局部应用抗骨质疏松药物/因子预防骨质疏松骨折高发部位骨折发生的生物学机制研究

Osteoporotic fracture harms the life quality and health of the eldly seriously. Traditional methods to prevent osteoporotic fracture lasting a long period and has many adverse effects.Osteoporotic fracture always happens at the hip and the spine. Our early research show that BMP2 could improve local bone intensity and new bone formation at the injected site where osteoporotic fracture always happen. According to above result, we suggest that medicine or/and biological factors may could be used locally to prevent the happening of osteoporotic fracture. According to the osteoporotic pathogenesis, we plan to research the possibility of increasing local bone quality by using anti-absorptive medicine/new bone formation cellular factors slow-releasing system where osteoporotic fracture always happen, and to explore the possible biological mechanism. This research on biological mechanism of using medicine and cellular factors locally where osteoporotic fracture mostly happen would supply theory and experimental proofs on our suggestion of prevent osteoporotic fracture locally.

骨质疏松骨折严重危害老年人生命健康和生活质量。传统全身用药预防骨质疏松骨折治疗周期长、副作用多，而骨折疏松骨折高发于髋部和脊柱。我们前期研究显示：骨质疏松骨折高发部位局部应用复合了BMP2的缓释系统，可提高注射部位骨形成能力，改善局部骨强度。据此，我们提出了“局部应用药物/因子定向干预预防骨质疏松骨折发生”的新思路。针对骨质疏松发病机制主要为骨吸收增强与骨形成减弱这两个原因，基于在局部应用细胞因子可改善局部骨强度的研究基础，本课题拟研究促骨形成因子/抗骨吸收药物单独和复合局部应用改善骨质量的可行性，探索骨质疏松骨折高发部位局部应用药物/因子预防骨质疏松骨折发生的生物学机制，为抗骨质疏松药物/因子在局部长期、定向、有效释放，预防骨质疏松骨折高发部位骨折的发生提供实验和理论依据。

制备成功了壳聚糖缓释微球，并本别制备了rhBMP-2、唑来磷酸钠微球-生物蛋白胶双重缓释系统，该双重缓释系统具有缓释时间长、平稳释放药物的特点。采用去势方法制备了兔骨质疏松动物模型，分成rhBMP-2、ZOL、rhBMP-2/ZOL和假手术四组，并向股骨颈部注射上述药物缓释系统，结果显示：注射后第12周，B+Z组的BMD值、BV/TV值、Tb.N值、和Tb.Th值均明显高于NON组（P＜0.05），Tb.Sp值则明显低于NON组（P ＜0.05）；同时B+Z组最大剪切强度、最大剪应变及剪切弹性模量均明显高于NON组（P＜0.05）。由此，课题组得出以下结论：rhBMP-2和ZOL分别应用时，尽管作用机理并不相同，但均可提高骨质疏松动物局部骨密度，增加骨小梁的数量、厚度，降低骨小梁的间距，并增强骨的生物力学强度，rhBMP-2组部分上述指标要优于ZOL组。rhBMP-2和ZOL联合应用效果优于rhBMP-2或ZOL单独应用。课题组同时发现：重要天麻素可以抑制骨吸收因子的表达，从而通过改善成骨细胞凋亡和分化抑制及间接抑制破骨细胞活化来对骨质疏松起保护作用。截止结题时间，核心期刊发表中文论著1篇，申报国家发明专利一项。