维生素D及其受体与临床相关疾病的研究

维生素D(Vitamin D,VitD)对人类健康特别是儿童健康具有重要意义,VitD缺乏性佝偻病是我国儿童重点防治的四病之一。临床发现VitD缺乏性佝偻病除骨骼病变外,同时可影响神经、肌肉、造血及免疫等组织器官的功能。近年来对VitD的研究取得了重大进展。     

Vitamin D metabolites (25-hydroxyvitamin D, 24,25-dihydroxyvitamin D and 1,25-dihydroxyvitamin D) and osteocalcin in β-thalassaemia

Serum levels of the vitamin D metabolites 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D. and of osteocalcin. C-tenninal parathyroid hormone and other biochemical indices related to bone metabolism, were determined in two groups of patients with β-thalassaemia aged 5–10 years (summer 7.8 ± 0.4 years, mean ± SEM. and winter 7.7 ± 0.4 years, group A, n= 15) and 11–23 years (16.6 ± 0.9 and 15.7 ± 0.9 years in summer and winter, respectively, group B, n= 22). Emphasis was given to populations of school and adolescent ages and to the seasons of summer and winter when vitamin D status demonstrates the widest extremes. The mean serum levels of 25-hydroxyvitamin D in patients aged 5–10 years did not differ from those of controls during both seasons studied. In contrast, in the age group 11–23 years these levels were found to be lower in patients than in controls both in winter (10.6 ± 0.9ng/ml vs 15.0 ± 2.0ng/ml, p < 0.05) and summer (20.2 ± 2.1 ng/ml vs 27.1 ± 2.0ng/ml, p < 0.05). The serum concentrations of 24,25-dihydroxyvitamin D were lower in the thalassaemic patients than in controls in both age groups and both seasons. In the patients under 10 years of age the mean values of this metabolite in winter were 1.06 ± 0.17 ng/ml vs 1.68 ± 0.20 ng/ml in the respective controls (p < 0.05), and in summer 1.44 ± 0.11 ng/ml vs 2.35 ± 0.36 ng/ml in controls (p < 0.05). In the group of patients aged 11–23 years, the mean levels of 24,25-dihydroxyvitamin D were in winter 0.65 ± 0.12 ng/ml vs 1.12 ± 0.19 ng/ml (p < 0.05) in controls and in summer 1.34 ± 0.12 ng/ml vs 1.84 ± 0.20 ng/ml (p < 0.05). The 1,25-dihydroxyvitamin D concentrations in both thalassaemic patient groups were significantly no different from those in the respective control groups. Serum osteocalcin, C-terminal parathyroid hormone, calcium, inorganic phosphate and alkaline phosphatase levels in the patients studied were not significantly different from those in controls, except for calcium and phosphate in the older group. In the older group of thalassaemic patients, serum calcium was lower than in the controls (2.26 ± 0.03 vs 2.37 ± 0.03 mmol/1, p < 0.05) in summer and serum phosphate higher than in the controls in winter (1.47 ± 0.05 mmol/1 vs 1.27 ± 0.06 mmol/1. p < 0.05).     

维生素D受体基因多态性与佝偻病易感性的研究进展

维生素D缺乏性佝偻病（简称佝偻病）是由于儿童体内维生素D不足引起钙、磷代谢紊乱,使正在生长的骨骼在成骨过程中不能正常沉着钙盐而产生的一种以骨骼病变为特征的全身慢性营养性疾病。目前认为环境因素,主要包括营养因素等是其主要致病原因,但遗传因素在其发生发展中的作用正逐渐受到重视。     

维生素D受体基因多态性与维生素D缺乏性佝偻病的关系

维生素D缺乏性佝偻病(简称佝偻病)是由于儿童体内维生素D不足引起钙、磷代谢紊乱,使正在生长的骨骼在成骨过程中不能正常沉着钙盐而产生的一种以骨骼病变为特征的全身慢性营养性疾病.目前认为环境因素及营养因素等是主要致病原因,但遗传因素在其发生发展中的作用正逐渐受到重视.维生素D是人体内钙稳态和骨代谢的主要调节因子之一,其在体内的主要活性代谢产物是1,25-(OH)2D3.维生素D受体(vitamin D receptor,VDR)是介导1,25-(OH)2D3发挥生物学效应的核内生物大分子,VDR是由VDR基因编码,因此VDR基因是研究骨代谢性疾病遗传基础的候选基因之一.文章就VDR基因多态性与佝偻病遗传易感性之间的关系作一综述.     

维生素D及其受体与佝偻病的研究进展

维生素D通过维生素D受体介导,在体内具有广泛的生物学作用,其中对钙磷代谢的调节作用对于正常的骨骼形成与骨矿化有重要影响.佝偻病为常见的儿童骨代谢性疾病,不同类型佝偻病的病因不同,但其病理生理过程、临床表现及治疗均与维生素D及其受体对骨代谢的影响密切相关.     

Vitamin D intoxication

Vitamin D intoxication (VDI) may result from supplementation rarely, but it has been reported more frequently in recent years. This may be attributable to an increase in vitamin D supplement intake due to an understanding of the role of vitamin D (25OHD) in the pathogenesis of several diseases. The symptoms and findings associated with VDI are closely related to serum calcium concentration and duration of hypercalcemia. In patients with VDI, hypercalcemia, normal or high serum phosphorus levels, normal or low levels of alkaline phosphatase (ALP), high levels of serum 25OHD, low serum parathyroid hormone (PTH), and high urine calcium/creatinine are usually present. Serum 25OHD levels above 150 ng/ml are considered as VDI. The main goal of treatment for VDI is correction of the hypercalcemia. When the calcium concentration exceeds 14 mg/dl, emergency intervention is necessary because of the adverse effects of hypercalcemia on cardiac, central nervous system, renal, and gastrointestinal functions. However, since vitamin D is stored in fat tissues, effects of toxicity may last for months despite the removal of the exogenous source of vitamin D. Treatment for VDI includes: discontinuation of intake, a diet with low calcium and phosphorus content, intravenous hydration with saline, loop diuretics, glucocorticoids, calcitonin, and bisphosphonates. In conclusion, the diagnosis of vitamin D deficiency rickets (VDDR) without checking serum 25OHD level may cause redundant treatment that leads to VDI. All patients who are clinically suspected of VDDR should be checked for serum vitamin D status and questioned for previous vitamin D administration before starting vitamin D therapy. On the other hand, parents of all infants should be asked whether they are using dietary or oral supplements, and serial questioning may be required during supplementation to avoid excessive intake.     

Treatment of malabsorption vitamin D deficiency myopathy with intramuscular vitamin D

A nearly 5 year-old boy presented with proximal muscle weakness, reduced muscle bulk, a positive Gower sign and Trendelenburg gait. He was known to have cholestatic liver disease. Investigations revealed markedly low serum total calcium, elevated alkaline phosphatase, very low serum 25-hydroxyvitamin D, and radiographs consistent with active rickets despite the ongoing administration of a water-soluble preparation of vitamin D. Only i.v. calcitriol acutely corrected the hypocalcemia, despite trying several oral preparations, suggesting that malabsorption secondary to chronic liver disease was the cause of his rickets. Intramuscular calciferol quickly corrected his muscle weakness and X-ray findings. Myopathy secondary to vitamin D deficiency is an uncommon diagnosis in children. Intermittent calciferol is an inexpensive and practical treatment for vitamin D deficiency, especially if associated with malabsorption.     

Vitamin D dependent rickets: Decreased sensitivity to 1,25-dihydroxyvitamin D

A patient with vitamin D dependent rickets with decreased sensitivity to 1,25-Dihydroxyvitamin D was observed. She suffered from bone pain of two years duration beginning at 12 years of age and was found to be suffering from hypocalcemia, secondary hyperparathyroidism and osteomalacia. Laboratory findings revealed normal serum 25-hydroxyvitamin D (27 ng/ml) and markedly elevated serum 1,25-dihydroxyvitamin D (131.9 pg/ml). The hypocalcemia was refractory in spite of administration of 25,000 units of vitamin D₂, but therapy with high doses of oral 1-hydroxyvitamin D₃ resulted in significant elevation of the serum calcium level. The clinical findings and course of the patient's disease were quite different from those of other patients with vitamin D dependent rickets reported by other authors.