The antirachitic effectiveness of la-hydroxyvitamin D3 (lα-OH-D3) was investigated by raising chicks on a vitamin D-deficient diet and chronically administering various levels of this synthetic sterol. Vitamin D3 (D3) and la, 25-dihydroxyvitamin D3 (lα, 25-(OH)2-D3) were concurrently tested as dietary supplements in order to compare the potency of these three sterols. Growth, plasma calcium and phosphorus concentration, percentage bone ash, calcium absorption, and radiographic appearance of bone were determined after treatment of the chicks with the sterols for 3 weeks. lα-OH-D3 was 5.1, 3.4 and 3.7 times more potent than D3 in stimulating weight gain, maintenance of plasma calcium and promotion of increased percent bone ash, respectively. Radiographic examination of tibiae and femurs from the various groups revealed that lα-OH-D3 effectively mediates normal bone calcification; lα-OH-D3 was 2-6 times more potent than D3 in this regard. The synthetic lα-OH-D3 was slightly more active than la, 25-(OH)2-D3 in most of the parameters tested, but appeared similar to la, 25-(OH)2-D3 in terms of preventing radiologic evidence of rickets. lα-OH-D3 was an efficient mediator of intestinal calcium absorption and exhibited a more sustained action than lα, 25-(OH)2-D3. Curative levels of all three sterols produced comparable suppression of renal 25-hydroxyvitamin D3-lα-hydroxylase, an enzyme which has been previously shown to be regulated by vitamin D and calcium status. In conclusion, these data establish that lα-OH-D3 is a potent analog of D3 which is capable of mimicking the natural hormone lα, 25-(OH)2-D3. The finding that lα-OH-D3 produces normal bone development at extremely low concentrations suggests that this analog may be a useful therapeutic agent in endocrine-related metabolic bone diseases.
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