Simvastatin improves fracture healing in mice
Simvastatin improves fracture healing in mice
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DOI：
10.1359/jbmr.2002.17.11.2004
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发表时间：
2002-11-01
影响因子：
6.2
通讯作者：
Aspenberg, P
中科院分区：
文献类型：
--
作者：
Skoglund, B;Forslund, C;Aspenberg, P
最近，已经发表了几篇关于他汀类药物对骨合成代谢影响的文章。Mundy及其同事发现，几种他汀类药物能够激活骨形态发生蛋白（BMP）2的启动子。此外，口服辛伐他汀和洛伐他汀增加大鼠松质骨体积，推测是BMP-2增加的作用。其他研究也随之而来，结果相互矛盾;一些人发现他汀类药物对骨代谢有积极影响，另一些人则没有。迄今为止发表的研究集中在骨质疏松症。在这项研究中，股骨骨折81成熟的雄性BALB/c小鼠和稳定的骨髓钉。给予41只小鼠用辛伐他汀制备的饲料，使得每只小鼠每天接受大约120 mg/kg体重的剂量。其余小鼠接受相同的饮食，除了辛伐他汀。分别于术后8、14、21天取双侧股骨，取出髓内钉，测量直径。通过三点弯曲的方式对42只小鼠进行生物力学测试。使用标准技术制备组织学标本。对于统计分析，使用ANOVA和Scheffe事后检验。在第8天，骨折骨痂太软，无法进行有意义的生物力学测试。在第14天，辛伐他汀治疗小鼠的骨痂横截面积比对照组大53%（p = 0.001），骨折所需的力大63%（p = 0.001），能量摄取增加150%（p = 0.0008）。刚度和弹性模量没有显着影响。21天时，骨折组织学愈合，力学差异消失。由于辛伐他汀治疗，对侧未断裂骨的横截面积略有增加，但对断裂骨所需的力或能量摄取没有显著影响。这些结果指出了骨折治疗的新可能性。
Recently, several articles have been published dealing with the anabolic effects on bone by statins. Mundy and associates discovered that several statins were able to activate the promotor of bone morphogenetic protein (BMP) 2. Additionally, oral simvastatin and lovastatin increased the cancellous bone volume in rats, presumably an effect of the increase of BMP-2. Other studies have followed, with conflicting results; some have found a positive bone metabolic effect of statins and others have not. Studies published so far have focused on osteoporosis. In this study, femur fractures were produced in 81 mature male BALB/c mice and stabilized with marrow-nailing. Forty-one mice were given a diet prepared with simvastatin, so that each mouse received an approximate dose of 120 mg/kg of body weight per day. The remaining mice received the same diet with the exception of the simvastatin. Bilateral femurs were harvested at 8, 14, and 21 days postoperatively (po), the marrow-nail was extracted, and diameters were measured. Biomechanical tests were performed on 42 mice, by way of three-point bending. Histological specimens were prepared using standard techniques. For statistical analysis, ANOVA with Scheffe's post hoc test was used. At 8 days, the fracture callus was too soft for meaningful biornechanical testing. At 14 days, the callus of the simvastatin-treated mice had a 53% larger transverse area than controls (p = 0.001), the force required to break the bone was 63% greater (p = 0.001), and the energy uptake was increased by 150% (p = 0.0008). Stiffness and modulus of elasticity were not significantly affected. At 21 days, the fractures were histologically healed and the mechanical differences had disappeared. The contralateral unbroken bone showed a slight increase in transverse area because of the simvastatin treatment, but there was no significant effect on the force required to break the bone or on energy uptake. These results point to a new possibility in the treatment of fractures.