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.
Bone Vitamin D Acidosis Phosphate
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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, 1977PubMedGoogle Scholar
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, 1932CrossRefGoogle Scholar
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, 1975PubMedGoogle Scholar
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, 1966PubMedGoogle Scholar
Richards, P., Chamberlain, M.J., Wrong, O.M.: Treatment of osteomalacia of renal tubular acidosis by sodium bicarbonate alone, Lancet2:994, 1972PubMedCrossRefGoogle Scholar
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, 1970Google Scholar
Bettice, J.A., Gamble, J.L., Jr.: Skeletal buffering of acute metabolic acidosis, Am. J. Physiol.229:1618, 1975PubMedGoogle Scholar
Beck, N., Webster, S.K.: Effects of acute metabolic acidosis on parathyroid hormone action and calcium mobilization, Am. J. Physiol.230:127, 1976PubMedGoogle Scholar
Bruin, W.J., Baylink, D.J., Wergedal, J.E.: Acute inhibition of mineralization and stimulation of bone resorption mediated by hypophosphatemia, Endocrinology96:394, 1975PubMedGoogle Scholar
Russell, J.E., Avioli, L.V.: Effect of experimental chronic renal insufficiency on bone mineral and collagen maturation, J. Clin. Invest.51:3072, 1972PubMedGoogle Scholar
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, 1977PubMedGoogle Scholar
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, 1967Google Scholar
Steele, T.H., DeLuca, H.F.: Influence of dietary phosphorus on renal phosphate reabsorption in the parathyroidectomized rat, J. Clin. Invest.57:867, 1976PubMedGoogle Scholar
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, 1976PubMedGoogle Scholar
Steele, T.H.: Renal resistance to parathyroid hormone during phosphorus deprivation, J. Clin. Invest.58:1461, 1976PubMedGoogle Scholar
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, 1970PubMedGoogle Scholar
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, 1972PubMedCrossRefGoogle Scholar
Termine, J.D., Posner, A.S.: Amorphous crystalline interrelationships in bone mineral, Calcif. Tissue Res.1:8, 1967PubMedCrossRefGoogle Scholar
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, 1978PubMedCrossRefGoogle Scholar
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, 1976PubMedCrossRefGoogle Scholar
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, 1975PubMedGoogle Scholar
Welbourne, T.C.: Acidosis activation of the pituitary-adrenal-renal glutaminase I axis, Endocrinology99:1071, 1976PubMedGoogle Scholar