Effect of 1 alpha-hydroxycholecalciferol on bone mass and composition of cortical bone in adult male rats.

High daily oral doses of 10 micrograms 1 alpha-hydroxycholecalciferol (1 alpha-OHD3) administered to adult rats produced toxic effects such as loss of body weight, hypercalcemia and bone resorption. However, small (0.09 microgram) and moderate (0.9 microgram) daily doses of 1 alpha-OHD3 did not produce toxic effects during six weeks of observation. Serum calcium level was only slightly raised, but bone mass, bone mineral and organic matter contents, including collagen and nucleic acids of the cortical bone matrix, significantly increased, while the amount of glycosaminoglycans was reduced. Treatment with small daily doses of 1 alpha-OHD3 (0.09 microgram/day for six weeks) produced a more pronounced effect on the variables studied than did the moderate dosage (0.9 microgram). 1 alpha-OHD3 promotes new bone formation in the mature rat skeleton after conversion to 1,25 dihydroxycholecalciferol [1,25(OH)2D3] in the liver, probably by exerting a direct effect on bone tissue rather than through indirect hormonal events.