Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1972 Dec;51(12):3072–3079. doi: 10.1172/JCI107134

Effect of Experimental Chronic Renal Insufficiency on Bone Mineral and Collagen Maturation

J E Russell 1,2, L V Avioli 1,2
PMCID: PMC332989  PMID: 4640950

Abstract

The effect of chronic renal disease on bone matrix and mineral maturation was evaluated in rats with experimental renal insufficiency of 2-11 wk duration utilizing bromoform-toluene gradient fractionation of bone powder, pulse labeling experiments with 45Ca and proline-3H differential extraction, and X-ray diffraction techniques.

Maturation defects in both collagen and mineral (45Ca) metabolism were documented as early as 2 wk after the induction of uremia, when total bone calcium, inorganic phosphate, and hydroxyproline content were unchanged. The maturational defect progressed with advancing uremia despite insignificant changes in plasma pH and calcium, and normal bone carbonate levels.

Although circulating levels of 25-hydroxycholecalciferol were significantly lower than normal in the uremic animals, pretreatment with either this vitamin D metabolite or vitamin D3 itself failed to alter the observed changes in skeletal maturation.

Full text

PDF
3072

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Avioli L. V., Birge S., Lee S. W., Slatopolsky E. The metabolic fate of vitamin D3-3H in chronic renal failure. J Clin Invest. 1968 Oct;47(10):2239–2252. doi: 10.1172/JCI105909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Avioli L. V., Scott S., Lee S. W., De Luca H. F. Intestinal calcium absorption: nature of defect in chronic renal disease. Science. 1969 Nov 28;166(3909):1154–1156. doi: 10.1126/science.166.3909.1154. [DOI] [PubMed] [Google Scholar]
  3. Black D. A. A perspective on uremic toxins. Arch Intern Med. 1970 Nov;126(5):906–909. [PubMed] [Google Scholar]
  4. Bornstein P. The cross-linking of collagen and elastin and its inhibition in osteolathyrism. Is there a relation to the aging process? Am J Med. 1970 Oct;49(4):429–435. doi: 10.1016/s0002-9343(70)80036-5. [DOI] [PubMed] [Google Scholar]
  5. CARTWRIGHT G. E., GUBLER C. J., WINTROBE M. M. Studies on copper metabolism. XI. Copper and iron metabolism in the nephrotic syndrome. J Clin Invest. 1954 Apr;33(4):685–698. doi: 10.1172/JCI102939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Canas F., Brnd J. S., Neuman W. F., Terepka A. R. Some effects of vitamin D 3 on collagen synthesis in rachitic chick cortical bone. Am J Physiol. 1969 May;216(5):1092–1096. doi: 10.1152/ajplegacy.1969.216.5.1092. [DOI] [PubMed] [Google Scholar]
  7. Deshmukh K., Nimni M. E. A defect in the intramolecular and intermolecular cross-linking of collagen caused by penicillamine. II. Functional groups involved in the interaction process. J Biol Chem. 1969 Apr 10;244(7):1787–1795. [PubMed] [Google Scholar]
  8. Duursma S. A., Visser W. J., Njio L. A quantitative histological study of bone in 30 patients with renal insufficiency. Calcif Tissue Res. 1972;9(3):216–225. doi: 10.1007/BF02061960. [DOI] [PubMed] [Google Scholar]
  9. Flanagan B., Nichols G., Jr Bone matrix turnover and balance in vitro. I. The effects of parathyroid hormone and thyrocalcitonin. J Clin Invest. 1969 Apr;48(4):595–606. doi: 10.1172/JCI106018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Garner A., Ball J. Quantitative observations on mineralised and unmineralised bone in chronic renal azotaemia and intestinal malabsorption syndrome. J Pathol Bacteriol. 1966 Apr;91(2):545–561. doi: 10.1002/path.1700910231. [DOI] [PubMed] [Google Scholar]
  11. Genuth S. M., Vertes V., Leonards J. R. Oral calcium absorption in patients with renal failure treated by chronic hemodialysis. Metabolism. 1969 Feb;18(2):124–131. doi: 10.1016/0026-0495(69)90106-1. [DOI] [PubMed] [Google Scholar]
  12. Gray R., Boyle I., DeLuca H. F. Vitamin D metabolism: the role of kidney tissue. Science. 1971 Jun 18;172(3989):1232–1234. doi: 10.1126/science.172.3989.1232. [DOI] [PubMed] [Google Scholar]
  13. Gulyassy P. F., Aviram A., Peters J. H. Evaluation of amino acid and protein requirements in chronic uremia. Arch Intern Med. 1970 Nov;126(5):855–859. [PubMed] [Google Scholar]
  14. HERMAN H., RICHELLE L. [Exchangeable calcium of the mineral substance of bone studied with the aid of Ca45. VII. Comparative activity of the fractions of total bone with different densities]. Bull Soc Chim Biol (Paris) 1961;43:273–282. [PubMed] [Google Scholar]
  15. Haddad J. G., Chyu K. J. Competitive protein-binding radioassay for 25-hydroxycholecalciferol. J Clin Endocrinol Metab. 1971 Dec;33(6):992–995. doi: 10.1210/jcem-33-6-992. [DOI] [PubMed] [Google Scholar]
  16. Hahn T. J., Avioli L. V. Effect of chronic uremia on collagen metabolism in skin and bone. Arch Intern Med. 1970 Nov;126(5):882–886. [PubMed] [Google Scholar]
  17. JACKSON D. S., BENTLEY J. P. On the significance of the extractable collagens. J Biophys Biochem Cytol. 1960 Feb;7:37–42. doi: 10.1083/jcb.7.1.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Katz E. P. The kinetics of mineralization in vitro. I. The nucleation properties of 640-angstrom collagen at 25 degrees. Biochim Biophys Acta. 1969 Nov 11;194(1):121–129. doi: 10.1016/0005-2795(69)90187-1. [DOI] [PubMed] [Google Scholar]
  19. Kaye M., Frueh A. J., Silverman M., Henderson J., Thibault T. A study of vertebral bone powder from patients with chronic renal failure. J Clin Invest. 1970 Mar;49(3):442–453. doi: 10.1172/JCI106253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kaye M., Silverman M. Calcium metabolism in chronic renal failure. J Lab Clin Med. 1965 Oct;66(4):535–548. [PubMed] [Google Scholar]
  21. Laitinen O. Parathyroid-induced changes in collagen and calcium metabolism in vivo. Endocrinology. 1967 May;80(5):815–824. doi: 10.1210/endo-80-5-815. [DOI] [PubMed] [Google Scholar]
  22. Lemann J., Jr, Litzow J. R., Lennon E. J. The effects of chronic acid loads in normal man: further evidence for the participation of bone mineral in the defense against chronic metabolic acidosis. J Clin Invest. 1966 Oct;45(10):1608–1614. doi: 10.1172/JCI105467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Miller E. J., Martin G. R., Mecca C. E., Piez K. A. The biosynthesis of elastin cross-links. The effect of copper deficiency and a lathyrogen. J Biol Chem. 1965 Sep;240(9):3623–3627. [PubMed] [Google Scholar]
  24. Mills B. G., Bavetta L. A. Bone collagen dynamics. Clin Orthop Relat Res. 1968 Mar-Apr;57:267–275. [PubMed] [Google Scholar]
  25. Nichols G., Jr, Flanagan B., van der Sluys Veer J., Johnson J. W., Hampers C. L., Merrill J. P. Metabolic studies of bone in uremia before and after treatment. Metabolism. 1972 Apr;21(4):317–328. doi: 10.1016/0026-0495(72)90076-5. [DOI] [PubMed] [Google Scholar]
  26. Nylen M. U., Eanes E. D., Termine J. D. Molecular and ultrastructural studies of non-crystalline calcium phosphates. Calcif Tissue Res. 1972;9(2):95–108. doi: 10.1007/BF02061948. [DOI] [PubMed] [Google Scholar]
  27. Oliver W. M., Leaver A. G., Scott P. G. The effects of deficiencies of calcium or of calcium and vitamin D on the rate of oral collagen synthesis in the rat. J Periodontal Res. 1972;7(1):29–34. doi: 10.1111/j.1600-0765.1972.tb00628.x. [DOI] [PubMed] [Google Scholar]
  28. PROCKOP D. J., UDENFRIEND S. A specific method for the analysis of hydroxyproline in tissues and urine. Anal Biochem. 1960 Nov;1:228–239. doi: 10.1016/0003-2697(60)90050-6. [DOI] [PubMed] [Google Scholar]
  29. Peck W. A., Dirksen T. R. The metabolism of bone tissue in vitro. Clin Orthop Relat Res. 1966 Sep-Oct;48:243–265. [PubMed] [Google Scholar]
  30. Pellegrino E. D., Biltz R. M. The composition of human bone in uremia. Observations on the reservoir functions of bone and demonstration of a labile fraction of bone carbonate. Medicine (Baltimore) 1965 Sep;44(5):397–418. doi: 10.1097/00005792-196509000-00002. [DOI] [PubMed] [Google Scholar]
  31. Potts J. T., Reita R. E., Deftos L. J., Kaye M. B., Richardson J. A., Buckle R. M., Aurbach G. D. Secondary hyperparathyroidism in chronic renal disease. Arch Intern Med. 1969 Oct;124(4):408–412. [PubMed] [Google Scholar]
  32. Rojkind M., Gutiérrez A. M. The binding of thiosemicarbazide to collagen in vro. Arch Biochem Biophys. 1969 Apr;131(1):116–122. doi: 10.1016/0003-9861(69)90111-8. [DOI] [PubMed] [Google Scholar]
  33. Siegel R. C., Martin G. R. Collagen cross-linking. Enzymatic synthesis of lysine-derived aldehydes and the production of cross-linked components. J Biol Chem. 1970 Apr 10;245(7):1653–1658. [PubMed] [Google Scholar]
  34. Stanbury S. W. Bone disease in uremia. Am J Med. 1968 May;44(5):714–724. doi: 10.1016/0002-9343(68)90253-2. [DOI] [PubMed] [Google Scholar]
  35. Stanbury S. W., Lumb G. A. Parathyroid function in chronic renal failure. A statistical survey of the plasma biochemistry in azotaemic renal osteodystrophy. Q J Med. 1966 Jan;35(137):1–23. [PubMed] [Google Scholar]
  36. Tanzer M. L., Monroe D., Gross J. Inhibition of collagen intermolecular cross-linking by thiosemicarbazide. Biochemistry. 1966 Jun;5(6):1919–1926. doi: 10.1021/bi00870a019. [DOI] [PubMed] [Google Scholar]
  37. Termine J. D., Peckauskas R. A., Posner A. S. Calcium phosphate formation in vitro. II. Effects of environment on amorphous-crystalline transformation. Arch Biochem Biophys. 1970 Oct;140(2):318–325. doi: 10.1016/0003-9861(70)90072-x. [DOI] [PubMed] [Google Scholar]
  38. Termine J. D., Posner A. S. Amorphous/crystalline interrelationships in bone mineral. Calcif Tissue Res. 1967;1(1):8–23. doi: 10.1007/BF02008070. [DOI] [PubMed] [Google Scholar]
  39. Uitto J., Laitinen O. Relation of collagen metabolism to calcium metabolism in the bone. Acta Chem Scand. 1968;22(3):1039–1040. doi: 10.3891/acta.chem.scand.22-1039. [DOI] [PubMed] [Google Scholar]
  40. WILLIS J. B. Determination of calcium in blood serum by atomic absorption spectroscopy. Nature. 1960 Apr 16;186:249–250. doi: 10.1038/186249a0. [DOI] [PubMed] [Google Scholar]
  41. Weber J. C., Pons V., Kodicek E. The localization of 1,25-dihydroxycholecalciferol in bone cell nuclei of rachitic chicks. Biochem J. 1971 Nov;125(1):147–153. doi: 10.1042/bj1250147. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES