Lindholm T S, Nilsson O S, Eriksson S
Isr J Med Sci. 1981 Jun;17(6):416-21.
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.
给成年大鼠每日口服高剂量10微克的1α-羟基胆钙化醇（1α-OHD3）会产生毒性作用，如体重减轻、高钙血症和骨吸收。然而，在为期六周的观察期内，每日小剂量（0.09微克）和中等剂量（0.9微克）的1α-OHD3并未产生毒性作用。血清钙水平仅略有升高，但骨量、骨矿物质和有机质含量，包括皮质骨基质中的胶原蛋白和核酸，均显著增加，而糖胺聚糖的量则减少。每日小剂量1α-OHD3（0.09微克/天，持续六周）治疗对所研究变量产生的影响比中等剂量（0.9微克）更为显著。1α-OHD3在肝脏中转化为1,25-二羟基胆钙化醇[1,25(OH)2D3]后，可能通过对骨组织施加直接作用而非通过间接激素作用促进成熟大鼠骨骼中的新骨形成。
