Zarrinkalam Mohammad-Reza, Schultz Christopher G, Parkinson Ian H, Moore Robert J
The Adelaide Centre for Spinal Research, SA Pathology, Adelaide, Australia ; Hanson Institute, SA Pathology, Adelaide, Australia.
J Osteoporos. 2012;2012:182509. doi: 10.1155/2012/182509. Epub 2012 Oct 2.
A validated ovine model of osteoporosis achieves severe bone loss in a relatively short period. This study investigated if osteoporotic features persist in this model after cessation of corticosteroid administration. Methods. Osteoporosis was induced in nine ewes by chronic corticosteroid injection, ovariectomy, and low calcium diet. Six ewes were used as controls. Bone mineral density (BMD) of the lumbar spine (LS) and body weight were assessed at regular intervals. After five months, corticosteroid treatment was withdrawn systematically over one month. Three months later, all animals were euthanised, and the LS was collected for histomorphometric analysis. Results. BMD in the LS of osteoporotic sheep was 25% lower than control sheep. Body weight of osteoporotic sheep was reduced in the first month of the corticosteroid withdrawal period but returned to baseline level thereafter. Trabecular bone volume of LS in osteoporotic sheep was 27% lower than controls and showed a heterogeneous structure. Conclusions. Osteoporotic characteristics remain in the vertebra after ceasing corticosteroid administration providing an opportunity to evaluate potential systemic or local treatments in vivo under realistic physiological conditions. The microstructural arrangement of vertebral trabecular bone in sheep is similar to humans demonstrating further relevance of this model for preclinical investigations.
一种经过验证的骨质疏松症绵羊模型在相对较短的时间内实现了严重的骨质流失。本研究调查了在停止给予皮质类固醇后,该模型中的骨质疏松特征是否仍然存在。方法。通过慢性皮质类固醇注射、卵巢切除术和低钙饮食诱导9只母羊患骨质疏松症。6只母羊用作对照。定期评估腰椎(LS)的骨矿物质密度(BMD)和体重。五个月后,在一个月内系统地停止皮质类固醇治疗。三个月后,对所有动物实施安乐死,并收集腰椎进行组织形态计量分析。结果。骨质疏松症绵羊腰椎的骨密度比对照绵羊低25%。骨质疏松症绵羊的体重在停止皮质类固醇治疗期的第一个月有所下降,但此后恢复到基线水平。骨质疏松症绵羊腰椎的小梁骨体积比对照低27%,且结构不均一。结论。停止给予皮质类固醇后,椎骨中的骨质疏松特征仍然存在,这为在现实生理条件下体内评估潜在的全身或局部治疗提供了机会。绵羊椎骨小梁骨的微观结构排列与人类相似,表明该模型在临床前研究中具有更大的相关性。