Glucocorticoids stimulate resorption in fetal rat parietal bones in vitro

Abstract

The effect of glucocorticoids on bone resorption was examined in a serum-free mineralizing organ culture system derived from 20 day fetal rat parietal bones. Bone resorption was assessed by prelabeling the fetal rats in utero with 45Ca and determining the daily release of 45Ca into the medium of cultured bones. During the first 24 h of treatment a transient stimulation of bone resorption was found; 4.5 +/- 0.3% of the total 45Ca was released into the medium with 1 nM corticosterone and 4.1 +/- 0.2% with 10 nM corticosterone compared to 2.9 +/- 0.2% in control bones. Treatment with 1 and 10 nM dexamethasone for 24 h also showed an increase in 45Ca release compared to control bones. During the same time period 45Ca release was 6.9 +/- 1.4% with 10 nM parathyroid hormone. At later time points 100 and 1000 nM corticosterone inhibited 45Ca release, but 1 and 10 nM corticosterone values were similar to controls. At 24 h the number of osteoclasts per mm2 tissue in bone lacunae was significantly elevated with 1-100 nM corticosterone and 10 nM parathyroid hormone compared to control bones. In control bones 0.10 +/- 0.05 osteoclasts per mm2 of tissue were found, but 0.59 +/- 0.21 osteoclasts per mm2 were seen with 10 nM corticosterone and 1.50 +/- 0.34 with 10 nM parathyroid hormone. An additional assay of bone resorption, the release of lysosomal beta-glucuronidase into the medium was also elevated in glucocorticoid and parathyroid hormone-treated cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

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

“…By contrast, other authors indicated a stimulatory effect of GC on osteoclastic resorption in rodents. Some studies have suggested a possible direct effect of GC on osteoclast-mediated bone resorption, as stimulation of bone osteoclastic resorption by GC was observed in organ cultures of fetal rat parietal bones and neonatal mouse calvariae (Gronowicz et al 1990, Conaway et al 1996. Furthermore, GC has been shown to stimulate osteoclast formation in bone marrow cultures in the mouse (Shuto et al 1994) and to extend the life span of preexisting osteoclasts in murine osteoclast cultures (Weinstein et al 2002).…”

“…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.…”

Alteration in Bone Mineral Metabolism in Children with Acute Lymphoblastic Leukemia (ALL): A Review

“…The stimulation may be due to an increase in osteoclast activity and is in accordance with effects observed in vivo. The mechanism of this increased activity is not known although it could involve the induction of interleukin-6(k-6) receptors in skeletal cells 21 .…”

Bone mineral metabolism in pediatric inflammatory bowel disease

“…Defective hepatic metabolism may be an additional important factor if IBDrelated liver disease develops (5 1). The iatrogenic effects of drug therapy, especially corticosteroids, cannot be underestimated (52)(53)(54)(55)(56).…”

“…Corticosteroids have been recognized to profoundly affect bone mineral metabolism in children and adolescents (53). A variety of mechanisms have been proposed: reduced calcium absorption, down-regulation of calcitriol synthesis, decreased gene expression of calcium binding protein, inhibition of osteoblast proliferation, and stimulation of bone resorption by osteoclasts (52)(53)(54)(55)(56). Pediatricians have emphasized the role of nutritional therapy in preference to corticosteroid therapy in the treatment of CD in an attempt to modify the double insult of decreased nutrient intake and inflammation during the years critical to growth and calcium deposition (6 1-64),…”