1,25-dihydroxyvitamin D3 and l,α-hydroxyvitamin D3 in children: Biologic and therapeutic effects in nutritional rickets and different types of vitamin D resistance

Abstract

This investigation confirms the high level of biologic activity and the similarity of the effects of small doses of 1,25-dihydroxyvitamin D3 (l,25-(OH)2-D3) and of its analog lα-hydroxyvitamin D3 (lα-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 l,25-(OH)2-D3. The com-parison of the therapeutic effects of long term oral administration of l,25-(OH)2-D3 or lα-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 lα-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. 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. © 1975 International Pediatric Research Foundation, Inc.