The effects of hydrocortisone, parathyroid hormone and the bisphosphonate, APD, on bone resorption in neonatal mouse calvaria.
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.
Reid
I R
IR
Katz
J M
JM
Ibbertson
H K
HK
Gray
D H
DH
D000818:Animals; D000831:Animals, Newborn; D001862:Bone Resorption / Q000187:drug effects*; D001842:Bone and Bones / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004164:Diphosphonates / Q000494:pharmacology*; D004347:Drug Interactions; D006854:Hydrocortisone / Q000494:pharmacology*; D006909:Hydroxyproline / Q000096:biosynthesis; D051379:Mice; D009924:Organ Culture Techniques; D000077268:Pamidronate; D010281:Parathyroid Hormone / Q000494:pharmacology*; D012886:Skull
D004164:Diphosphonates; D010281:Parathyroid Hormone; D004247:DNA; D000077268:Pamidronate; D006909:Hydroxyproline; D002118:Calcium; D006854:Hydrocortisone