al-Aqeel A, Ozand P, Sobki S, Sewairi W, Marx S
Department of Paediatrics, Riyadh Armed Forces Hospital, Saudi Arabia.
Clin Endocrinol (Oxf). 1993 Aug;39(2):229-37. doi: 10.1111/j.1365-2265.1993.tb01779.x.
Some patients with rickets are resistant to vitamin D and its analogues; we therefore assessed whether or not normal mineralization could be achieved in the absence of an intact 1,25(OH)2D3 receptor-effector system, by the use of intravenous high dose calcium infusion, followed by high dose oral calcium.
We studied two patients with vitamin D dependent rickets type II and with absent responses to either high dose calcitriol or to oral calcium alone. Daily infusions equivalent to up to 1.4 g elemental calcium supplemented with oral phosphate were given for a period of 3.5 months for the elder sister and 2 months in the younger brother. Both patients were then treated by weekly calcium infusions for 5 months, followed by maintenance on oral calcium equivalent to up to 6 g elemental calcium per day.
Two siblings of consanguineous parents, a girl aged 28 months and a boy aged 10 months with vitamin D dependent rickets type II.
Measurements of serum and urine calcium, phosphate and serum alkaline phosphatase were obtained before, during and after the calcium infusions. Twenty-four-hour urinary minerals, electrolytes, creatinine clearance, serum PTH and vitamin D metabolites were measured prior to calcium infusion, then repeated at 2-monthly intervals. Glomerular filtration rate, kidney ultrasound and CT scan were done at 6-monthly intervals. A scalp biopsy was done at the end of i.v. calcium treatment.
The daily infusions of calcium supplemented with oral phosphate resulted in biochemical responses with normalization of calcium and phosphate in 3-5 days, and of alkaline phosphatase and PTH in 1.5-2 months. Radiological evidence of healing was seen in 42 days. A total of 3.5 months of daily calcium infusion in the elder sister and 2 months in the younger brother resulted in complete healing biochemically and radiologically, with improvement in height. The patients are under current follow-up, with no evidence of nephrocalcinosis or deterioration of glomerular filtration rate.
(a) The use of intravenous high dose calcium infusions followed by high dose oral calcium is an effective method of treatment of vitamin D dependent rickets type II. (b) The treatment was more effective since it was started early in the course of the disease and led to early healing and better growth with prevention of bone deformities. (c) Early treatment may also lead to improvement in alopecia, the mechanism for which needs to be elucidated.
1,25(OH)2D3, 1,25-dihydroxyvitamin D3 (calcitriol); 24-OHase, 25-(OH)D(3),24-hydroxylase; 1 alpha-(OH)D3, 1 alpha-hydroxyvitamin D3; 25(OH)D3, 25-hydroxyvitamin D3; 1 alpha-OHase, 1 alpha-hydroxylase; PTH, parathyroid hormone.
一些佝偻病患者对维生素D及其类似物耐药；因此，我们评估了在缺乏完整的1,25(OH)₂D₃受体效应系统的情况下，通过静脉输注高剂量钙，随后口服高剂量钙，是否能够实现正常矿化。
我们研究了两名II型维生素D依赖性佝偻病患者，她们对高剂量骨化三醇或单独口服钙均无反应。对姐姐进行了为期3.5个月、相当于每日输注高达1.4 g元素钙并补充口服磷酸盐的治疗，对弟弟进行了为期2个月的治疗。之后，两名患者均接受了为期5个月的每周一次钙输注治疗，随后维持口服相当于每日高达6 g元素钙的钙剂。
两名近亲结婚父母的同胞，一名28个月大的女孩和一名10个月大的男孩，患有II型维生素D依赖性佝偻病。
在钙剂输注前、期间和之后，对血清和尿钙、磷以及血清碱性磷酸酶进行测量。在钙剂输注前测量24小时尿矿物质、电解质、肌酐清除率、血清甲状旁腺激素（PTH）和维生素D代谢产物，然后每2个月重复测量一次。每6个月进行一次肾小球滤过率、肾脏超声和CT扫描。在静脉补钙治疗结束时进行头皮活检。
每日输注钙剂并补充口服磷酸盐，在3 - 5天内使钙和磷恢复正常，在1.5 - 2个月内使碱性磷酸酶和PTH恢复正常，出现了生化反应。在第42天可见愈合的放射学证据。姐姐总共进行了3.5个月的每日钙剂输注，弟弟进行了2个月的输注，在生化和放射学上均实现了完全愈合，身高有所增加。患者目前正在接受随访，没有肾钙质沉着或肾小球滤过率恶化的迹象。
（a）静脉输注高剂量钙随后口服高剂量钙是治疗II型维生素D依赖性佝偻病的有效方法。（b）该治疗更有效，因为在疾病早期开始治疗，导致早期愈合和更好的生长，预防了骨骼畸形。（c）早期治疗也可能改善脱发，其机制有待阐明。
1,25(OH)₂D₃，1,25 - 二羟维生素D₃（骨化三醇）；24 - OHase，25 - (OH)D(3),24 - 羟化酶；1α - (OH)D₃，1α - 羟维生素D₃；25(OH)D₃，25 - 羟维生素D₃；1α - OHase，1α - 羟化酶；PTH，甲状旁腺激素。
