Medical uses of vitamin D compounds
With the discovery of the metabolic activation of vitamin D prior to its function in the body it became evident that some of the disorders that did not respond well to vitamin D might benefit from one of its metabolites. Subsequent chemical synthesis of these compounds and their analogs has allowed some clinical testing of their usefulness. Treatment with 1,25-(OH)2D3 has been found effective in some patients with renal osteodystrophy associated with chronic renal failure. The circulating level of this metabolite in these patients is hardly detectable, but because of the greatly reduced kidney function, other complicating metabolic imbalances are present, which make the condition difficult to manage. Other conditions that appear to benefit from 1,25-(OH)2D3 include hypoparathyroidism, vitamin D-dependent rickets, a rare genetic disease due to a defect in 1hydroxylase, and hypophosphatemic vitamin D-resistant rickets. The latter condition requires daily phosphate supplementation along with vitamin D because a defect in renal phosphate transport is the primary lesion that causes hypophosphatemia. These conditions have been rreated with massive doses of vitamin D or its synthetic analog, dihydrotachysterol. The former probably acts after conversion to 25-0H-D3, which in large doses is known to substitute for 1,25-(OH)2D3 in the target tissues.30 Dihydrotachysterol also is active in large doses without 1-hydroxylation.
Administration of 1,25-(OH)2D3 to postmenopausal osteoporotic women has been shown to increase intestinal calcium absorption and to improve calcium balance. Good discussions of metabolic defects involving vitamin D can be found in recent reviews.
