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Chronic administration of 1,25-dihydroxyvitamin D3: increased bone but impaired mineralization.

Abstract
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.
AuthorsT J Wronski, B P Halloran, D D Bikle, R K Globus, E R Morey-Holton
JournalEndocrinology (Endocrinology) Vol. 119 Issue 6 Pg. 2580-5 (Dec 1986) ISSN: 0013-7227 [Print] United States
PMID3780540 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Collagen
  • Proline
  • Calcitriol
  • Calcium
Topics
  • Animals
  • Calcification, Physiologic (drug effects)
  • Calcitriol (administration & dosage)
  • Calcium (metabolism)
  • Collagen (metabolism)
  • Dose-Response Relationship, Drug
  • Male
  • Osteogenesis (drug effects)
  • Proline (metabolism)
  • Rats

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