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1.
Arch Osteoporos ; 15(1): 154, 2020 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-33009959

RESUMO

The purpose was to determine if increasing serum 25(OH)D and calcium in postmenopausal women increased skeletal muscle size, strength, balance, and functional task performance while decreasing muscle fatigue. PCSA of the vastus lateralis increased and ascent of stairs time decreased after 6 months of increased serum 25(OH)D. PURPOSE: The Institute of Medicine recommends ≥ 20 ng/ml of serum 25-hydroxyvitamin D [25(OH)D] for bone and overall health. Serum 25(OH)D levels have been associated with physical performance, postural sway, and falls. The purpose of this study was to determine if increasing postmenopausal women's serum 25(OH)D levels from 20-30 ng/ml to 40-50 ng/ml improved skeletal muscle size, strength, balance, and functional performance while decreasing skeletal muscle fatigue. METHODS: Twenty-six post-menopausal women (60-85 years old) with baseline serum 25(OH)D levels between 20 and 30 ng/ml were recruited. Oral over-the-counter (OTC) vitamin D3 and calcium citrate were prescribed to increase subjects' serum 25(OH)D to levels between 40 and 50 ng/ml, serum calcium levels above 9.2 mg/dl, and PTH levels below 60 pg/ml, which were confirmed at 6 and 12 weeks. Outcome measures assessed at baseline and 6 months included muscle physiological cross-sectional area (PCSA), muscle strength, postural balance, time to perform functional tasks, and muscle fatigue. Repeated measures comparisons between baseline and follow-up were performed. RESULTS: Nineteen subjects completed the study. One individual could not afford the time commitment for the repeated measures. Three individuals did not take their vitamin D as recommended. Two subjects were lost to follow-up (lack of interest), and one did not achieve targeted serum 25(OH)D. Vastus lateralis PCSA increased (p = 0.007) and ascent of stair time decreased (p = 0.042) after 6 months of increasing serum 25(OH)D levels from 20-30 ng/ml to 40-50 ng/ml. Isometric strength was unchanged. Anterior-posterior center of pressure (COP) excursion and COP path length decreased (p < 0.1) albeit non-significantly, suggesting balance may improve from increased serum 25(OH)D and calcium citrate levels. CONCLUSIONS: Several measures of muscle structure and function were sensitive to elevated serum 25(OH)D and calcium levels indicating that further investigation of this phenomenon in post-menopausal women is warranted.


Assuntos
Citrato de Cálcio/administração & dosagem , Cálcio/sangue , Colecalciferol/administração & dosagem , Fadiga Muscular/efeitos dos fármacos , Força Muscular/efeitos dos fármacos , Pós-Menopausa/sangue , Deficiência de Vitamina D/prevenção & controle , Vitamina D/análogos & derivados , Absorciometria de Fóton/métodos , Idoso , Idoso de 80 Anos ou mais , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/uso terapêutico , Citrato de Cálcio/uso terapêutico , Colecalciferol/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Humanos , Pessoa de Meia-Idade , Atividade Motora/efeitos dos fármacos , Projetos Piloto , Análise e Desempenho de Tarefas , Resultado do Tratamento , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/tratamento farmacológico , Vitaminas/administração & dosagem , Vitaminas/uso terapêutico
2.
PLoS One ; 15(9): e0238248, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32877436

RESUMO

There is no clear evidence how effective the antiresorptive (AR) drugs alendronate and raloxifene are at reducing risk of second hip fracture and mortality in dialysis populations. The purpose of this study was to compare the risk of hospitalization for second hip fracture and risk of mortality between AR user and non-user groups in Taiwanese women on long-term dialysis with hip fractures. We conducted a retrospective cohort study using Taiwan National Health Insurance Research Datasets. Long-term dialysis women older than 50 years with newly diagnosed hip fractures and new to AR therapy from 2005 to 2011 were recruited. The patients were divided into AR users and non-users and matched by propensity score. We used Cox Proportional Hazards models to assess association of AR with risks of second hip fracture and mortality. Totally, 1,079 dialysis patients were included, and after matching, we were left with 74 AR users and 74 non-users. AR users did not show a significant reduction in the incidence of second hip fracture compared with non-users (adjusted Hazard Ratio (HR): 0.91, 95% CI: 0.30-2.76), and alendronate users exhibited higher risk of second hip fracture compared with raloxifene users (adjusted HR: 2.80, 95% CI: 0.42-18.79). In addition, AR users were found to have significantly lower 1- and 2-year mortality rates than the non-users (1- year: adjusted HR 0.25, 95% CI, 0.07-0.90; 2-year: 0.35, 95%CI: 0.17-0.72). AR treatment did not significantly improve the risk of second hip fracture but significantly reduce mortality in older women on dialysis. Further clinical trials on effectiveness of AR medications for dialysis populations should be warranted.


Assuntos
Alendronato/administração & dosagem , Conservadores da Densidade Óssea/administração & dosagem , Fraturas do Quadril/mortalidade , Cloridrato de Raloxifeno/administração & dosagem , Diálise Renal/mortalidade , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/terapia , Humanos , Incidência , Estudos Longitudinais , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Taiwan/epidemiologia
5.
Lancet Diabetes Endocrinol ; 8(8): 672-682, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32707115

RESUMO

BACKGROUND: The validation of bone mineral density (BMD) as a surrogate outcome for fracture would allow the size of future randomised controlled osteoporosis registration trials to be reduced. We aimed to determine the association between treatment-related changes in BMD, assessed by dual-energy x-ray absorptiometry, and fracture outcomes, including the proportion of treatment effect explained by BMD changes. METHODS: We did a pooled analysis of individual patient data from multiple randomised placebo-controlled clinical trials. We included data from multicentre, randomised, placebo-controlled, double-blind trials of osteoporosis medications that included women and men at increased osteoporotic fracture risk. Using individual patient data for each trial we calculated mean 24-month BMD percent change together with fracture reductions and did a meta-regression of the association between treatment-related differences in BMD changes (percentage difference, active minus placebo) and fracture risk reduction. We also used individual patient data to determine the proportion of anti-fracture treatment effect explained by BMD changes and the BMD change needed in future trials to ensure fracture reduction efficacy. FINDINGS: Individual patient data from 91 779 participants of 23 randomised, placebo-controlled trials were included. The trials had 1-9 years of follow-up and included 12 trials of bisphosphonate, one of odanacatib, two of hormone therapy (one of conjugated equine oestrogen and one of conjugated equine oestrogen plus medroxyprogesterone acetate), three of PTH receptor agonists, one of denosumab, and four of selective oestrogen receptor modulator trials. The meta-regression revealed significant associations between treatment-related changes in hip, femoral neck, and spine BMD and reductions in vertebral (r2 0·73, p<0·0001; 0·59, p=0·0005; 0·61, p=0·0003), hip (0·41, p=0·014; 0·41, p=0·0074; 0·34, p=0·023) and non-vertebral fractures (0·53, p=0·0021; 0·65, p<0·0001; 0·51, p=0·0019). Minimum 24-month percentage changes in total hip BMD providing almost certain fracture reductions in future trials ranged from 1·42% to 3·18%, depending on fracture site. Hip BMD changes explained substantial proportions (44-67%) of treatment-related fracture risk reduction. INTERPRETATION: Treatment-related BMD changes are strongly associated with fracture reductions across randomised trials of osteoporosis therapies with differing mechanisms of action. These analyses support BMD as a surrogate outcome for fracture outcomes in future randomised trials of new osteoporosis therapies and provide an important demonstration of the value of public access to individual patient data from multiple trials. FUNDING: Foundation for National Institutes of Health.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Densidade Óssea/efeitos dos fármacos , Interpretação Estatística de Dados , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Absorciometria de Fóton/métodos , Biomarcadores/metabolismo , Densidade Óssea/fisiologia , Humanos , Fraturas por Osteoporose/metabolismo , Análise de Regressão , Comportamento de Redução do Risco , Resultado do Tratamento
6.
J Bone Miner Res ; 35(6): 1009-1013, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32406536

RESUMO

Osteoporosis is a chronic condition that reflects reduced bone strength and an associated increased risk for fracture. As a chronic condition, osteoporosis generally requires sustained medical intervention(s) to limit the risks for additional bone loss, compromise of skeletal integrity, and fracture occurrence. Further complicating this issue is the fact that the abrupt cessation of some therapies can be associated with an increased risk for harm. It is in this context that the COVID-19 pandemic has brought unprecedented disruption to the provision of health care globally, including near universal requirements for social distancing. In this Perspective, we provide evidence, where available, regarding the general care of patients with osteoporosis in the COVID-19 era and provide clinical recommendations based primarily on expert opinion when data are absent. Particular emphasis is placed on the transition from parenteral osteoporosis therapies. It is hoped that these recommendations can be used to safely guide care for patients with osteoporosis until a return to routine clinical care standards is available. © 2020 American Society for Bone and Mineral Research.


Assuntos
Infecções por Coronavirus , Osteoporose/terapia , Pandemias , Pneumonia Viral , Absorciometria de Fóton , Biomarcadores/sangue , Densidade Óssea , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Continuidade da Assistência ao Paciente , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Denosumab/efeitos adversos , Denosumab/uso terapêutico , Gerenciamento Clínico , Esquema de Medicação , Terapia de Reposição de Estrogênios/efeitos adversos , Fraturas Espontâneas/prevenção & controle , Fraturas Espontâneas/terapia , Serviços de Assistência Domiciliar , Humanos , Imunossupressão/efeitos adversos , Osteoporose/sangue , Osteoporose/diagnóstico por imagem , Osteoporose/tratamento farmacológico , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Cloridrato de Raloxifeno/efeitos adversos , Cloridrato de Raloxifeno/uso terapêutico , Recidiva , Telemedicina , Trombofilia/induzido quimicamente , Trombofilia/etiologia , Procedimentos Desnecessários
8.
Osteoporos Int ; 31(7): 1189-1191, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32346775

RESUMO

As the world grapples with the crisis of COVID-19, established economies and healthcare systems have been brought to their knees. Tough decisions regarding redirection of resources away from the management of conditions deemed "nonessential" are being made. How can we balance urgent resourcing of our acute crisis while not abandoning the real need of patients with osteoporosis? This article offers a few practical solutions.


Assuntos
Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Alocação de Recursos para a Atenção à Saúde/organização & administração , Osteoporose/terapia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Reação de Fase Aguda/induzido quimicamente , Reação de Fase Aguda/diagnóstico , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/efeitos adversos , Infecções por Coronavirus/diagnóstico , Denosumab/administração & dosagem , Diagnóstico Diferencial , Difosfonatos/efeitos adversos , Esquema de Medicação , Humanos , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/prevenção & controle , Educação de Pacientes como Assunto , Pneumonia Viral/diagnóstico , Medição de Risco/métodos
9.
J Neuroimmunol ; 344: 577244, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32330748

RESUMO

Toll-like receptor 2 (TLR2) recognizes a wide range of microbial molecules and plays critical roles in the initiation of innate immune responses. In the present study, we aimed to investigate whether the depletion of microglia and macrophages with clodronate liposomes (Clod-Lips) attenuates the activation of mouse brain circuits for TLR2-mediated inflammation and hypothermia. The peripheral administration of the TLR2 agonist zymosan induced nuclear factor-κB activation in microglia and macrophages and Fos expression in astrocytes/tanycytes and neurons in the circumventricular organs (CVOs). The depletion of microglia and macrophages with Clod-Lips markedly decreased zymosan-induced Fos expression in astrocytes/tanycytes and neurons in the CVOs. The treatment with Clod-Lips significantly attenuated zymosan-induced hypothermia. These results indicate that microglia and macrophages in the CVOs participate in the initiation and transmission of inflammatory responses after the peripheral administration of zymosan.


Assuntos
Ácido Clodrônico/administração & dosagem , Hipotermia/metabolismo , Macrófagos/metabolismo , Microglia/metabolismo , Proteínas Proto-Oncogênicas c-fos/biossíntese , Zimosan/toxicidade , Fatores Etários , Animais , Conservadores da Densidade Óssea/administração & dosagem , Portadores de Fármacos/administração & dosagem , Expressão Gênica , Hipotermia/induzido quimicamente , Hipotermia/prevenção & controle , Lipossomos , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/genética , Receptor 2 Toll-Like/agonistas , Receptor 2 Toll-Like/metabolismo
10.
Arch Osteoporos ; 15(1): 58, 2020 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-32303862

RESUMO

This retrospective study reports 81% long-term (> 3 years) adherence to and 77% persistence with zoledronic acid (ZA) treatment in osteoporosis patients, with ZA being costfree for patients. Eight percent of patients discontinued treatment because of adverse events (AEs), with a tendency of higher discontinuation rate in older patients. PURPOSE: This study investigated (1) long-term adherence to and persistence with ZA treatment in a real-world setting, (2) extent to which an adverse reaction to ZA impacted on adherence and persistence, and (3) whether there were sex or age differences in patients that had early treatment termination (ETT) due to AEs and those who adhered to the regimen. METHODS: All patients treated with ZA at the Endocrinology Department at Linköping University Hospital, Linköping, Sweden between 2012 and 2017 were included. ETT was defined as < 3 ZA infusions, which was confirmed from patients' medical records. RESULTS: A total of 414 patients were treated with ZA, with 81% receiving > 3 ZA infusions. Three-year persistence was 77% for a treatment window of 365 days ± 90 days (75% with 365 days ± 60 days window). The most common reason for ETT was AEs (8%), followed by medical conditions (5%), biological aging (3%), and other (e.g., lost to follow-up [3%]). Most patients who discontinued treatment because of AEs reported symptoms of acute-phase reaction, and tended to be older than those who adhered to treatment (74 ± 9 vs 70 ± 13 years, p = 0.064). There was no difference in sex ratio between the 2 groups (85% vs 90% females, p = 0.367). CONCLUSION: Rates of long-term adherence to and persistence with ZA treatment were high with a pre-scheduled 3-year treatment regimen in the tax-financed Swedish healthcare system. AEs-mainly acute-phase reaction-were the most common reason for ETT, occurring in nearly 1 out of 10 patients.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Adesão à Medicação/estatística & dados numéricos , Osteoporose/tratamento farmacológico , Suspensão de Tratamento/estatística & dados numéricos , Ácido Zoledrônico/administração & dosagem , Idoso , Conservadores da Densidade Óssea/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Suécia , Fatores de Tempo , Ácido Zoledrônico/efeitos adversos
11.
JAMA ; 323(15): 1456-1466, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32315057

RESUMO

Importance: A proof-of-principle study suggested that intravenous zoledronic acid may reduce knee pain and the size of bone marrow lesions in people with knee osteoarthritis, but data from large trials are lacking. Objective: To determine the effects of intravenous zoledronic acid on knee cartilage volume loss in patients with symptomatic knee osteoarthritis and bone marrow lesions. Design, Setting, and Participants: A 24-month multicenter, double-blind placebo-controlled randomized clinical trial conducted at 4 sites in Australia (1 research center and 3 hospitals). Adults aged 50 years or older with symptomatic knee osteoarthritis and subchondral bone marrow lesions detected by magnetic resonance imaging (MRI) were enrolled from November 2013 through September 2015. The final date of follow-up was October 9, 2017. Interventions: Intravenous infusion with either 5 mg of zoledronic acid in a 100-mL saline solution (n = 113) or a placebo saline solution (n = 110) at baseline and 12 months. Main Outcomes and Measures: The primary outcome was absolute change in tibiofemoral cartilage volume assessed using MRI over 24 months (the minimum clinically important difference [MCID] has not been established). Three prespecified secondary outcomes were change in knee pain assessed by a visual analog scale (0 [no pain] to 100 [unbearable pain]; MCID, 15) and the Western Ontario and McMaster Universities Osteoarthritis Index (0 [no pain] to 500 [unbearable pain]; MCID, 75) over 3, 6, 12, 18, and 24 months and change in bone marrow lesion size over 6 and 24 months (the MCID has not been established). Results: Of 223 participants enrolled (mean age, 62.0 years [SD, 8.0 years]; 52% were female), 190 (85%) completed the trial. Change in tibiofemoral cartilage volume was not significantly different between the zoledronic acid group and the placebo group over 24 months (-878 mm3 vs -919 mm3; between-group difference, 41 mm3 [95% CI, -79 to 161 mm3]; P = .50). No significant between-group differences were found for any of the prespecified secondary outcomes, including changes in knee pain assessed by a visual analog scale (-11.5 in the zoledronic acid group vs -16.8 in the placebo group; between-group difference, 5.2 [95% CI, -2.3 to 12.8]; P = .17), changes in knee pain assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (-37.5 vs -58.0, respectively; between-group difference, 20.5 [95% CI, -11.2 to 52.2]; P = .21), and changes in bone marrow lesion size (-33 mm2 vs -6 mm2; between-group difference, -27 mm2 [95% CI, -127 to 73 mm2]; P = .60) over 24 months. Adverse events were more common with zoledronic acid than with placebo (96% vs 83%, respectively) and consisted mainly of acute reactions (defined as symptoms within 3 days of administration of infusion; 87% vs 56%). Conclusions and Relevance: Among patients with symptomatic knee osteoarthritis and bone marrow lesions, yearly zoledronic acid infusions, compared with placebo, did not significantly reduce cartilage volume loss over 24 months. These findings do not support the use of zoledronic acid in the treatment of knee osteoarthritis. Trial Registration: anzctr.org.au Identifier: ACTRN12613000039785.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Doenças da Medula Óssea/tratamento farmacológico , Cartilagem Articular/efeitos dos fármacos , Osteoartrite do Joelho/tratamento farmacológico , Ácido Zoledrônico/uso terapêutico , Idoso , Conservadores da Densidade Óssea/administração & dosagem , Medula Óssea/patologia , Doenças da Medula Óssea/complicações , Doenças da Medula Óssea/diagnóstico por imagem , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Método Duplo-Cego , Feminino , Humanos , Infusões Intravenosas , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/patologia , Falha de Tratamento , Ácido Zoledrônico/administração & dosagem
12.
Nutr. hosp ; 37(2): 327-334, mar.-abr. 2020. tab
Artigo em Inglês | IBECS | ID: ibc-190598

RESUMO

INTRODUCTION: vitamin D is involved in recovery after an osteoporotic hip fracture (OHF). Previous studies have reported decreased serum vitamin D levels during fracture healing. OBJECTIVES: our aim was to evaluate: a) serum 25-hydroxyvitamin D3 (25OHD3) levels in patients with OHF at hospital admission and 8 days post-admission, and b) the relationship between 25OHD levels and clinical outcomes. METHODS: a prospective study including 66 patients aged over 65 years hospitalized for OHF. We gathered data on baseline demographic characteristics, medical history, Mini Mental State (MMS) assessment, Activities of Daily Living (ADL) results, nutritional assessment, and type of fracture and surgery. Laboratory results were collected on bone biomarkers, albumin, 25OHD3, and IL6. Clinical outcomes included length of stay, complications, and mortality. In the statistical analysis, a t-test was used for continuous variables and a chi-square test for qualitative variables. Linear regression models were used for the multivariate analysis, adjusted for covariates. RESULTS: our study population had low serum vitamin D levels at admission, with a mean [(standard error of the mean (SEM)] of 12.04 (1.03) ng/mL. Both 25OHD3 and interleukin 6 (IL-6) levels significantly declined (p < 0.001) during the early post-fracture phase. A greater decline in 25OHD3 levels was significantly associated with longer hospital stay (p = 0.042, multivariate analysis). Serum 25OHD3 levels were also associated with cognitive status as assessed using the MMS exam. CONCLUSIONS: 25OHD3 levels were reduced in OHF patients at admission, and significantly decreased during the first 8 days post-admission. 25OHD3 levels were associated with MMS-assessed cognitive status. A greater decline in serum 25OHD3 was associated with a longer hospital stay


INTRODUCCIÓN: la vitamina D se ha relacionado con la recuperación tras la fractura osteoporótica de cadera (FOC). Estudios previos muestran un descenso de los niveles de vitamina D en la fase precoz tras la fractura. OBJETIVOS: evaluar: a) los niveles séricos de 25-hidroxivitamina D3 (25OHD3) al ingreso y a los 8 días del ingreso en hospitalizados por FOC; b) la relación de los niveles de 25OHD3 con los resultados clínicos, así como con el nivel cognitivo y funcional. MÉTODOS: estudio prospectivo de 66 pacientes (> 65 años) ingresados por FOC. Se estudiaron las características demográficas, los antecedentes personales, la valoración nutricional, el test Mini Mental State (MMS), el cuestionario Activities of Daily Living (ADL), el tipo de fractura y de cirugía, y parámetros bioquímicos del metabolismo óseo, la 25OHD3, la albúmina y la interleuquina 6. Como resultados clínicos se analizaron: estancia hospitalaria, complicaciones y mortalidad durante el ingreso. El análisis estadístico consistió en: a) prueba de la t para las variables continuas y χ2 para las cualitativas; b) análisis multivariable utilizando modelos de regresión lineal ajustados según el análisis de la covarianza. RESULTADOS: la población estudiada muestra niveles bajos de 25OHD3 al ingreso: media [± error estándar de la media (EEM)] = 12,04 (1,03) ng/mL. Durante el ingreso, 25OHD3 e interleuquina 6 decrecen significativamente (p < 0,001). El descenso de 25OHD3 se asocia con la estancia hospitalaria (p = 0,042 en análisis multivariable). Los valores disminuidos de 25OHD3 se asocian a un bajo nivel cognitivo (p = 0,042). CONCLUSIONES: los pacientes ingresados por fractura osteoporótica de cadera tienen niveles bajos de 25OHD3 que decrecen significativamente tras 8 días de ingreso. El descenso de 25OHD3 se asocia significativamente a la estancia hospitalaria. Los niveles disminuidos de 25OHD3 se asocian a un peor estado cognitivo evaluado mediante el MMS


Assuntos
Humanos , Masculino , Feminino , Idoso , Conservadores da Densidade Óssea/administração & dosagem , Lesões do Quadril/complicações , Fraturas por Osteoporose/complicações , 25-Hidroxivitamina D 2/administração & dosagem , Deficiência de Vitamina D/complicações , Estudos Prospectivos , Valor Nutritivo , Receptores de Calcitriol/administração & dosagem , Estado Nutricional , Vitamina D/sangue , 25-Hidroxivitamina D 2/sangue
13.
Poult Sci ; 99(3): 1241-1253, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32111302

RESUMO

Genetic selection and intensive nutrition for increased growth rate in meat-type ducks has resulted in an imbalance between pectorales increment and sternal mass, which is detrimental to productivity and welfare. Reducing body weight and increasing sternal mass probably reverses these adverse effects. Therefore, 2 experiments (Expt.) were conducted to investigate the effects of 25-hydroxycholecalciferol (25-OH-D3), a vitamin D3 metabolites, on sternal mass. In Expt. 1, 512 1-day-old male ducks were randomly assigned to 4 low-nutrient density diets and received following treatments in a 2 × 2 factorial arrangement: (i) NRC or China Agricultural industry standards (NY/T) vitamin premixes and (ii) 0.069 mg/kg 25-HyD in feed or not. At 49 D of age, regardless of 25-OH-D3, NY/T vitamin regimen inhibited bone turnover and consequently increased sternal trabecular bone volume and mineral deposition compared with NRC vitamin premix. Supplementing 25-OH-D3 to NRC but not NY/T vitamin regimen significantly improved sternal microarchitecture and mineral content, which companied by decreased serum bone resorption markers concentration, as well as downregulation of the gene expressions of osteoclast differentiation and activity. In Expt. 2, 256 1-day-old male ducks were fed a standard nutrient density diet contained NRC vitamin premix with 0 or 0.069 mg/kg of 25-OH-D3. Results also showed that 25-OH-D3 treatment significantly improved sternal mineral accumulation and microarchitecture, along with decreasing osteoblast and osteoclast numbers in bone surface, declining serum bone turnover markers levels, and increasing serum Ca concentration. Collectively, these findings indicated that the dietary administration of 25-OH-D3 increased sternal mass in NRC vitamin diet by suppressing bone resorption in 49-day-old meat duck.


Assuntos
Conservadores da Densidade Óssea/metabolismo , Calcifediol/metabolismo , Patos/fisiologia , Esterno/fisiologia , Vitaminas/metabolismo , Ração Animal/análise , Animais , Conservadores da Densidade Óssea/administração & dosagem , Calcifediol/administração & dosagem , Dieta/veterinária , Suplementos Nutricionais/análise , Masculino , Tamanho do Órgão , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Distribuição Aleatória
15.
J Oncol Pharm Pract ; 26(5): 1180-1189, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32122232

RESUMO

While bone-modifying agents such as bisphosphonates and denosumab are crucial to preventing skeletal-related events in patients with bone metastases, the optimal duration remains undefined. Extended duration may be associated with adverse effects such as osteonecrosis of the jaw and atypical femoral fracture. Although uncommon, atypical femoral fracture represents a serious consequence of prolonged bone-modifying agent use and are characterized by a prodrome and distinct radiographic findings. The oncology setting encompasses a unique set of atypical femoral fracture risk factors and considerations, with hormonal therapy in early stage disease, bone metastases in the advanced setting, and new targeted agents that may affect bone homeostasis. As outcomes in cancer treatment continue to improve, the questions of risks versus benefits of long-term bone-modifying agents and how to mitigate atypical femoral fracture risk become increasingly pertinent.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Neoplasias Ósseas/tratamento farmacológico , Difosfonatos/administração & dosagem , Fraturas do Fêmur/prevenção & controle , Conservadores da Densidade Óssea/efeitos adversos , Denosumab/administração & dosagem , Denosumab/efeitos adversos , Difosfonatos/efeitos adversos , Fraturas do Fêmur/induzido quimicamente , Humanos , Osteonecrose/induzido quimicamente , Osteonecrose/prevenção & controle , Fatores de Risco
16.
Rev. osteoporos. metab. miner. (Internet) ; 12(1): 20-27, ene.-mar. 2020. graf
Artigo em Espanhol | IBECS | ID: ibc-192306

RESUMO

OBJETIVO: El bazedoxifeno es un SERM de 3ª generación con efectos agonistas sobre el hueso y sobre el útero y el tejido mamario. Nuestro objetivo ha sido estudiar los efectos del bazedoxifeno sobre la calidad ósea en un modelo experimental de ratas ovariectomizadas. MATERIAL Y MÉTODOS: Se utilizaron 3 grupos de 15 ratas Wistar hembras de 6 meses de edad: uno control; otro de ratas ovariectomizadas; y un tercer grupo de ratas ovariectomizadas tratadas con bazedoxifeno (0,33 mg/kg/día). Tras 8 meses se estudiaron la densitometría ósea lumbar y femoral, los parámetros microtomográficos, los marcadores bioquímicos de remodelado y los parámetros biomecánicos del hueso. RESULTADOS: La ovariectomía descendió la densidad ósea femoral y lumbar. La última se recuperó parcialmente con bazedoxifeno. El remodelado óseo aumentó, recuperando el bazedoxifeno los niveles de formación. El bazedoxifeno recuperó la fracción volumétrica ósea (BV/TV), la densidad de superficie ósea (BS/TV), el aumento en la separación trabecular (Tb. Sp), la disminución en el número de trabéculas (Tb. N), el aumento del factor de patrón trabecular (Tb. Pf) y el índice de modelo estructural (SMI). La superficie relativa cortical aumentó tras la ovariectomía, normalizándose con bazedoxifeno. También recuperó la deformación máxima antes de la rotura producida por la ovariectomía, y amortiguó parcialmente la ganancia de peso de las ratas ovariectomizadas. CONCLUSIONES: Nuestro estudio muestra resultados positivos del bazedoxifeno sobre la calidad ósea. Este fármaco podría estar especialmente indicado para mujeres jóvenes postmenopáusicas con osteoporosis o en riesgo de padecerla


OBJETIVE: Bazedoxifene is a 3rdgeneration SERM with agonistic effects on the bones, uterus and breast tissue. Our goalhas been to study the effects of bazedoxifene on bone quality of an experimental group of ovariectomized rats. MATERIAL AND METHODS:3 groups of 15 6‐month‐old Wistar female rats were used: a control group, a group of untreatedovariectomized rats and a group of ovariectomized rats treated with bazedoxifene (0.33 mg/kg/day). After 8 monthswe studied the lumbar and femur bone densitometry, the microtomographic parameters, the biochemical markers forbone remodelling and the bone biomechanical parameters. RESULTS:The ovariectomy depleted the femur and lumbar bone density. After receiving bazedoxifene, the lumbar bonedensity showed partial healing. Bone remodelling increased recovering bazedoxifene formation levels. Bazedoxifenepromoted the recovery of the bone volume fraction (BV/TV), the bone surface density (BS/BV), the trabecular number(Tb. N), the trabecular spacing (Tb. Sp), the trabecular pattern factor (Tb. Pf) and the structural model index (SMI). Thecortical surface increased after the ovariectomy and returned to normal levels with the administration of bazedoxifene. The maximum deformation showed before the ovariectomy was also restored, partially cushioning the ovariectomizedrats' weight gain. CONCLUSIONS:Our study has shown bazedoxifene positive results on bone quality. This specific drug could be particularlysuitable for young postmenopausal women suffering or at risk of suffering osteoporosis


Assuntos
Animais , Feminino , Ratos , Conservadores da Densidade Óssea/administração & dosagem , Remodelação Óssea/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Microtomografia por Raio-X , Fatores de Tempo , Ovariectomia , Ratos Wistar
17.
J Manag Care Spec Pharm ; 26(2): 197-202, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32011964

RESUMO

BACKGROUND: Few studies have examined factors that determine bisphosphonate (BP) continuation beyond 5 years in clinical practice. OBJECTIVE: To investigate factors associated with BP continuation among women who completed 5 years of BP therapy. METHODS: Women who received 5 consecutive years of oral BP treatment entered the cohort during 2002-2014 and were followed up to 5 additional years. Multivariable logistic regression was used to evaluate the association of demographic and clinical factors with adherent treatment continuation. RESULTS: The cohort included 19,091 women with a median age of 72 years. Baseline and time-varying factors associated with increased odds of BP continuation after 5 years were (a) most recent bone mineral density (BMD) T-score -2 to -2.4 (OR = 1.31, 95% CI = 1.25-1.38), T-score -2.5 to -2.9 (OR = 1.48, 95% CI = 1.39-1.57), and T-score ≤ -3.0 (OR = 1.57, 95% CI = 1.47-1.68) versus T-scores above -2.0; (b) index date before 2008 (OR =1.35, 95% CI = 1.29-1.41); and (c) diabetes mellitus (OR = 1.08, 95% CI = 1.01-1.16). In contrast, factors associated with decreased odds of BP continuation were (a) recent hip (OR = 0.61, 95% CI = 0.52-0.71) or humerus (OR = 0.79, 95% CI = 0.66-0.94) fracture or fracture other than hip, wrist, spine, or humerus (OR = 0.90, 95% CI = 0.84-0.97); (b) Charlson Comorbidity Index score > 2 (OR = 0.91, 95% CI = 0.84-0.98); (c) history of rheumatoid arthritis (OR = 0.89, 95% CI = 0.80-0.99); (d) Hispanic (OR = 0.89, 95% CI=0.85-0.94) or Asian (OR = 0.90, 95% CI = 0.85-0.94) race/ethnicity; and (e) use of proton pump inhibitors (OR = 0.65, 95% CI = 0.59-0.71). Patient age and fracture before BP initiation were not associated with treatment continuation. CONCLUSIONS: Clinical factors predicting continued BP treatment beyond 5 years include low BMD T-score, absence of recent fracture, and earlier era of treatment. Use of proton pump inhibitors was associated with lower likelihood of BP continuation. Other clinical and demographic factors were also noted to have variable effects on BP treatment continuation. DISCLOSURES: This study was supported by a grant from the National Institute on Aging and National Institute of Arthritis, Musculoskeletal and Skin Diseases at the National Institutes of Health (NIH; R01AG047230, S1). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or Kaiser Permanente. Lo has received previous research funding from Amgen and Sanofi, unrelated to the current study. Adams has received previous research funding from Merck, Amgen, Otsuka, and Radius Health, unrelated to the current study. Ettinger has served as an expert witness for Teva Pharmaceuticals, unrelated to the current study. Ott previously attended a scientific advisory meeting for Amgen but declined the honorarium. The other authors have nothing to disclose. These data were presented at the 2018 Annual Meeting of the American Society of Bone and Mineral Research (ASBMR), September 28-October 1, 2018, Montreal, Quebec, Canada.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Difosfonatos/administração & dosagem , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose/complicações , Fraturas por Osteoporose/epidemiologia , Inibidores da Bomba de Prótons/administração & dosagem , Fatores de Tempo
18.
Expert Opin Pharmacother ; 21(6): 721-732, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32004105

RESUMO

INTRODUCTION: Glucocorticoid (GC) induced osteoporosis (GIOP) is the most common form of secondary osteoporosis. It develops in a dose and time dependent manner, due to a rapid and transient increase in bone resorption, followed by the inhibition of bone formation. AREAS COVERED: In this review, the authors summarize the pathophysiology of GIOP and give discussion to the clinical management of patients taking GCs, focusing on the currently available drugs that have antiresorptive or anabolic activity on bone. EXPERT OPINION: Despite the widespread use of GCs and their well-established detrimental skeletal effects, GIOP remains an under-diagnosed and under-treated condition. Indeed, the clinical management of GIOP is still debated, so that the recent guidelines differ in their indications for pharmacological intervention. Either bone mineral density (BMD) or algorithms such as FRAX do not completely account for the remarkable and rapid increase in fracture risk of most GC-treated patients. Moreover, while oral bisphosphonates remain the most used and cost-effective option, the potential increased benefits of more potent antiresorptive agents (e.g. denosumab and zoledronate) or anabolic compounds (e.g. teriparatide) warrant further investigation. Despite the above limitations, the assessment of fracture risk is recommended for all individuals committed to receiving oral GCs for 3 months or longer.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Reabsorção Óssea/prevenção & controle , Fraturas Ósseas/prevenção & controle , Glucocorticoides/efeitos adversos , Osteoporose/tratamento farmacológico , Algoritmos , Conservadores da Densidade Óssea/administração & dosagem , Análise Custo-Benefício , Denosumab/uso terapêutico , Difosfonatos/uso terapêutico , Fraturas Ósseas/complicações , Glucocorticoides/uso terapêutico , Humanos , Osteoporose/induzido quimicamente , Teriparatida/uso terapêutico
20.
Niger J Clin Pract ; 23(2): 154-158, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32031088

RESUMO

Background: There are a lot study confirmed the relationship of bone serum markers changes and skeletal irregularities. But there is no sufficient case control studies about the role of these markers on bisphosphonate induced osteonecrosis of jaws (BRONJ). Aims: The aim of this study is to find out if there is any derangement of bone markers in bisphosphonate-treated patients with ONJ. Methods: We obtained serum bone markers and other relevant endocrine assays on 20 patients with osteonecrosis of the jaw (ONJ) and 20 randomized healthy volunteers. All of the ONJ group treated with zoledronic acid and had been withdrawn from bisphosphonate for at least 6 months. Diagnostic criteria for ONJ were those formulated by the American Association of Oral and Maxillofacial Surgeons. Serum levels of several indices of bone remodeling were evaluated using commercial enzyme-linked immunosorbent assays. The biochemical assays were performed on N-Telopeptides of type I collagen (NTX), bone-specific alkaline phosphatase (ALP), calcitonin, osteocalcin, intact parathyroid hormone (PTH), T3, T4, TSH, and Vitamin D 25 hydroxy (Vit-D). Results: In ONJ group, PTH level is statistically higher and TSH, Vit-D, osteocalcin and NTX levels statistically lower compared to control group. Conclusion: We conclude that these changes in PTH, Vit-D, TSH, osteocalcin and NTX levels maybe have a role in the pathophysiology of BRONJ. But the data need to be confirmed by future studies.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/sangue , Conservadores da Densidade Óssea/efeitos adversos , Remodelação Óssea/efeitos dos fármacos , Colágeno Tipo I/sangue , Difosfonatos/efeitos adversos , Hormônio Paratireóideo/sangue , Vitamina D/sangue , Fosfatase Alcalina/sangue , Biomarcadores/sangue , Conservadores da Densidade Óssea/administração & dosagem , Estudos de Casos e Controles , Difosfonatos/administração & dosagem , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteocalcina , Peptídeos , Ácido Zoledrônico/uso terapêutico
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