Department of Orthopaedics, University of Medicine, Dentistry of New Jersey-New Jersey Medical School, 185 South Orange Avenue, 90 Bergen Street, Suite 7300, Newark, NJ 07103, USA.
J Orthop Res. 2013 May;31(5):776-82. doi: 10.1002/jor.22287. Epub 2012 Dec 13.
A significant number of lower extremity fractures result in mal-union necessitating effective treatments to restore ambulation. Prior research in diabetic animal fracture models demonstrated improved healing following local insulin application to the fracture site and indicated that local insulin therapy can aid bone regeneration, at least within an insulin-dependent diabetic animal model. This study tested whether local insulin therapy could accelerate femur fracture repair in normal, non-diabetic rats. High (20 units) and low (10 units) doses of insulin were delivered in a calcium sulfate carrier which provided sustained release of the exogenous insulin for 7 days after fracture. Histomorphometry, radiographic scoring, and torsional mechanical testing were used to measure fracture healing. The fracture calluses from rats treated with high-dose insulin had significantly more cartilage than untreated rats after 7 and 14 days of healing. After 4 weeks of healing, femurs from rats treated with low-dose insulin had significantly higher radiographic scores and mechanical strength (p < 0.05), compared to the no treatment control groups. The results of this study suggest that locally delivered insulin is a potential therapeutic agent for treating bone fractures. Further studies are necessary, such as large animal proof of concepts, prior to the clinical use of insulin for bone fracture treatment.
大量的下肢骨折导致畸形愈合，需要有效的治疗方法来恢复步行能力。先前在糖尿病动物骨折模型中的研究表明，局部应用胰岛素到骨折部位可以改善愈合，并表明局部胰岛素治疗可以促进骨再生，至少在胰岛素依赖型糖尿病动物模型中是这样。本研究测试了局部胰岛素治疗是否可以加速正常非糖尿病大鼠的股骨骨折修复。在硫酸钙载体中给予高（20 单位）和低（10 单位）剂量的胰岛素，在骨折后 7 天内持续释放外源性胰岛素。组织形态计量学、影像学评分和扭转力学测试用于测量骨折愈合。在 7 天和 14 天愈合后，接受高剂量胰岛素治疗的大鼠的骨折痂中软骨含量明显多于未治疗的大鼠。在 4 周的愈合后，与未治疗对照组相比，接受低剂量胰岛素治疗的大鼠的 X 线评分和机械强度显著更高（p < 0.05）。本研究的结果表明，局部给予胰岛素是治疗骨骨折的一种有潜力的治疗剂。在胰岛素用于骨骨折治疗的临床应用之前，还需要进行大动物概念验证等进一步的研究。
