Chronic Administration of 1,25-Dihydroxyvitamin D3: Increased Bone but Impaired Mineralization

TJ Wronski, BP Halloran, DD Bikle, RK Globus… - …, 1986 - academic.oup.com
TJ Wronski, BP Halloran, DD Bikle, RK Globus, ER Morey-Holton
Endocrinology, 1986academic.oup.com
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 sc 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 …
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. (Endocrinology119: 2580-2585, 1986)
Oxford University Press