Clinical effect of alfacalcidol in children with Henoch-Schönlein purpura: a prospective randomized controlled trial / 中国当代儿科杂志

OBJECTIVES@#To study the effects of alfacalcidol on serum 25-(OH)D@*METHODS@#A total of 200 children with HSP were prospectively enrolled from June 2018 to June 2020. According to the random number table method, they were divided into an observation group and a control group (@*RESULTS@#After treatment, the observation group showed a significantly higher serum 25-(OH)D@*CONCLUSIONS@#Alfacalcidol can increase the serum 25-(OH)D

Factors associated with bone mineral content in adults: a population-based study / Fatores associados ao conteúdo mineral ósseo em adultos: estudo de base populacional

ABSTRACT Objective To determine the association among bone mineral content, sociodemographic, anthropometric and behavioral factors, and health status of Brazilian adults. Methods This was a cross-sectional, population-based study including 701 individuals from both sexes aged between 20 and 59 years. DEXA was used to evaluate dependent variable. The associations were evaluated using linear regression models stratified by sex. Results When mean bone mineral content values were compared, we found significant differences related to sex and all the independent variables evaluated. In the adjusted models, we identified an inverse association between bone mineral content and age in both sexes. Among men, to be overweight and/or obese, be highly educated, and have almost sufficiency of 25(OH)D were associated with higher bone mineral content values. On the other hand, among women, to be non-white skin color, overweight and/or obese were associated with better bone health. The main factors associated with low total bone mineral density were advanced age, white skin color, low level of formal education, eutrophy, and 25(OH)D deficiency. Conclusion Our results may help to identify adults who are at higher risk, and these findings should be used as guidelines for prevention and early diagnosis.

RESUMO Objetivo Verificar a associação entre o conteúdo mineral ósseo e fatores sociodemográficos, antropométricos, comportamentais e condições de saúde em adultos brasileiros. Métodos Estudo transversal, de base populacional, realizado com 701 indivíduos de ambos os sexos, com idade entre 20 e 59 anos. A variável dependente foi avaliada por DEXA. As associações foram avaliadas por modelos de regressão linear estratificados baseados no sexo dos indivíduos. Resultados Quando comparados os valores médios do conteúdo mineral ósseo, observamos diferença estatisticamente significante em relação aos sexos e para todas as variáveis independentes avaliadas. Nos modelos ajustados, identificamos associação inversa entre o conteúdo mineral ósseo e a idade em ambos os sexos. Entre os homens, sobrepeso e obesidade, alta escolaridade e suficiência de 25(OH)D foram associados a maiores valores de conteúdo mineral ósseo. Entre as mulheres, por sua vez, cor da pele não branca, sobrepeso e obesidade foram associados a melhor saúde óssea. Os principais fatores associados à baixa massa óssea total foram idade avançada, cor da pele branca, baixa escolaridade, eutrofia e deficiência de 25(OH)D. Conclusão Esses resultados podem auxiliar na identificação de adultos com maior risco e que devem ser alvo de medidas de prevenção e diagnóstico precoce.

Normal physiological functions in two animal species with highly different vitamin d status compared to that of humans / Funciones fisiológicas normales en dos especies animales con estatus de vitamina d muy diferentes del actual en seres humanos

Mole rats live in permanent darkness, in networks of underground tunnels (which extend up to 1 km in the subsoil), excavated with their incisors, in warm and semi-arid areas of South Africa. Mole rats have an unusually impoverished vitamin D3 status with undetectable and low plasma concentrations of 25- hydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3, respectively. They express 25-hydroxylase in the liver and 1-hydroxylase and 24-hydroxylase in their kidneys. The presence of specific receptors (VDR) was confirmed in the intestine, kidney, Harderʼs glands and skin. In spite of their poor vitamin D3 status, the apparent fractional intestinal absorption of calcium, magnesium and phosphate was high, always greater than 90%. Oral supplementation with cholecalciferol to mole rats did not improve the efficiency of gastrointestinal absorption of these minerals. Mole ratsdo not display the typical lesion of rickets: hypertrophic and radiolucent growth cartilages. Histological studies reported normal parameters of trabecular and cortical bone quality. Marmosets (monkeys of the New World) are not hypercalcaemic, eventhough they exhibit much higher levels of 25-hydroxyvitamin D3, 1α,25-dihydroxyvitamin D3 and parathyroid hormonethan that of rhesus monkeys and humans. Fed a high vitamin D3 intake (110 IU/day/100 g of body weight), a fraction of the experimental group was found to display osteomalacic changes in their bones: distinct increases in osteoid surface, relative osteoid volume, and active osteoclastic bone resorption. These findings suggest that some marmosets appears to suffer vitamin D-dependent rickets, type II. The maximum binding capacity of the VDR or the dissociation constant of VDR1α,25(OH)2D3 complex of mole rats and New World monkeys are distinctly different of VDR isolated from human cells. Health status of those species appears to be adaptations to the mutations of their VDR. Though rare, as mutations may occur at any time in any patient, the overall message of this review to clinicians may be: recent clinical studies strongly suggests that the normality of physiological functions might be a better indicator of the health status than the serum levels of vitamin D metabolites. (AU)

Las ratas topo viven en la oscuridad permanente, en redes de túneles subterráneos excavadas con sus incisivos (que se extienden hasta 1 km en el subsuelo), en áreas cálidas y semiáridas de Sudáfrica. Las ratas topo tienen un estatus de vitamina D3 inusualmente empobrecido con concentraciones plasmáticas indetectables de 25-hidroxivitamina D3 y bajas de 1α, 25-dihidroxivitamina D3. Poseen 25-hidroxilasa en el hígado y 1-hidroxilasa y 24-hidroxilasa en sus riñones. La presencia de receptores específicos (VDR) ha sido confirmada en el intestino, el riñón, las glándulas de Harder y la piel. A pesar de su pobre estatus de vitamina D3,la absorción fraccional intestinal aparente de calcio, magnesio y fosfato fue alta, siempre superior al 90%. La suplementación oral con colecalciferol a las ratas topo no mejoró la eficacia de la absorción gastrointestinal de estos minerales. No muestran la lesión típica del raquitismo: cartílagos de crecimiento hipertróficos y radiolúcidos. Varios estudios histológicos confirman los hallazgos radiológicos y se informan parámetros normales de la calidad ósea trabecular y cortical. Los titíes (monos del Nuevo Mundo) exhiben calcemias normales con niveles más elevados de 25-hidroxivitamina D3, 1α,25-dihidroxivitamina D3 y hormona paratiroidea que los monos rhesus y los seres humanos. Un tercio de un grupo de titíes alimentados con una alta ingesta de vitamina D3 (110 I/día/100 g de peso corporal) exhibió cambios osteomalácicos en sus huesos: aumento en la superficie osteoide, volumen osteoide y activa reabsorción osteoclástica. Estos hallazgos sugieren que una fracción de la población de titíes padece raquitismo dependiente de vitamina D, tipo II. Debido a mutaciones ocurridas hace millones de años, las máximas capacidades de ligamiento del VDR o los valores de la constante de disociación del complejo VDR-1α,25(OH)2D3 de las ratas topo o monos del Nuevo Mundo son muy diferentes de los verificables en receptores aislados de células humanas actuales. El mensaje de esta revisión a los médicos clínicos podría ser: varios estudios clínicos recientes indican que la normalidad de las funciones fisiológicas de un paciente es un mejor indicador de su salud que los niveles séricos de los metabolitos de la vitamina D. (AU)

Caso clínico: hipofosfatasia de la niñez. Seguimiento clínico / Clinical case: childhood hypophosphatasia. Clinical follow-up

La hipofosfatasia (HP) es una enfermedad congénita, causada por mutaciones con pérdida de función en el gen ALPL que codifica la isoenzima no específica de tejido de la fosfatasa alcalina (TNSALP). Su expresión clínica es muy variable, desde casos de muerte intraútero por alteración grave de la mineralización ósea, hasta casos solo con caída prematura de la dentición. Se presenta el caso clínico de un varón al que se le diagnosticó odontohipofosfatasia a los 30 meses por pérdida temprana de piezas dentarias y niveles anormalmente bajos de fosfatasa alcalina, sin signos de raquitismo ni deformidades óseas. Durante su seguimiento, hasta los 13 años, presentó síntomas compatibles con HP infantil leve, como cansancio al caminar, incoordinación en la marcha y dolor en miembros inferiores que aumentaban con la actividad física. Ante la aparición de edema bimaleolar y poca respuesta al tratamiento con calcitonina y antiinflamatorios, se descartaron patologías infecciosas o reumáticas o ambas y se diagnosticó, por biopsia de tibia y peroné, periostitis sin detección de cristales de pirofosfato. Los controles radiológicos durante su evolución mostraron ensanchamiento metafisario en muñeca, falta de remodelado de metacarpianos, hojaldrado perióstico en tibia y peroné e hipomineralización en metáfisis tibiales, con "lenguas radiolúcidas" características de HP. Como conclusión, la hipofosfatasia debe considerarse como una entidad clínica para descartar en niños que presentan pérdida temprana de dientes. La presencia de este cuadro clínico es en general suficiente para realizar el diagnóstico de HP de la niñez. (AU)

Hypophosphatasia (HP) is a congenital disease, caused by mutations with loss of function in the gene ALPL that encodes the non-specific tissue isoenzyme of alkaline phosphatase (TNSALP). Its clinical expression displays considerable variability, from cases of intrauterine death due to severe alteration of bone mineralization, to cases with only early loss of teeth. We report the case of a male, diagnosed as odontohypophosphatasia at 30 months of age due to early loss of teeth and abnormally low levels of alkaline phosphatase, without signs of rickets or bone deformities. During follow-up, up to 13 years of age, he presented symptoms consistent with mild infantile HP such as tiredness when walking, lack of gait coordination, and pain in lower limbs, especially after physical activity. Due to the appearance of bimalleolar edema and poor response to treatment with calcitonin and anti-inflammatory drugs, infectious and / or rheumatic pathologies were ruled out. Periostitis without pyrophosphate crystal detection was diagnosed by tibial and fibular biopsy. Radiological controls during follow up showed metaphyseal wrist enlargement, lack of remodeling of metacarpals, periosteal flaking in the tibia and fibula and hypomineralization in the tibial metaphysis, with "radiolucent tongues"; characteristic of HP. In conclusion, hypophosphatasia should be considered as a clinical entity in children who present early loss of teeth. The presentation of this clinical case is generally sufficient to make the diagnosis of childhood HP. (AU)

Niveles de 25(oh)-vitamina D en pacientes con diabetes mellitus tipo 2 con y sin síndrome metabólico / 25(OH)-Vitamin D levels in type 2 diabetes with and without metabolic syndrome

Los bajos niveles de 25-hidroxivitamina D (25OHD) se han vinculado con el desarrollo de enfermedad cardiovascular, diabetes mellitus tipo 2, obesidad, dislipidemia e hipertensión arterial, todos componentes del síndrome metabólico (SM). Además, se ha reportado una asociación inversa entre 25OHD y el SM, resistencia a la insulina, deterioro de la función celular ß e intolerancia a la glucosa. El objetivo de este trabajo fue evaluar los niveles de 25OHD en pacientes diabéticos tipo 2 con y sin SM. Se llevó a cabo un estudio observacional de corte transversal. Se evaluaron 108 pacientes diabéticos tipo 2 (grupo DM2) y 89 pacientes sin DM2 (GC) con y sin SM, en los cuales se determinó la concentración de 25OHD total. Se calculó el cociente de probabilidad (OR) e intervalo de confianza del 95% (IC95) para la deficiencia de 25OHD (<20 ng/ml). Resultados: el grupo DM2 presentó niveles menores de 25OHD (19,8 ng/ml vs. 25,0 ng/ml) y mayor proporción de pacientes con deficiencia de 25OHD respecto del GC (50,9% vs. 28,1%, OR 2,7, IC95%: 1,5-4,8). No se halló una correlación entre 25OHD y HbA1c. Se halló asociación significativa entre deficiencia de 25OHD y presencia de diabetes, obesidad y SM. Sin embargo, en el análisis multivariado solo la presencia del SM presentó asociación negativa significativa con la deficiencia de 25OHD (OR=4,04, IC95% 1,48-11,68). En conclusión, nuestros datos demuestran una elevada prevalencia de hipovitaminosis D en pacientes con diabetes mellitus tipo 2 a expensas, principalmente, del elevado porcentaje de pacientes que padecen SM. El SM incrementa cuatro veces el riesgo de deficiencia de vitamina D independientemente de la presencia de diabetes mellitus tipo 2. (AU)

Low levels of 25-hydroxyvitamin D (25OHD) have been linked to cardiovascular disease, type 2 diabetes mellitus, obesity, dyslipidemia and hypertension, all components of the metabolic syndrome. An inverse association has been observed between 25OHD and metabolic syndrome, insulin resistance, impaired ß-cell function and glucose intolerance. The aim of this study was to evaluate the 25OHD levels in type 2 diabetic patients with and without metabolic syndrome. An observational cross-sectional study was carried out. We included 108 type 2 diabetic patients (DM2 group) and 89 patients without DM2 (CG) with and without metabolic syndrome, in which the total 25OHD levels were measured. The odds ratio (OR) and 95% confidence interval (95%CI) for 25OHD deficiency (<20 ng/ml) were estimated. Results: The DM2 group had lower 25OHD levels (19.8 ng/ml vs 25.0 ng/ml) and higher proportion of patients with a 25OHD deficiency compared to the CG (50.9% vs 28.1%, OR 2.7, 95%CI: 1.5-4.8). No correlation was found between 25OHD and HbA1c. A significant association was found between 25OHD deficiency and the presence of diabetes, obesity, and the presence of metabolic syndrome. However, in the multivariate analysis only the presence of metabolic syndrome had a significant negative association with the 25OHD deficiency (OR=4.04, 95%CI 1.48-11.68). In conclusion, we found a high prevalence of hypovitaminosis D in DM2 and the metabolic syndrome increases the risk of 25OHD deficiency by four times. (AU)

Concentrações séricas de 25 (OH) e perfil metabólico mediados pela adiposidade / Serum 25 (OH) D and metabolic profile mediated by adiposity

Introdução: Baixas concentrações séricas de hidroxivitamina D (25[OH]D) e o excesso de peso atingiram níveis epidêmicos em todo o mundo. Estudos relatam que concentrações séricas de vitamina D estão associadas às alterações lipídicas, glicolíticas e inflamatórias; e estas alterações são conhecidamente mediadas pela adiposidade. Dessa forma, a vitamina D pode atuar de forma benéfica sobre o perfil metabólico em adolescentes, adultos e idosos. Objetivo: Investigar e descrever as associações entre as concentrações séricas de 25(OH)D e o perfil metabólico, mediadas pela adiposidade em adolescentes, adultos e idosos. Metodologia: Inicialmente, foi utilizada subamostra do Inquérito de Saúde de São Paulo (ISA-Capital), estudo transversal, de base populacional (n=281), para investigar a associação entre as concentrações séricas de vitamina D e marcadores inflamatórios em adultos brasileiros. Posteriormente, foram utilizados dados do estudo Healthy Lifestyle in Europe by Nutrition in Adolescents-(HELENA), estudo multicêntrico transversal da população de adolescentes européia, com o intuito de avaliar as alterações nos marcadores lipídicos e de homeostase da glicose mediados pela deficiência de vitamina D e obesidade. aparentemente.

Introduction: Low serum of hydroxyvitamin D (25 [OH] D) and excess weight reached epidemic levels in worldwide. Studies have reported that vitamin D serum concentrations are associated with lipid, glycolytic and inflammatory alterations; and these alterations are known to be mediated by adiposity. Thus, vitamin D may have a benefic action on the metabolic profile in adolescents, adults and elderly. Objective: To investigate and describe the associations between 25(OH)D concentrations and the metabolic profile mediated by adiposity in adolescents, adults and elderly. Methods: Initially, was used a subsample from the Health Survey of São Paulo (HS-SP), cross-sectional, population-based study (n = 281), to investigate the association between vitamin D concentrations and inflammatory biomarkers in Brazilian adults. Later, was used data from Healthy Lifestyle in Europe by Nutrition in Adolescents study - (HELENA), cross-sectional and multicenter study of the European adolescents, in order to evaluate the alterations in lipid markers and glucose homeostasis mediated by vitamin D deficiency and obesity. Finally, was analyzed the sample from PHYSMED study, a cross-sectional study with non-institutionalized elderly, to examine associations between vitamin D concentration, lipid profile and body composition in apparently healthy elderly Spanish.

Efeito combinado do ácido zoledrônico e do alfacalcidol no tratamento da osteoporose por desuso em ratos / Additive effect of zoledronic acid and alfacalcidol in the treatment of disuse osteoporosis in rats

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. .

Effect of Qing'e formula on circulating sclerostin levels in patients with postmenopausal osteoporosis / 华中科技大学学报（医学）（英德文版）

Serum sclerostin is positively associated with serum 25 hydroxyvitamin D concentration. Our preliminary studies confirmed that Qing'e formula (QEF) could effectively increase serum 25 hydroxyvitamin D concentration in patients with postmenopausal osteoporosis (PMOP), but the effect of supplementation with QEF on serum sclerostin is unknown. This study investigated the effects of supplementation of QEF on serum sclerostin levels in patients with PMOP. Totally 120 outpatients and inpatients with PMOP treated in our hospital between January and October 2012 were randomly divided into QEF+calcium group, alfacalcidol+calcium group, and placebo+calcium group (n=40 each), with a follow-up period of 2 years. The serum levels of sclerostin, 25 hydroxyvitamin D, and bone turnover markers (β-CTX, N-MID and T-PINP) at baseline and at the 6th month, 1st year, 1.5th year, and 2nd year after treatment were measured. The results showed that the levels of circulating sclerostin were increased significantly at the 6th month after treatment in QEF+calcium group and alfacalcidol+calcium group as compared with placebo+calcium group (P<0.05), but there was no significant difference between the former two groups (P>0.05). The levels of β-CTX, N-MID and T-PINP in serum were decreased in both QEF+calcium group and alfacalcidol+calcium group at the 6th month after treatment, without significant difference between the two groups (P>0.05). But the levels were significantly lower than that in placebo+calcium group (P<0.05). These results suggest that the mechanism by which QEF modulates bone metabolism in patients with PMOP might be related with the effect of QEF in increasing sclerostin expression. Our findings provide a scientific rationale for using QEF as an effective drug to prevent bone loss in PMOP.

Vitamin D enhances IL-1 beta secretion and restricts growth of Mycobacterium tuberculosis in macrophages from TB patients

The emergence of multidrug-resistant strains of Mycobacterium tuberculosis [MTB], the bacterium responsible for tuberculosis [TB], has rekindled the interest in the role of nutritional supplementation of micronutrients, such as vitamin D, as adjuvant treatment. Here, the growth of virulent MTB in macrophages obtained from the peripheral blood of patients with and without TB was studied. The H37Rv strain genetically modified to express Vibrio harveyi luciferase was used to determine the growth of MTB by luminometry in the human monocyte-derived macrophages [hMDMs] from study subjects. Determination of cytokine levels in culture supernatants was performed using a flow cytometry-based bead array technique. No differences in intracellular growth of MTB were observed between the different study groups. However, stimulation with 100 nM 1,25-dihydroxyvitamin D significantly enhanced the capacity of hMDMs isolated from TB patients to control the infection. This effect was not observed in hMDMs from the other groups. The interleukin [IL]-1 beta and IL-10 release by hMDMs was clearly increased upon stimulation with 1,25-dihydroxyvitamin D. Furthermore, the 1,25-dihydroxyvitamin D stimulation also led to elevated levels of TNF-alpha [tumor necrosis factor-alpha] and IL-12p40. It was concluded that vitamin D triggers an inflammatory response in human macrophages with enhanced secretion of cytokines, as well as enhancing the capacity of hMDMs from patients with active TB to restrict mycobacterial growth

Severe isolated primary hypoparathyroidism in an adult

A man aged 42 years, presented with 3 years history of paraesthesias in hands and feet and muscle cramps off and on, progressing to severe carpopedal spasm, a couple of times, relieved by intravenous calcium gluconate at the emergency reception of the hospital. On examination, Trousseau's sign and Chvostek's sign were positive. Thyroid gland was not enlarged. Right eye showed mature cataract. Total serum calcium, corrected serum calcium, serum phosphate, ionized serum calcium, serum alkaline phosphatase, serum parathormone [PTH] level were deranged favouring hypoparathyroidism. He was diagnosed to be suffering from isolated primary hypoparathyroidism and put on alfacalcidol and oral calcium carbonate, with which he is asymptomatic now

To be or not to be exposed to direct sunlight vitamin D deficiency in Oman

Only small amounts of vitamin D come from dietary sources as it is mainly synthesized in the skin from the ultraviolet B [UVB] fraction of sunlight if the person is sufficiently exposed to direct sunlight. Vitamin D deficiency has been well documented in Oman. The "2004 Oman National Micronutrients Survey" and other recent studies revealed that vitamin D3 stores are low among healthy Omani females of childbearing age and pregnant women. This situation is confusing as Oman is known to be one of the sunniest countries in the world. However, it is known that most Omani women are well covered and for various reasons avoid sun exposure. The article addresses a question about the balance that should be maintained between excessive sun exposure that to maintain adequate vitamin D levels. In order to avoid vitamin D deficiency, sun exposure or protection messages must be tailored according to different situations, in recognition of the complex combination of personal, cultural and social factors that affect vitamin D synthesis in the skin

Osteomalacia inducida por tumor / Tumor-induced osteomalacia

La osteomalacia inducida por tumor es un síndrome paraneoplásico secundario en la mayoría de los casos a tumores de origen mesenquimal. Se caracteriza por pérdida aumentada de fosfato a nivel urinario por el efecto inhibidor que ejerce el factor de crecimiento fibroblástico 23 sobre el transporte de fósforo en el túbulo renal proximal. Debe sospecharse en un paciente con debilidad y dolor osteomuscular generalizado que se presente con hipofosfatemia, normocalcemia, fosfatasa alcalina elevada y niveles de 25 hidroxivitamina D y PTH normales. El tratamiento definitivo de la enfermedad es la resección quirúrgica del tumor. Cuando se desconozca la neoplasia primaria o no sea posible el tratamiento quirúrgico debe iniciarse reposición de fósforo y calcitriol. En este artículo se presenta el primer caso de una paciente con osteomalacia inducida por tumor asociada a un carcinoma lobulillar infiltrante de seno.

The tumor-induced osteomalacia is a paraneoplastic syndrome secondary in most cases to tumors of mesenchymal origin. It is characterized by increased lost of urinary phosphate by the inhibitory effect exerted by the fibroblast growth factor 23 on phosphorus transport in the proximal renal tubule. Should be suspected in a patient with weakness and generalized muscle in addition to hypophosphatemia, normocalcemia, elevated alkaline phosphatase and normal serum 25-hydroxyvitamin D and PTH. The definitive treatment of the disease is surgical resection of the tumor. When the primary tumor is unknown or is not possible the surgical treatment should be initiated replacement of phosphorus and calcitriol. This paper presents the first case of a patient with tumor-induced osteomalacia associated with lobular breast cancer.

Autosomal Dominant Hypocalcemia Caused by an Activating Mutation of the Calcium-Sensing Receptor Gene: The First Case Report in Korea

Hypoparathyroidism is an abnormality of calcium metabolism characterized by low serum levels of parathyroid hormone in spite of hypocalcemia. The causes of hypoparathyroidism are numerous. Activating mutations in the calcium-sensing receptor (CaSR) gene are well-known causes of familial isolated hypoparathyroidism, also known as autosomal dominant hypocalcemia (ADH). Here we describe members of a Korean family with a heterozygous Pro221Leu mutation causing ADH. This case is the first report in Korea.

Variação sazonal de níveis de 25-hidroxivitamina d sérica e ingestão dietética de vitamina d em crianças e adolescentes com baixa estatura / Seasonal variation of 25-hydroxyvitamin d serum levels and vitamin d dietary intake in short children and adolescents

Introdução: A baixa estatura sem causa clínica evidente pode estar relacionada com deficiências nutricionais. A vitamina D é um hormônio fundamental para o desenvolvimento ósseo, obtida através da dieta e exposição solar. Objetivo: Avaliar os níveis séricos de 25(OH)D, a variação sazonal deste metabólito e a ingestão de vitamina D em crianças e adolescentes com o déficit estatural sem causas clínicas evidentes. Métodos: Cinquenta e cinco crianças e adolescentes com baixa estatura, sem doenças crônicas, endócrinas ou genéticas, responderam a três recordatórios de 24h para estimar o consumo de vitamina D. O nível sérico de 25(OH)D foi avaliado por Cromatografia Líquida de Alta Eficiência (HPLC) no Laboratório Fleury/SP. A classificação do fototipo foi realizada através dos parâmetros de Fitzpatrick. Os dados meteorológicos foram obtidos junto ao VIII Distrito de Meteorologia de Porto Alegre, do Instituto Nacional de Meteorologia. Resultados: Verificou-se o consumo dietético de Vitamina D abaixo do recomendado em 96% (N=53) dos pacientes e níveis insuficientes de 25(OH)D (<30 ng/ml) em 60% (N=33). A concentração de 25(OH)D sérica foi mais alta nas amostras coletadas durante o outono (P<0,05), não se correlacionando com a insolação (P =0,13) ou consumo dietético de Vitamina D (P=0,32). A média de 25(OH)D sérica foi maior (P<0,05) no grupo de pacientes com fototipos I, II e III. Conclusão: A 25(OH)D sérica apresentou variação sazonal. Níveis séricos de 25(OH)D baixos reforçam a importância da vitamina D obtida através da dieta ou suplementação nos meses onde há uma menor incidência de radiação ultravioleta.

Background: Short stature without evident medical cause may be related to nutritional deficiencies. Vitamin D is an essential hormone for bone development, being obtained through diet and sun exposure. Aim: To evaluate 25(OH)D serum levels, as well as the seasonal variation of this metabolite and vitamin D intake in children and adolescents with short stature without evident clinical causes. Methods: Fifty-five short children and adolescents, without endocrine or genetic chronic diseases, completed three 24-hour dietary recalls to estimate the intake of vitamin D. 25(OH)D serum levels were evaluated using high performance liquid chromatography (HPLC) at Laboratory Fleury, state of São Paulo, Brazil. The phototype classification was performed using the Fitzpatrick parameters. Meteorological data were obtained from the VIII District of Meteorology of Porto Alegre, National Institute of Meteorology. Results: The dietary intake of vitamin D was lower than recommended in 96% (N= 53) of patients and there were insufficient levels of 25(OH)D (<30 ng/ml) in 60% (N=33). The concentration of 25(OH)D levels was higher in samples collected during the fall (P<0.05), without correlation with sunshine (P=0.13) or dietary intake of vitamin D (P=0.32). The mean 25(H)D level was higher (P<0.05) in patients with phototypes I, II and III. Conclusion: 25(OH)D levels showed seasonal variation. Low serum 25(OH)D levels reinforce the importance of vitamin D obtained from diet or supplements in the months during which there is lower incidence of ultraviolet radiation.

Diagnóstico y tratamiento de la deficiencia de vitamina D / Diagnosis and treatment of vitamin D deficiency

Nutritional status of vitamin D has regained importance in the last few years because its deficiency is highly prevalent, and because, apart from its well known effects on bone metabolism, this vitamin participates in cellular proliferation and differentiation and muscle strength and balance, among other effects. The active molecule is 1,25(OH)2D, but serum concentration of total 25 OH vitamin D (i.e. including ergocalciferol or vitamin D2 plus chole calciferol or vitamin D3) is the preferred indicator of vitamin D status. Recent evidences suggest the need to increase dietary recommendations in adults up to 1,000 IU/day. However, in deficiency states it is often necessary to supplement with pharmaceutical preparations, which contain higher doses of this vitamin since the amounts previously employed were not able to return levels to normal. In the present article we present the entire list of vitamin D preparations commercially available in Chile. The difficulty of choosing the most adequate product for an individual patient becomes clear, because there are only few formulations containing more than 800IU and, in addition they are usually combined with calcium, biphosphonates or multiple minerals and other vitamins.

El estado nutricional de vitamina D ha cobrado importancia en los últimos a±os debido a que su deficiencia es altamente prevalente, y además por sus conocidos efectos en el metabolismo óseo, participa en la diferenciación y proliferación celular, función muscular y equilibrio, entre otros. La molécula activa es la 1,25(OH)2D, pero se recomienda medir niveles séricos de 25 OH vitamina D total (es decir la suma de ergocalciferol o vitamina D2 y colecalciferol o vitamina D3), como reflejo del status de vitamina D. La evidencia actual sugiere la necesidad de elevar las recomendaciones para la ingesta dietaria en adultos, hasta cifras cercanas a 1.000 Ul/día. Sin embargo en casos de deficiencia puede ser necesario utilizar suplementos farmacéuticos conteniendo dosis superiores de esta vitamina, por cuanto aquellas utilizadas en el pasado no lograban corregir el déficit. En este artículo se presenta un listado de los preparados comerciales que contienen vitamina D disponibles en Chile. Al analizarlo se pone de mamfiesto la dificultad que representa elegir el preparado más adecuado para corregir la deficiencia en un paciente individual, debido a que son pocas las preparaciones que contienen más de 800 UI, además de que habitualmente se encuentra en asociación con calcio, bifosfonatos o múltiples otros minerales y vitaminas.

Comparison of the Effects of Alendronate and Alfacalcidol on Hip Bone Mineral Density and Bone Turnover in Japanese Men Having Osteoporosis or Osteopenia with Clinical Risk Factors for Fractures

PURPOSE: The comparative effects of alendronate and alfacalcidol on bone mineral density (BMD) and bone turnover have already been established in postmenopausal women with osteoporosis. An open-labeled prospective study was conducted to compare the treatment effects of alendronate and alfacalcidol on hip BMD and bone turnover in Japanese men with osteoporosis or osteopenia with clinical risk factors for fractures. MATERIALS AND METHODS: One hundred twelve men with osteoporosis or osteopenia with clinical risk factors for fractures (mean age: 71.4 years) were randomly divided into two groups of 56 patients each: the alendronate (5 mg daily) and alfacalcidol (1 microgram daily) groups. The BMD of the total hip, urinary level of cross-linked N-terminal telopeptides of type I collagen (NTX), and serum levels of bone-specific alkaline phosphatase (BSAP) were measured during the 12-month-treatment period. RESULTS: Forty-five patients in the alendronate group and 42 patients in the alfacalcidol group completed the trial. Alendronate increased BMD (+2.3% at 12 months) following reductions in the urinary level of NTX (-46.4% at 3 months) and serum level of BSAP (-34.1% at 12 months), while alfacalcidol sustained BMD (-1.9% at 12 months) as well as the urinary level of NTX (+13.2% at 3 months) and serum level of BSAP (+1.8% at 12 months). CONCLUSION: The present study confirmed that alendronate has better efficacy than alfacalcidol (active control) in increasing hip BMD and reducing bone turnover in Japanese men with osteoporosis or osteopenia with clinical risk factors for fractures.

Comparison of the Effects of Alendronate and Alfacalcidol on Hip Bone Mineral Density and Bone Turnover in Japanese Men Having Osteoporosis or Osteopenia with Clinical Risk Factors for Fractures

PURPOSE: The comparative effects of alendronate and alfacalcidol on bone mineral density (BMD) and bone turnover have already been established in postmenopausal women with osteoporosis. An open-labeled prospective study was conducted to compare the treatment effects of alendronate and alfacalcidol on hip BMD and bone turnover in Japanese men with osteoporosis or osteopenia with clinical risk factors for fractures. MATERIALS AND METHODS: One hundred twelve men with osteoporosis or osteopenia with clinical risk factors for fractures (mean age: 71.4 years) were randomly divided into two groups of 56 patients each: the alendronate (5 mg daily) and alfacalcidol (1 microgram daily) groups. The BMD of the total hip, urinary level of cross-linked N-terminal telopeptides of type I collagen (NTX), and serum levels of bone-specific alkaline phosphatase (BSAP) were measured during the 12-month-treatment period. RESULTS: Forty-five patients in the alendronate group and 42 patients in the alfacalcidol group completed the trial. Alendronate increased BMD (+2.3% at 12 months) following reductions in the urinary level of NTX (-46.4% at 3 months) and serum level of BSAP (-34.1% at 12 months), while alfacalcidol sustained BMD (-1.9% at 12 months) as well as the urinary level of NTX (+13.2% at 3 months) and serum level of BSAP (+1.8% at 12 months). CONCLUSION: The present study confirmed that alendronate has better efficacy than alfacalcidol (active control) in increasing hip BMD and reducing bone turnover in Japanese men with osteoporosis or osteopenia with clinical risk factors for fractures.

Presence of 25(OH) D deficiency in a rural North Indian village despite abundant sunshine.

BACKGROUND AND OBJECTIVE: Several studies have shown wide prevalence of vitamin D deficiency with serum 25(OH)D <49.9 nmol/L in urban Indians related to their poor sunshine exposure and skin pigmentation. However, there is limited information in rural Indians. We hypothesized presence of higher 25(OH)D in rural subjects as compared to urban because of farming related abundant sunshine exposure. DESIGN AND METHODS: We assessed serum 25(OH)D levels in residents of a North Indian village with 200 families, located 90 km East of Delhi during February (winter). Fifty seven subjects (32 males and 25 females) from 50 families consented for the study. RESULTS: The mean 25(OH)D values of all subjects in the rural area was 36.4 +/- 22.5 nmol/l/L. Males had significantly higher 25(OH)D values than females. When compared to urban subjects, the mean 25(OH)D value of rural males and females was six and three folds higher, respectively. However even with five hours of daily sunshine exposure only 31.5% had serum 25(OH)D levels > or = 50 nmol/L. CONCLUSIONS: Thus, with longer sunshine exposure subjects residing in rural area had better mean 25(OH)D values than that of urbans. However, 70% of them were still vitamin D deficient. These facts indicate the need for the countrywide vitamin D food fortification program irrespective of rural or urban setting.

Profilaxis de raquitismo en niños sanos de Ushuaia. Efecto de dos dosis de 100.000 UI de vitamina D durante el invierno / Rickets prophylaxis in healthy children fron Usuahia. Effect of 2 doses of 100.000 UI of vitamin D during winter

Como provilaxis de raquitismo, se administró a niños sanos de Ushuaia (55ºS), una doble suplemenación de vitamina D de 100.000 UI al inicio del invierno (marzo 2004), y tres meses después durante el invierno (junio 2004). Se midió 25-hidroxivitamina D sérica (250HD) antes, 1 mes después de la primera suplementación, y 3 meses después de la segunda suplementación (marzo, abril y septiembre). Se estudiaron 18 niños sanos, edad (media más menos DS) 7.3 más menos 4.4 años (rango 1.2 a 14.6), 7 niñas y 11 niños. Antes del tratamiento, la 250 HD sérica fue 29.3 más menos 5.9 ng/ml. Aumentó significativamente 1 mes después de la primera suplementación (Abril): 35.3 más menos 4.4 ng/ml (p<0.001), y disminuyo significativamente 3 meses después de la segunda suplementación 22.4 más menos 4.6 ng/ml (Septiembre (p<0.01). Ningún niño tuvo deficiencia (<10 ng/ml) ni insuficiencia (10-15 bg/ml) de vitamina D. En abril, 1 mes después de la primera suplementación, ningún niño tuvo intoxicación de vitamina D (>50 ng/ml). Conclusión: los resultados sugieren que la doble suplementación con 100.000 UI de vitamina D durante otoño e invierno, previene la deficiencia de vitamina D de niños que habitan en zonas de riesgo del sur de nuestro país.