Glucocorticoid-induced osteopenia in the mouse as assessed by histomorphometry, microcomputed tomography, and biochemical markers
Glucocorticoid-induced osteopenia in the mouse as assessed by histomorphometry, microcomputed tomography, and biochemical markers
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DOI：
10.1016/s8756-3282(02)00737-8
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发表时间：
2002-06-01
期刊：
影响因子：
4.1
通讯作者：
Farrow, SN
中科院分区：
文献类型：
--
作者：
McLaughlin, F;Mackintosh, J;Farrow, SN
糖皮质激素是有效的抗炎分子，用于治疗哮喘、类风湿性关节炎、炎性肠病和其他炎性和皮肤病，以及移植后免疫治疗。虽然糖皮质激素已被处方多年，但口服给药时，其潜在的副作用可能会阻止其长期使用。临床上观察到的最严重的副作用是糖皮质激素诱导的骨质疏松症（GIOP）。为了开发一种小动物模型来表征糖皮质激素诱导的骨丢失，我们使用BALB/c小鼠进行了一系列实验，每天腹腔内给予合成糖皮质激素地塞米松。通过标准组织形态计量学评估，地塞米松治疗后，小鼠出现骨质减少，骨形成率和矿物质沉积率显着下降。此外，地塞米松治疗3周导致骨小梁厚度和骨小梁数量减少，股骨远端骨小梁的表面积与体积比增加，如使用显微计算机断层扫描（micro-CT）测量的。血清骨形成标志物骨钙素在所有地塞米松治疗的小鼠中呈剂量依赖性降低，并显示出与骨形成率变化平行的调节程度。此外，血清瘦素水平，最近被确定为在调节骨量中发挥作用，增加地塞米松治疗后。因此，BALB/c小鼠代表了一个有用的模型系统，其中糖皮质激素对骨的有害影响可以进行研究。(C)2002年，Elsevier Science Inc. All rights reserved.
Glucocorticoids are potent anti-inflammatory molecules used in the treatment of asthma, rheumatoid arthritis, inflammatory bowel disease, and other inflammatory and dermatological diseases, as well as in postitransplantation immunotherapy. Although glucocorticoids have been prescribed for many years, their potential side effects, when administered orally, can prevent their long-term use. The most serious side effect observed in the clinic is glucocorticoid-induced osteoporosis (GIOP). To develop a small animal model to characterize glucocorticoid-induced bone loss, we carried out a series of experiments using BALB/c mice given daily intraperitoneal doses of the synthetic glucocorticoid, dexamethasone. Following dexamethasone treatment, the mice became osteopenic, with highly significant decreases in bone formation rate and mineral apposition rate, as assessed by standard histomorphometry. Moreover, 3 week treatment with dexamethasone resulted in a decrease in trabecular thickness and trabecular number with an increase in surface-to-volume ratio of trabeculae in the distal femur, as measured using microcomputed tomography (micro-CT). The serum bone formation marker, osteocalcin, was dose-dependently decreased in all mice treated with dexamethasone and showed a parallel extent of regulation to the bone formation rate changes. In addition, serum levels of leptin, recently identified as playing a role in the regulation of bone mass, increased following dexamethasone treatment. BALB/c mice therefore represent a useful model system in which the detrimental effects of glucocorticoids on bone can be studied. (C) 2002 by Elsevier Science Inc. All rights reserved.