Influence of glucocorticoid on bone in 3-, 6-, and 12-month-old rats as determined by bone mass and histomorphometry.
The influence of glucocorticoid (GC) on bone in rats at different ages was investigated in order to provide insight into human glucocorticoid induced osteoporosis (GCOP). Three-, 6-, and 12-month-old female Wistar rats were divided into four groups: Zero-time control (ZT), vehicle (Cont), prednisolone (PSL) 2 mg/kg (P-L), PSL 20 mg/kg (P-H). PSL was subcutaneously administered every day for 4 weeks. Bone mineral density (BMD) at the proximal metaphysis and diaphysis of the tibia was measured by peripheral quantitative computed tomography. Histomorphometry of the tibia was performed for 3- and 6-month-old rats. GC increased trabecular and cortical BMD at the metaphysis in all 3-month-old rats with time. Trabecular BMD at the metaphysis in the P-L and P-H groups was significantly higher than in the control group. Histomorphometric parameters for both bone formation and resorption were also increased by GC treatment. In the 6-month-old rats, the metaphyseal trabecular BMD did not significantly change in any group, but the diaphyseal trabecular BMD significantly increased in the control group with time. The trabecular BMD of the metaphysis and diaphysis was significantly lower in the P-L and P-H groups than in the control group at week 4. Histomorphometric parameters for bone formation and resorption were both reduced by GC treatment. The BMD remained unchanged in all 12-month-old rats. Six-month-old rats treated with 20 mg/kg GC are suitable models for GC-induced osteoporosis with dominant cancellous bone decrease and reduced bone turnover. The pathology induced by 20 mg/kg prednisolone in 6-month-old female rats seems to be most similar to glucocorticoid-induced osteoporosis in humans.
Ogoshi
Tomofumi
T
Department of Orthopedic Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, Tottori, 683-8504, Japan. tomofumi-o@nifty.com
Hagino
Hiroshi
H
Fukata
Satoru
S
Tanishima
Shinji
S
Okano
Toru
T
Teshima
Ryota
R
D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects*; D001862:Bone Resorption / Q000188:drug therapy; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D010012:Osteogenesis / Q000187:drug effects; D010024:Osteoporosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D011239:Prednisolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013977:Tibia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014057:Tomography, X-Ray Computed
D005938:Glucocorticoids; D011239:Prednisolone; C021322:prednisolone hemisuccinate