RESUMO
Objetivos: O desuso pelo repouso no leito, pela imobilização de membros ou por missões espaciais provoca a perda óssea rápida. Fez-se este estudo para investigar os efeitos terapêuticos do ácido zoledrônico (ZOL), isoladamente e em combinação ao alfacalcidol (ALF), em um modelo de rato com osteoporose por desuso. Métodos: Ratos Wistar machos de três meses foram submetidos à imobilização da pata traseira direita (IPTD) por 10 semanas para induzir a osteopenia; em seguida, foram divididos em quatro grupos: 1 – IPTD para controle positivo; 2 – IPTD mais ZOL (50 µg/kg, dose única intravenosa); 3 – IPTD mais ALF (0,5 µg/kg, via oral diariamente); 4 – IPTD mais ALF (0,5 µg/kg, via oral diariamente) mais ZOL (50 µg/kg, dose única intravenosa) por outras 10 semanas. Um grupo de ratos não imobilizados foi usado como controle negativo. No fim do tratamento, os fêmures foram removidos e testaram-se a porosidade do osso e suas propriedades mecânicas, além do peso seco e das cinzas do osso. Resultados: A terapia combinada com ZOL mais ALF foi mais eficaz em reduzir a porosidade do osso do que a monoterapia com um dos fármacos administrado isoladamente em ratos submetidos à IPTD. No que diz respeito à melhoria da resistência mecânica da diáfise femoral média, o tratamento combinado com ZOL mais ALF foi mais eficaz do que a monoterapia com um dos fármacos administrado isoladamente. Além disso, a terapia combinada com ZOL mais ALF foi mais eficaz na melhoria do peso seco e das cinzas do osso do que a monoterapia com ZOL ou ALF em ratos submetidos à IPTD. Conclusões: Esses dados sugerem que a terapia combinada com ZOL mais ALF representa uma opção terapêutica potencialmente útil para o tratamento da osteoporose por desuso. .
Objectives: Disuse by bed rest, limb immobilization or space flight causes rapid bone loss. We conducted the present study to investigate the therapeutic effects of zoledronic acid (ZOL), alone and in combination with alfacalcidol (ALF) in a rat model of disuse osteoporosis. Methods: In the present study, 3-month-old male Wistar rats had their right hind-limb immobilized (RHLI) for 10 weeks to induce osteopenia, then were divided into four groups: 1 – RHLI positive control; 2 – RHLI plus ZOL (50 µg/kg, i.v. single dose); 3 – RHLI plus ALF (0.5 µg/kg, oral gauge daily); 4 – RHLI plus ALF (0.5 µg/kg, oral gauge daily) plus ZOL (50 µg/kg, i.v. single dose) for another 10 weeks. One group of non-immobilized rats was used as negative control. At the end of the treatment, the femurs were removed and tested for bone porosity, bone mechanical properties, and bone dry and ash weight. Results: Combination therapy with ZOL plus ALF was more effective in decreasing bone porosity than each drug administered as monotherapy in RHLI rats. With respect to improvement in the mechanical strength of the femoral mid-shaft, the combination treatment of ZOL plus ALF was more effective than each drug administered as a monotherapy. Moreover, combination therapy using ZOL plus ALF was more effective in improving dry bone and ash weight, than single-drug therapy using ZOL or ALF in RHLI rats. Conclusions: These data suggest that combination therapy with ZOL plus ALF represents a potentially useful therapeutic option for the treatment of disuse osteoporosis. .
Assuntos
Ratos , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Hidroxicolecalciferóis/uso terapêutico , Imidazóis/uso terapêutico , Osteoporose/tratamento farmacológico , Conservadores da Densidade Óssea/farmacologia , Difosfonatos/farmacologia , Modelos Animais de Doenças , Sinergismo Farmacológico , Elevação dos Membros Posteriores , Hidroxicolecalciferóis/farmacologia , Imidazóis/farmacologia , Osteoporose/etiologiaRESUMO
OBJECTIVES: Disuse by bed rest, limb immobilization or space flight causes rapid bone loss. We conducted the present study to investigate the therapeutic effects of zoledronic acid (ZOL), alone and in combination with alfacalcidol (ALF) in a rat model of disuse osteoporosis. METHODS: In the present study, 3-month-old male Wistar rats had their right hind-limb immobilized (RHLI) for 10 weeks to induce osteopenia, then were divided into four groups: 1- RHLI positive control; 2- RHLI plus ZOL (50 µg/kg, i.v. single dose); 3- RHLI plus ALF (0.5 µg/kg, oral gauge daily); 4- RHLI plus ALF (0.5 µg/kg, oral gauge daily) plus ZOL (50 µg/kg, i.v. single dose) for another 10 weeks. One group of non-immobilized rats was used as negative control. At the end of the treatment, the femurs were removed and tested for bone porosity, bone mechanical properties, and bone dry and ash weight. RESULTS: Combination therapy with ZOL plus ALF was more effective in decreasing bone porosity than each drug administered as monotherapy in RHLI rats. With respect to improvement in the mechanical strength of the femoral mid-shaft, the combination treatment of ZOL plus ALF was more effective than each drug administered as a monotherapy. Moreover, combination therapy using ZOL plus ALF was more effective in improving dry bone and ash weight, than single-drug therapy using ZOL or ALF in RHLI rats. CONCLUSIONS: These data suggest that combination therapy with ZOL plus ALF represents a potentially useful therapeutic option for the treatment of disuse osteoporosis.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Hidroxicolecalciferóis/uso terapêutico , Imidazóis/uso terapêutico , Osteoporose/tratamento farmacológico , Animais , Conservadores da Densidade Óssea/farmacologia , Difosfonatos/farmacologia , Modelos Animais de Doenças , Sinergismo Farmacológico , Elevação dos Membros Posteriores , Hidroxicolecalciferóis/farmacologia , Imidazóis/farmacologia , Masculino , Osteoporose/etiologia , Ratos , Ratos Wistar , Ácido ZoledrônicoRESUMO
BACKGROUND: Vitamin D (vitD) insufficiency is common in end-stage renal disease. Seasonal and ethnic differences in vitD status have been reported previously. We hypothesized that vitD status in Afro-Caribbean patients on hemodialysis (HD) living in a country with a constant sunny climate would be better than that in African-American HD patients living in countries with a winter season. METHOD: A cross-sectional study was conducted in 152 Afro-Caribbean HD patients in a dialysis center located in Guadeloupe. We evaluated the prevalence of vitD insufficiency, defined as serum 25-hydroxyvitamin D (25(OH)D) levels below 30 ng/mL, compared with those results previously reported in African-American HD patients (88%). RESULTS: Prevalence of vitD insufficiency was 60% and thus lower than that in the African-American patients considered as the reference population (p<0.001). In our diabetic patients, this prevalence was 72.4%. Globally, 9.2% of patients had 25(OH)D below 15 ng/mL. Alfacalcidol therapy was prescribed in 29%. Mean 25(OH)D levels were higher in treated than in untreated patients (32 vs. 27 ng/mL; p=0.009). Patients with vitD insufficiency had dyslipidemia and diabetes more frequently. No significant differences were found between patients with and without vitD insufficiency for serum calcium, phosphorus and parathyroid hormone (PTH). In untreated patients, no significant correlation was found between 25(OH)D and PTH levels. CONCLUSION: Prevalence of vitD insufficiency in Afro-Caribbean HD patients was lower than that previously reported in African Americans undergoing HD in the United States. This finding may be due to the constantly sunny weather with a high intensity of UVB radiation in Guadeloupe.
Assuntos
População Negra/estatística & dados numéricos , Nefropatias/terapia , Diálise Renal , Pigmentação da Pele , Luz Solar , Deficiência de Vitamina D/etnologia , Negro ou Afro-Americano/estatística & dados numéricos , Idoso , Análise de Variância , Biomarcadores/sangue , Cálcio/sangue , Distribuição de Qui-Quadrado , Comorbidade , Estudos Transversais , Diabetes Mellitus/etnologia , Dislipidemias/etnologia , Feminino , Guadalupe/epidemiologia , Humanos , Hidroxicolecalciferóis/uso terapêutico , Nefropatias/sangue , Nefropatias/etnologia , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fósforo/sangue , Prevalência , Diálise Renal/efeitos adversos , Estados Unidos/epidemiologia , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/tratamento farmacológicoRESUMO
A male infant with malignant osteopetrosis was treated with high doses of 1 alpha-hydroxyvitamin D3 and interferon gamma. Therapy with 1 alpha-hydroxyvitamin D3 increased the serum calcium level despite the markedly elevated serum level of 1 alpha, 25-dihydroxyvitamin D before treatment. Recombinant human interferon gamma increased neither the bone mineral nor matrix turnover, and was not tolerated because of bone marrow suppression.
Assuntos
Hidroxicolecalciferóis/uso terapêutico , Interferon gama/uso terapêutico , Osteopetrose/terapia , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Humanos , Hidroxicolecalciferóis/farmacologia , Lactente , Interferon gama/farmacologia , Masculino , Osteopetrose/diagnóstico , Osteopetrose/metabolismo , Proteínas RecombinantesRESUMO
Los niveles plasmáticos de 25(-)hidroxivitamina D (25(OH)D), son representativos del nivel endogéno de vitamina D y provienen de la síntesis en piel de esta vitamina durante la exposición a los rayos solares y, en menor medida, de su aporte nutricional. Se ha desarrollado un método para la cuantificación de 25(OH)D sérico, que consta de una primera purificación por elución en columnas de Sephadex LH 20 y una posterior cuantificación por ensayo de competición proteica. Los niveles séricos de 25(OH)D en 30 hombres y mujeres normales de la población de Buenos Aires, no muestran diferencias entre sexos y presentan un nivel promedio de 20,7ñ1,9ng/ml (xñ1ES). No se encontró correlacicón entre los niveles séricos de 25(OH)D, Ca, P y PTH. En 12 sujetos normales que fueron estudiados secuencialmente en invierno y verano, los valores de 25(OH)D sérico fueron de 18,7ñ1,7 y 23,5ñ1,9ng/ml, respectivamente (p<0,01). En diversas patologías fue posible detectar niveles de 25 (OH)D disminuidos o elevados en relación a los valores normales, demonstrando la utilidad de la medición para efectuar diagnósticos diferenciales. Los niveles normales de 25(OH)D sérico en la población de Buenos Aires fueron comparables a los encontrados en países con alta exposición solar, indicando que no existe en la población estudiada una deficiencia subclínica de vitamina D
Assuntos
Adulto , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , Hidroxicolecalciferóis/sangue , Estações do Ano , Argentina , Doença Celíaca/sangue , Hidroxicolecalciferóis/uso terapêutico , Nefropatias/sangue , Valores de ReferênciaRESUMO
Los niveles plasmáticos de 25(-)hidroxivitamina D (25(OH)D), son representativos del nivel endogéno de vitamina D y provienen de la síntesis en piel de esta vitamina durante la exposición a los rayos solares y, en menor medida, de su aporte nutricional. Se ha desarrollado un método para la cuantificación de 25(OH)D sérico, que consta de una primera purificación por elución en columnas de Sephadex LH 20 y una posterior cuantificación por ensayo de competición proteica. Los niveles séricos de 25(OH)D en 30 hombres y mujeres normales de la población de Buenos Aires, no muestran diferencias entre sexos y presentan un nivel promedio de 20,7ñ1,9ng/ml (xñ1ES). No se encontró correlacicón entre los niveles séricos de 25(OH)D, Ca, P y PTH. En 12 sujetos normales que fueron estudiados secuencialmente en invierno y verano, los valores de 25(OH)D sérico fueron de 18,7ñ1,7 y 23,5ñ1,9ng/ml, respectivamente (p<0,01). En diversas patologías fue posible detectar niveles de 25 (OH)D disminuidos o elevados en relación a los valores normales, demonstrando la utilidad de la medición para efectuar diagnósticos diferenciales. Los niveles normales de 25(OH)D sérico en la población de Buenos Aires fueron comparables a los encontrados en países con alta exposición solar, indicando que no existe en la población estudiada una deficiencia subclínica de vitamina D (AU)
Assuntos
Adulto , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , Hidroxicolecalciferóis/sangue , Estações do Ano , Valores de Referência , Doença Celíaca/sangue , Nefropatias/sangue , Hidroxicolecalciferóis/uso terapêutico , ArgentinaRESUMO
A prospective study of renal osteodystrophy in moderate renal insufficiency was undertaken to assess the effects of 25(OH)D3 (Calcifediol) on healing of bone lesions and improvement of linear growth. One year after entering the study, the mean group growth velocity increased into the normal range and remained there in the next two therapy years. A significant correlation existed between pretherapy and one-year therapy values of growth velocity and serum 25(OH)D3 concentration. Qualitative bone histology obtained by transilial bone biopsy was also evaluated during the course of study. Catch-up growth was not seen, but potential for such growth may exist in later years in our patients.
Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/tratamento farmacológico , Crescimento/efeitos dos fármacos , Hidroxicolecalciferóis/uso terapêutico , Criança , Pré-Escolar , Distúrbio Mineral e Ósseo na Doença Renal Crônica/complicações , Humanos , Hidroxicolecalciferóis/sangue , Falência Renal Crônica/complicações , Masculino , Estudos ProspectivosRESUMO
Combined treatment with oral phosphate and 1 alpha (OH)D3 was carried out in nine children with familial hypophosphatemic rickets. All nine had positive responses over a four- to six-year period as judged by healing of rickets, change in growth rate, decrease in alkaline phosphatase activity, and symptomatic improvement. In two patients therapy was stopped for a short time because of hypercalcemia. In one patient in whom therapy was effective there was a significant reduction in creatinine clearance which necessitated cessation of treatment. The results of this study suggest that combined treatment with 1 alpha(OH)D3 and oral phosphate is an effective form of therapy for this condition, but that the balancing of these two modalities of therapy in each patient is essential if hypercalcemia and hypercalciuria, on the one hand, and secondary hyperparathyroidism, on the other, are to be avoided. A simple means of balancing these therapeutic modalities is suggested.
Assuntos
Hidroxicolecalciferóis/uso terapêutico , Hipofosfatemia Familiar/tratamento farmacológico , Assistência de Longa Duração/métodos , Fosfatos/uso terapêutico , Administração Oral , Adolescente , Fosfatase Alcalina/sangue , Fosfatase Alcalina/metabolismo , Desenvolvimento Ósseo , Criança , Desenvolvimento Infantil/efeitos dos fármacos , Pré-Escolar , Feminino , Fêmur/diagnóstico por imagem , Fêmur/metabolismo , Transtornos do Crescimento/tratamento farmacológico , Humanos , Hidroxicolecalciferóis/efeitos adversos , Hipercalcemia/induzido quimicamente , Lactente , Masculino , RadiografiaRESUMO
Nine patients with vitamin D-dependency type I were studied. We observed that treatment with large doses of vitamin D altered the phenotypic expression of the disease, thus making a delayed diagnosis difficult. At the time of entry, eight children had hypocalcemia, and seven had hypophosphatemia. Elevated serum immunoreactive parathyroid hormone and low (less than 3 SD from control mean) 1 alpha,25-dihydroxyvitamin D values were constant findings, with no vitamin D deficiency. Despite the elevated serum iPTH, three children had normal urinary phosphate excretion and five had normal urinary cAMP excretion. In the five children tested before treatment, there was no significant change in renal phosphate excretion during an acute parathyroid hormone infusion, although in all a significant rise of urinary cAMP occured. Treatment with calcitriol (0.25 to 2 microgram/day) returned all the biochemical values to normal within four months. In two patients, both supplemented with vitamin D, histomorphometric analysis of iliac crest biopsies revealed severe osteomalacia. After nine and ten months of treatment with calcitriol, there was histologic evidence for improvement of bone mineralization. Since calcitriol requirements may vary during the course of treatment, careful monitoring of biochemical variables is essential.
Assuntos
Calcitriol/análogos & derivados , Di-Hidroxicolecalciferóis/uso terapêutico , Hidroxicolecalciferóis/uso terapêutico , Hipofosfatemia Familiar/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Vitamina D/uso terapêutico , Adolescente , Adulto , Análise Química do Sangue , Criança , Pré-Escolar , Colestanotriol 26-Mono-Oxigenase , Ensaios Clínicos como Assunto , AMP Cíclico/urina , Feminino , Humanos , Hipocalcemia/induzido quimicamente , Injeções Intravenosas , Estudos Longitudinais , Masculino , Hormônio Paratireóideo/sangue , Hormônio Paratireóideo/urina , Fosfatos/sangue , Fosfatos/urina , Esteroide Hidroxilases/sangue , Vitamina D/efeitos adversosRESUMO
Osteodystrophy frequently accompanies severe childhood hepatobiliary disease. Proposed causes include malabsorption of vitamin D and calcium, and diminished 25-hydroxylation of vitamin D. Two children, ages 23 and 35 months, with radiographic and biochemical evidence of rickets with extrahepatic biliary atresia, were treated with 1,25-dihydroxyvitamin D3. The minimal effective therapeutic dose and efficacy of 1,25-(OH)2D3 in the treatment of rickets associated with severe childhood hepatic disease were determined. Oral 1,25-(OH)2D3 was ineffective at doses of 0.10 microgram/kg/day. Parenteral doses of 0.20 microgram/kg/day effectively produced radiographic, bone mineral (photon absorptiometric), and biochemical evidence of healing. The need for four times the physiologic dose of 1,25-(OH)2D3 by the parenteral route suggested enhanced catabolism of, or end-organ resistance to, 1,25-(OH)2D3 in our patients with severe cholestatic liver disease treated with phenobarbital.
Assuntos
Di-Hidroxicolecalciferóis/uso terapêutico , Hidroxicolecalciferóis/uso terapêutico , Hepatopatias/complicações , Raquitismo/tratamento farmacológico , Ductos Biliares/anormalidades , Feminino , Humanos , Lactente , Masculino , Raquitismo/etiologiaAssuntos
Di-Hidroxicolecalciferóis/uso terapêutico , Hidroxicolecalciferóis/uso terapêutico , Hipocalcemia/prevenção & controle , Doenças do Prematuro/prevenção & controle , Cálcio/metabolismo , Di-Hidroxicolecalciferóis/farmacologia , Humanos , Hidroxicolecalciferóis/sangue , Recém-Nascido , Absorção Intestinal/efeitos dos fármacos , Magnésio/sangue , Hormônio Paratireóideo/sangue , Fósforo/sangue , Estudos ProspectivosRESUMO
Two children who were receiving maintenance hemodialysis were treated with 1 to 4 microng/day of 1 alpha-hydroxyvitamin D3 for 500 to 700 days, respectively. Sequential parathyroid hormone levels and radiologic evaluations showed considerable improvement in one patient. The second patient initially responded with healing of the bone disease. Subsequent deterioration may be related either to medical noncomplicance and/or interference by diphenylhydantoin in the subsequent hepatic 25-hydroxylation of 1 alpha-OH-D3.
Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/tratamento farmacológico , Hidroxicolecalciferóis/uso terapêutico , Diálise Renal , Adolescente , Criança , Feminino , Glomerulosclerose Segmentar e Focal/terapia , Humanos , Infecções Urinárias/terapiaAssuntos
Di-Hidroxicolecalciferóis/uso terapêutico , Hidroxicolecalciferóis/uso terapêutico , Pseudo-Hipoparatireoidismo/tratamento farmacológico , Administração Oral , Adulto , Fosfatase Alcalina/sangue , Cálcio/sangue , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Hormônio Paratireóideo/sangue , Fósforo/sangue , Pseudo-Hipoparatireoidismo/sangue , Pseudo-Hipoparatireoidismo/genética , Pseudopseudo-Hipoparatireoidismo/genética , Tireotropina/sangue , Tiroxina/sangueRESUMO
In children with extrahepatic biliary atresia, impaired hydroxylation and defective intestinal absorption of cholecalciferol may lead to a deficiency of vitamin D and rickets. The data presented herein demonstrate that in such patients serum levels of vitamin D measured as 25-hydroxycalciferol are reduced. A moderate therapeutic oral dose of 25-hydroxycholecalciferol, by circumventing the hepatic conversion of cholecalciferol to 25-hydroxycholecalciferol, will replete vitamin D stores and maintain the serum concentration of 25-hydroxycalciferol required to prevent or heal rickets in these patients.
Assuntos
Ductos Biliares/anormalidades , Hidroxicolecalciferóis/uso terapêutico , Raquitismo/tratamento farmacológico , Administração Oral , Pré-Escolar , Colecalciferol/metabolismo , Humanos , Hidroxicolecalciferóis/administração & dosagem , Hidroxicolecalciferóis/metabolismo , Hidroxilação , Lactente , Absorção Intestinal , Fígado , Raquitismo/etiologiaRESUMO
A permature male infant required intravenous alimentation for six weeks following extensive surgery for ileal and cecal necrosis. At 3 months he developed evidence of hepatitis. Subsequently osteoporosis and the Fanconi syndrome appeared. Urine phosphate clearance was 83 percent of creatinine clearance at a serum phosphate concentration of 1.6 mg/dl. Concentration of plasma immunoreactive parathyroid hormone was elevated at 550 pg/ml. 25-Hydroxycholecalciferol was given at 240 mug/day. Aminoaciduria disappeared and bone healing occurred. Serum phosphate rose to 6.5 mg/dl and phosphate clearance fell to 2 percent of creatinine clearance. Upon cessation of 25-OHCC therapy, the Fanconi syndrome recurred despite administration of vitamin D2. 25-OHCC was then administered at 40 mug/day, and the urine abnormalities were reversed. The patient probably developed hyperparathyroidism, secondary malabsorption, and hepatitis. The Fanconi syndrome was the consequence of the hyperparathyroidism. 25-OHCC therapy was more effective than vitamin D in reversing the disordered state, possibly because of impaired hepatic metabolism of vitamin D2.