Ogoshi Tomofumi, Hagino Hiroshi, Fukata Satoru, Tanishima Shinji, Okano Toru, Teshima Ryota
Department of Orthopedic Surgery, School of Medicine, Tottori University Faculty of Medicine, 36-1 Nishi-cho, Yonago, Tottori, 683-8504, Japan.
Mod Rheumatol. 2008;18(6):552-61. doi: 10.1007/s10165-008-0096-2. Epub 2008 Jul 23.
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.
为深入了解人类糖皮质激素性骨质疏松症（GCOP），研究了糖皮质激素（GC）对不同年龄大鼠骨骼的影响。将3个月、6个月和12个月大的雌性Wistar大鼠分为四组：零时对照组（ZT）、溶剂对照组（Cont）、泼尼松龙2mg/kg组（P-L）、泼尼松龙20mg/kg组（P-H）。每天皮下注射PSL，持续4周。通过外周定量计算机断层扫描测量胫骨近端干骺端和骨干的骨密度（BMD）。对3个月和6个月大的大鼠进行胫骨组织形态计量学分析。随着时间的推移，GC使所有3个月大大鼠干骺端的小梁骨和皮质骨BMD增加。P-L组和P-H组干骺端的小梁骨BMD显著高于对照组。GC治疗还增加了骨形成和骨吸收的组织形态计量学参数。在6个月大大鼠中，任何组的干骺端小梁骨BMD均无显著变化，但对照组的骨干小梁骨BMD随时间显著增加。在第4周时，P-L组和P-H组干骺端和骨干的小梁骨BMD显著低于对照组。GC治疗使骨形成和骨吸收的组织形态计量学参数均降低。所有12个月大大鼠的BMD保持不变。用20mg/kg GC治疗的6个月大大鼠是GC诱导的骨质疏松症的合适模型，其特征为松质骨明显减少和骨转换降低。20mg/kg泼尼松龙在6个月大雌性大鼠中诱导的病理变化似乎与人类糖皮质激素性骨质疏松症最为相似。
