Intestinal Calcium Absorption in Exogenous Hypercortisonism

Abstract

A B S T R A C T 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 ofcorticosteroids (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 ,ug

Regulation of vitamin D-1alpha-hydroxylase and -24-hydroxylase expression by dexamethasone in mouse kidney

“…The hypercalcemia induced by a pharmacologic dose of dexamethasone may reflect an overwhelming degree of bone resorption (Gronowicz et al 1990, Conaway et al 1996, although glucocorticoids decrease intestinal absorption of calcium (Klein et al 1977, Aloia et al 1984 and increase urinary calcium excretion (Suzuki et al 1983, Reid & Ibbertson 1987, Cosman et al 1994. Plasma levels of 1,25(OH) 2 D 3 are unlikely to cause the increased concentrations of plasma calcium seen in dexamethasone-treated mice, since steroid administration did not affect the plasma 1,25(OH) 2 D 3 concentrations in normally fed or LCD mice.…”

“…Increased concentrations of glucocorticoids are thought to alter bone remodeling by decreasing bone formation and increasing bone resorption, resulting in a net loss of bone volume in humans and animals (Lukert & Raisz 1990, Reid 1997. Furthermore, glucocorticoids decrease net intestinal calcium absorption (Klein et al 1977, Aloia et al 1984, although details of the mechanism are still unclear. Glucocorticoids have been shown to increase renal calcium excretion (Suzuki et al 1983, Reid & Ibbertson 1987, Cosman et al 1994.…”

A novel 11β-HSD1 inhibitor improves diabesity and osteoblast differentiation

“…Glucocorticoid promotes the expression of receptor activator of nuclear factor-kB ligand (RANKL) and decreases osteoprotegerin expression in osteoblasts, thus stimulating osteoclastic bone resorption (Hofbauer et al 1999). Additionally, glucocorticoid suppresses intestinal absorption of calcium and gonadal hormones (Klein et al 1977).…”

Dexamethasone Enhances Osteoclast Formation Synergistically with Transforming Growth Factor-β by Stimulating the Priming of Osteoclast Progenitors for Differentiation into Osteoclasts

“…Although GCs are effective for the treatment of a wide variety of disorders ranging from autoimmune diseases to acute situations such as spinal cord injury, long-term therapy with GCs causes osteoporosis, resulting in severe bone loss that, at present, has become a big clinical problem (22)(23)(24)(25). GCs decrease calcium absorption in the gastrointestinal system and increase calcium excretion in the renal system, resulting in a high level of parathyroid hormone (26,27). Therefore, GCinduced osteoporosis has been accepted for a long time to be caused by the secondary hyperparathyroidism (26).…”