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In Vivo Studies in Chicks and Rats of Bone Calcium Mobilization by 1,25-Dihydroxycholecalciferol (Calcitriol) and its Congeners

Department of Cell Biology, Roche Research Center, Nutley, New Jersey 07110

Calcitriol, 1 µg/chick, given subcutaneously (sc), did not cause elevation of serum radioactivity 1 to 10 hours after dosing in normal chicks pre-labeled with ⁴⁵Ca. Doses up to 40 µg/chick, sc were ineffective at 5 hours. In contrast, parathyroid hormone (PTH), 100 units/chick, sc elevated serum ⁴⁵Ca at 1, 2 and 4 hours after injection. Vitamin D-deficient chicks given 1 µg/chick, sc of calcitriol showed significant stimulation of intestinal ⁴⁵Ca absorption at 4, 6, 24 and 30 hours, but the same dose did not cause movement of ⁴⁵Ca from bone to serum at the same time intervals in pre-labeled, vitamin D-deficient chicks. In normal, pre-labeled rats, calcitriol at oral doses up to 3 µg/rat was ineffective in mobilizing bone ⁴⁵Ca 18 hours after dosing. Cholecalciferol and six of its congeners elevated serum calcium in vitamin D-deficient rats in a linear log dose dependent manner irrespective of the availability of dietary calcium. Doses required to elevate serum calcium in the absence of dietary calcium were considerably higher than those needed in its presence. These data suggest that calcitriol and related compounds lack significant in vivo bone libility relative to their effects on intestinal calcium absorption, and that the elevation of serum calcium in vitamin D-deficient animals fed a calcium deficient diet and given vitamin D compounds may be due to the restoration of bone responsiveness to PTH, rather than direct compound promotion of bone resorption.

KEY WORDS: • calcitriol • vitamin D • vitamin D metabolites • vitamin D analogs • bone calcium mobilization • 1,25-dihydroxycholecalciferol

Manuscript received 21 March 1979.