Summary
The effects of two different glucocorticoids, prednisone and deflazacort, (an oxazoline derivative of prednisolone) on bone metabolism were analyzed in 10 patients with disorders that required glucocorticoid therapy. Significant elevations in blood immunoreactive parathyroid hormone, alkaline phosphatase and urinary calcium, phosphate, hydroxyproline and nephrogenous cyclic AMP were observed during prednisone therapy in addition to an increase in the exchangeable calcium pool as estimated by47Ca-kinetic analyses. In contrast to these changes, deflazacort therapy induced minimal, and in some instances, no changes in these indices. In fact, in studies wherein prednisone therapy was followed by deflazacort alterations in bone metabolism, iPTH, and nephrogenous cAMP observed during prednisone were reversed. The data are consistent with the fact that the skeletal effects of prednisone therapy are mediated, at least in part, by increased parathyroid hormone activity, and that deflazacort is less potent in this regard.
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Raisz LG, Trummel CL, Wener JA, Simmons H (1972) Effect of glucocorticoids on bone resorption in tissue culture. Endocrinology 90:961–967
Peck WA, Brandt J, Miller I (1967) Hydrocortisone-induced inhibition of protein synthesis and uridine incorporation in isolated bone cells. Proc Nat Acad Sci 57:1599–1606
Chen TL, Aronow L, Feldman D (1977) Glucocorticoid receptors and inhibition of bone cell growth in primary culture. Endocrinology 100:619–628
Choe J, Stern P, Feldman D (1978) Receptor-mediated glucocorticoid inhibition of protein synthesis in isolate bone cells. J Steroid Biochem 9:265–271
Chen TL, Feldman D (1979) Glucocorticoid receptors and actions in subpopulation of cultures rat bone cells. Mechanism of dexamethasone potentiation of parathyroid hormone-stimulated cyclic AMP production. J Clin Invest 63:750–758
Wajchenberg BL, Pereira VG, Kieffer J, Ursic S (1969) Effect of dexamethasone on calcium metabolism and47Ca kinetics in normal subjects. Acta Endocrinol. 61:173–192
Caniggia A, Gennari C (1971) Etudes des effets des corticoides sur le metabolisme calcique. Actualites Endocr, “La Pitie 1971”:281–289
Kimberg DV, Baerg RD, Gershon E, Graudusius RT (1971) Effect of cortisone treatment on the active transport of calcium by the small intestine. J Clin Invest 50:1309–1321
Gallagher JC, Aaron J, Horsman A, Wilkinson R, Nordin, BEC: Corticosteroid osteoporosis. Clinics Endocrinol Metab 2:355–368
Williams GA, Peterson WC, Bowser EN, Henderson WJ, Hargis GK, Martinez, NJ (1974) Interrelationships of parathyroid and adrenocortical function in calcium homeostasis in the rat. Endocrinology 95:707–712
Luckert BP, Adams JS (1976) Vitamin D metabolism in man. Effect of corticosteroids. Arch Intern Med 136:1241–1248
Klein RG, Arnaud SB, Gallagher JC, DeLuca HF, Riggs BL (1977) Intestinal calcium absorption in exogenous hypercortisolism: role of 25-hydroxyvitamin D and corticosteroid dose. J Clin Invest 60:253–259
Hahn TJ, Halstead LR, Teitelbaum SL, Hahn BH (1979) Altered mineral metabolism in glucocorticoid-induced osteopenia: effect of 25-hydroxyvitamin D administration. J Clin Invest 64:655–665.
Frost HM, Villanueva AR (1961) Human osteoblastic activity III. The effect of cortisone on lamellar osteoblastic activity. Henry Ford Hosp Med Bull 9:97–99
Jowsey J, Riggs BL (1970) Bone formation in hypercortisolism. Acta Endocrinol 63:21–28
Bressot C, Meunier PJ, Chapuy MC, LeJeune E, Edouard C, Darby AJ (1979) Histomorphometric profile, pathophysiology, and reversibility of corticosteroid-induced osteoporosis. Metab Bone Dis Rel Res 1:303–311
Fucick RF, Kukresa, SC, Hargis GK, Bowser, EN, Henderson WJ, Williams GA (1975) Effects of glucocorticoids on function of the parathyroid glands in man. J Clin Endocr Metab 49:152–155
Shovik DM, Neer, RM, Ohman JL, Lowell FC, Clark, MB, Segre GV, Potts JT Jr (1980) Parathyroid hormone and 25-hydroxyvitamin D levels in glucocorticoid-treated patients. Clin Endocrinol 12:243–248
Seeman E, Kumar R, Hundar GG, Scott M, Heath H III, Riggs BL (1980) Production, degradation, and circulating levels of 1,25-dihydroxyvitamin D in health and in chronic glucocorticoid excess. J Clin Invest 66:664–669
Caniggia A, Gennari C (1973a) Cortisone osteoporosis: an approach to the metabolic problem. In: Frame B, Parfitt M, Duncan H (eds) Clinical aspects of metabolic bone disease. Excerpta Medica, Amsterdam, p 333
Caniggia A, Marchetti M, Gennari C, Vattimo A, Nicholis FB (1977) Effects of a new glucocorticoids, oxazacort, on some variables connected with bone metabolism in man: a comparison with prednisone. Int J Clin Pharmacol 15:126–134
Hahn TJ, Halstead LR, Strates B, Imbimbo B, Baran DT (1980) Comparison of subacute effects of oxazacort and prednisone on mineral metabolism in man. Calcif Tissue Int 31:109–115
Criscuolo D, Fraioli F, Bonifacio V, Paolucci D, Isidori A (1980) Effects of a new glucocorticoid, deflazacort, on pituitary-adrenal function in man: a comparison with prednisone, Int J Clin Pharmacol Biopharm 18:37–41
Prockop DJ, Kivirikko KI (1967) Relationship of hydroxyproline excretion in urine to collagen metabolism. Ann Intern Med 66:1243–1247
Haddad JD Jr, Couranz S, Avioli LV (1970) Nondialyzable urinary hydroxyproline as an index of bone collagen formation. J Clin Endocrinol Metab 30:282–287
Tovey KC, Holdham KG, Whelan GAM (1974) A simple direct assay for cyclic AMP in plasma and other biological samples using an improved competitive protein binding technique. Clin Chim Acta 56:221–234
Broadus AE, Mahaffey JE, Bartter FC, Neer RM (1977) Nephrogenous cyclic adenosine monophosphate as a parathyroid function test. J Clin Invest 60:771–783
Nordin BEC, Horsman A, Aaron J (1976) Diagnostic procedures. In: Nordin BEC (ed) Calcium, phosphate and magnesium metabolism. Churchill Livingstone, Edinburgh, pp 469–524
Aubert JP, Milhaud G (1960) Methods de mesure des principales voies du metabolisme calcique chez l'homme. Biochim Biophis Acta 39:122–139
Caniggia A, Gennari C, Cesari L (1964) Intestinal absorption of45Ca and dinamycs of45Ca in gastrectomy osteoporosis. Acta Med Scand 176:599–605
ICRP: Evaluation of radiation doses to body tissues from internal contamination due to occupational exposure. International Commission on Radiological Protection No. 10, Pergamon Press, Oxford, 1967
Box, GEP, Cox DR (1964) Analysis of transformations. J Pog Stated Soc B26:211–252
Dagnelie P (1975) Les presses agronomiques de Gembloux. In: Analyse statistique a plusieurs variables. Diffusion Vander, Bruxelles, p 181
Avioli LV, Birge SJ, Lee SW (1968) Effects of prednisone on vitamin D metabolism in man. J Clin Endocrinol Metab 28:1341–1346
Spanos E, Colston KW, MacIntyre I (1977) Effects of glucocorticoids on vitamin D metabolism. FEBS Lett 75:73–76
Aloia JF, Roginsky M, Ellis K, Shukla K, Cohen S (1974) Skeletal metabolism and body composition in Cushing's syndrome. J Clin Endocrinol Metab 39:981–985
Hahn TJ, Halstead LR, Haddad JG Jr (1977) Serum 25-hydroxyvitamin D concentrations in patients receiving chronic corticosteroid therapy. J Lab Clin Med 90:399–404
Hahn TJ, Halstead LR, Baran DT (1981) Effects of shortterm glucocorticoid administration on intestinal calcium absorption and circulating vitamin D metabolite concentrations in man. J Clin Endocrinol Metab 52:111–115
Caniggia A, Gennari C (1973b) Effect of 25-hydroxycholecalciferol (25-Hcc) on intestinal absorption of47Ca in four cases of iatrogenic Cushing's syndrome. Helv Med Acta 37:227–234
Chesney RW, Mazess RB, Hamstra AJ, DeLuca HF, O'Reagan S (1978) Reduction of serum 1,25-dehydroxyvitamin D in children receiving glucocorticoids. Lancet ii:1123–1125
Crilly RG, Peacock M, Taylor GA, Nordin BCF (1981) Effects of corticosteroid therapy on plasma 1,25-dihydroxyvitamin D levels, Clin Sci 60:26P
Carre' M, Ayigbede' O, Miravet L, Rasmussen H (1974) The effects of prednisone upon the metabolism and action of 25-hydroxy- and 1,25-dihydroxyvitamin D3. Proc Natl Acad Sci 71:2996–3000
Feher JJ, Wasserman RH (1979) Intestinal calcium-binding protein and calcium absorption in cortisol-treated chicks. Effects of vitamin D3 and 1,25-dihydroxyvitamin D3. Endocrinology 104:547–551
Pechet MM, Bowers B, Bartter FC (1960) Metabolic studies with a new series of 1,4-diene steroids. Effects on normal subjects of prednisone, prednisolone and 9-fluroprednisolone. J Clin Invest 38:681–690
Laake H (1960) The action of corticosteroid on the renal absorption of calcium. Acta Endocrinol 34:60–64
Molinatti GM, Camanni F, Olivetti M (1960) A study on the metabolism of calcium in the hyperadrenocortical syndrome. Acta Endocrinol 34:323–334
Fuller PL, Funder JW (1976) Mineralcorticoid and glucocorticoid receptors in human kidney. Kidney Int 10:154–157
Agus ZS, Gardener LB, Beck LH, Goldberg M (1973) Effects of parathyroid hormone on renal tubular reabsorption of calcium, sodium, and phosphate. Am J Physiol 224:1143–1148
Manolagas SC, Anderson DC, Lumb GA (1979) Glucocorticoids regulate the concentration of 1,25-dihydroxycholecalciferol receptors in bone. Nature 277:314–315
DeLuca HF (1976) Recent advances in our understanding of the vitamin D endocrine system. J Lab Clin Med 87:7–26
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Gennari, C., Imbimbo, B., Montagnani, M. et al. Effects of prednisone and deflazacort on mineral metabolism and parathyroid hormone activity in humans. Calcif Tissue Int 36, 245–252 (1984). https://doi.org/10.1007/BF02405325
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DOI: https://doi.org/10.1007/BF02405325