Summary
Prolonged therapeutic administration of prednisone or other corticosteroids frequently produces severe osteopenia with an increased incidence of bone fractures. Recent efforts to decrease the severity of corticosteroid-induced osteopenia have included the development of corticosteroid analogues designed to possess diminished bone-wasting effects relative to their anti-inflammatory activity. We compared the effects of an oxazoline derivative of prednisolone, oxazacort (azacortinol), with those of prednisone on mineral metabolism in man. After a 12-day equilibration period on a 600 mg/day calcium diet, normal volunteers were studied for 15 days during treatment with either prednisone (20 mg/day, 12 subjects) or oxazacort (25 mg/day, 10 subjects). There was no difference between the two groups with regard to the effects of each corticosteroid on serum ionized calcium, phosphate, alkaline phosphatase, immunoreactive parathyroid hormone (iPTH), and 25-hydroxyvitamin D (25OHD) concentrations. Both corticosteroids suppressed intestinal47Ca absorption to a similar degree after 15 days of treatment (prednisone: −28.5±7.5, oxazacort: −30.2±4.4% of initial values). Although both corticosteroids increased 24-h urinary calcium excretion significantly above pretreatment values, this effect was less marked in the oxazacort-treated subjects. The mean cumulative 15-day increase in urinary calcium excretion in the prednisone-treated group (+326 ± 54 mg/g creatinine/24 h) was more than twice as great as that in the oxazacort-treated group (+146 ± 48 mg/g creatinine/24 h), a difference significant atP<0.001. It is concluded that the increase in urinary calcium excretion, and presumably the negative calcium balance, produced by a 2-week administration of oxazacort is significantly less pronounced than that produced by an equivalent dose of prednisone.
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Miravet, L., Hioco, D., Debeyre, N., Dryll, A., Ryckewaert, A., de Seze, S.: La cinétique du calcium au cours de l'ostéoporose cortisonique. Effet d'un anabolisant de synthése, Sem. Hop. Paris [Suppl.]42:60–64, 1966
Wajchenberg, B.L., Pereira, V.G., Kieffer, J., Ursic, S.: Effect of dexamethasone on calcium metabolism and47Ca kinetics in normal subjects, Acta Endocrinol. (Kbh.)61:173–192, 1969
Gallagher, J.C., Aaron, J., Horsman, A., Wilkinson, R., Nordin, B.E.C.: Corticosteroid osteoporosis, Clin. Endocrinol. Metab.2:355–368, 1973
Teotia, M., Teotia, S.P.S., Raman, T., Sharma, N.L., Singh, R.K.: Intestinal absorption of calcium and phosphorus: experiments on interaction between vitamin D and adrenocortical hormone, Indian J. Pediatr.42:1–9, 1975
Lukert, B.P., Adams, J.S.: Calcium and phosphorus homeostasis in man: effect of corticosteroids, Arch. Intern. Med.136:1249–1253, 1976
Klein, R.G., Arnaud, S.B., Gallagher, J.C., DeLuca, H.F., Riggs, B.L.: Intestinal calcium absorption in exogenous hypercortisolism: role of 25-hydroxy-vitamin D and corticosteroid dose, J. Clin. Invest.60:253–259, 1977
Hahn, T.J., Halstead, L.R., Teitelbaum, S.L., Hahn, B.H.: Altered mineral metabolism in glucocorticoid-induced osteopenia: effect of 25-hydroxyvitamin D administration, J. Clin. Invest.64:655–665, 1979
Curtiss, P.H., Clark, W.S., Herndon, C.H.: Vertebral fractures resulting from prolonged cortisone and corticotrophin therapy, J.A.M.A.156:467–469, 1954
Bradley, B.W.D., Ansell, B.M.: Fractures in Still's disease, Ann. Rheum. Dis.19:135–142, 1960
Saville, P.D., Kharmosh, O.: Osteoporosis of rheumatoid arthritis: Influence of age, sex and corticosteroids, Arthritis Rheum.10:423–430, 1967
Hahn, T.J., Boisseau, V.C., Avioli, L.V.: Effect of chronic corticosteroid administration on diaphyseal and metaphyseal bone mass, J. Clin. Endocrinol. Metab.39:274–282, 1974
Frost, H.M., Villaneuva, A.R.: Human osteoblastic activity. III. The effect of cortisone on lamellar osteoblastic activity, Henry Ford Hosp. Med. Bull.9:97–99, 1961
Jowsey, J., Riggs, B.L.: Bone formation in hypercortisolism, Acta Endocrinol. (Kbh.)63:21–28, 1970
Peck, W.A., Brant, J., Miller, I.: Hydrocortisone-induced inhibition of protein synthesis and uridine incorporation in isolated bone cellsin vitro, Proc. Natl. Acad. Sci. U.S.A.57:1599–1606, 1967
Aloia, J.F., Roginsky, M., Ellis, K., Shukla, K., Cohn, S.: Skeletal metabolism and body composition in Cushing's syndrome, J. Clin. Endocrinol. Metab.39:981–985, 1974
Hahn, T.J., Halstead, L.R., Haddad, Jr., J.G.: Serum 25-hydroxyvitamin D concentrations in patients receiving chronic corticosteroid therapy, J. Lab. Clin. Med.90:399–404, 1977
Avioli, L.V., Birge, S.J., Lee, S.W.: Effects of prednisone on vitamin D metabolism in man, J. Clin. Endocrinol. Metab.28:1341–1346, 1968
Klein, R.G., Arnaud, S.B., Gallagher, J.C., DeLuca, H.F., Riggs, B.L.: Intestinal calcium absorption in exogenous hypercortisolism: role of 25-hydroxyvitamin D and corticosteroid dose, J. Clin. Invest.60:253–259, 1977
Chesney, R.W., Hamstra, A.J., Mazeso, R.B., DeLuca, H.F.: Reduction of serum 1,25-dihydroxyvitamin D3 in children receiving glucocorticoids, Lancetii:1123–1125, 1978
Hahn, T.J., Baran, D.T., Halstead, L.R.: Alteration in mineral and vitamin D metabolism produced by subacute prednisone administration in man. Proc. 61st Ann. Meet. Endocr. Soc., June 13–15, 1979, p. 195 (abst.)
Jackson, W.P.U., Lancaster, C.A.: Consideration of the hypercalciuria in sarcoidosis, idiopathic hypercalciuria and that produced by vitamin D. A new suggestion regarding calcium metabolism, J. Clin. Endocrinol. Metab.19:658–680, 1959
Laake, H.: The action of corticosteroids on the renal absorption of calcium, Acta Endocrinol (Kbh.)34:60, 1960
Bijovet, O.L.M.: Kidney function in calcium and phosphate metabolism. In L.V. Avioli, S.M. Krane, (eds.): Metabolic Bone Disease, Vol. 1, pp. 49–140. Academic Press, New York, 1977
Cannigia, A., Marchetti, M., Gennari, C., Vattimo, A., Nicolis, F.B.: Effects of a new glucocorticoid, oxazacort, on some variables connected with bone metabolism in man: a comparison to prednisone, Int. J. Clin. Pharmacol.15:126–134, 1977
Clinical Investigator's Brochure—DL-458, Clinical Investigation—Medical Department, The Dow Chemical Co., Indianapolis, Indiana, 1978
Hahn, T.J., Hendin, B.A., Scharp, C.R., Haddad, J.G., Jr.: Effect of chronic anticonvulsant therapy on serum 25-hydroxycalciferol levels in adults, N. Engl. J. Med.287:900–904, 1972
Tilden, R.L.: New advantageous approach to the direct radioimmunoassay of cortisol, Clin. Chem.23:211–215, 1977
Slatapolsky, E., Cagbar, S., Pennell, J.P., Canterbury, J.M., Reiss, E., Bricker, N.: On the pathogenesis of hyperparathyroidism in chronic experimental renal insufficiency in the dog, J. Clin. Invest.50:492–499, 1971
Haddad, J.G., Jr., Chyu, K.J.: Competitive protein-binding radioassay for 25-hydroxycholecalciferol, J. Clin. Endocrinol. Metab.33:992–995, 1971
Prockop, D.J., Udenfriend, S.: A specific method for the analysis of hydroxyproline in tissues and urine, Anal. Biochem.1:228–237, 1960
Walton, R.J., Bijvoet, O.L.M.: Nomogram for the derivation of renal threshold phosphate concentration, Lancet2:309–310, 1975
Fucik, R.F., Kukreja, S.C., Hargis, G.K.: Effect of glucocorticoids on function of the parathyroid glands in man, J. Clin. Endocrinol. Metab.40:152–155, 1975
Segre, G.V., Niall, H.D., Habener, J.F., Potts, J.T., Jr.: Metabolism of parathyroid hormone: physiologic and clinical significance, Am. J. Med.56:774–778, 1974
Haddad, J.G., Jr., Couranz, S., Avioli, L.V.: Non-dialyzable hydroxyproline as an index of bone collagen formation. J. Clin. Endocrinol. Metab.30:282–287, 1970
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Hahn, T.J., Halstead, L.R., Strates, B. et al. Comparison of subacute effects of oxazacort and prednisone on mineral metabolism in man. Calcif Tissue Int 31, 109–115 (1980). https://doi.org/10.1007/BF02407171
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DOI: https://doi.org/10.1007/BF02407171