (95% CI, -3.7 to 0.1) in the 4000 IU group and -4.1 mg HA/cm3 in the 10 000 IU group (95% CI, -6.0 to -2.2), with mean percent change values of -0.4% (400 IU), -1.0% (4000 IU), and -1.7% (10 000 IU). There were no significant differences for changes in failure load (radius, P = .06; tibia, P = .12). Conclusions and Relevance: Among healthy adults, treatment with vitamin D for 3 years at a dose of 4000 IU per day or 10 000 IU per day, compared with 400 IU per day, resulted in statistically significant lower radial BMD; tibial BMD was significantly lower only with the 10 000 IU per day dose. There were no significant differences in bone strength at either the radius or tibia. These findings do not support a benefit of high-dose vitamin D supplementation for bone health; further research would be needed to determine whether it is harmful. Trial Registration: ClinicalTrials.gov Identifier: NCT01900860.


Assuntos
Densidade Óssea/efeitos dos fármacos , Colecalciferol/administração & dosagem , Suplementos Nutricionais , Vitaminas/administração & dosagem , Absorciometria de Fóton , Administração Oral , Idoso , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Análise de Elementos Finitos , Resistência à Flexão , Humanos , Masculino , Pessoa de Meia-Idade , Rádio (Anatomia)/anatomia & histologia , Rádio (Anatomia)/diagnóstico por imagem , Tíbia/anatomia & histologia , Tíbia/diagnóstico por imagem , Falha de Tratamento , Vitamina D/análogos & derivados , Vitamina D/sangue
13.
Z Rheumatol ; 78(7): 636-644, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31338681

RESUMO

BACKGROUND: In juvenile idiopathic arthritis and related chronic inflammatory diseases, proinflammatory cytokines inhibit bone formation and stimulate bone resorption. Anti-inflammatory drugs, such as glucocorticoids and nonsteroidal antirheumatic drugs (NSARD) have as a side effect the potential to inhibit growth and maintenance of bone. These issues are of particular importance for the growing skeleton in childhood and adolescence. OBJECTIVE: This article presents a narrative overview about the dimension of the problem, a critical evaluation of diagnostic procedures and a discussion of available countermeasures. METHODS: A systematic literature search was carried out and the available evidence was evaluated based on the authors' knowledge and clinical experience as experts in the field. RESULTS AND CONCLUSION: In recent years solid data have been accumulated with respect to the interpretation of bone mineral density (BMD) measurements in children and adolescents. Based on these data from the literature and given that the radiation exposure is also very low, it is now possible to clinically apply BMD measurements in this population using dual energy X­ray absorption (DXA) technology for risk evaluation and diagnosis, taking the respective phase of development and body length into consideration. Dynamic measurements over time appear to be especially valuable in the context of individual clinical data. Hence, BMD measurements can be helpful in monitoring bone health, especially in juvenile idiopathic arthritis and other related inflammatory diseases. Apart from the specific indications for extended diagnostics and bone targeted pharmacological treatment, this method can also contribute to the management of preventive measures, such as sufficient calcium and vitamin D intake and targeted exercise interventions. Even in times of extremely effective antirheumatic drugs, children with chronic inflammatory diseases still bear a risk for bone health.


Assuntos
Artrite Juvenil , Densidade Óssea , Osso e Ossos/efeitos dos fármacos , Glucocorticoides/efeitos adversos , Absorciometria de Fóton , Adolescente , Artrite Juvenil/complicações , Artrite Juvenil/tratamento farmacológico , Osso e Ossos/fisiologia , Criança , Fraturas Ósseas , Glucocorticoides/uso terapêutico , Humanos , Radiografia
14.
Yonsei Med J ; 60(8): 742-750, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31347329

RESUMO

PURPOSE: Muscle mass, strength, and composition determine muscle quantity and quality. However, data on muscle properties in relation to bone mass or insulin resistance are limited in Asian populations. This study aimed to investigate the relative importance of muscle measurements in regards to their relationship with lower bone mass and insulin resistance. MATERIALS AND METHODS: In this study, 192 postmenopausal women (age, 72.39±6.07 years) were enrolled. We measured muscle cross-sectional area (CSA) and attenuation at the gluteus maximus and quadriceps muscles through quantitative computed tomography. Muscle strength and physical performance were evaluated with the hand grip test and Short Physical Performance Battery (SPPB). Pearson correlation analysis and linear regression were performed to evaluate the relationship between muscle properties and homeostatic model assessment-insulin resistance (HOMA-IR) or bone mineral density (BMD). RESULTS: Muscle CSA, hand grip strength, and SPPB score held positive correlations with spine and hip BMDs, but not with insulin resistance. In contrast, muscle attenuation of the gluteus maximus or quadriceps was inversely related to HOMA-IR (r=-0.194, p=0.018 and r=-0.292, p<0.001, respectively), but not BMD. Compared with the control group, muscle CSA was significantly decreased in patients with osteoporosis; however, decreased muscle attenuation, indicating high fat infiltration, was found only in patients with diabetes. CONCLUSION: Muscle mass, strength, and physical performance were associated with low bone mass, and accumulation of intramuscular fat, a histological hallmark of persistently damaged muscles, may play a major role in the development of insulin resistance in Korean postmenopausal women.


Assuntos
Osso e Ossos/anatomia & histologia , Resistência à Insulina , Força Muscular/fisiologia , Músculo Esquelético/anatomia & histologia , Músculo Esquelético/fisiologia , Pós-Menopausa/fisiologia , Idoso , Índice de Massa Corporal , Densidade Óssea/fisiologia , Estudos Transversais , Diabetes Mellitus/fisiopatologia , Feminino , Força da Mão/fisiologia , Humanos , Tamanho do Órgão , Osteoporose/fisiopatologia , República da Coreia
15.
Zhongguo Gu Shang ; 32(6): 535-538, 2019 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-31277537

RESUMO

OBJECTIVE: To study and compare the clinical effects of Rehmannia Decoction and alendronate sodium for the treatment of primary osteoporosis. METHODS: From January 2016 to December 2017, 72 patients with primary osteoporosis who took Dihuang Decoction(DHD) orally and alendronate regularly for more than one year were randomly divided into 2 groups:experimental group and control group. The experimental group consisted of 14 males and 22 females, with an average age of(63.97±3.70) years old. The patients in the experimental group took Chinese medicine DHD, one dose each time, one time in the morning and one time in the evening, twice a week. The control group consisted of 16 males and 20 females with an average age of(63.36±3.07) years old. Patients in the control group were given alendronate 70 mg orally once a week. The basic treatment for osteoporosis remained unchanged in both groups(600 mg of calcium carbonate D3 and 0.5 µg of calcitriol capsules were taken daily). Bone mineral density (BMD) of femoral neck and lumbar vertebrae was measured by dual energy X-ray absorptiometry before and after treatment for one year. The levels of serum collagen type I C-terminal peptide (beta-CTX) and serum osteoclast (SOST) were measured before and after treatment for two groups. RESULTS: The age, bone mineral density, SOST and beta-CTX baseline values between the two groups before and after anti-osteoporosis treatment were compared. The difference was not statistically significant(P>0.05). Compared with the two groups, the BMD of femoral neck and lumbar vertebrae were increased after 1 year of anti-osteoporosis treatment. The differences were statistically significant (P<0.001). The value of serum beta-CTX was significantly lower than before. The t values were 52.002 and 50.071 respectively. The value of serum SOST was increased than that before treatment. The t values were -29.242 and -30.807 respectively. The differences were statistically significant (P<0.001). BMD of the femoral neck and lumbar spine was compared between the two groups after treatment. The P values were 0.294 and 0.478 respectively. The difference was not statistically significant (P>0.05). The serum beta-CTX values were compared between the two groups after treatment. The P value was 0.908. The serum SOST values were compared between the two groups after treatment. The P value was 0.888. The difference was not statistically significant (P>0.05). CONCLUSIONS: In this study, traditional Chinese medicine DHD is used to treat osteoporosis. It is found that DHD and alendronate have a good effect. The DHD can be used as a choice of Chinese medicine in the treatment of primary osteoporosis.


Assuntos
Alendronato/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Osteoporose , Absorciometria de Fóton , Idoso , Densidade Óssea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/tratamento farmacológico
16.
N Engl J Med ; 381(9): 803-815, 2019 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-31339677

RESUMO

BACKGROUND: Two drugs under consideration for inclusion in antiretroviral therapy (ART) regimens for human immunodeficiency virus (HIV) infection are dolutegravir (DTG) and tenofovir alafenamide fumarate (TAF). There are limited data on their use in low- and middle-income countries. METHODS: We conducted a 96-week, phase 3, investigator-led, open-label, randomized trial in South Africa, in which we compared a triple-therapy combination of emtricitabine (FTC) and DTG plus either of two tenofovir prodrugs - TAF (TAF-based group) or tenofovir disoproxil fumarate (TDF) (TDF-based group) - against the local standard-of-care regimen of TDF-FTC-efavirenz (standard-care group). Inclusion criteria included an age of 12 years or older, no receipt of ART in the previous 6 months, a creatinine clearance of more than 60 ml per minute (>80 ml per minute in patients younger than 19 years of age), and an HIV type 1 (HIV-1) RNA level of 500 copies or more per milliliter. The primary end point was the percentage of patients with a 48-week HIV-1 RNA level of less than 50 copies per milliliter (as determined with the Snapshot algorithm from the Food and Drug Administration; noninferiority margin, -10 percentage points). We report the primary (48-week) efficacy and safety data. RESULTS: A total of 1053 patients underwent randomization from February 2017 through May 2018. More than 99% of the patients were black, and 59% were female. The mean age was 32 years, and the mean CD4 count was 337 cells per cubic millimeter. At week 48, the percentage of patients with an HIV-1 RNA level of less than 50 copies per milliliter was 84% in the TAF-based group, 85% in the TDF-based group, and 79% in the standard-care group, findings that indicate that the DTG-containing regimens were noninferior to the standard-care regimen. The number of patients who discontinued the trial regimen was higher in the standard-care group than in the other two groups. In the per-protocol population, the standard-care regimen had equivalent potency to the other two regimens. The TAF-based regimen had less effect on bone density and renal function than the other regimens. Weight increase (both lean and fat mass) was greatest in the TAF-based group and among female patients (mean increase, 6.4 kg in the TAF-based group, 3.2 kg in the TDF-based group, and 1.7 kg in the standard-care group). No resistance to integrase inhibitors was identified in patients receiving the DTG-containing regimens. CONCLUSIONS: Treatment with DTG combined with either of two tenofovir prodrugs (TAF and TDF) showed noninferior efficacy to treatment with the standard-care regimen. There was significantly more weight gain with the DTG-containing regimens, especially in combination with TAF, than with the standard-care regimen. (ADVANCE ClinicalTrials.gov number, NCT03122262.).


Assuntos
Adenina/análogos & derivados , Antirretrovirais/administração & dosagem , Infecções por HIV/tratamento farmacológico , HIV-1 , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Ácidos Fosforosos/administração & dosagem , Adenina/administração & dosagem , Adenina/efeitos adversos , Adolescente , Adulto , Antirretrovirais/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Contagem de Linfócito CD4 , Quimioterapia Combinada , Feminino , Inibidores de Integrase de HIV/administração & dosagem , HIV-1/genética , HIV-1/isolamento & purificação , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Ácidos Fosforosos/efeitos adversos , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Pró-Fármacos/administração & dosagem , RNA Viral/sangue , Uracila/administração & dosagem , Uracila/análogos & derivados , Carga Viral , Adulto Jovem
17.
Medicine (Baltimore) ; 98(27): e16096, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277108

RESUMO

Osteoporosis (OP) is a disease characterized by decreased bone mineral density (BMD) and an increased risk of osteoporotic fractures. Nutritional factors (including glucose and fats lipids), have been implicated in OP.We hypothesized that the levels of blood glucose and lipids could be biomarkers for predicting the risk of OP. To test this hypothesis, we evaluated the potential relationship between BMD and levels of blood glucose and lipids via a community-based study in China.This was a community-based cross-section analysis, and a total of 8584 cases were investigated. The BMD of the left calcaneus was measured using an ultrasonic bone densitometer. The levels of blood glucose (fasting blood glucose [FBG], 2-h blood glucose [2hBG], and glycosylated hemoglobin [HbAlc]), and lipids (triglyceride [TG], total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], and high-density lipoprotein cholesterol [HDL-C]) were measured and analyzed.In our study population, the levels of FBG, 2hBG, HbAlc, TC, LDL-C and HDL-C were higher in the OP group than in the low bone density and the normal bone density groups, while the levels of HbAlc, TC, and LDL-C in the low bone density group were higher than those in the normal bone density group. In males, the level of blood LDL-C in the low bone density group was higher than that in the normal bone density group. In postmenopausal subjects, the levels of FBG, 2hBG and HbA1C were higher than those in the normal bone density groups, and the level of HbA1C in the low bone density group was higher than that in the normal bone density group. Pearson linear trend analysis demonstrated that BMD was positively associated with TC and LDL-C in males and negatively associated with FBG, 2hBG and HbA1C in postmenopausal females. Moreover, logistic analysis showed that BMD was correlated with TC in premenopausal females and HbA1C in postmenopausal females.OP is generally associated with abnormal levels of blood glucose and/or lipids; nevertheless, the relationship between OP and abnormal levels of blood glucose and/or lipids is complicate and different subpopulations may have different susceptibilities. Therefore, further detailed studies are warranted.


Assuntos
Glicemia/análise , Densidade Óssea/fisiologia , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Osteoporose/sangue , Absorciometria de Fóton , Adulto , Idoso , Biomarcadores/sangue , Calcâneo/diagnóstico por imagem , Estudos Transversais , Feminino , Teste de Tolerância a Glucose , Hemoglobina A Glicada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Fatores de Risco , Inquéritos e Questionários
18.
J Zoo Wildl Med ; 50(2): 375-382, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31260203

RESUMO

Musculoskeletal problems are one of the top five causes of disease in elephants. However, recent blood chemistry analysis is the only routine protocol for bone mineral status evaluation, with no assessment method currently available for the direct measurement of elephant bone mineral density (BMD). This work applied the the dual-energy X-ray technique (DXA) technique for bone density assessment. The elephant's tail was chosen for the analysis to avoid the radiation harm. Twelve live Asian elephants (Elephas maximus) comprising eight males and four females with ages in the range of 4-77 yr were investigated. The BMD was calculated based on radiographic images acquired using the DXA technique carried out at 40 kVp 2 mAs and 50 kVp 2 mAs. Blood serum analysis of total calcium (Ca), phosphorus (Phos) and alkaline phosphatase (ALP) content was conducted in parallel with the physical examination to correlate age and BMD. Analyses produced an overall mean BMD value in the range of 0.54-1.39 g/cm2, with that of the males higher than that of the females. The BMD was found to be negatively correlated with age, Ca, and Phos, but not with ALP. In summary, the BMD analysis of an elephant's tail might be used with blood serum Ca and Phos to predict the overall bone mineral status of the animal.


Assuntos
Absorciometria de Fóton/veterinária , Densidade Óssea/fisiologia , Elefantes/anatomia & histologia , Cauda/anatomia & histologia , Animais , Elefantes/fisiologia , Feminino , Masculino , Cauda/diagnóstico por imagem
19.
J Zoo Wildl Med ; 50(2): 447-452, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31260212

RESUMO

Giant South American turtles (Podocnemis expansa) are at a risk of extinction because of the rapid decline in their population over the last few decades. Metabolic bone disease (MBD) is common in captive testudines, but is often not diagnosed until a later stage. The authors present the cases of four captive giant South American turtles with carapace deformity secondary to MBD that underwent computed tomography (CT) scans of the carapace bones and vertebral column. Findings indicative of changes in geometry were found in both. The cancellous bone pattern was characterized by varying degrees of increased trabecular spacing and cortical thinning of the pleural bones. Bone densitometry analysis of the pleural and neural bones and at the level of the body of the third, fourth, and fifth dorsal vertebrae showed mean density values much lower than those found in two adult specimens of the same species that were considered healthy. In conclusion, CT contributed important information on the degree of demineralization and possible structural changes due to MBD and should be considered a relevant tool for diagnosis of this condition.


Assuntos
Densidade Óssea/fisiologia , Doenças Ósseas Metabólicas/veterinária , Tomografia Computadorizada por Raios X/veterinária , Tartarugas , Animais , Doenças Ósseas Metabólicas/diagnóstico por imagem , Doenças Ósseas Metabólicas/patologia , Feminino , Masculino
20.
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
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