(9R)-9-chloro-11-17-dihydroxy-17-(2-hydroxy-1-oxoethyl)-10-13-16-trimethyl-6-7-8-11-12-14-15-16-octahydrocyclopenta[a]phenanthren-3-one and Weight-Gain

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.

Topics: Acid Phosphatase; Animals; Beclomethasone; Biomarkers; Bone Development; Dose-Response Relationship, Drug; Femur; Glucocorticoids; Isoenzymes; Male; Organ Size; Prednisolone; Pregnenediones; Rats, Sprague-Dawley; Tartrate-Resistant Acid Phosphatase; Thymus Gland; Weight Gain

Mometasone furoate (MF) is a topical glucocorticoid used for atopic dermatitis, allergic rhinitis, and bronchial asthma. To elucidate the usefulness of MF, the dissociation between local anti-inflammatory effects and systemic effects of MF was compared with that of beclomethasone 17,21-dipropionate (BDP). MF was more potent than BDP in croton oil-induced ear edema tests in mice. Oral systemic effects of MF were inversely lower than that of BDP on thymolysis, plasma corticosterone lowering, and suppression of body weight gain in mice. These results indicate that MF has a higher therapeutic index and superior clinical usefulness as a topical glucocorticoid compared to BDP.

Topics: Administration, Oral; Administration, Topical; Animals; Anti-Inflammatory Agents; Beclomethasone; Corticosterone; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Male; Mice; Mice, Inbred ICR; Mometasone Furoate; Pituitary-Adrenal System; Pregnadienediols; Thymus Gland; Weight Gain