Vitamin D Analogs: Perspectives for Treatment

Abstract

Vitamin D therapy is widely used for the treatment of secondary hyperparathyroidism associated with chronic renal failure. However, administration of 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] or its precursor 1α(OH)D₃, especially in combination with calcium-based phosphate binders, often produces hypercalcemia. Several vitamin D analogs have been developed that retain the direct suppressive action of 1,25(OH)₂D₃ on the parathyroid glands but have less calcemic activity. These analogs offer a safer and more effective means of controlling secondary hyperparathyroidism. 22-Oxa-1,25(OH)₂D₃ (22-oxacalcitriol or OCT), 19-nor-1,25(OH)₂D₂ (19-norD₂) and 1α(OH)D₂ have been tested in animal models of uremia and in clinical trials. Intravenous 19-norD₂ and oral 1α(OH)D₂ 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 glands are under investigation. The low calcemic activity of OCT has been attributed to its rapid clearance which prevents sustained effects on intestinal calcium absorption and bone resorption, but still allows a prolonged suppression of PTH gene expression. The selectivity of 19-norD₂ and 1α(OH)D₂ is achieved by a distinct mechanism(s). Knowledge of how these compounds exert their selective actions on the parathyroid glands may allow the design of more effective analogs in the future.

Combination of 22-oxa-1,25-dihydroxyvitamin D3, a vitamin D3 derivative, with vitamin K2 (VK2) synergistically enhances cell differentiation but suppresses VK2-inducing apoptosis in HL-60 cells

“…12,13 22-oxa-1,25-dihydroxyvitamin D 3 (OCT: oxa carcitriol) is a unique vitamin D analogue with less calcemic activity than calcitriol, and it effectively suppresses parathyroid hormone (PHT) secretion in uremic patients receiving dialysis therapy. [14][15][16] In the present study, we focused on the combined effects of VK2 and OCT on leukemia cells. Our data clearly demonstrates that a combination of OCT and VK2 synergistically enhances induction of monocytic differentiation of HL-60 cells, suggesting the clinical benefit of the combined use of these vitamins.…”

Vitamin D analogs: Actions and role in the treatment of secondary hyperparathyroidism

“…12 Currently, there are 3 vitamin D analogs and 2 synthetic prohormones that have been introduced for the treatment of secondary hyperparathyroidism. The structures of these vitamin D sterols are depicted in Figure 1.…”

Pharmacologic Targets and Peritoneal Membrane Remodeling

“…In recent years, research has aimed to develop VDR activators that retain many of the anti-inflammatory properties of 1,25-dihydroxy-vitamin D, the bioactive form of vitamin D 3 , but with less intestinal calcium absorption (80,81). Treatment of uremic rats with Escherichia coli lipopolysaccharide induced inflammation; oral paricalcitol, a synthetic VDR activator, or calcitriol reduced the associated cytokine levels.…”