Dosing-time dependent effect of dexamethasone on bone density in rats.
OBJECTIVE
While glucocorticoids are widely used to treat patients with various diseases, they often cause adverse effects such as bone fractures. In this study, we investigated whether the decrease in bone density induced by glucocorticoid therapy was ameliorated by optimizing a dosing-time.


METHODS
Rats were administered with dexamethasone (Dex) orally (1mg/kg/day) for 6weeks at a resting or an active period. After the end of the treatment, bone density of femur, biomarkers of bone formation and resorption, and other biomedical variables were measured.


RESULTS
Bone density of femur was significantly decreased by the 6-week treatment with Dex, and the degree of decrease in the 14 HALO (hours after light on) dosing group (an active period) was larger than that in the 2 HALO dosing group (a resting period). Although urinary calcium excretion was accelerated by Dex treatment, secondary hyperparathyroidism was not detected. Histomorphometry analysis showed that Dex suppressed bone resorption, which was larger in the 2 HALO than in the 14 HALO groups. These data indicate that Dex equally suppressed bone formation in the 2 and 14 HALO groups, but inhibited bone resorption more in the 2 HALO than in the 14 HALO groups.


CONCLUSIONS
This study shows that the decrease in bone density induced by Dex was changed by its dosing-time.
Takahashi
Masaki
M
Division of Clinical Pharmacology, Department of Pharmacology, Jichi Medical University, Tochigi 329-0498, Japan.
Ushijima
Kentarou
K
Hayashi
Yohei
Y
Maekawa
Tomohiro
T
Ando
Hitoshi
H
Tsuruoka
Shu-ichi
S
Fujimura
Akio
A
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects*; D001862:Bone Resorption / Q000175:diagnosis; D002118:Calcium / Q000097:blood / Q000652:urine; D024042:Collagen Type I / Q000652:urine; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects*; D004334:Drug Administration Schedule; D004435:Eating / Q000187:drug effects; D005269:Femur / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D008297:Male; D015675:Osteocalcin / Q000097:blood; D010281:Parathyroid Hormone / Q000097:blood; D051381:Rats; D017208:Rats, Wistar
D024042:Collagen Type I; D005938:Glucocorticoids; D010281:Parathyroid Hormone; D015675:Osteocalcin; D003907:Dexamethasone; D002118:Calcium