Dosing-time dependent effect of dexamethasone on bone density in rats

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• 作者：Masaki Takahashi ; Kentarou Ushijima ; Yohei Hayashi ; Tomohiro Maekawa ; Hitoshi Ando ; Shu-ichi Tsuruoka ; Akio Fujimura
• 关键词：Chronopharmacology ; Dexamethasone ; Osteoclasts ; Osteoporosis ; Urinary calcium
• 刊名：Life Sciences
• 出版年：2010
• 出版时间：2 January 2010
• 年：2010
• 卷：86
• 期：1-2
• 页码：24-29
• 全文大小：519 K

文摘

Aims

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.

Main methods

Rats were administered with dexamethasone (Dex) orally (1 mg/kg/day) for 6 weeks 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.

Key findings

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.

Significance

This study shows that the decrease in bone density induced by Dex was changed by its dosing-time.