Endocrine Abstracts (2005) 10 S39

Vitamin D analogues: pharmacology and therapeutic uses

R Bouillon


Katholieke Universiteit Leuven, Leuven, Belgium.


Vitamin D is a substrate for the active hormone, 1α, 25-dihydroxyvitamin D3, which binds to a single vitamin D receptor (VDR) belonging to the class of nuclear transcription factors.

Ligand activated VDR regulates about 3 % the mouse/human genome and has a wide variety of physiologic actions. Its regulates calcium and bone homeostasis by increasing transepithelial calcium transport (intestine, kidney) and regulates the functions of bone and parathyroid cells. VDR.1α,25-(OH)2D3 also also has major effects on many other target tissues as demonstrated in VDR KO mice and man (keratinocytes and hair follicles: alopecia’s; high renin hypertension; muscle cell maturation defect; differentiation of immune cells). Finally all VDR+ cells react to VDR.1,25-(OH)2D by inhibition of proliferation regulated by a coherent action on cell cycle genes.

More than 3000 synthetic analogues of vitamin D have been tested including a large number of non-steroidal analogues and some cholic acid derivatives. An increasing number of such analogues show clear selective receptor modulating activity as demonstrated by their antiproliferative or immune modulatory effects while minimizing their calcemic activity; or alternatively by selective increase of bone mass or density with limited effects on serum calcium homeostasis.

The mode of action of superagonistic and/or selective activation of VDR is not completely understood but involves extra– and intracellular pharmacokinetics, VDR stability and above all selective recruitment of coactivators.

The clinical use of vitamin D analogues is presently limited to topical application for skin disorders and systemic use for secondary hyperparathyroidism but it is likely that new indications will be found for some selective VDR modulators.

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