Biological activity of 1α hydroxycholecalciferol, a synthetic analog of the hormonal form of vitamin D₃

1,25 Dihydroxycholecalciferol, the apparent active hormonal form of cholecalciferol (vitamin D₃), is formed from cholecalciferol by specific and sequential hydroxylations of the sterol at carbons 25 and 1. Recently, 1α hydroxycholecalciferol was synthesized and the authors report on its biological activity in rachitic chicks. 1α Hydroxycholecalciferol is identical in potency to 1,25 dihydroxycholecalciferol in stimulation of intestinal calcium absorption; either sterol elicits a near maximal effect at a dose of 0.3 to 0.6 nmol. The time course of action of 1α hydroxycholecalciferol also parallels that of the active metabolite 1,25 dihydroxycholecalciferol with a maximal increase in calcium transport occurring 5 to 10 hr after administration of sterol to vitamin D deficient chicks. 6.5 nmol of 1α hydroxycholecalciferol causes a doubling in calcium absorption in only 2 to 3 hr, which is the most rapid physiologic response yet detected for a vitamin D sterol. 1α Hydroxycholecalciferol is active also in enhancing bone calcium resorption and, like 1,25 dihydroxycholecalciferol, is at least 10 times as active as cholecalciferol in mobilizing bone calcium and raising plasma calcium concentration. It is concluded that 1α hydroxycholecalciferol represents a synthetic analog of 1,25 dihydroxycholecalciferol that can be used both to study the mechanism of action of this hormone and as a therapeutic agent in the treatment of patients with certain metabolic bone diseases.