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糖皮质激素治疗对骨强度的影响。

Effects of glucocorticoid treatment on bone strength.

机构信息

ORC, Creighton University, Suite 4820, 610N, 30th Street, Omaha, NE 68131, USA.

出版信息

J Bone Miner Metab. 2010 Sep;28(5):532-9. doi: 10.1007/s00774-009-0156-5. Epub 2010 Jan 27.

Abstract

Glucocorticoids (GCs) are prescribed for the treatment of several diseases, but their long-term use causes osteoporosis. Current research suggests that GCs suppress the canonical Wnt/beta pathway, resulting in decreased expression of critical bone proteins. This study examined how bone structure and strength of high bone mass (HBM) mice and low density lipoprotein receptor-related protein 5 (LRP5) knockout (KO+/-) mice are affected by GC treatment in comparison to wild-type (WT) mice, and if changes were specific to either trabecular or cortical bone. Mice were treated with either prednisone or placebo. The femurs and L4 vertebral bodies were analyzed by micro-CT for structure and mechanically tested to determine strength and apparent material strength properties. Differences in all measured variables corresponding to GC treatment and genotype were tested using two-way ANOVA. GC treatment caused decreased structural strength parameters, weakened apparent material strength properties, and disruption of bone structure in HBM, but not LRP5+/- or WT, mice. Despite treatment-related loss, trabecular bone structure and strength remained elevated as compared to LRP5+/- and WT mice. In HBM femurs, both cortical and trabecular structure, but not strength parameters, were negatively affected by treatment. In HBM vertebral bodies, both structural and strength parameters were negatively affected by treatment.

摘要

糖皮质激素(GCs)被用于治疗多种疾病,但长期使用会导致骨质疏松症。目前的研究表明,GCs 抑制了经典的 Wnt/β 通路,导致关键骨蛋白的表达减少。本研究比较了高骨量(HBM)小鼠和低密度脂蛋白受体相关蛋白 5(LRP5)敲除(KO+/-)小鼠与野生型(WT)小鼠在 GC 治疗下的骨结构和骨强度如何受到影响,以及这些变化是否特定于小梁骨或皮质骨。用泼尼松龙或安慰剂对小鼠进行治疗。通过 micro-CT 分析股骨和 L4 椎体的结构,并进行机械测试以确定强度和表观材料强度特性。使用双因素方差分析检验与 GC 治疗和基因型相关的所有测量变量的差异。GC 治疗导致 HBM 小鼠的结构强度参数降低、表观材料强度特性减弱以及骨结构破坏,但 LRP5+/-或 WT 小鼠没有。尽管存在与治疗相关的损失,但与 LRP5+/-和 WT 小鼠相比,小梁骨结构和强度仍然较高。在 HBM 股骨中,皮质骨和小梁骨的结构都受到了治疗的负面影响,但强度参数没有受到影响。在 HBM 椎体中,结构和强度参数都受到了治疗的负面影响。

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