Cui L, Cheng H, Song C, Li C, Simonet W S, Ke H Z, Li G
Guangdong Key Laboratory for R&D of Natural Drug, Guangdong Medical College, Zhanjiang 524023, Guangdong, PR China.
J Musculoskelet Neuronal Interact. 2013 Jun;13(2):178-84.
Treatment with Sclerostin antibody (Scl-Ab) has shown to enhance fracture healing in rodent and non-human primate models. The current study investigated the time-dependent changes during Scl-Ab treatment in a mouse osteotomy model.
1 day after osteotomy, C57BL mice received subcutaneous injection with vehicle or Scl-Ab at 25 mg/kg, twice/week for 2, 4, or 6 weeks. 20 mice from each group were necropsied at weeks 2, 4, and 6 for Micro-CT, histomorphmetry and mechanical testing examinations.
The bone mineral apposition rate at fracture callus was significantly higher in the Scl-Ab treated groups at all the time points. Micro-CT analysis showed that the volumetric bone mineral density (vBMD) and bone volume over tissue volume (BV/TV) in the Scl-Ab treated groups at 4 and 6 weeks were significantly greater than that of vehicle control groups. Mechanical testing showed that the maximum load of failure at the fracture callus increased significantly by 68% at 6 weeks in the Scl-Ab treated groups.
This study confirmed that mice treated with Scl-Ab increased bone formation from 2 weeks, bone mineral density and bone volume at 4 weeks, followed by significant increase in bone strength at the fracture site at 6 weeks. These results suggest that applying sclerostin antibody at early stage fracture healing promotes fracture healing.
在啮齿动物和非人类灵长类动物模型中，使用硬化蛋白抗体（Scl-Ab）治疗已显示可促进骨折愈合。本研究在小鼠截骨模型中调查了Scl-Ab治疗期间随时间的变化。
截骨术后1天，C57BL小鼠皮下注射赋形剂或25mg/kg的Scl-Ab，每周两次，持续2、4或6周。每组20只小鼠在第2、4和6周进行尸检，以进行微型计算机断层扫描（Micro-CT）、组织形态计量学和力学测试检查。
在所有时间点，Scl-Ab治疗组骨折痂处的骨矿物质沉积率均显著更高。Micro-CT分析显示，Scl-Ab治疗组在第4周和第6周时的体积骨矿物质密度（vBMD）和骨体积与组织体积之比（BV/TV）显著高于赋形剂对照组。力学测试表明，Scl-Ab治疗组在第6周时骨折痂处的最大破坏载荷显著增加了68%。
本研究证实，用Scl-Ab治疗的小鼠在2周时骨形成增加，4周时骨矿物质密度和骨体积增加，随后在6周时骨折部位的骨强度显著增加。这些结果表明，在骨折愈合早期应用硬化蛋白抗体可促进骨折愈合。
