Glucocorticoid-induced osteoporosis

The mechanism responsible for the negative effect of glucocorticoids on calcium and phosphate absorption is still unclear. Glucocorticoid receptors have been demonstrated in the small intestine of rats (Pressley and Funder, 1975) and glucocorticoids could competitively interfere with the uptake of 1,25-dihydroxy vitamin D at this level, as recently shown in animal studies (Chan et al, 1984; Korkor et al, 1985). Furthermore, the glucocorticoids may act by altering either the synthesis of a specific protein (Feher and Wasserman, 1979) or the regulatory effects of some enzymes in the mucosal cell (Krawitt, 1972). Finally, the deleterious effect of glucocorticoids on the intestinal transport of calcium and phosphate may be due, at least in part, to an alteration in the membrane transport of other elements, such as sodium, glucose and water (Fox et al, 1985). In conclusion, the cellular mechanism by which glucocorticoids interfere with the intestinal absorption processes of calcium and phosphate is still enigmatic and further work is necessary to clarify it. From our studies in man, it appears evident that: (1) glucocorticoids precociously interfere with the intestinal transport processes of both calcium and phosphate; this side-effect is related to the dose and duration of treatment, but not to the circulating vitamin D metabolite levels; (2) calcium intestinal absorption is reduced before that of phosphate; this effect indicates a dissociation between the two transport systems; (3) different glucocorticoids affect the calcium and phosphate transport processes to different degrees, probably as a result of their different molecular structures, thereby resulting in different affinities for glucocorticoid receptors at the intestinal cell level.