Chronic administration of 1,25-dihydroxyvitamin D3: increased bone but impaired mineralization.
Male Sprague-Dawley rats were infused continuously for 13 days with vehicle or 75 pmol (31.2 ng)/day 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] by means of Alzet osmotic minipumps implanted s.c. Animals infused with 1,25-(OH)2D3 exhibited mild hypercalcemia (11.2 vs. 10.2 mg/dl in controls), a 136% increase in the serum concentration of 1,25-(OH)2D3 (187 vs. 79 pg/ml), and a 59% decrease in serum 25-hydroxyvitamin D (12 vs. 29 ng/ml). The proximal tibial metaphysis of these animals was characterized by increased trabecular bone volume (15% vs. 6.5%), osteoid accumulation (4.2% vs. 0.1%), increased osteoblast surface and number (31% and 19/mm vs. 21% and 14/mm, respectively), and decreased osteoclast surface and number (11% and 2/mm vs. 36% and 6/mm, respectively). Similar but less striking changes were seen in the lumbar vertebra. Increases in the fat-free weight and calcium content of the tibia and lumbar vertebra were consistent with the increase in trabecular bone volume after 1,25-(OH)2D3 infusion. However, tetracycline labeling and the incorporation of 45Ca in these bones were reduced by 1,25-(OH)2D3 infusion. In addition, mineralization lag time was prolonged in the lumbar vertebrae of 1,25-(OH)2D3-infused rats. Our findings indicate that chronic 1,25-(OH)2D3 administration increases bone mass, but at the cost of impaired bone mineralization.
D000818:Animals; D002113:Calcification, Physiologic / Q000187:drug effects; D002117:Calcitriol / Q000008:administration & dosage*; D002118:Calcium / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D010012:Osteogenesis / Q000187:drug effects*; D011392:Proline / Q000378:metabolism; D051381:Rats
D003094:Collagen; D011392:Proline; D002117:Calcitriol; D002118:Calcium