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Effects of prednisone and deflazacort on mineral metabolism and parathyroid hormone activity in humans

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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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References

  1. Raisz LG, Trummel CL, Wener JA, Simmons H (1972) Effect of glucocorticoids on bone resorption in tissue culture. Endocrinology 90:961–967

    CAS  PubMed  Google Scholar 

  2. 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

    CAS  PubMed  Google Scholar 

  3. Chen TL, Aronow L, Feldman D (1977) Glucocorticoid receptors and inhibition of bone cell growth in primary culture. Endocrinology 100:619–628

    Article  CAS  PubMed  Google Scholar 

  4. Choe J, Stern P, Feldman D (1978) Receptor-mediated glucocorticoid inhibition of protein synthesis in isolate bone cells. J Steroid Biochem 9:265–271

    Article  CAS  PubMed  Google Scholar 

  5. 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

    CAS  PubMed  Google Scholar 

  6. 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

    CAS  PubMed  Google Scholar 

  7. Caniggia A, Gennari C (1971) Etudes des effets des corticoides sur le metabolisme calcique. Actualites Endocr, “La Pitie 1971”:281–289

    Google Scholar 

  8. 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

    CAS  PubMed  Google Scholar 

  9. Gallagher JC, Aaron J, Horsman A, Wilkinson R, Nordin, BEC: Corticosteroid osteoporosis. Clinics Endocrinol Metab 2:355–368

  10. 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

    CAS  PubMed  Google Scholar 

  11. Luckert BP, Adams JS (1976) Vitamin D metabolism in man. Effect of corticosteroids. Arch Intern Med 136:1241–1248

    Article  Google Scholar 

  12. 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

    CAS  PubMed  Google Scholar 

  13. 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.

    CAS  PubMed  Google Scholar 

  14. 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

    CAS  PubMed  Google Scholar 

  15. Jowsey J, Riggs BL (1970) Bone formation in hypercortisolism. Acta Endocrinol 63:21–28

    CAS  PubMed  Google Scholar 

  16. 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

    Article  Google Scholar 

  17. 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

    Google Scholar 

  18. 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

    Google Scholar 

  19. 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

    CAS  PubMed  Google Scholar 

  20. 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

    Google Scholar 

  21. 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

    CAS  Google Scholar 

  22. 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

    CAS  PubMed  Google Scholar 

  23. 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

    CAS  Google Scholar 

  24. Prockop DJ, Kivirikko KI (1967) Relationship of hydroxyproline excretion in urine to collagen metabolism. Ann Intern Med 66:1243–1247

    CAS  Google Scholar 

  25. 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

    CAS  PubMed  Google Scholar 

  26. 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

    Article  CAS  PubMed  Google Scholar 

  27. Broadus AE, Mahaffey JE, Bartter FC, Neer RM (1977) Nephrogenous cyclic adenosine monophosphate as a parathyroid function test. J Clin Invest 60:771–783

    CAS  PubMed  Google Scholar 

  28. Nordin BEC, Horsman A, Aaron J (1976) Diagnostic procedures. In: Nordin BEC (ed) Calcium, phosphate and magnesium metabolism. Churchill Livingstone, Edinburgh, pp 469–524

    Google Scholar 

  29. Aubert JP, Milhaud G (1960) Methods de mesure des principales voies du metabolisme calcique chez l'homme. Biochim Biophis Acta 39:122–139

    Article  CAS  Google Scholar 

  30. Caniggia A, Gennari C, Cesari L (1964) Intestinal absorption of45Ca and dinamycs of45Ca in gastrectomy osteoporosis. Acta Med Scand 176:599–605

    Article  CAS  PubMed  Google Scholar 

  31. 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

    Google Scholar 

  32. Box, GEP, Cox DR (1964) Analysis of transformations. J Pog Stated Soc B26:211–252

    Google Scholar 

  33. Dagnelie P (1975) Les presses agronomiques de Gembloux. In: Analyse statistique a plusieurs variables. Diffusion Vander, Bruxelles, p 181

    Google Scholar 

  34. Avioli LV, Birge SJ, Lee SW (1968) Effects of prednisone on vitamin D metabolism in man. J Clin Endocrinol Metab 28:1341–1346

    CAS  PubMed  Google Scholar 

  35. Spanos E, Colston KW, MacIntyre I (1977) Effects of glucocorticoids on vitamin D metabolism. FEBS Lett 75:73–76

    Article  CAS  PubMed  Google Scholar 

  36. 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

    CAS  PubMed  Google Scholar 

  37. 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

    CAS  PubMed  Google Scholar 

  38. 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

    CAS  PubMed  Google Scholar 

  39. 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

    Google Scholar 

  40. 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

    Article  Google Scholar 

  41. Crilly RG, Peacock M, Taylor GA, Nordin BCF (1981) Effects of corticosteroid therapy on plasma 1,25-dihydroxyvitamin D levels, Clin Sci 60:26P

    Google Scholar 

  42. 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

    Google Scholar 

  43. 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

    Article  CAS  PubMed  Google Scholar 

  44. 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

    Article  Google Scholar 

  45. Laake H (1960) The action of corticosteroid on the renal absorption of calcium. Acta Endocrinol 34:60–64

    CAS  PubMed  Google Scholar 

  46. Molinatti GM, Camanni F, Olivetti M (1960) A study on the metabolism of calcium in the hyperadrenocortical syndrome. Acta Endocrinol 34:323–334

    CAS  PubMed  Google Scholar 

  47. Fuller PL, Funder JW (1976) Mineralcorticoid and glucocorticoid receptors in human kidney. Kidney Int 10:154–157

    CAS  PubMed  Google Scholar 

  48. 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

    CAS  PubMed  Google Scholar 

  49. Manolagas SC, Anderson DC, Lumb GA (1979) Glucocorticoids regulate the concentration of 1,25-dihydroxycholecalciferol receptors in bone. Nature 277:314–315

    Article  CAS  PubMed  Google Scholar 

  50. DeLuca HF (1976) Recent advances in our understanding of the vitamin D endocrine system. J Lab Clin Med 87:7–26

    CAS  Google Scholar 

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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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