Calcitriol treatment in vitamin D-dependent and vitamin D-resistant rickets

Use of 1,25(OH)2D3 (calcitriol) can be of benefit in the treatment of two hereditary types of rickets and osteomalacia, vitamin D dependency type I (VDD1) and X-linked hypophosphatemic vitamin D-resistant rickets (HPDR). VDD1 is due to inadequate activation of 25(OH)D to 1,25(OH)2D, leading to very low circulating levels of 1,25(OH)2D in plasma; the basic abnormality appears to be an alteration in renal 1 alpha-hydroxylase activity. In VDD1, replacement therapy with calcitriol results in complete correction of the abnormal phenotype. By contrast, in HPDR, plasma levels of 25(OH)D and 1,25(OH)2D are in the normal range, although it has been demonstrated that the ability of patients to produce 1,25(OH)2D under conditions of stress is impaired. When started early in life, the use of phosphate salts in HPDR generally results in healing of rickets, normal growth, and correction of lower limb deformities. However, osteomalacia is not corrected by treatment with phosphate, either alone or in combination with vitamin D. By pharmacologically increasing the level of 1,25(OH)2D3 in these patients, there is often a dramatic improvement in the appearance of the trabecular surface, leading to correction of the osteomalacic component of HPDR; in addition, the secondary hyperparathyroidism observed in previous patients treated with phosphate and vitamin D is easier to control. Closed medical follow-up allows the prevention of renal damage that could result from long-term administration of calcitriol.