INSERM U606, University Paris 7, Hôpital Lariboisière, Paris, France.
Osteoporos Int. 2011 Jan;22(1):289-97. doi: 10.1007/s00198-010-1193-6. Epub 2010 Mar 4.
Young mice over-expressing Runx2 fail to gain bone relative to wild type mice with growth and present spontaneous fractures. It allows, for the first time in rodents, direct assessment of anti-fracture efficacy of strontium ranelate which was able to decrease caudal vertebrae fracture incidence through an improvement of trabecular and cortical architecture.
The aim was to investigate whether strontium ranelate was able to decrease fracture incidence in mice over-expressing Runx2, model of severe developmental osteopenia associated with spontaneous vertebral fractures.
Transgenic mice and their wild type littermates were treated by oral route with strontium ranelate or vehicle for 9 weeks. Caudal fracture incidence was assessed by repeated X-rays, resistance to compressive loading by biochemical tests, and bone microarchitecture by histomorphometry.
Transgenic mice receiving strontium ranelate had significantly fewer new fractures occurring during the 9 weeks of the study (-60%, p < 0.05). In lumbar vertebrae, strontium ranelate improves resistance to compressive loading (higher ultimate force to failure, +120%, p < 0.05) and trabecular microarchitecture (higher bone volume and trabecular number, lower trabecular separation, +60%, +50%, -39%, p < 0.05) as well as cortical thickness (+17%, p < 0.05). In tibiae, marrow cavity cross-section area and equivalent diameter were lower (-39%, -21%, p < 0.05). The strontium level in plasma and bone was in the same range as the values measured in treated postmenopausal women.
This model allows, for the first time, direct assessment of anti-fracture efficacy of strontium ranelate treatment in rodents. In these transgenic mice, strontium ranelate was able to decrease caudal vertebral fracture incidence through an improvement of trabecular and cortical architecture.
与野生型小鼠相比，过度表达 Runx2 的年轻小鼠的生长速度并未增加，并且出现自发性骨折。这使得首次能够在啮齿动物中直接评估雷奈酸锶的抗骨折疗效，雷奈酸锶能够通过改善小梁和皮质结构来降低尾部椎骨骨折的发生率。
目的是研究雷奈酸锶是否能够降低过度表达 Runx2 的小鼠的骨折发生率，该模型为与自发性椎体骨折相关的严重发育性骨质疏松症模型。
通过口服途径用雷奈酸锶或载体对转基因小鼠及其野生型同窝仔鼠进行治疗 9 周。通过重复 X 射线评估尾部骨折的发生率，通过生化试验评估抗压强度，通过组织形态计量学评估骨微观结构。
接受雷奈酸锶治疗的转基因小鼠在研究的 9 周内发生的新骨折明显减少（减少 60%，p<0.05）。在腰椎中，雷奈酸锶可改善抗压强度（极限破坏力更高，增加 120%，p<0.05）和小梁微观结构（骨体积和小梁数量更高，小梁分离度更低，分别增加 60%、50%和减少 39%，p<0.05）以及皮质厚度（增加 17%，p<0.05）。在胫骨中，骨髓腔横截面积和等效直径较低（分别减少 39%和 21%，p<0.05）。血浆和骨中的锶水平与接受治疗的绝经后妇女的测量值相同。
该模型首次允许在啮齿动物中直接评估雷奈酸锶治疗的抗骨折疗效。在这些转基因小鼠中，雷奈酸锶能够通过改善小梁和皮质结构来降低尾部椎体骨折的发生率。
