Vitamin D analogs: Perspectives for treatment

Vitamin D therapy is widely used for the treatment of secondary hyperparath yroidism associated with chronic renal failure. However, administration of 1,25-dihydroxy-vitamin D-3 [1,25(OH)(2)D-3] or its precursor 1 alpha(OH)D-3 , especially in combination with calcium-based phosphate binders, often pro duces hypercalcemia, Several vitamin D analogs have been developed that ret ain the direct suppressive action of 1,25(OH)(2)D-3 on the parathyroid glan ds but have less calcemic activity. These analogs offer a safer and more ef fective means of controlling secondary hyperparathyroidism, 22-0xa-1,25(OH) (2)D-3 (22-oxacalcitriol or OCT), 19-nor-1,25(OH)(2)D-2 (19-norD(2)) and 1 alpha(OH)D-2 have been tested in animal models of uremia and in clinical tr ials. Intravenous 19-norD(2) and oral 1 alpha(OH)D-2 have been approved for use in the United States; OCT is currently under review. The mechanisms by which these analogs exert their selective actions on the parathyroid gland s are under investigation. The low calcemic activity of OCT has been attrib uted to its rapid clearance which prevents sustained effects on intestinal calcium absorption and bone resorption, but still allows a prolonged suppre ssion of PTH gene expression. The selectivity of 19-norD(2) and 1 alpha(OH) D-2 is achieved by a distinct mechanism(s). Knowledge of how these compound s exert their selective actions on the parathyroid glands may allow the des ign of more effective analogs in the future. Copyright (C) 2000 S. Karger A G, Basel.