Skoglund Björn, Aspenberg Per
Division of Orthopedics and Sports Medicine, Department of Neuroscience and Locomotion, Faculty of Health Sciences, Linköping University, SE 581 85 Linkoping, Sweden.
BMC Musculoskelet Disord. 2007 Sep 27;8:98. doi: 10.1186/1471-2474-8-98.
HMG-CoA reductase inhibitors, statins, are widely prescribed to lower cholesterol. High doses of orally administered simvastatin has previously been shown to improve fracture healing in a mouse femur fracture model. In this study, simvastatin was administered either subcutaneously or directly to the fracture area, with the goal of stimulating fracture repair at acceptable doses.
Femur fractures were produced in 70 mature male Balb-C mice and stabilized with marrow-nailing. Three experiments were performed. Firstly, 20 mice received subcutaneous injections of either simvastatin (20 mg) or vehicle. Secondly, 30 mice were divided into three groups of 10 mice receiving continuous subcutaneous delivery of the vehicle substance, the vehicle with 5 mg or with 10 mg of simvastatin per kg bodyweight per day. Finally, in 20 mice, a silicone tube was led from an osmotic mini-pump to the fracture area. In this way, 10 mice received an approximate local dose of simvastatin of 0.1 mg per kg per day for the duration of the experiment and 10 mice received the vehicle compound. All treatments lasted until the end of the experiment. Bilateral femurs were harvested 14 days post-operative. Biomechanical tests were performed by way of three-point bending. Data was analysed with ANOVA, Scheffé's post-hoc test and Student's unpaired t-test.
With daily simvastatin injections, no effects could be demonstrated for any of the parameters examined. Continuous systemic delivery resulted in a 160% larger force at failure. Continuous local delivery of simvastatin resulted in a 170% larger force at failure as well as a twofold larger energy uptake.
This study found a dramatic positive effect on biomechanical parameters of fracture healing by simvastatin treatment directly applied to the fracture area.
HMG-CoA还原酶抑制剂，即他汀类药物，被广泛用于降低胆固醇。先前已证明，高剂量口服辛伐他汀可改善小鼠股骨骨折模型中的骨折愈合情况。在本研究中，通过皮下注射或直接注射到骨折部位给予辛伐他汀，目的是以可接受的剂量刺激骨折修复。
对70只成熟雄性Balb-C小鼠制造股骨骨折，并采用髓内钉固定。进行了三项实验。首先，20只小鼠皮下注射辛伐他汀（20毫克）或赋形剂。其次，30只小鼠分为三组，每组10只，分别接受持续皮下注射赋形剂、每天每千克体重含5毫克或10毫克辛伐他汀的赋形剂。最后，在20只小鼠中，将硅胶管从渗透微型泵引至骨折部位。通过这种方式，10只小鼠在实验期间接受每天每千克约0.1毫克的辛伐他汀局部剂量，10只小鼠接受赋形剂化合物。所有治疗持续到实验结束。术后14天采集双侧股骨。通过三点弯曲进行生物力学测试。数据采用方差分析、谢费事后检验和学生非配对t检验进行分析。
每日注射辛伐他汀，未发现对所检测的任何参数有影响。持续全身给药导致破坏时的力增大160%。辛伐他汀持续局部给药导致破坏时的力增大170%，以及能量吸收增加两倍。
本研究发现，直接应用于骨折部位的辛伐他汀治疗对骨折愈合的生物力学参数有显著的积极影响。
