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Journal of Nutrition Vol. 108 No. 12 December 1978, pp. 1899-1906
Copyright © 1978 by American Society for Nutrition
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Evidence for the Promotion of Bone Mineralization by 1{alpha},25-Dihydroxycholecalciferol in the Rat Unrelated to the Correction of Deficiencies in Serum Calcium and Phosphorus

Alfred Boris, James F. Hurley, Thelma Trmal, John P. Mallon and Diana S. Matuszewski

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

Concurrent administration of 1{alpha},25-dihydroxycholecalciferol [1{alpha},25-(OH)2-CC] to intact and thyroparathyroidectomized rats treated with ethane-1-hydroxy-1,1-diphosphonate (EHDP) prevented or reversed the EHDP-induced inhibition of bone mineralization as measured by changes in epiphyseal plate width and ash content of bone. An analog, 1{alpha}-hydroxycholecalciferol, was also effective. Recovery of bone after EHDP treatment was also significantly improved by administration of 1{alpha},25-(OH)2-CC as evidenced by enhanced uptake of 45Ca by epiphyseal plates and decreased plate widths. Cholecalciferol (CC), ergocalciferol, dihydrotachysterol2, 5,6-trans-CC, 25-OH-CC, 5,6-trans-25-OH-CC, and 1{alpha},24R,25-(OH)3-CC also blocked EHDP-induced epiphyseal plate widening, but required high, pharmacological dose levels. 24R,25-(OH)2-CC was inactive at doses up to 10 µg/day. Since EHDP-treated rats are not deficient in calcium or phosphate, these data suggest that 1{alpha},25-dihydroxycholecalciferol promoted bone mineralization independently of effects upon the intestinal absorption of calcium and phosphate.

KEY WORDS: • bone mineralization • 1{alpha},25-dihydroxycholecalciferol • ethane hydroxy diphosphonate • vitamin D metabolites • vitamin D analogs

Manuscript received 15 February 1978.




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