Department of Veterinary Sciences, Agricultural and Veterinary Sciences School, University of Trás-os-Montes e Alto Douro (UTAD), Quinta de Prados, 5000-801, Vila Real, Portugal.
3B's Research Group-Biomaterials, Biodegradables and Biomimetics, Department of Polymer Engineering, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark-Parque da Ciência e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017, Guimarães, Portugal.
Curr Osteoporos Rep. 2018 Apr;16(2):182-197. doi: 10.1007/s11914-018-0431-2.
This review summarizes research on the use of sheep and goats as large animal models of human osteoporosis for preclinical and translational studies.
The most frequent osteoporotic sheep model used is the ovariectomized sheep with 12 months post-operatively or more and the combined treatment of ovariectomized sheep associated to calcium/vitamin D-deficient diet and glucocorticoid applications for 6 months, but other methods are also described, like pinealectomy or hypothalamic-pituitary disconnection in ovariectomized sheep. The goat model for osteoporosis research has been used in a very limited number of studies in osteoporosis research relative to sheep. These osteoporotic small ruminant models are applied for biomaterial research, bone augmentation, efficacy of implant fixation, fragility fracture-healing process improvement, or bone-defect repair studies in the osteopenic or osteoporotic bone. Sheep are a recognized large animal model for preclinical and translational studies in osteoporosis research and the goat to a lesser extent. Recently, the pathophysiological mechanism underlying induction of osteoporosis in glucocorticoid-treated ovariectomized aged sheep was clarified, being similar to what occurs in postmenopausal women with glucocorticoid-induced osteoporosis. It was also concluded that the receptor activator of NF-κB ligand was stimulated in the late progressive phase of the osteoporosis induced by steroids in sheep. The knowledge of the pathophysiological mechanisms at the cellular and molecular levels of the induction of osteoporosis in small ruminants, if identical to humans, will allow in the future, the use of these animal models with greater confidence in the preclinical and translational studies for osteoporosis research.
本综述总结了绵羊和山羊作为人类骨质疏松症大动物模型在临床前和转化研究中的应用研究。
最常使用的骨质疏松绵羊模型是术后 12 个月或更长时间的去卵巢绵羊，以及去卵巢绵羊联合钙/维生素 D 缺乏饮食和糖皮质激素应用 6 个月的治疗，但是也描述了其他方法，如去卵巢绵羊的松果切除术或下丘脑-垂体切除术。骨质疏松症研究中使用的山羊模型在骨质疏松症研究中相对较少。这些骨质疏松症小反刍动物模型应用于生物材料研究、骨增强、植入物固定效果、脆弱性骨折愈合过程的改善或骨质疏松性或骨质疏松性骨的骨缺损修复研究。绵羊是骨质疏松症临床前和转化研究的公认大动物模型，山羊的应用程度较小。最近，糖皮质激素治疗去卵巢老年绵羊诱导骨质疏松症的病理生理机制得到了阐明，类似于绝经后妇女的糖皮质激素诱导性骨质疏松症。还得出结论，在绵羊类固醇诱导的骨质疏松症的晚期进展阶段，NF-κB 配体受体激活剂受到刺激。如果小反刍动物诱导骨质疏松症的细胞和分子水平的病理生理机制与人类相同，那么在未来，这些动物模型将在骨质疏松症的临床前和转化研究中得到更广泛的应用。
