DIFFERENTIAL-EFFECTS OF GLUCOCORTICOIDS ON HUMAN OSTEOBLASTIC CELL-METABOLISM IN-VITRO

Clinical observations suggest that the onset and severity of glucocort icoid (GC) induced osteoporosis is dependent on the duration of the GC treatment and the applied GC compound. To test whether these in vivo observations are reflected by different in vitro effects of various sy nthetic GCs on human bone cell metabolism we isolated human osteoblast -like cells (HOC) from bone biopsies of healthy (no clinical symptoms of arthritis or arthrosis) adults who underwent selective orthopedic s urgery. HOC were identified as bone cells by 1,25-vitamin D-3-stimulat ed increase of specific alkaline phosphatase (ALP) activity, secretion of osteocalcin and type-I procollagen peptide, and the ability to for m mineral in vitro. We investigated the effects of dexamethasone (dexa ), methylprednisolone (mpred), prednisolone (pred), and deflazacort (d efla) on DNA-synthesis, ALP, and osteocalcin (OC)- and type-I procolla gen peptide secretion of HOC in vitro. In summary, (1) GC exposure sti mulates DNA synthesis after 6-12-hour treatment periods; (2) dex and m pred strongly inhibit DNA (48-hour treatment) and collagen synthesis b ut stimulate ALP, whereas pred and defla exhibit smaller effects on DN A synthesis, ALP, and collagen production; and (3) all tested glucocor ticoids inhibit OC secretion by HOC in vitro. Thus, the effect of GC o n DNA synthesis of HOC varies with the duration of GC exposure, and de x and mpred more potently affect HOC metabolism in vitro than pred and defla.