Orthopaedic Research Laboratory, Department of Orthopaedics O, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense C, Denmark.
Spine (Phila Pa 1976). 2010 Feb 15;35(4):363-70. doi: 10.1097/BRS.0b013e3181b8e0ff.
Glucocorticoid with low calcium and phosphorus intake induces osteopenia in cancellous bone of sheep.
To validate a large animal model for spine fusion and biomaterial research.
A variety of ovariectomized animals has been used to study osteoporosis. Most experimental spine fusions were based on normal animals, and there is a great need for suitable large animal models with adequate bone size that closely resemble osteoporosis in humans.
Eighteen female skeletal mature sheep were randomly allocated into 3 groups, 6 each. Group 1 (GC-1) received prednisolone (GC) treatment (0.60 mg/kg/day, 5 times weekly) for 7 months. Group 2 (GC-2) received the same treatment as GC-1 for 7 months followed by 3 months without treatment. Group 3 was left untreated and served as the controls. All sheep received restricted diet with low calcium and phosphorus during experiment. After killing the animals, cancellous bone specimens from the vertebra, femurs, and tibias were micro-CT scanned and tested mechanically. Serum biomarkers were determined.
In lumbar vertebra, the GC treatment resulted in significant decrease of cancellous bone volume fraction and trabecular thickness, and bone strength. However, the microarchitecture and bone strength of GC-2 recovered to a similar level of the controls. A similar trend of microarchitectural changes was also observed in the distal femur and proximal tibia of both GC treated sheep. The bone formation marker serum-osteocalcin was largely reduced in GC-1 compared to the controls, but recovered with a rebound increase at month 10 in GC-2.
The current investigation demonstrates that the changes in microarchitecture and mechanical properties were comparable with those observed in humans after long-term GC treatment. A prolonged GC treatment is needed for a long-term observation to keep osteopenic bone. This model resembles long-term glucocorticoid treated osteoporotic model, and is useful in preclinical studies.
低钙磷饮食联合糖皮质激素可导致绵羊松质骨骨质疏松。
验证脊柱融合及生物材料研究的大型动物模型。
多种去卵巢动物已被用于研究骨质疏松症。大多数实验性脊柱融合都是基于正常动物，因此非常需要具有足够骨大小且与人类骨质疏松症密切相似的合适大型动物模型。
18 只骨骼成熟的雌性绵羊被随机分为 3 组，每组 6 只。GC-1 组接受泼尼松龙（GC）治疗（0.60mg/kg/天，每周 5 次）7 个月。GC-2 组接受与 GC-1 相同的治疗 7 个月，然后停药 3 个月。第 3 组未接受治疗，作为对照组。所有绵羊在实验过程中均接受低钙磷限制饮食。处死动物后，对脊柱、股骨和胫骨的松质骨标本进行微 CT 扫描和力学测试。测定血清生物标志物。
腰椎处，GC 治疗导致松质骨体积分数和骨小梁厚度及骨强度显著降低。然而，GC-2 的微结构和骨强度恢复到与对照组相似的水平。GC 治疗羊的股骨远端和胫骨近端也观察到类似的微结构变化趋势。与对照组相比，GC-1 中血清骨钙素的骨形成标志物大大减少，但在 GC-2 中在第 10 个月时出现反弹增加。
目前的研究表明，微观结构和机械性能的变化与长期 GC 治疗后人类观察到的变化相似。需要长期 GC 治疗以长期观察维持骨质疏松状态。该模型类似于长期糖皮质激素治疗的骨质疏松模型，可用于临床前研究。
