Summary
Vitamin D and phosphate deficiency were produced in rats in order (a) to evaluate the degree of bone mineral and matrix maturation using a bromoform/toluene density gradient technique; and (b) to compare the aforementioned bone maturational changes due to vitamin D and phosphate deprivation to those produced with superimposed severe acidosis. Rats were fed a diet deficient in vitamin D and phosphorus (0.2%) from 3 weeks through 7 weeks of age. To examine the additional contribution of dietary calcium, we gave one-half of the animals either a low (0.06%) or high (1.3%) calcium diet. Following the 4 weeks of vitamin D deficiency, one-half of each group was given 1.8% NH4Cl in the drinking water for 4 succeeding days to induce an acute, severe acidosis. The degree of bone maturation was quantitated via bromoformtoulene density gradient fractionation; total mineral and hydroxyproline (collagen) levels were quantitated as well.
The vitamin D-deficient rats deprived of adequate dietary phosphate responded by conserving phosphorus, and as a consequence total bone phosphorus levels were maintained within that level for control rats. This conservation was independent of calcium intake but was extremely sensitive to acute acid loading, where a significant reduction in total bone phosphorus was noted.
The bone maturational profile obtained from the vitamin D-phosphate deficient rats, however, revealed a significant accumulation of less mature or dense bone collagen and mineral with a corresponding decrease in the most mature or dense moieties. In contrast to the reduction of the total bone phosphorus content by acute acidosis, the skeletal collagen-mineral maturational profile was not significantly affected by the short-term systemic acidosis.
The observed retardations in the bone collagen and mineral maturation of the vitamin D-deficient, phosphate-deprived state provide an additional observation which may well relate to the progressive osteopenia documented in states of chronic, mild acidosis.
Similar content being viewed by others
References
Lee, S.W., Russell, J.E., Avioli, L.V.: 25-Hydroxycholecalciferol: conversion impaired by systemic metabolic acidosis, Science195:994, 1977
Emmett, M., Goldfarb, S., Agus, S.S., Narins, R.G.: The pathophysiology of acid-base changes in chronically phosphate-depleted rats, J. Clin. Invest.59:291, 1977
Jaffee, H.L., Bodansky, A., Chandler, J.P.: Ammonium chloride decalcification, as modified by calcium intake: the relation between generalized osteoporosis and ositis fibrosa, J. Exp. Med.56:823, 1932
Barzel, U.S.: Studies in osteoporosis: the long-term effect of oophorectomy and of ammonium chloride ingestion on the bone of mature rats, Endocrinology96:1304, 1975
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.45:1608, 1966
Richards, P., Chamberlain, M.J., Wrong, O.M.: Treatment of osteomalacia of renal tubular acidosis by sodium bicarbonate alone, Lancet2:994, 1972
Nguygen, V.V., Jowsey, J.: Bone metabolism. The acute effects of hormones, vitamin D, and acidosis during in vivo perfusion of adult dog forelimbs, J. Bone Joint Surg.52:1041, 1970
Bettice, J.A., Gamble, J.L., Jr.: Skeletal buffering of acute metabolic acidosis, Am. J. Physiol.229:1618, 1975
Beck, N., Webster, S.K.: Effects of acute metabolic acidosis on parathyroid hormone action and calcium mobilization, Am. J. Physiol.230:127, 1976
Bruin, W.J., Baylink, D.J., Wergedal, J.E.: Acute inhibition of mineralization and stimulation of bone resorption mediated by hypophosphatemia, Endocrinology96:394, 1975
Russell, J.E., Avioli, L.V.: Effect of experimental chronic renal insufficiency on bone mineral and collagen maturation, J. Clin. Invest.51:3072, 1972
Letteri, J.M., Biltz, R.M., Ellis, K.J., Martino, A., Yasumura, S., Brook, D., Cohn, S.H., Pellegrino, E.D.: Arrested bone growth and mineral maturation in sub-totally nephrectomized rats, Clin. Sci. Mol. Med.53:479, 1977
Quinaux, N., Richelle, L.O.: X-ray diffraction and infrared analysis of bone specific gravity fraction in the growing rat, Isr. J. Med. Sci.3:677, 1967
Steele, T.H., DeLuca, H.F.: Influence of dietary phosphorus on renal phosphate reabsorption in the parathyroidectomized rat, J. Clin. Invest.57:867, 1976
Trohler, U., Bonjour, J.P., Fleisch, H.: Inorganic phosphate homeostasis. Renal adaption to the dietary intake in intact and thyroparathyroidectomized rats, J. Clin. Invest.57:264, 1976
Steele, T.H.: Renal resistance to parathyroid hormone during phosphorus deprivation, J. Clin. Invest.58:1461, 1976
Barzel, U.S.: Parathyroid hormone, blood phosphorus, and acid-base metabolism, Lancet1:1329, 1971
Baylink, D.J., Stauffer, M., Wergedal, J., Rich, C.: Formation, mineralization and resorption of bone in vitamin D-deficient rats, J. Clin. Invest.49:1122, 1970
Mechanic, G.L., Toverud, S.U., Ramp, W.K., Gonnerman, W.A.: Quantitative changes of bone collagen crosslinks and precursors in vitamin D deficiency, Biochem. Biophys. Res. Commun.47:760, 1972
Termine, J.D., Posner, A.S.: Amorphous crystalline interrelationships in bone mineral, Calcif. Tissue Res.1:8, 1967
McSherry, E., Morris, R.C., Jr.: Attainment and maintenance of normal stature with alkali therapy in infants and children with classical renal tubular acidosis, J. Clin. Invest.61:509, 1978
Mautalen, C., Montoreano, R., Labarrere, C.: Early skeletal effect of alkali therapy upon the osteomalacia of renal tubular acidosis, J. Clin. Endocrinol. Metab.42:875, 1976
Russell, J.E., Termine, J.D., Avioli, L.V.: Experimental renal osteodystrophy: the response to 25-hydroxycholecalciferol and dichloromethylene diphosphonate therapy, J. Clin. Invest.56:548, 1975
Welbourne, T.C.: Acidosis activation of the pituitary-adrenal-renal glutaminase I axis, Endocrinology99:1071, 1976
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Russell, J.E., Avioli, L.V. Bone maturation in the vitamin D, phosphate deficient rat and the response to acid loading. Calcif Tissue Int 27, 233–237 (1979). https://doi.org/10.1007/BF02441191
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02441191