Skoglund Bjorn, Forslund Carina, Aspenberg Per
Department of Neuroscience and Locomotion, Faculty of Health Sciences, Linkoping, Sweden.
J Bone Miner Res. 2002 Nov;17(11):2004-8. doi: 10.1359/jbmr.2002.17.11.2004.
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 Scheffés post hoc test was used. At 8 days, the fracture callus was too soft for meaningful biomechanical 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.
最近，有几篇文章发表，探讨了他汀类药物对骨骼的合成代谢作用。蒙迪及其同事发现，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可增加大鼠的松质骨体积，这可能是BMP - 2增加的结果。随后又有其他研究，但结果相互矛盾；一些研究发现他汀类药物对骨代谢有积极作用，而另一些则没有。迄今为止发表的研究主要集中在骨质疏松症方面。在本研究中，对81只成熟雄性BALB/c小鼠造成股骨骨折，并用髓内钉固定。41只小鼠给予含辛伐他汀的饮食，使每只小鼠每天摄入约120毫克/千克体重的剂量。其余小鼠接受不含辛伐他汀的相同饮食。术后第8、14和21天（po）采集双侧股骨，取出髓内钉并测量直径。对42只小鼠进行三点弯曲的生物力学测试。使用标准技术制备组织学标本。进行统计分析时，采用方差分析和谢费尔事后检验。在第8天，骨折痂太软，无法进行有意义的生物力学测试。在第14天，辛伐他汀治疗组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），能量吸收增加了150%（p = 0.0008）。刚度和弹性模量没有受到显著影响。在第21天，骨折在组织学上愈合，力学差异消失。由于辛伐他汀治疗，对侧未骨折的骨头横截面积略有增加，但对骨折所需的力或能量吸收没有显著影响。这些结果为骨折治疗指出了一种新的可能性。
