title: Relative potencies of three glucocorticoids to induce hypoplasia of the physis and concomitant biochemical alterations in the rat.
abstract: Although inhaled glucocorticoids are known to have systemic effects on bone metabolism, there is little comparative information on their relative potencies. The effects of three standard glucocorticoids in causing changes in bone metabolism and growth, therefore, were investigated in relation to other systemic effects in the rat. Given to male Sprague-Dawley rats, 4.5-5.5 weeks old, subcutaneously (s.c.), at doses of 0.3-10 mg/kg daily for 7 days, beclomethasone dipropionate, prednisolone and ciclesonide all dose-dependently inhibited thymus body mass index (BMI) (by 57%, 44% and 76% at 3 mg/kg). Ciclesonide, potently and prednisolone, less effectively, also repressed femoral bone growth (by 41% and 18% at 10 mg/kg), significantly reducing body weight gain (both by 100% at 10 mg/kg), and serum concentrations of acid phosphatase (ACP) and tartarate resistant acid phosphatase (TRACP) (by >30% at 10 mg/kg); both increased serum glucose and triglycerides levels. Serum alkaline phosphatase (ALP) was not affected. Beclomethasone dipropionate had little or no effect on these additional variables. In conclusion, ciclesonide showed pronounced bone growth inhibiting activity after s.c. administration to the rat while other two glucocorticoids showed differences in activity on bone metabolism. However, this model is sufficiently sensitive and specific for testing the effect of glucocorticoids on bone metabolism.
authors.affiliation: Galapagos Research Centre Zagreb Limited , Zagreb , Croatia .
authors.forename: Boška
authors.initials: B
authors.lastname: Hrvačić
authors.forename: Kristina
authors.initials: K
authors.lastname: Šitum
authors.forename: Koraljka
authors.initials: K
authors.lastname: Đurić
authors.forename: Berislav
authors.initials: B
authors.lastname: Bošnjak
authors.forename: Željko
authors.initials: Ž
authors.lastname: Ferenčić
authors.forename: Karmen
authors.initials: K
authors.lastname: Brajša
authors.forename: Stribor
authors.initials: S
authors.lastname: Marković
authors.forename: Ines
authors.initials: I
authors.lastname: Glojnarić
mesh_terms: D000135:Acid Phosphatase / Q000097:blood; D000818:Animals; D001507:Beclomethasone / Q000633:toxicity*; D015415:Biomarkers / Q000097:blood; D001846:Bone Development / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005269:Femur / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D005938:Glucocorticoids / Q000633:toxicity*; D007527:Isoenzymes / Q000097:blood; D008297:Male; D009929:Organ Size; D011239:Prednisolone / Q000633:toxicity*; D011282:Pregnenediones / Q000633:toxicity*; D017207:Rats, Sprague-Dawley; D000071681:Tartrate-Resistant Acid Phosphatase; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology; D015430:Weight Gain / Q000187:drug effects
chemical_list: D015415:Biomarkers; D005938:Glucocorticoids; D007527:Isoenzymes; D011282:Pregnenediones; D011239:Prednisolone; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D001507:Beclomethasone; C120481:ciclesonide
keywords: Beclomethasone dipropionate; ciclesonide; growth plate; prednisolone; rat; serum phosphatases