1,25-Dihydroxyvitamin D3 and 1,α-Hydroxyvitamin D3 in Children: Biologic and Therapeutic Effects in Nutritional Rickets and Different Types of Vitamin D Resistance
1,25-Dihydroxyvitamin D3 and 1,α-Hydroxyvitamin D3 in Children: Biologic and Therapeutic Effects in Nutritional Rickets and Different Types of Vitamin D Resistance
复制标题
儿童 1,25-二羟基维生素 D3 和 1,α-羟基维生素 D3：对营养性佝偻病和不同类型维生素 D 抵抗的生物学和治疗作用
作者：
S. Balsan;M. Garabédian;R. Sorgniard;Michael F. Holick;H. F. DeLuca
摘要：本研究证实了小剂量 1,25-二羟基维生素 D3 (1,25-(OH)2-D3) 及其类似物 1α-羟基维生素 D3 (1α-OH-D3) 对患有营养性佝偻病、“假性缺乏”佝偻病 (PDR)、遗传性低磷血症、慢性特发性甲状旁腺功能减退症和慢性肾功能衰竭。它还表明，胱氨酸患者在疾病末期可能对1,25-(OH)2-D3产生一定程度的耐药性。对两名 D 缺乏儿童和两名 PDR 同胞长期口服 1,25-(OH)2-D3 或 1α-OH-D3 的治疗效果进行比较，结果显示敏感性存在差异。在患有营养性佝偻病的患者中，0.5/μg/24小时的任一药物均可纠正生化异常，在28天内开始骨骼病变的愈合，并在治疗60天内治愈干骺端病变。相比之下，对 D 缺乏性佝偻病具有治疗作用的任何一种药物的剂量似乎在 PDR 中仅部分有效。这些观察结果表明，PDR 患者中 25-羟基胆钙化醇 1α-羟化酶缺陷的假设必须等待更直接的证据来证实，并且即使得到证实，这种缺陷也可能无法解释这种遗传性疾病患者中观察到的所有生化和骨骼变化。推测：本研究中观察到的 1,25-(OH)2-D3 和 1α-OH-D3 作用的相似性提供了额外的证据： 1α-OH-D3 可以被认为是激素形式胆钙化醇的有价值的替代品，特别是对于治疗患有慢性肾功能衰竭、甲状旁腺功能减退症或假性缺乏性佝偻病的儿童。在后一种疾病中，任一药物的有效治疗剂量似乎大于治疗简单营养性佝偻病所需的量。这一观察结果表明，必须继续对假性缺乏性佝偻病的发病机制进行研究，以证实或推翻我们和其他人提出的假设，即这种遗传性疾病可能与 25-羟基胆钙化醇 1α-羟化酶的缺乏有关。
Extract: This investigation confirms the high level of biologic activity and the similarity of the effects of small doses of 1,25-dihydroxyvitamin D3 (1,25-(OH)2-D3) and of its analog 1α-hydroxyvitamin D3 (1α-OH-D3) on children with nutritional rickets, “pseudodeficiency” rickets (PDR), hereditary hypophosphatemia, chronic idiopathic hypoparathyroidism, and chronic renal failure. It also shows that cystinotic patients may develop, at the end stage of the disease, a certain degree of resistance to 1,25-(OH)2-D3. The comparison of the therapeutic effects of long term oral administration of 1,25-(OH)2-D3 or 1α-OH-D3 to two D-deficient children and two sibs with PDR demonstrates differences in sensitivity. In the patients with nutritional rickets, 0.5/μg/24 hr of either drug corrects the biochemical abnormalities, initiates healing of skeletal lesions in 28 days, and cures the metaphyseal lesions in 60 days of therapy. In contrast, it appears that doses of either drug that are curative in D deficiency rickets are only partly active in PDR. These observations indicate that the hypothesis of a deficit in 25-hydroxycholecalciferol 1α-hydroxylase in patients with PDR must await for confirmation more direct evidences, and that such a deficit, even if proven, may not account for all of the biochemical and skeletal alterations seen in patients with this inherited disorder.Speculation: The similarity of action of 1,25-(OH)2-D3 and 1α-OH-D3 observed in the present study presents additional evidence that 1α-OH-D3 can be considered a valuable substitute for the hormonal form of cholecalciferol, especially for the management of children with chronic renal failure, hypoparathyroidism, or pseudo-deficiency rickets. In this latter disease, the active therapeutic doses of either drug appear to be greater than the amount required for the treatment of simple nutritional rickets. This observation indicates that investigations on the pathogenesis of pseudodeficiency rickets must be continued in order to confirm or invalidate the hypothesis suggested by us and others that this inherited disorder might be related to a deficit in 25-hydroxycholecalciferol 1α-hy-droxylase.