Lovastatin combined with insulin effects on fracture healing in rat models of bilateral ovariectomized type 2 diabetic mellitus / 中国组织工程研究

ABSTRACT

BACKGROUND: Osteoporotic fracture combined with type 2 diabetic mellitus in female patients is often accompanied by dyslipidemia and hyperglycemia. In addition to insulin treatment, statins are often prescribed for combination therapy, but the combined effect of these two drugs on fracture healing has not been reported in such patients. OBJECTIVE; To investigate the effect of lovastatin combined with insulin on the fracture healing of bilateral ovariectomized rats suffering from type 2 diabetic mellitus. METHODS: The study was approved by the Ethical Committee of North China University of Science and Technology. Thirty-two female Sprague-Dawley rats were divided into control, diabetic ovariectomized, insulin and combined groups. A model of type 2 diabetes and osteoporosis fracture was established in all rats except for the control group. At 7 days after the type 2 diabetic model was successfully established by injection of streptozotocin, the rats in the insulin and combined groups received the subcutaneous injection of insulin (2-4 U in the morning, and 4-6 U in the evening) until the end of the experiment. The rats in the combined group were given 20 mg/kg lovastatin via gavage daily, and those in the other two groups were not treated. All rats were sacrificed at 3 weeks after fracture. Radiographic, clinical and histomorphometric detections of the callus were performed. The expression levels of bone morphogenetic protein 2, vascular endothelial growth factor and collagen type II were detected. All above results were used to analyze the fracture healing in each group. RESULTS AND CONCLUSION: (1)The radiographic score, micro-CT index, histologic score and the expression levels of vascular endothelial growth factor and collagen type II in the diabetic ovariectomized group were significantly poorer than those in the control group (P < 0.05). (2) All above indexes in the insulin group were significantly improved compared with the diabetic ovariectomized group (P < 0.05), which promoted the fracture healing of model rats. (3) After combined with lovastatin, although the expression levels of vascular endothelial growth factor and bone morphogenetic protein 2 in the callus were significantly increased (P < 0.05), there was no significant improvement in the radiographic appearance and microstructure of the callus.