Vitamin D comprises a number of structurally related sterol compounds having similar biological properties in that they prevent or cure the vitamin D deficiency diseases, rickets and osteomalacia. The important forms are:
• D2 or ergocalciferol (calciferol) made by ultraviolet irradiation of ergosterol
• D3 or colecalciferol made by ultraviolet irradiation of 7-dehydrocholesterol; it is the form that occurs in natural foods and is formed in the skin.
Vitamins D2 and D3 are made more active by two hydroxylation reactions: (a) 25-hydroxylation in the liver, and (b) la-hydroxylation in the kidney (under the control of parathormone) to form, la-25-dihydroxycholecalciferol; this, the most active natural form of vitamin D, is available as calcitriol. In renal disease this final rate-limited renal a-hydroxylation is inadequate, and administration of the less biologically active precursors is therefore liable to lack efficacy.
Subsequently there was introduced a la-hydroxylated form (la-hydroxycholecalciferol) alfacalcidol (One-Alpha), that requires only hepatic hydroxylation to become the highly active la-25-dihydroxycholecalciferol (calcitriol). Alfacalcidol (and of course calcitriol) is therefore effective in renal failure since the defective renal hydroxylation stage is bypassed. Its extraordinary potency and efficacy is indicated by the usual adult maintenance dose, often only 0.25-1 micrograms/d.
In addition there is a structural variant of vitamins D2 and D3 dihydrotachysterol (ATIO, Tachyrol), which is also biologically activated by hepatic 25-hydroxylation.
Advantages of alfacalcidol and dihydrotachysterol include a fast onset and short duration of clinical effect (days) which renders them suitable for rapid adjustment of plasma calcium, e.g. in hypoparathyroidism. Such factors are not relevant to the slower adjustment of plasma calcium (weeks) with vitamins D2 and D3 in the ordinary management of vitamin D deficiency.
Actions are complex. Vitamin D promotes the active transport (absorption) of calcium and therefore of phosphate from the gut, to control, with parathormone, the mineralisation of bone and to
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