Calcified Tissue International

, Volume 38, Issue 2, pp 79–86

Stimulation of undermineralized matrix formation by 1,25 dihydroxyvitamin D3 in long bones of rats

  • J. M. Hock
  • M. Gunness-Hey
  • J. Poser
  • H. Olson
  • N. H. Bell
  • L. G. Raisz
Laboratory Investigations

DOI: 10.1007/BF02556834

Cite this article as:
Hock, J.M., Gunness-Hey, M., Poser, J. et al. Calcif Tissue Int (1986) 38: 79. doi:10.1007/BF02556834

Summary

We previously reported that pharmacologic doses of 1,25 dihydroxyvitamin D3 (1,25-(OH)2D3) given for 2–3 days, inhibited osteoblastic collagen synthesis in young rats. In this study, we tested the effects of 5, 25, and 125 ng of 1,25(OH)2D3 injected subcutaneously into 6-week-old rats for 12 or 18 days. In rats given 125 ng, cortical bone of distal half femurs exhibited decreased calcium (Ca) content but dry weight and hydroxyproline (Hyp) content were no different from control. Trabecular bone Ca was not different from control but dry weight and Hyp were increased. When cortical and trabecular bone were combined, there was a decrease in Ca, an increase in Hyp, and a 50% decrease in Ca:Hyp. Fluorescent labels given after 8 days of treatment were either diffuse or absent in calcified sections from rats given 125 ng, indicating impaired mineralization. The 25 and 125 ng doses produced hypercalcemia with normal serum phosphate. There was a dose-related increase in serum immunoreactive bone gla protein (BGP) and serum 1,25(OH)2D3 and a decrease in serum 25 (OH)D3. At the 5 ng dose, no adverse effects were seen on body growth. With 25 ng and 125 ng, growth was inhibited. Increased serum urea nitrogen and histologic evidence of nephrocalcinosis occurred at the 125 ng dose. When 125 ng was given for 12 days and then withdrawn for 6 days, systemic toxicity decreased and bone Hyp and Ca increased so that Ca:Hyp remained low and comparable to that of rats treated with 1,25(OH)2D3 continuously We conclude that pharmacologic doses of 1,25(OH)2D3 stimulate trabecular bone matrix formation but produce impairment of mineralization, despite a high Ca×Pi product.

Key words

Bone formation Mineralization Rat long bones 1,25 dihydroxyvitamin D3 

Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • J. M. Hock
    • 1
  • M. Gunness-Hey
    • 1
  • J. Poser
    • 2
  • H. Olson
    • 2
  • N. H. Bell
    • 3
  • L. G. Raisz
    • 1
  1. 1.Dept. Restorative Dentistry School of Dental MedicineUniversity of ConnecticutFarmington
  2. 2.Dept. Restorative Dentistry, School of Dental MedicineProcter and Gamble CompanyCincinnati
  3. 3.Dept. Restorative Dentistry, School of Dental MedicineVeterans Administration Medical CenterCharleston

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