An update on the therapeutic potential of vitamin D analogues.
The review provides an evaluation of the therapeutic potential of vitamin D analogues in the context of the current understanding of vitamin D biochemistry, molecular biology and physiology. Vitamin D activity results from several circulating and intracellular physiological metabolites acting simultaneously through at least three receptors. Common analogues are reviewed. Although most vitamin D analogues have traditionally been analogues of 1,25-dihydroxyvitamin D, it may be better to deliver high doses of base vitamin or (analogues) of 25-hydroxyvitamin D. This would permit physiological endocrine, paracrine and autocrine vitamin D metabolism. Agonists or antagonists of tissue-specific vitamin D metabolic pathways could be coadministered. The importance of measuring endogenous vitamin D metabolites during in vivo studies and the pitfalls of extending data across species and time are emphasised. Human vitamin D analogue trials should include direct comparison against the related endogenous metabolite.
Stein
Mark S
MS
Department of Diabetes and Endocrinology, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
Wark
John D
JD
D002986:Clinical Trials as Topic; D006801:Humans; D018167:Receptors, Calcitriol / Q000378:metabolism; D013329:Structure-Activity Relationship; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use*
D018167:Receptors, Calcitriol; D014807:Vitamin D