The effects of hydrocortisone, parathyroid hormone and the bisphosphonate, APD, on bone resorption in neonatal mouse calvaria

Abstract

The effects of hydrocortisone and parathyroid hormone (PTH) upon bone resorption rates in neonatal mouse calvaria have been studied. Bone resorption (measured as 45Ca release) was significantly increased by hydrocortisone (10(-7) M and 10(-6) M) and there was a dose-dependent rise with PTH (0.3-0.9 micrograms/liter). When both PTH 0.3 micrograms/liter and hydrocortisone 10(-8) M were present in the incubating medium, bone resorption did not differ from control, but increasing the hydrocortisone concentration to 10(-7) M augmented 45Ca release by 25% (P less than 0.02) and doubling of the PTH level was associated with a 10% increase (nonsignificant). When both PTH and hydrocortisone were present in the higher concentrations (0.6 micrograms/liter and 10(-7) M, respectively) 45Ca release increased by 39% (P less than 0.005) above that resulting from the lower levels of both hormones (0.3 micrograms/l and 10(-8) M, respectively). (3-Amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) in concentrations of 3 X 10(-5) M and 10(-4) M, produced inhibition of basal and hydrocortisone/PTH-stimulated bone resorption without evidence of toxicity. These results indicate that hydrocortisone stimulates bone resorption in neonatal mouse calvaria in vitro, in contrast to the results found in fetal rat bone culture systems. PTH has a similar effect, which is additive to that of hydrocortisone and the combined stimulation can be overcome by APD. The possible relevance of these results to the development and prevention of glucocorticoid-induced osteoporosis is discussed.

Effect of corticosteroids on human osteoclast formation and activity

“…Glucocorticoids have been reported to inhibit bone resorption in fetal rat long bone cultures, but to increase resorption in mouse calvarial cultures (Teitelbaum et al 1981, Reid et al 1986. Glucocorticoids have also been found to exert dose-dependent inhibition of lacunar bone resorption by rat osteoclasts (Tobias & Chambers 1989).…”

“…Although the precise manner in which corticosteroids stimulate osteoclast formation is unclear, these compounds are known to enhance osteoclast formation from marrow precursors in vitro and to increase and decrease respectively osteoblast expression of RANKL and osteoprotegerin, the soluble decoy receptor for RANK (Hofbauer et al 1999). The effect of corticosteroids on osteoclast bone-resorbing activity is controversial, with both enhancement and inhibition of the activity of bone-resorbing cells being reported (Raisz et al 1972, Teitelbaum et al 1981, Reid et al 1986, Tobias & Chambers 1989. Corticosteroids are also believed to influence osteoclastic bone resorption by enhancing osteoclast apoptosis (Tobias & Chambers 1989, Dempster et al 1997.…”

Cortisol Inhibits Acid-Induced Bone Resorption In Vitro

“…Glucocorticoids stimulate net bone resorption in vivo; however, both inhibition (36,39,40) as well as stimulation (41,42) of bone resorption have been reported using bone organ culture systems. Glucocorticoids have been shown to inhibit bone cell proliferation (43) and have a biphasic effect on type I collagen synthesis, a principal function of the osteoblast (16,44 -46).…”

Cortisol mobilizes mineral stores from vertebral skeleton in the European eel: an ancestral origin for glucocorticoid-induced osteoporosis?

“…In vivo models have provided many data on the deleterious effects of GC excess on bone (rat: Lindgren et al 1983, Jowell et al 1987, Goulding & Gold 1988mouse: Altman et al 1992, Weinstein et al 1998ewes: Chavassieux et al 1997;dogs: Quarles 1992). However, in vitro studies in rodents have been contradictory with either stimulation (rat: Gronowicz et al 1990; mouse: Reid et al 1986, Conaway et al 1996, Weinstein et al 2002 or inhibition (rat: Stern 1969, Raisz et al 1972, Tobias & Chambers 1989, Dempster et al 1997) of bone resorption.…”