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1.
Medicine (Baltimore) ; 99(40): e22542, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019463

RESUMO

BACKGROUND: The goal of this study was to review relevant randomized controlled trials or case-control studies to determine the clinical efficacy of minodronate in the treatment of osteoporosis. METHOD: The relevant studies were identified on PubMed, Cochrane, and Embase databases using appropriate keywords. Pertinent sources in the literature were also reviewed, and all articles published through October 2019 were considered for inclusion. For each study, we assessed odds ratios, mean difference, and 95% confidence interval (95% CI) to evaluate and synthesize outcomes. RESULT: Thirteen studies comprising 3740 patients were included in this study. Compared with other drugs, minodronate significantly decreased N-telopeptide of type I collagen/creatinine (weighted mean difference [WMD]: -13.669, 95% confidence interval [CI]: -23.108 to -4.229), bone alkaline phosphatase (BAP) (WMD: -1.26, 95% CI: -2.04 to -0.47) and tartrate-resistant acid phosphatase 5b (WMD: -154.11, 95% CI: -277.85 to -30.37). Minodronate combined with other drugs would significantly decrease BAP (WMD: -3.10, 95% CI: -5.20 to -1.00) than minodronate. Minodronate-naïve would significantly decrease BAP (WMD: -3.00, 95% CI: -5.47 to 0.53) and tartrate-resistant acid phosphatase 5b (WMD: -128.20, 95% CI: -198.11 to -58.29) than minodronate-switch. The incidence of vertebral fracture was significantly decreased in the minodronate group than the other drugs (relative risk: 0.520, 95% CI: 0.363-0.744). CONCLUSION: Minodronate has better clinical efficacy in the treatment of osteoporosis than other drugs (alendronate, risedronate, raloxifene, or eldecalcitol).


Assuntos
Difosfonatos/uso terapêutico , Imidazóis/uso terapêutico , Osteoporose/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Alendronato/uso terapêutico , Fosfatase Alcalina/efeitos dos fármacos , Conservadores da Densidade Óssea/uso terapêutico , Estudos de Casos e Controles , Colágeno Tipo I/efeitos dos fármacos , Creatinina , Quimioterapia Combinada/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cloridrato de Raloxifeno/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Ácido Risedrônico/uso terapêutico , Fraturas da Coluna Vertebral/epidemiologia , Fosfatase Ácida Resistente a Tartarato/efeitos dos fármacos , Resultado do Tratamento , Vitamina D/análogos & derivados , Vitamina D/uso terapêutico
2.
Drug Discov Ther ; 14(2): 77-83, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32378649

RESUMO

Tacrolimus, a calcineurin inhibitor, affects bone metabolism and increases the risk of fracture due to marked bone loss. Bisphosphonates increase the bone mineral density (BMD) in osteoporosis patients. Menatetrenone has less positive effects on BMD but reduces the risk of fracture by improving bone quality. In this study, we investigated the effectiveness of the combined administration of risedronate and menatetrenone against bone loss induced by tacrolimus. Wistar rats were divided into four groups: [1] control, [2] tacrolimus at 1.5 mg/kg, [3] tacrolimus + risedronate at 1.0 mg/kg, and [4] tacrolimus + risedronate + menatetrenone at 20 mg/kg. After the drugs were administered for 4 weeks, bone histomorphometric analysis was performed and bone strength was evaluated using a three point bending method. BMD was measured using quantitative computed tomography. Tacrolimus significantly reduced the BMD and strength properties of the lower limb bones. These tacrolimusinduced decreases were suppressed by risedronate treatment. The combined administration of risedronate and menatetrenone more significantly improved bone strength properties than risedronate alone. Bone histomorphometric analysis revealed a significant increase in bone resorption with tacrolimus. Risedronate alone significantly suppressed the tacrolimus-induced increase in bone resorption but simultaneously reduced bone formation. On the other hand, the combined administration of risedronate and menatetrenone suppressed the tacrolimus-induced increase in bone resorption, in addition to the significant risedronate-induced decrease in bone formation. This study suggests that the combined administration of risedronate and menatetrenone improves bone strength in tacrolimus-treated rats by preventing and ameliorating the risedronate-induced suppression of bone formation.


Assuntos
Doenças Ósseas Metabólicas/tratamento farmacológico , Imunossupressores/efeitos adversos , Ácido Risedrônico/uso terapêutico , Tacrolimo/efeitos adversos , Vitamina K 2/análogos & derivados , Animais , Densidade Óssea/efeitos dos fármacos , Doenças Ósseas Metabólicas/induzido quimicamente , Quimioterapia Combinada , Fêmur/efeitos dos fármacos , Fêmur/fisiologia , Masculino , Osteogênese/efeitos dos fármacos , Ratos Wistar , Tíbia/efeitos dos fármacos , Tíbia/fisiologia , Vitamina K 2/uso terapêutico
3.
J Bone Miner Metab ; 38(4): 501-510, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32140785

RESUMO

INTRODUCTION: High-turnover bone disease is a major consequence of SHPT and may explain the high risk for fracture in patients with advanced chronic kidney disease (CKD). Bisphosphonates suppress bone turnover and improve bone strength, but their effects have not been fully characterized in advanced CKD with severe SHPT. Bisphosphonates also increase 1,25-dihydroxyvitamin D levels in normal and uremic rats, but the underlying mechanism remains to be determined. MATERIALS AND METHODS: We investigated the skeletal and mineral metabolic effects of RIS, a pyridinyl bisphosphonate, in rats with severe SHPT induced by 5/6 nephrectomy plus a high phosphate diet. RESULTS: Nephrectomized rats developed severe SHPT, along with hyperphosphatemia, low 1,25-dihydroxyvitamin D, and markedly increased FGF23. Moreover, these rats exhibited characteristic features of high-turnover renal osteodystrophy, including increased indices of trabecular bone turnover, decreased cortical bone thickness, inferior cortical biomechanical properties, and a prominent increase in peritrabecular fibrosis. RIS treatment increased bone volume and partially attenuated trabecular bone remodeling, cortical bone loss, and mechanical properties, whereas it produced a marked improvement in peritrabecular fibrosis along with a corresponding decrease in osteogenic gene markers. RIS treatment also suppressed the elevation of FGF23, which was associated with increased 1,25-dihydroxyvitamin D. CONCLUSIONS: In a rat model of severe SHPT, treatment with RIS partially attenuated histological manifestations of high-turnover bone disease. RIS treatment also suppressed the elevation of FGF23, which may explain the increased 1,25-dihydroxyvitamin D production during the treatment.


Assuntos
Remodelação Óssea , Osso e Ossos/patologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/tratamento farmacológico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/fisiopatologia , Minerais/metabolismo , Ácido Risedrônico/uso terapêutico , Animais , Fenômenos Biomecânicos , Nitrogênio da Ureia Sanguínea , Remodelação Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/fisiopatologia , Cálcio/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Creatinina/sangue , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Nefrectomia , Fragmentos de Peptídeos/sangue , Fósforo/sangue , Pró-Colágeno/sangue , Ratos Sprague-Dawley , Ácido Risedrônico/farmacologia
4.
Medicine (Baltimore) ; 99(7): e19042, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32049802

RESUMO

BACKGROUND: This meta-analysis was conducted to compare the effects and safety of teriparatide with risedronate in the treatment of osteoporosis. MATERIAL AND METHODS: PubMed, Embase, Web of Science and Cochrane library database were systematically reviewed for studies published up to February 24, 2019. Eligible studies that compared the effects of teriparatide with risedronate in osteoporosis were included in this meta-analysis. The outcomes included percentage change in bone mineral density (BMD) of lumbar spine, femoral neck, and total hip, the incidence of clinical fractures, serum bone markers, and adverse events. A random-effects or fixed-effects model was used to pool the estimate, according to the heterogeneity among the included studies. RESULTS: Seven studies were included in this meta-analysis. Compared with risedronate, teriparatide was associated with a significant increase in lumbar spine BMD [weight mean difference (WMD)=4.24, 95%CI: 3.11, 5.36; P < .001], femoral neck BMD (WMD=2.28, 95%CI: 1.39, 3.18; P < .001), and total hip BMD (WMD = 1.19, 95%CI: 0.47, 1.91; P = .001). Moreover, patients in teriparatide group had significantly lower incidences of clinical fracture (risk ratio [RR] = 0.48, 95%CI: 0.32, 0.72; P < .001), new vertebral fracture (RR = 0.45, 95%CI: 0.32, 0.63; P < .001), and non-vertebral fracture (RR = 0.63, 95%CI: 0.40, 0.98; P = .042) than those in risedronate group. There were significant differences between the 2 groups in serum change, including P1NP (WMD = 122.34, 95%CI: 68.89, 175.99; P < .001), CTx (WMD = 0.62, 95%CI: 0.29, 0.96; P < .001), and iPTH (WMD = -13.18, 95%CI: -15.04, -11.33; P < .001). The incidence of adverse events was similar between the 2 groups (RR = 0.93, 95%CI: 0.69, 1.25; P = .610). CONCLUSION: This study suggested that teriparatide was more effective than risedronate for increasing the BMD in lumbar spine, femoral neck, and total hip, as well as reducing the incidences of clinical fracture, new vertebral fracture and non-vertebral fracture. There was no significant difference in incidence of adverse events between the 2 drugs. Considering the potential limitations in the present study, further large-scale, well-performed randomized trials are needed to verify our findings.


Assuntos
Osteoporose/tratamento farmacológico , Ácido Risedrônico/uso terapêutico , Teriparatida/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Ácido Risedrônico/efeitos adversos , Ácido Risedrônico/farmacologia , Teriparatida/efeitos adversos , Teriparatida/farmacologia , Resultado do Tratamento
5.
J Bone Miner Metab ; 38(1): 86-98, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31420748

RESUMO

Absorption of oral immediate-release (IR) risedronate tablets is reduced by food intake, thus a delayed-release (DR) tablet has been developed to overcome the necessity of taking IR tablets under fasting conditions. This randomized, double-blind, phase II/III study compared efficacy and safety of risedronate IR once-daily (QD) and DR once-monthly (QM) tablets in Japanese patients with involutional osteoporosis. Patients received 2.5 mg IR on awakening QD, or 25 or 37.5 mg DR on awakening, following breakfast, or 30 min after breakfast, QM for 12 months. Primary endpoint was non-inferiority in mean percent change from baseline to end of study (month 12, last observation carried forward [M12, LOCF]) in mean lumbar spine (L2-L4) bone mineral density (BMD) between risedronate IR on awakening and DR following breakfast. Mean percent changes in (L2-L4) BMD at M12, LOCF were 5.07% (IR at awakening, n = 190), 3.36% (25 mg DR following breakfast, n = 194), and 4.11% (37.5 mg DR following breakfast, n = 181). Mean percent change in (L2-L4) BMD was numerically lower in the DR following breakfast groups versus the respective on awakening and 30 min after breakfast DR groups. Overall incidences of treatment-emergent adverse events (TEAEs) were comparable between groups. In the DR groups, 1.5-4.0% of patients reported TEAEs potentially associated with acute-phase reactions versus 0% in the IR group. In this study, non-inferiority could not be declared for 37.5 or 25 mg DR following breakfast QM (p = 0.1346 or p = 0.6711, respectively) versus 2.5 mg IR on awakening QD.


Assuntos
Grupo com Ancestrais do Continente Asiático , Osteoporose/tratamento farmacológico , Ácido Risedrônico/uso terapêutico , Idoso , Biomarcadores/metabolismo , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Masculino , Osteoporose/complicações , Cooperação do Paciente , Ácido Risedrônico/efeitos adversos , Ácido Risedrônico/farmacologia , Fraturas da Coluna Vertebral/complicações , Resultado do Tratamento
6.
J Bone Miner Metab ; 38(2): 240-247, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31667583

RESUMO

INTRODUCTION: In terms of the balance between benefits and risks of long-term treatment with bisphosphonate, uncertainties remain regarding the optimal treatment duration. We investigated effects of continuous long-term treatment for 10 years with bisphosphonate in postmenopausal osteoporosis patients. MATERIALS AND METHODS: Fifty five patients in the outpatient clinic of our hospital have been continuously treated with alendronate or risedronate for 10 years. All data were retrospectively collected. The age, height, weight, total muscle volume, total fat volume, and BMD at the lumbar spine, total hip and distal 1/3 radius, alkaline phosphatase (ALP), urinary type I collagen cross-linked N-telopeptide (uNTX) and tartrate-resistant acid phosphatase-5b (TRAP5b), calcium (Ca) and phosphate (P) levels were measured pre- and after the start of 10-year continuous treatment. RESULTS: BMD at the lumbar spine increased continuously over the 10-year period, while BMD at the total hip slightly but significantly decreased, and that at the 1/3 radius did not show any significant change over the 10 years. Serum Ca value was significantly decreased after the start of treatment, and became stable within the reference range from the second year. Bone resorption markers such as uNTX and TRAP5b significantly decreased from the second year after the start of treatment and no significant changes were observed thereafter. There were no serious medical adverse events including atypical femoral fractures and osteonecrosis of the jaw. CONCLUSION: We believe that the continuous use of alendronate and risedronate for 10 years could be an option for the treatment of postmenopausal osteoporosis patients.


Assuntos
Grupo com Ancestrais do Continente Asiático , Difosfonatos/uso terapêutico , Osteoporose/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Alendronato/farmacologia , Alendronato/uso terapêutico , Fosfatase Alcalina/sangue , Densidade Óssea/efeitos dos fármacos , Cálcio/sangue , Colágeno Tipo I/sangue , Difosfonatos/farmacologia , Feminino , Humanos , Japão , Osteoporose/sangue , Osteoporose/induzido quimicamente , Osteoporose/fisiopatologia , Osteoporose Pós-Menopausa/tratamento farmacológico , Peptídeos/sangue , Fósforo/sangue , Estudos Retrospectivos , Ácido Risedrônico/uso terapêutico , Fosfatase Ácida Resistente a Tartarato/sangue , Fatores de Tempo , Resultado do Tratamento
7.
Artigo em Português | Coleciona SUS, CONASS, SES-GO | ID: biblio-1117753

RESUMO

Tecnologia: Ácido zoledrônico e bifosfonados orais (alendronato e risedronato de sódio). Indicação: Prevenção de fraturas em pessoas com osteoporose. Pergunta: Em pessoas com osteoporose, o ácido zoledrônico é mais eficaz e seguro que os bifosfonados orais para prevenção de fraturas e outros desfechos de interesse? Métodos: Levantamento bibliográfico foi realizado nas bases eletrônicas Pubmed e BVS usando estratégias de buscas predefinidas. Foi feita avaliação da qualidade metodológica das revisões sistemáticas com a ferramenta Assessing the Methodological Quality of Systematic Reviews (AMSTAR). Resultados: Foram selecionadas e incluídas 5 revisões sistemáticas. Conclusão: O ácido zoledrônico é similar aos bifosfonados orais para prevenir fraturas em mulheres com osteoporose. Seu efeito sobre a densidade mineral óssea femoral é similar ao do alendronato e superior ao do risedronato. Um tratamento por 3 anos com ácido zoledrônico ou por 5 anos com alendronato de sódio é suficiente para prevenir fraturas vertebrais e não vertebrais. Bifosfonados têm similar risco de eventos adversos que o placebo, incluindo transtornos cardiovasculares e taxa de abandono do tratamento devido a distúrbios gastrointestinais. O ácido zoledrônico tem maior incidência de sintomas influenza-like que o placebo. O ácido zoledrônico não provoca eventos adversos do tipo esofágicos, gastrointestinais sérios ou do trato gastrointestinal superior, mas tem maior risco de náuseas, que pode estar relacionada à infusão intravenosa de grandes doses


Technology: Zoledronic acid and oral bisphosphonates. Indication: Prevention of osteoporotic fractures. Question: In people with osteoporosis, is zoledronic acid more effective and safer than oral bisphosphonates for preventing fractures and other outcomes? Methods: Bibliographic search was performed on PUBMED and BVS, using predefined search strategies. Evaluation of the methodological quality of systematic reviews was done by the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) tool. Results: 5 systematic reviews were selected and included. Conclusion: Zoledronic acid is similar to bisphosphonates for preventing fractures in women with osteoporosis and his effect on femoral bone mineral density is similar to that of alendronate and superior to risedronate. A 3 years treatment with zoledronic acid or for 5 years with sodium alendronate is sufficient to prevent vertebral and non-vertebral fractures. Bisphosphonates have a similar risk of adverse events than placebo, including cardiovascular disorders and risk of attrition due to gastrointestinal events. Zoledronic acid has a higher incidence of influenza-like symptoms (myalgia and arthralgia) than placebo, limited to the first dose and lasting a few days. Zoledronic acid does not cause esophageal, serious gastrointestinal or upper gastrointestinal tract adverse events, but has a higher risk of nausea, which can be caused by large doses of intravenous infusion


Assuntos
Humanos , Feminino , Osteoporose/tratamento farmacológico , Alendronato/uso terapêutico , Fraturas por Osteoporose/prevenção & controle , Ácido Risedrônico/uso terapêutico , Ácido Zoledrônico/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Resultado do Tratamento , Alendronato/efeitos adversos
8.
Artigo em Português | LILACS, Coleciona SUS, CONASS, SES-GO | ID: biblio-1118551

RESUMO

Tecnologia: Denosumabe e bifosfonados. Indicação: tratamento de osteoporose para prevenção de fraturas. Pergunta: O denosumabe é mais eficaz e seguro que os bifosfonados orais para tratamento da osteoporose e prevenção de fraturas secundárias à osteoporose? Métodos: Levantamento bibliográfico realizado na PUBMED seguindo estratégia de busca predefinida. Avaliação da qualidade metodológica das revisões sistemáticas com a ferramenta AMSTAR (Assessing the Methodological Quality of Systematic Reviews). Resultados: Foram selecionadas e incluídas 3 revisões sistemáticas, com pontuação de 9 a 11 no AMSTAR. Conclusão: Denosumabe tem menor risco relativo que alendronato e risedronato de sódio para fraturas vertebrais e maior efeito sobre densidade óssea mineral femoral, com risco similar de outros tipos de fratura e eventos adversos (infecções, transtornos cardiovasculares, óbito por infecção, morte cardiovascular ou por qualquer causa). Denosumabe evita 0,00154 fraturas, previne 0,00025 institucionalizações (ou cuidados permanentes de enfermagem no domicílio) e promove um ganho de 0,0018 anos de vida a mais que o alendronato de sódio por paciente tratado. Denosumabe é um pouco mais eficaz e tão seguro quanto os bifosfonados, mas a diferença de eficácia é mínima


Technology: Denosumab and bisphosphonates. Indication: osteoporosis treatment for fracture prevention. Question: Denosumab is more effective and safer than oral bisphosphonates for treating osteoporosis and preventing fractures related to osteoporosis? Methods: Bibliographic search was performed on PUBMED, following predefined search strategies. Evaluation of the methodological quality of systematic reviews was carried out using the AMSTAR (Assessing the Methodological Quality of Systematic Reviews) tool. Results: We selected and included 3 systematic reviews. Their scores ranged from 9 to 11 on AMSTAR. Conclusion: Denosumab has a lower relative risk than sodium alendronate and risedronate for vertebral fractures and greater effect on femoral mineral bone density, with a similar risk for non-vertebral fractures and adverse events (infections, cardiovascular disorders, death caused by infection, cardiovascular death or any cause mortality). Denosumab avoids 0.00154 fractures, prevents 0.00025 nursing home/ residential care admissions and get 0.0018 years of life gained per treated patient more than sodium alendronate. Denosumab is slightly more effective and as safe as bisphosphonates, but the effectiveness difference is minimal


Assuntos
Humanos , Osteoporose/tratamento farmacológico , Alendronato/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Fraturas por Osteoporose/prevenção & controle , Ácido Risedrônico/uso terapêutico , Denosumab/uso terapêutico , Resultado do Tratamento , Alendronato/efeitos adversos , Medicina Baseada em Evidências , Ácido Risedrônico/efeitos adversos , Denosumab/efeitos adversos
9.
Biomed Res Int ; 2019: 2594149, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31828096

RESUMO

Purpose: To investigate the comparative efficacies of the five most commonly used bisphosphonates for the secondary prevention of osteoporotic fractures in a Bayesian network meta-analysis. Methods: Five databases and the reference lists of all acquired articles from inception to July 2017 were searched. A Bayesian random-effects model was employed, and vertebral, hip and nonvertebral nonhip fractures were assessed by odds ratios (ORs) and 95%credible intervals. Furthermore, with respect to each endpoint, rank probabilities for each bisphosphonate were evaluated using the surface under the cumulative ranking curve (SUCRA) value. Results: Thirteen eligible studies were identified involving 11,822 patients with osteoporotic fractures. Overall in the pairwise meta-analyses, bisphosphonate use significantly reduced the risk of new vertebral, hip, and nonvertebral nonhip fractures, with ORs and 95% confidence intervals of 0.56 (0.49-0.64), 0.69 (0.48-0.98), and 0.82 (0.70-0.97), respectively. In network meta-analyses, significant differences were found between placebo and any one of the five bisphosphonates for new vertebral fractures. The rank probability plot and the SUCRA calculation results suggested that alendronate was the best intervention (14.6%) for secondary prevention of vertebral fractures, followed by zoledronate (15.3%) and etidronate (22.1%). In terms of the incidence of new hip fractures, alendronate was associated with the lowest incidence (18.5%), followed by zoledronate (43.1%) and risedronate (52.5%). However, zoledronate ranked lowest (16.6%) regarding the incidence of new nonvertebral nonhip fractures, followed by risedronate (23.8%) and alendronate (44.1%). Conclusions: Bisphosphonates show significant efficacy for secondary prevention of new vertebral fractures, and alendronate is most likely to be successful at secondary prevention of vertebral and hip fractures compared with the other four bisphosphonates.


Assuntos
Difosfonatos/uso terapêutico , Fraturas por Osteoporose/tratamento farmacológico , Idoso , Alendronato/uso terapêutico , Teorema de Bayes , Conservadores da Densidade Óssea/uso terapêutico , Ácido Etidrônico/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Ácido Risedrônico/uso terapêutico , Prevenção Secundária/métodos , Ácido Zoledrônico/uso terapêutico
10.
Actual. osteol ; 15(2): 94-102, mayo - ago. 2019. tab.
Artigo em Espanhol | LILACS | ID: biblio-1048478

RESUMO

El propósito de la terapia en el desorden del metabolismo óseo mineral asociado a la enfermedad renal crónica (IRC) consiste en restaurar el balance mineral, y, en la osteoporosis, mantener o aumentar la masa ósea. Ambas terapias tratan de evitar la fractura ósea. La mayoría de los osteoactivos están contraindicados en la insuficiencia renal crónica avanzada (estadios 4 y 5), y las terapias son empíricas. Algunos autores opinan que sin anomalías bioquímicas del desorden del metabolismo óseo mineral asociado a la enfermedad renal crónica avanzada se podría intentar el tratamiento estándar para la osteoporosis. Antes de intentar la terapia osteoactiva se debe corregir el desorden mineral óseo que pudiera presentarse asociado a la IRC, y en la indicación del tipo de osteoactivo se sugiere seleccionar al paciente según su estado óseo. Se aconseja que la administración de los antirresortivos se realice a dosis menores con respecto a los que tienen mejor función renal junto con aportes adecuados de calcio y vitamina D, antes y durante el tratamiento para prevenir el riesgo de severas hipocalcemias y un efecto óseo excesivo. Se presenta el caso clínico de una mujer de 65 años, con diagnóstico de osteoporosis de etiología multifactorial, fractura de pelvis, múltiples fracturas vertebrales e insuficiencia renal crónica avanzada, entre otras comorbilidades, y probable enfermedad ósea adinámica. Recibió inicialmente terapia con teriparatide y luego con denosumab, complicándose con hipocalcemia asintomática. (AU)


The purpose of therapy for the bone mineral metabolism disorder associated with chronic kidney disease is to restore the mineral balance; and to maintain or increase bone mass in osteoporosis. The goal of both types of therapy is to avoid bone fractures. Most antiosteoporotic drugs are contraindicated in advanced chronic renal failure (CRF) stages 4 and 5, and the therapies are empirical. Some authors believe that without biochemical abnormalities of the mineral bone metabolism disorder associated with advanced chronic kidney disease, standard treatment for osteoporosis could be attempted. Before attempting antiosteoporotic therapy, the bone mineral disorder that may be associated with CRF must be corrected, and in the indication of the type drug it is suggested that the patient be selected according to their bone status. It is advised that the administration of anti-resorptives be performed at lower doses in individuals with poor renal function compared to those with better renal function together with adequate calcium and vitamin D, before and during treatment to prevent the risk of severe hypocalcemia, and an excessive bone effect. We present the clinical case of a 65-year-old woman with a diagnosis of osteoporosis of multifactorial etiology, pelvic fracture, multiple vertebral fractures and advanced chronic renal failure, among other comorbidities and probable adynamic bone disease. The patient received initial therapy with teriparatide and followed by denosumab administration and exhibited asymptomatic hypocalcemia. (AU)


Assuntos
Humanos , Feminino , Idoso , Distúrbio Mineral e Ósseo na Doença Renal Crônica/tratamento farmacológico , Fraturas Ósseas/prevenção & controle , Osteoporose/terapia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/complicações , Distúrbio Mineral e Ósseo na Doença Renal Crônica/metabolismo , Distúrbio Mineral e Ósseo na Doença Renal Crônica/terapia , Vitamina D/administração & dosagem , Vitamina D/uso terapêutico , Cálcio/administração & dosagem , Cálcio/uso terapêutico , Alendronato/uso terapêutico , Teriparatida/administração & dosagem , Teriparatida/efeitos adversos , Teriparatida/uso terapêutico , Difosfonatos/administração & dosagem , Difosfonatos/efeitos adversos , Difosfonatos/uso terapêutico , Cinacalcete/uso terapêutico , Ácido Risedrônico/uso terapêutico , Denosumab/administração & dosagem , Denosumab/efeitos adversos , Denosumab/uso terapêutico , Hipocalcemia/prevenção & controle
11.
Osteoporos Int ; 30(11): 2311-2319, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31317249

RESUMO

Characteristics of patients starting oral bisphosphonate therapy changed over time, reflecting trends in osteoporosis management (e.g., new drugs to market), and general healthcare delivery (e.g., benzodiazepine use declined, statin use increased). When designing studies that examine osteoporosis drug effects, potential time-related biases must be considered. INTRODUCTION: To describe the type of oral bisphosphonate initiated and characteristics of patients starting oral bisphosphonate therapy over time. METHODS: We identified community-dwelling older adults (ages ≥ 66 years) initiating oral bisphosphonate therapy from April 1996 to March 2016 (1996 to 2015 fiscal years) using healthcare administrative data in Ontario. Patients with conditions other than osteoporosis that may impact bisphosphonate prescribing were excluded. The bisphosphonate initiated and patient characteristics were summarized by fiscal year and stratified by sex. RESULTS: We identified 560,817 eligible patients (81% women). Most patients initiated cyclical etidronate from 1996 until 2005, and then weekly regimens became dominant. In 2008, risedronate became the main oral bisphosphonate (46% risedronate, 43% alendronate, 11% etidronate); with its use increasing after availability of monthly and delayed-release risedronate formulations. In 2015, 71% of patients started risedronate, 28% started alendronate, and less than 2% started etidronate. Characteristics of patients changed over time, reflecting changes in osteoporosis management and general healthcare delivery. Over time, a larger proportion of men (9% to 28%) and patients with diabetes (women 10% to 17%, men 14% to 22%) initiated therapy; benzodiazepine (women 22% to 13%, men 20% to 10%) and estrogen-based hormone replacement therapy (12% to 15% of women 1996-2002 to 3% since 2008) decreased, while statin use increased (women 15% to 39%, men 14% to 52%). CONCLUSIONS: The characteristics of patients starting oral bisphosphonate therapy have changed over time. Consideration must be given to these time trends when designing studies that examine osteoporosis drug effects.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Alendronato/uso terapêutico , Esquema de Medicação , Ácido Etidrônico/uso terapêutico , Feminino , Humanos , Masculino , Ontário/epidemiologia , Farmacoepidemiologia/tendências , Ácido Risedrônico/uso terapêutico , Fatores Sexuais , Fatores de Tempo
12.
J Microencapsul ; 36(4): 338-355, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31190594

RESUMO

Delivery of bisphosphonates-like risedronate has been a major challenge till date due to its poor bioavailability and gastrointestinal tract adverse effects. In this study, we explored the prospective use of risedronate functionalised chitosan nanoparticle (RISCN) for management and treatment of osteoporosis. The prepared nanoparticle was characterised by using scanning electron microscopy, atomic force microscopy, and dynamic light scattering technique. Osteoporosis was induced on quarantined female Wistar rats and treated with RISCN. Docking studies were performed to establish the molecular mechanism of RISCN in improving the bone microarchitecture. Results indicated that there was a significant improvement in bone mineral density and healing of trabecular microarchitecture with less cortical porosity on the bone surfaces of the treatment groups. Docking studies indicated a high affinity and binding of chitosan and RISCN towards the human farnesyl diphosphate synthase (FDPS). Thus, a novel risedronate-loaded chitosan nanoparticle revealed promising results in an effective bone bridging process and osteoporosis treatment.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Quitosana/química , Portadores de Fármacos/química , Nanopartículas/química , Osteoporose/tratamento farmacológico , Ácido Risedrônico/administração & dosagem , Animais , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/uso terapêutico , Feminino , Ratos Wistar , Ácido Risedrônico/uso terapêutico
13.
Bone ; 124: 83-88, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31028957

RESUMO

Anastrozole has been shown to prevent breast cancer in postmenopausal women at high risk of the disease, but has been associated with substantial accelerated loss of bone mineral density (BMD) and increased fractures. Here, we investigate the effect of risedronate on BMD after 5 years of follow-up in the IBIS-II prevention trial. 1410 women were enrolled in the bone sub-study and stratified into three strata according to the lowest baseline T-score at spine or femoral neck. The objective was to compare the effect of oral risedronate (35 mg weekly) versus placebo in osteopenic women in stratum II who were randomised to anastrozole in the main study. 258 osteopenic, postmenopausal women at high risk of developing breast cancer for whom baseline and follow-up bone mineral density measurements were available. 5-year mean BMD change at the lumbar spine for osteopenic women randomised to anastrozole and risedronate was -0.4% compared to -4.2% for those not on risedronate (P < 0.0001) but not significantly different between risedronate users and non-users at the hip (P = 0.2). 5-year mean PINP change was -20% for those randomised to anastrozole and risedronate compared to 3% for those not on risedronate but on anastrozole (P < 0.0001). Our results confirm the bone loss associated with the use of anastrozole and show that anastrozole-induced BMD loss in the spine can be controlled with risedronate treatment. However, our results suggest that weekly oral risedronate is unable to completely prevent anastrozole induced bone loss at the hip.


Assuntos
Anastrozol/efeitos adversos , Doenças Ósseas Metabólicas/epidemiologia , Reabsorção Óssea/induzido quimicamente , Reabsorção Óssea/prevenção & controle , Neoplasias da Mama/epidemiologia , Ácido Risedrônico/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Reabsorção Óssea/sangue , Reabsorção Óssea/fisiopatologia , Feminino , Fraturas Ósseas/induzido quimicamente , Humanos , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Placebos , Pró-Colágeno/sangue , Ácido Risedrônico/farmacologia , Fatores de Risco
14.
Brasília; CONITEC; abr. 2019.
Não convencional em Português | BRISA/RedTESA | ID: biblio-1024261

RESUMO

INTRODUÇÃO: A doença de Paget óssea (DPO) ou osteíte deformante é uma doença osteometabólica local em que ocorre remodelação óssea intensa, uni ou multifocal. A reabsorção óssea aumentada se associa subsequentemente à atividade de neoformação óssea, mediada por osteoblastos, produzindo um osso estruturalmente inferior nos locais afetados, facilmente deformado por sobrecargas ou forças tensionais musculares. Atualmente, os bisfosfonatos IV são considerados tratamento de escolha para a DPO por serem altamente efetivos em suprimir o turnover ósseo aumentado, sendo o ácido zoledrônico (ZOL) a melhor alternativa na falha ou contraindicação dos bisfosfonatos orais. A CONITEC avaliou as evidências do ZOL para o tratamento da Doença de Paget óssea, conforme relatório de recomendação Nº 416, e recomendou sua incorporação no tratamento da DPO como primeira linha de tratamento. PERGUNTA: O uso do pamidronato dissódico é eficaz, seguro e custo-efetivo em pacientes com Doença de Paget óssea quando comparado aos bisfosfonatos disponíveis no SUS? EVIDÊNCIAS CIENTÍFICAS: Foram selecionados quatro estudos que avaliaram o pamidronato na Doença de Paget. O ZOL demonstrou ser superior ao pamidronato nos desfechos de resposta terapêutica e na dor óssea. Houve melhora leve e não significativa na qualidade de vida para os dois bisfosfonatos intravenosos. A resposta ao ZOL é independente da idade, do sexo, da Faz basal e de tratamento anterior para a DPO, ao contrário do pamidronato cuja resposta é influenciada negativa e significativamente pelos níveis basais de FAs e pelo tratamento prévio com bisfosfonatos. Em relação aos eventos adversos, o ZOL apresentou o mesmo perfil de eventos do pamidronato. No entanto, houve resistência ao pamidronato em número substancial de pacientes, o que não está descrito para o ácido zoledrônico. Os achados mostram um regime de tratamento com o ZOL mais efetivo, conveniente e sustentado ao comparar com pamidronato. AVALIAÇÃO ECONÔMICA: No processo de incorporação do ZOL para DPO no SUS, foi realizada uma análise de custo-efetividade comparando os bisfosfonatos entre si. A razão de custo efetividade incremental (RCEI) indicou que o risedronato dominou o alendronato e o pamidronato, mas não o ZOL, que foi mais efetivo que o risedronato, porém com maior custo. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: Observou-se um declínio dos registros de utilização do pamidronato para DPO no SUS entre 2013 e 2017 e a ausência de registros de sua utilização nos anos de 2016 e 2017. Com isso, supõe-se que não haveria um impacto econômico significativo com a exclusão do pamidronato do SUS para doença de Paget. CONSIDERAÇÕES GERAIS: O ZOL demonstrou ser superior ao pamidronato nos desfechos de resposta terapêutica e na dor óssea. Houve melhora leve e não significativa na qualidade de vida para os dois bisfosfonatos intravenosos. Em relação aos eventos adversos, o ZOL apresentou o mesmo perfil de eventos do pamidronato. No entanto, houve resistência ao pamidronato em número substancial de pacientes. Os achados mostram um regime de tratamento com o ZOL mais efetivo, conveniente e sustentado ao comparar com pamidronato. RECOMENDAÇÃO PRELIMINAR DA Conitec: O plenário, em reunião da CONITEC realizada no dia 06 de fevereiro de 2019, recomendou que o tema fosse submetido à consulta pública com recomendação preliminar favorável à exclusão no SUS do pamidronato dissódico para Doença de Paget. Considerou-se que o ácido zoledrônico, incorporado recentemente, demonstrou superioridade ao pamidronato e que o mesmo apresenta benefícios quanto ao esquema terapêutico, visto que é administrado em dose única, sem necessidade de repetição antes de 12 meses, enquanto o pamidronato requer múltiplas doses e o tratamento estendido até 6 semanas e repetido de 6 em 6 meses. CONSULTA PÚBLICA: Foram recebidas apenas 2 contribuições, sendo uma delas não referente ao tema apresentado. A outra contribuição foi contrária à recomendação inicial da Conitec, no entanto não apresentou comentários para sua discordância. RECOMENDAÇÃO FINAL DA CONITEC: Os membros da CONITEC presentes na 76ª reunião ordinária, nos dias 03 e 04 de abril de 2019, deliberaram, por unanimidade, por recomendar a exclusão ao SUS do pamidronato para tratamento de pacientes com Doença de Paget. Foi assinado o Registro de Deliberação nº 433/2019. DECISÃO: Excluir o pamidronato dissódico para o tratamento da doença de Paget, no âmbito do Sistema Único de Saúde - SUS. Dada pela Portaria nº 75, seção 1, página 142, em 18 de abril de 2019.


Assuntos
Humanos , Osteíte Deformante/tratamento farmacológico , Alendronato/uso terapêutico , Ácido Risedrônico/uso terapêutico , /uso terapêutico , Avaliação da Tecnologia Biomédica , Sistema Único de Saúde , Brasil , Análise Custo-Benefício/economia
15.
Arthritis Rheumatol ; 71(7): 1174-1184, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30816640

RESUMO

OBJECTIVE: Clinical trial results have shown that, in glucocorticoid-treated patients, treatment with denosumab 60 mg subcutaneously once every 6 months (Q6M) increased spine and hip bone mineral density (BMD) at month 12 significantly more than treatment with risedronate 5 mg orally once daily (QD). The present analysis was performed to compare efficacy and characterize safety through month 24. METHODS: This phase III study enrolled men and women ≥18 years old who had received ≥7.5 mg daily prednisone or equivalent for <3 months (glucocorticoid-initiating) or for ≥3 months (glucocorticoid-continuing) before screening. All patients <50 years old had a history of osteoporotic fracture. Glucocorticoid-continuing patients ≥50 years old had T scores of -2.0 or less (or -1.0 or less with fracture history). Patients were randomized (1:1) to receive denosumab 60 mg subcutaneously Q6M or risedronate 5 mg orally QD for 24 months, with daily calcium and vitamin D. RESULTS: Of 795 patients, 590 (74.2%) completed the study (in the glucocorticoid-initiating group, 109 of 145 patients treated with denosumab and 117 of 145 patients treated with risedronate; in the glucocorticoid-continuing group, 186 of 253 patients treated with denosumab and 178 of 252 patients treated with risedronate). Denosumab was superior to risedronate in increasing lumbar spine and total hip BMD at all time points assessed, among glucocorticoid-initiating patients (24-month lumbar spine: BMD increase of 6.2% versus 1.7%, respectively [P < 0.001]; 24-month total hip: BMD increase of 3.1% versus 0.0% [P < 0.001]) and among glucocorticoid-continuing patients (24-month lumbar spine: BMD increase of 6.4% versus 3.2% [P < 0.001]; 24-month total hip: BMD increase of 2.9% versus 0.5% [P < 0.001]). Adverse events, serious adverse events (including infections), and fractures were similar between treatment groups. CONCLUSION: Denosumab was superior to risedronate in terms of increases in spine and hip BMD through month 24, and the safety profile was similar between treatment groups. Denosumab may offer a new osteoporosis treatment option for glucocorticoid-treated patients.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea , Denosumab/uso terapêutico , Glucocorticoides/efeitos adversos , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Ácido Risedrônico/uso terapêutico , Absorciometria de Fóton , Idoso , Remodelação Óssea , Colágeno Tipo I/metabolismo , Método Duplo-Cego , Feminino , Colo do Fêmur/diagnóstico por imagem , Quadril/diagnóstico por imagem , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Osteoporose/induzido quimicamente , Osteoporose/metabolismo , Fragmentos de Peptídeos/metabolismo , Peptídeos/metabolismo , Pró-Colágeno/metabolismo , Resultado do Tratamento
16.
Respir Med ; 148: 13-23, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30827469

RESUMO

RATIONALE: Various determinants of osteoporosis have been previously identified. However, only a few longitudinal studies have examined related factors. We aimed to investigate factors predicting and modifying rapid decline of bone mineral density in patients with chronic obstructive pulmonary disease. METHODS: We analyzed patients with chronic obstructive pulmonary disease whose bone mineral density were measured at least three times over three years (n = 111). We divided annual per cent changes of bone mineral density in different body parts into tertiles. Rapid decliners (n = 33) were defined as those with the largest decline in at least two parts; all other participants were defined as non-rapid decliners (n = 78). RESULTS: At enrollment, bone mineral density did not differ between the two groups. However, rapid decliners had a significantly greater rate of new vertebral fractures over 3 years compared with non-rapid decliners. On multivariate logistic regression analysis, age, moderate to severe emphysema, no daily exercise habits, and anemia increased the likelihood of rapid decliners. Furthermore, patients who newly started and continued bisphosphonate exhibited higher annual per cent changes of bone mineral density than did those without bisphosphonate use. CONCLUSIONS: A rapid decline in bone mineral density correlates to a higher likelihood of vertebral fracture. We clarified the predictors of bone mineral density decline and demonstrated that bisphosphonate use might modify bone mineral density in patients with chronic obstructive pulmonary disease.


Assuntos
Densidade Óssea/efeitos dos fármacos , Osteoporose/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/complicações , Enfisema Pulmonar/diagnóstico por imagem , Fraturas da Coluna Vertebral/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea/fisiologia , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Comorbidade , Feminino , Humanos , Estudos Longitudinais , Masculino , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Valor Preditivo dos Testes , Prevalência , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Enfisema Pulmonar/epidemiologia , Ácido Risedrônico/administração & dosagem , Ácido Risedrônico/efeitos adversos , Ácido Risedrônico/uso terapêutico , Fraturas da Coluna Vertebral/epidemiologia
17.
Osteoporos Int ; 30(3): 649-658, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30701342

RESUMO

The use of gastro-resistant risedronate, a convenient dosing regimen for oral bisphosphonate therapy, seems a cost-effective strategy compared with weekly alendronate, generic risedronate, and no treatment for the treatment of postmenopausal women with osteoporosis in France. INTRODUCTION: Gastro-resistant (GR) risedronate tablets are associated with improved persistence compared to common oral bisphosphonates but are slightly more expensive. This study assessed its cost-effectiveness compared to weekly alendronate and generic risedronate for the treatment of postmenopausal women with osteoporosis in France. METHODS: A previously validated Markov microsimulation model was used to estimate the lifetime costs (expressed in €2017) per quality-adjusted life-years (QALY) of GR risedronate compared with weekly alendronate, generic risedronate, and no treatment. Pooled efficacy data for bisphosphonates derived from a previous meta-analysis were used for all treatment options, and persistence data (up to 3 years) were obtained from a large Australian longitudinal study. Evaluation was done for high-risk women 60-80 years of age, with a bone mineral density (BMD) T-score ≤ - 2.5 and/or prevalent vertebral fractures. RESULTS: In all of the simulated populations, GR risedronate was cost-effective compared to alendronate, generic risedronate, and no treatment at a threshold of €60,000 per QALY gained. In women with a BMD T-score ≤ - 2.5 and prevalent vertebral fractures, the cost per QALY gained of GR risedronate compared to alendronate, generic risedronate, and no treatment falls below €20,000 per QALY gained. In women aged 75 years and older, GR risedronate was even shown to be dominant (more QALYs, less costs) compared to alendronate, generic risedronate, and no treatment. CONCLUSION: This study provides the first economic results about GR risedronate, suggesting that it represents a cost-effective strategy compared with weekly alendronate and generic risedronate for the treatment of postmenopausal women with osteoporosis in France.


Assuntos
Conservadores da Densidade Óssea/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Osteoporose Pós-Menopausa/economia , Ácido Risedrônico/economia , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Alendronato/economia , Alendronato/uso terapêutico , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/uso terapêutico , Análise Custo-Benefício , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/economia , Preparações de Ação Retardada/uso terapêutico , Custos de Medicamentos/estatística & dados numéricos , Feminino , França , Humanos , Cadeias de Markov , Pessoa de Meia-Idade , Modelos Econométricos , Osteoporose Pós-Menopausa/tratamento farmacológico , Fraturas por Osteoporose/economia , Fraturas por Osteoporose/prevenção & controle , Anos de Vida Ajustados por Qualidade de Vida , Ácido Risedrônico/administração & dosagem , Ácido Risedrônico/uso terapêutico
18.
Osteoporos Int ; 30(4): 817-828, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30607457

RESUMO

In this prospective cohort of 6120 participants aged 50+, nitrogen-bisphosphonates but not non-nitrogen bisphosphonates were associated with a significant 34% mortality risk reduction compared to non-treated propensity score matched controls. These findings open new avenues for research into mechanistic pathways. INTRODUCTION: Emerging evidence suggests that bisphosphonates (BP), first-line treatment of osteoporosis, are associated with reduced risks for all-cause mortality. This study aimed to determine the association between different BP types and mortality risk in participants with or without a fracture. METHODS: A prospective cohort study of users of different BPs matched to non-users by propensity score (age, gender, co-morbidities, fragility fracture status) and time to starting the BP medication from the population-based Canadian Multicentre Osteoporosis Study from nine Canadian centres followed from 1995 to 2013. Mortality risk for bisphosphonate users vs matched non-users was assessed using pairwise multivariable Cox proportional hazards models. RESULTS: There were 2048 women and 308 men on BP and 1970 women and 1794 men who did not receive medication for osteoporosis. The relationship between BP and mortality risk was explored in three separate 1:1 propensity score-matched cohorts of BP users and no treatment (etidronate, n = 599, alendronate, n = 498, and risedronate n = 213). Nitrogen BP (n-BP) (alendronate and risedronate) was associated with lower mortality risks [pairwise HR, 0.66 (95% CI, 0.48-0.91)] while the less potent non-n-BP, etidronate, was not [pairwise HR: 0.89 (95% CI, 0.66-1.20)]. A direct comparison between n-BP and etidronate (n = 340 pairs) also suggested a better survival for n-BP [paired HR, 0.47 (95%CI, (95% CI, 031-0.70)] for n-BP vs. etidronate]. CONCLUSION: Compared to no treatment, nitrogen but not non-nitrogen bisphosphonates appear to be associated with better survival.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Idoso , Alendronato/uso terapêutico , Canadá/epidemiologia , Ácido Etidrônico/uso terapêutico , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Osteoporose/mortalidade , Fraturas por Osteoporose/mortalidade , Estudos Prospectivos , Ácido Risedrônico/uso terapêutico , Fatores de Risco , Comportamento de Redução do Risco
19.
J Steroid Biochem Mol Biol ; 188: 124-130, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30611910

RESUMO

Bisphosphonates like risedronate inhibit osteoclast-mediated bone resorption and are therefore used in the prevention and treatment of osteoporosis. Also vitamin D3 and calcium supplementation is commonly used in the prevention or treatment of osteoporosis. Combined therapy of risedronate with 1,25(OH)2D3, the active metabolite of vitamin D3, may be advantageous over the use of either monotherapy, but bears a risk of causing hypercalcemia thereby decreasing the therapeutic window for osteoporosis treatment. In this study, we evaluated the effect on bone mass of the combination of risedronate with the 17-methyl 19-nor five-membered D-ring vitamin D3 analog WY 1048 in a mouse ovariectomy model for postmenopausal osteoporosis. Ovariectomy-induced bone loss was restored by administration of risedronate or a combination of risedronate with 1,25(OH)2D3. However, the combination of WY 1048 with risedronate induced an even higher increase on total body and spine bone mineral density and on trabecular and cortical bone mass. Our data indicate that combination therapy of risedronate with WY 1048 was superior in restoring and improving bone mass over a combination of risedronate with 1,25(OH)2D3 with minimal calcemic side effects.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Colecalciferol/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Ácido Risedrônico/uso terapêutico , Vitaminas/uso terapêutico , Animais , Densidade Óssea/efeitos dos fármacos , Colecalciferol/análogos & derivados , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Osteoporose Pós-Menopausa/patologia , Vitaminas/química
20.
Intern Med ; 58(8): 1049-1056, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30626809

RESUMO

Objective The incidence of osteoporosis is increasing with the rapid aging of the Japanese population. Bisphosphonates are first-line agents used for the treatment of osteoporosis, but they can cause upper gastrointestinal mucosal injury. This study investigated symptoms and upper gastrointestinal mucosal injury associated with oral bisphosphonates. Methods Symptoms were evaluated using the F-scale questionnaire, and esophageal mucosal injury and gastroduodenal ulceration were assessed by endoscopy. Patients were stratified by the type of bisphosphonate (alendronate, risedronate, or minodronate), treatment schedule (once weekly or every four weeks), and the concomitant use of other medications [antithrombotic agents, nonsteroidal anti-inflammatory drugs (NSAIDs), or acid suppressants]. Patients The subjects included 221 patients treated with oral bisphosphonates for at least one month. Results The median F-scale total score was 4 (0-34), reflux score was 2 (0-20), and the mean dyspepsia score was 2 (0-16). Endoscopy showed esophageal mucosal injury of Grade A or worse (Los Angeles classification) in 22/221 patients (10.0%) and gastroduodenal ulcers in 9 patients (4.1%). The dyspepsia score in patients who took minodronate every four weeks was significantly lower (p<0.05) in comparison to patients who took other bisphosphonates. The dyspepsia score was significantly higher (p<0.05) and mucosal injury was significantly more frequent in patients who also used antithrombotic agents and NSAIDs. Conclusion Symptoms and upper gastrointestinal mucosal damage were not necessarily frequent or severe in patients treated with bisphosphonates. However, the concomitant use of bisphosphonates with antithrombotic agents and NSAIDs increased both symptoms and mucosal injury. The symptoms were milder in patients using minodronate once monthly.


Assuntos
Alendronato/efeitos adversos , Conservadores da Densidade Óssea/efeitos adversos , Trato Gastrointestinal/efeitos dos fármacos , Membrana Mucosa/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Ácido Risedrônico/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Alendronato/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Feminino , Trato Gastrointestinal/lesões , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Membrana Mucosa/lesões , Ácido Risedrônico/uso terapêutico
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