Influência do status de vitamina D na absorção intestinal do estrôncio
Data
2013-08-28
Autores
Vilaça, Tatiane Silva 
Orientadores
Lazaretti-Castro, Marise
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Introdução: O estrôncio e o cálcio são metais alcalinoterrosos com múltiplas semelhanças. Estudos sugeriram que ambos utilizam a mesma via de absorção intestinal, o que motivou o uso do estrôncio para avaliação indireta da absorção
intestinal do cálcio. Extensa investigação já foi realizada sobre os fatores que regulam a absorção intestinal do cálcio, destacando-se o papel da vitamina D, entretanto pouco se sabe sobre a regulação da absorção do estrôncio. A influência
deste sobre a homeostase do cálcio também não está esclarecida. Como o paratormônio (PTH) é o principal regulador da homeostase do cálcio, torna-se importante avaliar o seu comportamento na presença do estrôncio. Assim, os objetivos deste trabalho são avaliar a influência do status de vitamina D na absorção intestinal do ranelato de estrôncio e descrever o comportamento do PTH diante da sobrecarga oral desse mineral. Pacientes e métodos: Cinquenta pacientes do sexo feminino na pós-menopausa com osteopenia ou osteoporose com função renal normal, em acompanhamento no
ambulatório de Doenças Osteometabólicas, foram recrutadas e divididas em dois grupos de acordo com seu status de vitamina D: 25 suficientes (SUF) e 25 deficientes (DEF). Foram considerados SUF níveis de 25(OH) vitamina D maiores que 30 ng/mL e DEF, níveis menores que 20 ng/mL. Após coleta de exames para avaliação inicial em jejum (incluindo dosagem sérica de Sr), cada paciente recebeu 1 gr de ranelato de estrôncio dissolvido em 200 mL de água deionizada. A seguir, foram colhidas amostras para dosagem sérica de estrôncio e PTH após 30, 60, 120 e 240 minutos. As 25 pacientes DEF em vitamina D foram tratadas e submetidas a novo teste após alcançar níveis maiores que 30 ng/mL. A absorção intestinal do
estrôncio foi avaliada através da fração absorvida (FA) em cada tempo e da área total sob a curva concentração de Sr x tempo. Para cálculo da FA foi utilizada a fórmula: FA= (Sr t- Sr0) x 15% peso dividido pela Dose administrada de Sr
Sendo Sr t a concentração sérica de Sr no tempo selecionado e Sr0 a concentração basal de Sr (tempo 0). Resultados: Os dois grupos, DEF e SUF, eram semelhantes, exceto pelos níveis de 25OHD (15,4 ± 5,4 x 39,36 ± 7,32ng/mL p<0,001), 1,25(OH)2D (24,97 ± 4,64 x 36,3 ± 10,2 pg/mL p< 0,001) e dose de colecalciferol em uso (808,76 ± 689,5 x 1712,4 ± 724,8 UI/d p< 0,001). O tratamento da deficiência de vitamina D resultou em aumento significativo de 1,25(OH)2D ( 24,97 ± 4,64 x 34,62 ± 9,14 pg/mL p< 0,001) e redução de PTH (73,87 ± 37,50 x 58,24 ± 20,13 pg/mL p=0,006). Não houve
diferença na absorção de estrôncio entre DEF e SUF. O tratamento do grupo deficiente tampouco resultou em aumento da absorção. A sobrecarga de estrôncio associou-se com diminuição significativa dos níveis de PTH seguida de recuperação, nas pacientes DEF e SUF. Não houve diferença na magnitude da variação do PTH nos dois grupos.
Conclusão: A correção da deficiência de vitamina D foi eficaz para elevar seu metabólito ativo 1,25(OH)2D e reduzir PTH. A ingestão oral de Sr associou-se a queda aguda nos níveis de PTH. O tratamento da deficiência de vitamina D é recomendado, entretanto os dados demonstram que o status da vitamina D parece não ser determinante na absorção intestinal do ranelato de estrôncio.
Abstract Strontium (Sr) and calcium are alcaline Earth metals with multiple similarities. It has been suggested that they share the same path of intestinal absorption. Sr has even been used as a surrogate of calcium absorption. The features that regulate calcium absorption had been extensively investigated. Vitamin D role is remarkable. However, little is known about strontium intestinal absorption´s regulation. Moreover, the effects of strontium in calcium homeostasis are not well established. PTH is the major regulator of calcium homeostasis. Thus, the aims of this study are to evaluate the influence of vitamin D status in strontium ranelate intestinal absorption and to describe PTH behavior during strontium oral overload. Patients and Methods Fifty patients presenting osteopenia or osteoporosis and normal renal function from a Bone Disease clinic were invited to join the study. Twenty-five patients with vitamin D deficiency (25OHD <20 ng/mL) and 25 with vitamin D sufficiency (25OHD >30 ng/mL) were submitted to an oral strontium overload test. Strontium and PTH were measured at baseline and at 30, 60, 120 and 240 minutes after the ingestion of 1 gr of strontium ranelate. The deficient patients were treated until the reach of adequate vitamin D levels (25(OH)D > 30 ng/mL) and the test was repeated. Strontium absorption was evaluated as the fraction of the absorbed dose and the area under the strontium concentration X time curve. Results The two groups were similar, except for 25OHD levels, by design, (15,4 ± 5,4 x 39,36 ± 7,32ng/mL p<0,001), 1,25(OH)2D (24.97 ± 4.64 x 34.62 ± 9.14 pg/mL p< 0,001) and cholecalciferol dose in use (808,76 ± 689,5 x 1712,4 ± 724,8 UI/d p<0,001). Vitamin D treatment resulted in significant increase in 1,25(OH)2D (24.97 ± 4.64 x 34.62 ± 9.14 pg/mL p< 0,001) and a reduction in PTH (73.87 ± 37.50 x 58.24 ± 20.13 pg/mL p=0,006). No differences were found in the parameters used to evaluate Sr absorption between the vitamin D deficient and sufficient groups. Moreover, no difference in Sr absorption was found in the deficient group following treatment. The Sr increment on blood was followed by a significant decrease in PTH levels followed by recovery. The variation was similar between deficient and sufficient groups,with mean PTH decrement of 27.7% for sufficient, 23.8% for deficient and 26.6% after Vitamin D correction. Interestingly, this decrease was transient, despite crescent concentrations of Sr, with most patients reaching a nadir at 60 min. Conclusion: The correction of vitamin D deficiency resulted in significant increase in 1,25(OH)2D and reduction in PTH. Oral ingestion of Sr was associated with acute decrease of PTH levels. Taking into account the benefits of adequate vitamin D status in osteoporotic patients, we strongly recommend treatment of vitamin D deficiency. However the data show that vitamin D status does not determine of Sr intestinal absorption.
Abstract Strontium (Sr) and calcium are alcaline Earth metals with multiple similarities. It has been suggested that they share the same path of intestinal absorption. Sr has even been used as a surrogate of calcium absorption. The features that regulate calcium absorption had been extensively investigated. Vitamin D role is remarkable. However, little is known about strontium intestinal absorption´s regulation. Moreover, the effects of strontium in calcium homeostasis are not well established. PTH is the major regulator of calcium homeostasis. Thus, the aims of this study are to evaluate the influence of vitamin D status in strontium ranelate intestinal absorption and to describe PTH behavior during strontium oral overload. Patients and Methods Fifty patients presenting osteopenia or osteoporosis and normal renal function from a Bone Disease clinic were invited to join the study. Twenty-five patients with vitamin D deficiency (25OHD <20 ng/mL) and 25 with vitamin D sufficiency (25OHD >30 ng/mL) were submitted to an oral strontium overload test. Strontium and PTH were measured at baseline and at 30, 60, 120 and 240 minutes after the ingestion of 1 gr of strontium ranelate. The deficient patients were treated until the reach of adequate vitamin D levels (25(OH)D > 30 ng/mL) and the test was repeated. Strontium absorption was evaluated as the fraction of the absorbed dose and the area under the strontium concentration X time curve. Results The two groups were similar, except for 25OHD levels, by design, (15,4 ± 5,4 x 39,36 ± 7,32ng/mL p<0,001), 1,25(OH)2D (24.97 ± 4.64 x 34.62 ± 9.14 pg/mL p< 0,001) and cholecalciferol dose in use (808,76 ± 689,5 x 1712,4 ± 724,8 UI/d p<0,001). Vitamin D treatment resulted in significant increase in 1,25(OH)2D (24.97 ± 4.64 x 34.62 ± 9.14 pg/mL p< 0,001) and a reduction in PTH (73.87 ± 37.50 x 58.24 ± 20.13 pg/mL p=0,006). No differences were found in the parameters used to evaluate Sr absorption between the vitamin D deficient and sufficient groups. Moreover, no difference in Sr absorption was found in the deficient group following treatment. The Sr increment on blood was followed by a significant decrease in PTH levels followed by recovery. The variation was similar between deficient and sufficient groups,with mean PTH decrement of 27.7% for sufficient, 23.8% for deficient and 26.6% after Vitamin D correction. Interestingly, this decrease was transient, despite crescent concentrations of Sr, with most patients reaching a nadir at 60 min. Conclusion: The correction of vitamin D deficiency resulted in significant increase in 1,25(OH)2D and reduction in PTH. Oral ingestion of Sr was associated with acute decrease of PTH levels. Taking into account the benefits of adequate vitamin D status in osteoporotic patients, we strongly recommend treatment of vitamin D deficiency. However the data show that vitamin D status does not determine of Sr intestinal absorption.
Descrição
Citação
VILAÇA, Tatiane Silva. Influência do status de vitamina D na absorção intestinal do estrôncio. São Paulo, 2013. 61 f. Dissertação (Mestrado em Medicina Translacional) – Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2013.