Abstract
Pharmacologic doses of corticosteroids impair intestinal calcium absorption and contribute to negative calcium balance. However, the relationship between the impaired calcium absorption and a possible defect in the conversion of vitamin D to its physiologically active form, 1,25-dihydroxyvitamin D, is unknown. We compared fractional calcium absorption (double-isotope method, 100-mg carrier) and serum 25-hydroxyvitamin D (25-OH-D) (Haddad method) in 27 patients receiving pharmacologic doses of prednisone with 27 age-, sex-, and season-matched normal subjects. In patients receiving high daily doses of prednisone (15-100 mg/day), calcium absorption (P < 0.02) and serum 25-OH-D (P < 0.001) were decreased. However, in patients receiving low doses (8-10 mg/day) or high doses (30-100 mg) of prednisone on an alternate-day schedule, both of these parameters were normal. Calcium absorption in the patients treated with daily prednisone correlated inversely with the dose of corticosteroids (r = −0.52, P < 0.025) and, in all steroid-treated patients, correlated directly with serum 25-OH-D (r = 0.58, P < 0.01). In four patients who received high-dose corticosteroid therapy for an average of 4 wk, serum 25-OH-D decreased by 35.5% from pretreatment values. Administration of a physiologic or near-physiologic dose of synthetic 1,25-dihydroxyvitamin D3 (0.4 μg daily for 7 days) to patients receiving high-dose corticosteroids led to an increase in calcium absorption in all patients. These results suggest that calcium malabsorption in the corticosteroid-treated patients is due to a dose-related abnormality of vitamin D metabolism and not to a direct effect of corticosteroids on depressing transmucosal intestinal absorption of calcium.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aloia J. F., Roginsky M., Ellis K., Shukla K., Cohn S. Skeletal metabolism and body composition in Cushing's syndrome. J Clin Endocrinol Metab. 1974 Dec;39(6):981–985. doi: 10.1210/jcem-39-6-981. [DOI] [PubMed] [Google Scholar]
- Arnaud S. B., Goldsmith R. S., Lambert P. W., Go V. L. 25-Hydroxyvitamin D3: evidence of an enterohepatic circulation in man. Proc Soc Exp Biol Med. 1975 Jun;149(2):570–572. doi: 10.3181/00379727-149-38853. [DOI] [PubMed] [Google Scholar]
- Arnaud S. B., Stickler G. B., Haworth J. C. Serum 25-hydroxyvitamin D in infantile rickets. Pediatrics. 1976 Feb;57(2):221–225. [PubMed] [Google Scholar]
- Avioli L. V., Birge S. J., Lee S. W. Effects of prednisone on vitamin D metabolism in man. J Clin Endocrinol Metab. 1968 Sep;28(9):1341–1346. doi: 10.1210/jcem-28-9-1341. [DOI] [PubMed] [Google Scholar]
- BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
- Balsan S., Garabedian M., Sorgniard R., Holick M. F., Deluca H. F. 1,25-dihydroxyvitamin D3 and 1, alpha-hydroxyvitamin D3 in children: biologic and therapeutic effects in nutritional rickets and different types of vitamin D resistance. Pediatr Res. 1975 Jul;9(7):586–593. doi: 10.1203/00006450-197507000-00007. [DOI] [PubMed] [Google Scholar]
- Birge S. J., Peck W. A., Berman M., Whedon G. D. Study of calcium absorption in man: a kinetic analysis and physiologic model. J Clin Invest. 1969 Sep;48(9):1705–1713. doi: 10.1172/JCI106136. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brickman A. S., Coburn J. W., Massry S. G., Norman A. W. 1,25 Dihydroxy-vitamin D3 in normal man and patients with renal failure. Ann Intern Med. 1974 Feb;80(2):161–168. doi: 10.7326/0003-4819-80-2-161. [DOI] [PubMed] [Google Scholar]
- COLLINS E. J., GARRET E. R., JOHNSTON R. L. Effect of adrenal steroids on radio-calcium metabolism in dogs. Metabolism. 1962 Jul;11:716–726. [PubMed] [Google Scholar]
- Carré M., Ayigbedé O., Miravet L., Rasmussen H. The effect of Prednisolone upon the metabolism and action of 25-hydroxy-and 1,25-dihydroxyvitamin D3. Proc Natl Acad Sci U S A. 1974 Aug;71(8):2996–3000. doi: 10.1073/pnas.71.8.2996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Coburn J. W., Koppel M. H., Brickman A. S., Massry S. G. Study of intestinal absorption of calcium in patients with renal failure. Kidney Int. 1973 Apr;3(4):264–272. doi: 10.1038/ki.1973.40. [DOI] [PubMed] [Google Scholar]
- Conney A. H. Pharmacological implications of microsomal enzyme induction. Pharmacol Rev. 1967 Sep;19(3):317–366. [PubMed] [Google Scholar]
- De Luca H. F. Recent advances in our understanding of the vitamin D endocrine system. J Lab Clin Med. 1976 Jan;87(1):7–26. [PubMed] [Google Scholar]
- Favus M. J., Kimberg D. V., Millar G. N., Gershon E. Effects of cortisone administration on the metabolism and localization of 25-hydroxycholecalciferol in the rat. J Clin Invest. 1973 Jun;52(6):1328–1335. doi: 10.1172/JCI107304. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Favus M. J., Walling M. W., Kimberg D. V. Effects of 1,25-dihydroxycholecalciferol on intestinal calcium transport in cortisone-treated rats. J Clin Invest. 1973 Jul;52(7):1680–1685. doi: 10.1172/JCI107349. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gallagher J. C., Aaron J., Horsman A., Wilkinson R., Nordin B. E. Corticosteroid osteoporosis. Clin Endocrinol Metab. 1973 Jul;2(2):355–368. doi: 10.1016/s0300-595x(73)80048-9. [DOI] [PubMed] [Google Scholar]
- Gelehrter T. D. Enzyme induction (second of three parts). N Engl J Med. 1976 Mar 11;294(11):589–595. doi: 10.1056/NEJM197603112941105. [DOI] [PubMed] [Google Scholar]
- HARRISON H. E., HARRISON H. C. Transfer of Ca45 across intestinal wall in vitro in relation to action of vitamin D and cortisol. Am J Physiol. 1960 Aug;199:265–271. doi: 10.1152/ajplegacy.1960.199.2.265. [DOI] [PubMed] [Google Scholar]
- Haddad J. G., Chyu K. J. Competitive protein-binding radioassay for 25-hydroxycholecalciferol. J Clin Endocrinol Metab. 1971 Dec;33(6):992–995. doi: 10.1210/jcem-33-6-992. [DOI] [PubMed] [Google Scholar]
- Haddad J. G., Stamp T. C. Circulating 25-hydroxyvitamin D in man. Am J Med. 1974 Jul;57(1):57–62. doi: 10.1016/0002-9343(74)90768-2. [DOI] [PubMed] [Google Scholar]
- Hahn T. J., Birge S. J., Scharp C. R., Avioli L. V. Phenobarbital-induced alterations in vitamin D metabolism. J Clin Invest. 1972 Apr;51(4):741–748. doi: 10.1172/JCI106868. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Holick M. F., DeLuca H. F. A new chromatographic system for vitamin D3 and its metabolites: resoluation of a new vitamin D3 metabolite. J Lipid Res. 1971 Jul;12(4):460–465. [PubMed] [Google Scholar]
- Kimberg D. V., Baerg R. D., Gershon E., Graudusius R. T. Effect of cortisone treatment on the active transport of calcium by the small intestine. J Clin Invest. 1971 Jun;50(6):1309–1321. doi: 10.1172/JCI106610. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kimberg D. V. Effects of vitamin D and steroid hormones on the active transport of calcium by the intestine. N Engl J Med. 1969 Jun 19;280(25):1396–1405. doi: 10.1056/NEJM196906192802510. [DOI] [PubMed] [Google Scholar]
- Lukert B. P., Stanbury S. W., Mawer E. B. Vitamin D and intestinal transport of calcium: effects of prednisolone. Endocrinology. 1973 Sep;93(3):718–722. doi: 10.1210/endo-93-3-718. [DOI] [PubMed] [Google Scholar]
- Melby J. C. Drug spotlight program: systemic corticosteroid therapy: pharmacology and endocrinologic considerations. Ann Intern Med. 1974 Oct;81(4):505–512. doi: 10.7326/0003-4819-81-4-505. [DOI] [PubMed] [Google Scholar]
- Norman A. W., Henry H. The role of the kidney and vitamin D metabolism in health and disease. Clin Orthop Relat Res. 1974 Jan-Feb;(98):258–287. doi: 10.1097/00003086-197401000-00032. [DOI] [PubMed] [Google Scholar]
- Stamp T. C., Round J. M., Rowe D. J., Haddad J. G. Plasma levels and therapeutic effect of 25-hydroxycholecalciferol in epileptic patients taking anticonvulsant drugs. Br Med J. 1972 Oct 7;4(5831):9–12. doi: 10.1136/bmj.4.5831.9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Szymendera J., Heaney R. P., Saville P. D. Intestinal calcium absorption: concurrent use of oral and intravenous tracers and calculation by the inverse convolution method. J Lab Clin Med. 1972 Apr;79(4):570–578. [PubMed] [Google Scholar]
- Teotia M., Teotia S. P., 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. 1975 Jan;42(324):1–9. doi: 10.1007/BF02753608. [DOI] [PubMed] [Google Scholar]
- WILLIAMS G. A., BOWSER E. N., HENDERSON W. J., UZGIRIES V. Effects of vitamin D and cortisone on intestinal absorption of calcium in the rat. Proc Soc Exp Biol Med. 1961 Mar;106:664–666. doi: 10.3181/00379727-106-26436. [DOI] [PubMed] [Google Scholar]
- Wajchenberg B. L., Pereira V. G., Kieffer J., Ursic S. Effect of dexamethasone on calcium metabolism and 47Ca kinetics in normal subjects. Acta Endocrinol (Copenh) 1969 May;61(1):173–192. doi: 10.1530/acta.0.0610173. [DOI] [PubMed] [Google Scholar]