Skip to main content
SpringerLink
Log in

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

  • Laboratory Investigations
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

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 When 125 ng was given for 12 days and then withdrawn for 6 days, systemic toxicity decreased and bone Hyp and Ca increased so that Ca:Hyp remained low and comparable to that of rats treated with 1,25(OH)2D3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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Larsson SE, Lorentzon R, Boquist L (1977) Low doses of 1,25-dihydroxycholecalciferol increase mature bone mass in adult normal rats. Clin Orthop Rel Res 127:228–235

    CAS  Google Scholar 

  2. Lindholm TS, Nilsson OS, Lindholm TC (1981) Effect of 1-alpha-hydroxyvitamin D3 on cancellous bone matrix. An experimental study in rats. Acta Orthop Scand 52:497–503

    Article  CAS  PubMed  Google Scholar 

  3. Boyce RW, Weisbrode SE (1983) Effect of dietary calcium on the bone response to 1,25(OH)2D3. Lab Invest 48:683–689

    CAS  PubMed  Google Scholar 

  4. Narbaitz R, Fragiskos W (1984) Hypervitaminosis D in chick embryo: comparative study on the activity of various vitamin D3 metabolites. Calcif Tissue Int 36:392–400

    Article  CAS  PubMed  Google Scholar 

  5. Schmid RN, Reilly CN (1957) New complexon for titration of calcium in the presence of magnesium. Anal Chem 29:264–258

    Article  CAS  Google Scholar 

  6. Chen PS, Toribara TY, Warner H (1956) Microdetermination of phosphorus. Anal Chem 28:1756–1759

    Article  CAS  Google Scholar 

  7. Price PA, Nishimoto SK (1980) Radioimmunoassay for the vitamin K-dependent protein of bone and its discovery in plasma. Proc Natl Acad Sci 77:2234–2235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Belseyre RE, DeLuca HF, Potts JR (1974) A rapid assay for 25OH-D3 without preparative chromatography. J Clin Endocrinol Metab 38:1046–1051

    Article  Google Scholar 

  9. Reinhardt TA, Horst RL, Orf JW, Hollis BW (1984) A microassay for 1,25 dihydroxyvitamin D3 not requiring high performance liquid chromatography: application to clinical studies. J Clin Endocrinol Metab 58:91–98

    Article  CAS  PubMed  Google Scholar 

  10. Gunness-Hey M, Hock JM (1984) Increased trabecular bone mass in rats treated with human synthetic parathyroid hormone. Metab Bone Dis Rel Res

  11. Cheng PM (1969) An improved method for the determination of hydroxyproline in rat skin. J Invest Dermatol 53:112–115

    Article  CAS  PubMed  Google Scholar 

  12. Snedecor GW, Cochran WC (1967) Statistical Methods. Iowa State U. Press, Ames, Ia

    Google Scholar 

  13. Jonckheere A (1954) A distribution-free k-sample test against ordered alternatives. Biometrika 41:133–143

    Article  Google Scholar 

  14. Lindholm TS, Sevastikoglou JA, Lindgren U (1978) Interim report on treatment of osteoporotic patients with I-alpha(OH)D3 and calcium. Clin Orthop 135:232–240

    Google Scholar 

  15. Gallagher JC (1982) 1,25-dihydroxyvitamin D3 short- and long-term effects on bone and calcium metabolism in patients with postmenopausal osteoporosis. Proc Natl Acad Sci 79:3325–3329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Ham AW, Lewis MD (1934) Hypervitaminosis D Rickets, the action of vitamin D. Br J Exp Pathol 15:228–234

    CAS  PubMed Central  Google Scholar 

  17. Harris LJ, Innes JRM (1931) The mode of action of vitamin D. Studies on hypervitaminosis D. The influence of the calcium-phosphate intake. Biochem J 25:367–390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Hass GM, Trueheart RE, Taylor CB, Stumpe M (1958) An experimental histologic study of hypervitaminosis D. Am J Pathol 34:395–431

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Storey E (1960) Osteosclerosis after intermittent administration of large doses of vitamin D in the rat. J Bone Joint Surg (Br) 42:606–625

    Google Scholar 

  20. Giaconelli F, Spiro D, Weiner J (1964) A study of metatastic renal calcification at the cellular level. J Cell Biol 22:189–206

    Article  Google Scholar 

  21. Norrdin RW, de Barros CSL, Queille ML, Carre M, Miravet L (1979) Acute effects of Solanum Malacoxylon on bone formation rates in growing rats. Calcif Tissue Int 28:239–243

    Article  CAS  PubMed  Google Scholar 

  22. Raisz LG, Kream BE, Smith MD, Simmons HA (1980) Comparison of the effects of the vitamin D metabolites on collagen synthesis and resorption of fetal rat bone in organ culture. Calcif Tissue Int 32:135–138

    Article  CAS  PubMed  Google Scholar 

  23. Hock JM, Kream BE, Raisz LG (1982) Autoradiographic study on the effects of 1,25-dihydroxyvitamin D3 on bone collagen matrix synthesis in vitamin D replete rats. Calcif Tissue Int 34:347–351

    Article  CAS  PubMed  Google Scholar 

  24. Dos Santos MN (1976) Solanum malacoxylon toxicity: inhibition of bone resorption. Cornell Vet 66:565–588

    Google Scholar 

  25. Rasmussen P (1969) The action of vitamin D deficiency on bone tissue and the epiphyseal plate in rats given adequate amounts of calcium and phosphorus in the diet. Arch Oral Biol 14:1293–1304

    Article  CAS  PubMed  Google Scholar 

  26. Harrard RB, Green RM, Hartles RL (1966) A study in the rat of the interaction between the effects of calcium and phosphorus content of the diet at two different levels and the presence or absence of vitamin D. Br J Nutr, 20:55–60

    Article  Google Scholar 

  27. Holtrop ME, Cox KA, Clark MB, Holick MF, Anast CS (1981) 1,25-dihydroxycholecalciferol stimulates osteoclasts in rat bones in the absence of parathyroid hormone. Endocrinology 108:2293–2301

    Article  CAS  PubMed  Google Scholar 

  28. Underwood JL, DeLuca HF (1984) Vitamin D is not directly necessary for bone growth and mineralisation. Am J Physiol 246:E493–498

    CAS  PubMed  Google Scholar 

  29. Weinstein RS, Underwood JL, Hutson MS, DeLuca HF (1984) Bone histomorphometry in vitamin D-deficient rats infused with calcium and phosphorus. Am J Physiol 246:E499–505

    CAS  PubMed  Google Scholar 

  30. Follis RH (1955) Studies on hypervitaminosis D. Am J Pathol 31:568 (Abstract)

    Google Scholar 

  31. Bordier P, Rasmussen H, Marie P, Miravet L, Gueris J, Ryckwaert A (1978) Vitamin D metabolites and bone mineralisation in man. J Clin Endocrinol Metab 46:284–294

    Article  CAS  PubMed  Google Scholar 

  32. Goodman WG, Baylink DJ, Sherrard DJ (1984) 24,25(OH)2D3, bone formation and bone resorption in vitamin D-deficient azotemic rats. Calcif Tissue Int 36:206–213

    Article  CAS  PubMed  Google Scholar 

  33. Miravet L, Redel J, Carre M, Queille ML, Bordier P (1976) The biological activity of synthetic 25,26 dihydroxychole calciferol and 24,25 dihydroxycholecalciferol in vitamin D-deficient rats. Calcif Tissue Int 21:145–152

    Article  CAS  Google Scholar 

  34. Kanis JA, Cundy T, Bartlett M, Smith R, Heynen G, Warner GT, Russell RGG (1978) Is 24,25 dihydroxycholecalciferol a calcium-regulating hormone in man. Br Med J 1 (6124):1382–1386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Gallagher JA, Beneton M Harvey L, Lawson DEM (1983) Response of rachitic rat bones to 1,25(OH)2D3: biphasic effect on mineralisation and lack of effect on bone resorption. Calcif Tissue Int (Suppl 2) 36:S64 (Abstract)

    Google Scholar 

  36. Canterbury J (1978) Inhibition of parathyroid secretion by 25-hydroxycalciferol and 24,25-dihydroxycalciferol in dogs. J Clin Invest 61:1375–1383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Weinstein RS (1982) Decreased mineralisation in hemodialysis patients after subtotal parathyroidectomy. Calcif Tissue Int 34:16–20

    Article  CAS  PubMed  Google Scholar 

  38. Felsenfeld AJ (1982) Osteomalacia after parathyroidectomy in patients with uremia. Ann Int Med 96:34–39

    Article  CAS  PubMed  Google Scholar 

  39. Price PA, Williamson MK, Lothringer JW (1981) Origin of the vitamin K-dependent protein found in plasma and its clearance by kidney and bone. J Biol Chem 256:12760–12766

    CAS  PubMed  Google Scholar 

  40. Price PA, Baukol SA (1980) 1,25 dihydroxyvitamin D3 increases synthesis of the vitamin K-dependent bone protein by osteosarcome cells. J Biol Chem 255:11660–11663

    CAS  PubMed  Google Scholar 

  41. Price PA, Baukol SA (1981) 1,25 dihydroxyvitamin D3 increases serum levels of the vitamin K-dependent bone protein. Biochem Biophys Res Comm 99:928–935

    Article  CAS  PubMed  Google Scholar 

  42. Price P (1984) The effect of 1,25 dihydroxyvitamin D3 on the synthesis of the vitamin K-dependent protein of bone. In: Kumar R (ed) Vitamin D. Basic and Clinical Aspects. M Nijhoft, Boston, pp. 397–410

    Google Scholar 

  43. Poser JW, Price PA (1979) A method for decarboxylation of gamma-carboxyglutamic acid in proteins. J Biol Chem 254:431–436

    CAS  PubMed  Google Scholar 

  44. Price PA (1982) Excessive mineralization with growth plate closure in rats on chronic Warfarin treatment. Proc Natl Acad Sci 79:7734–7738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Price PA, Sloper SA (1983) Concurrent Warfarin treatment further reduces bone mineral levels in 1,25-dihydroxyvitamin D3-treated rats. J Biol Chem 258:6004–6007

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dept. Restorative Dentistry School of Dental Medicine, University of Connecticut, 06032, Farmington, St.

    J. M. Hock, M. Gunness-Hey & L. G. Raisz

  2. Dept. Restorative Dentistry, School of Dental Medicine, Procter and Gamble Company, Cincinnati, Ohio

    J. Poser & H. Olson

  3. Dept. Restorative Dentistry, School of Dental Medicine, Veterans Administration Medical Center, Charleston, South Carolina

    N. H. Bell

Authors
  1. J. M. Hock
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Gunness-Hey
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Poser
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Olson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N. H. Bell
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. L. G. Raisz
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hock, J.M., Gunness-Hey, M., Poser, J. et al. Stimulation of undermineralized matrix formation by 1,25 dihydroxyvitamin D3 in long bones of rats. Calcif Tissue Int 38, 79–86 (1986). https://doi.org/10.1007/BF02556834

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02556834

Key words

Search

Navigation