EFFECTS OF CONTINUOUS GLUCOCORTICOID INFUSION ON BONE METABOLISM IN THE RAT

The effects of continuous administration of supraphysiologic doses of dexamethasone (DEX) on bone metabolism were examined in rats. Adult, m ale, Sprague Dawley rats were infused with DEX at a constant rate of 1 6.25 mu g/day for 19 days. Despite soft tissue catabolism, DEX treatme nt led to a significant increase in bone volume in all experiments. Th is was accompanied by a significant gain in femoral weight and calcium content. These findings were also observed in DEX-treated parathyroid ectomized animals indicating that intact parathyroid function was not required for this effect. DEX treatment did not affect mean levels of serum calcium or phosphorus but led to significant declines in circula ting levels of PTH and 1,25(OH)(2)D and in the urinary calcium/creatin ine ratio. This latter finding was also observed in PTX animals in whi ch 1,25(OH)(2)D levels did not change. Serum concentrations of osteoca lcin and tartrate-resistant acid phosphatase both declined in a time-d ependent manner with DEX treatment suggesting a slowing of bone turnov er with the net effect favoring formation. However, histomorphometric findings were variable. Two of three experiments demonstrated a decrea se in cellular parameters of formation and resorption and in one exper iment, these indices increased. Mineralized surface increased with DEX treatment. We conclude that, in marked contrast to the findings in ma n and certain other species, DEX treatment increases bone mass in rats . This may in part relate to a relatively greater suppression of resor ption vis a vis formation.