Effects of continuous glucocorticoid infusion on bone metabolism in the rat

Abstract

The effects of continuous administration of supraphysiologic doses of dexamethasone (DEX) on bone metabolism were examined in rats. Adult, male, Sprague Dawley rats were infused with DEX at a constant rate of 16.25 microg/day for 19 days. Despite soft tissue catabolism, DEX treatment led to a significant increase in bone volume in all experiments. This was accompanied by a significant gain in femoral weight and calcium content. These findings were also observed in DEX-treated parathyroidectomized 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 circulating levels of PTH and 1,25(OH)2D and in the urinary calcium/creatinine ratio. This latter finding was also observed in PTX animals in which 1,25(OH)2D levels did not change. Serum concentrations of osteocalcin and tartrate-resistant acid phosphatase both declined in a time-dependent manner with DEX treatment suggesting a slowing of bone turnover with the net effect favoring formation. However, histomorphometric findings were variable. Two of three experiments demonstrated a decrease in cellular parameters of formation and resorption and in one experiment, these indices increased. Mineralized surface increased with DEX treatment. We conclude that, in marked contrast to the findings in man and certain other species, DEX treatment increases bone mass in rats. This may in part relate to a relatively greater suppression of resorption vis à vis formation.

Effects of Methylprednisolone on Bone Formation and Resorption in Rats

“…In the present study, however, the administration of mPSL for 4 weeks dose-dependently increased the BMD of the tibial metaphysis in rats. Although our present findings were contrary to previous findings in humans and in certain animal species (8 -12, 22, 23), they are consistent with the data from previous studies using rats that showed increased bone mass or BMD after the treatment with GCs (24,25,33,34).…”

“…A recent study by Okazaki et al (26) demonstrated that the administration of prednisolone prevented a decrease in bone mass in rats with adjuvant-induced arthritis by reducing the increase in bone resorption and the decrease of bone formation at both the local and systemic levels. King et al (24) and Turner et al (25) also reported that treatment with dexamethasone or prednisone increased the bone mass in normal rats or ovariectomized rats, which might be due to a greater suppression of resorption rather than formation. In contrast to the increase in BMD in the metaphysis, BMD in the tibial diaphysis decreased in a dose-dependent fashion (Fig.…”

Glucocorticoid Inhibits Bone Regeneration after Osteonecrosis of the Femoral Head in Aged Female Rats

“…Numerous previous papers have reported that high- dose steroids suppress bone resorption in rats (Jee et al 1970;King et al 1996;Kondo et al 2006). Our histological findings were consistent with those previous studies.…”

Clinical application of biochemical markers of bone turnover

“…For example, markers of bone turnover may reflect changes in bone metabolism induced by oophorectomy (57,125), hyperparathyroidism (126,127), Paget's disease (128), physical exercise (129), immobilisation (32,130), alcoholism (131), smoking (132), vitamin D deficiency (33,35,37,133), chronic inflammatory bowel disease (134,135), chronic starvation (136), thyroid disorders (52,137) as well as the pharmacological effects of glucocorticosteroids (48,139,140), androgens (6,7,141), gonadotropin-releasing hormone agonists (142), warfarin (143), growth hormone or insulin-like growth factors (144). Bone turnover markers may be useful in the diagnosis and management of certain of the above conditions, but in most cases has not been rigorously examined.…”