Evaluation of Simvastatin in the Process of Fracture Healing in Tibiae of Rats

Abstract

Objective Evaluate the effects of simvastatin in the process of fracture healing in rat tibia. Methods Thirty-six rats were subjected to diaphyseal fracture of the leg bones and divided in the statin group (GE) and control group (GC), being subdivided into three subgroups according to days post-fracture (7th, 14th and 28th day) to assess bone healing. In GE was administered by gavage a solution of simvastatin to the sacrifice. In the control group was administered saline by the same route of SG. Immobilization was not used. After the sacrifice was made to limb amputation in the distal femur and conducted the clinical, radiological and histological analysis. Clinical evaluation was made as to the mobility of the fracture. Then the samples were radiographed and evaluated for callus diameter. Histological examination was performed with cuts of 5 micrometers and stained with hematoxylin-eosin, Masson's trichrome and Alcian blue pH 2.5. The level of significance to exclude the null hypothesis was 5%. Results All GE animals showed greater stability of the fracture and higher callus area. There were no significant changes in the histological study. Conclusion Simvastatin accelerates the consolidation process by increasing the callus, but does not alter the histology of the newly formed bone.

Prospective Role of Simvastatin on Wound Healing: Review of the Literature

“…SIM can induce a significant cell death in a wide range of human tumor cell lines including glioblastoma, astrocytoma, neuroblastoma, lung adenocarcinoma, and breast cancer via decreasing mevalonate formation and downstream farnesyl pyrophosphate (FPP) [39]. FPP inhibits epithelialization and wound healing through the glucocorticoid receptor and its reduction can enhance the epithelialization [40]. SIM also showed anabolic effect on bone with stimulation of bone tissue formation, Oxlund and Andreessen found that treatment with SIM at a dose of 20 mg/kg orally partially impeded bone loss in female Wistar rats that were subjected to ovariectomy, and also increased cortical bone formation.…”

Effect of Omeprazole on Fracture Healing in the Random-Patterned Rat Tibial Fracture Model: An Experimental Study

“…This scale involves scoring fibrous tissue, cartilage tissue, immature and mature bone ratios within the healing area formed on the proximal and distal sides of the fracture line as indicators of healing. In other studies, the assessment scale described by Vasconcelos et al 26 was adopted. This scale employs a 0-4 scoring system to indicate the stage of the healing tissue.…”

The Impact of Systemic Simvastatin on Bone Remodeling Following Rapid Maxillary Expansion: An In Vivo Study

“…Statins are a group of lipid-lowering drugs widely used to prevent cardiovascular events; they act on cholesterol-lowering activity and have pleiotropic effects, including bone stimulation, promotion of vasculogenesis and immunomodulation of anti-inflammatory effects [14]. Several studies have indicated that statins act on bone remodeling and the formation of bone tissue, being an osteoinductive substance [15].…”

“…Statins act by inhibiting the mevalonate pathway, a precursor for the formation of steroids and steroid isoprenoids; they also inhibit the activity of 3-hydroxy-3-methylglutarylcoenzyme A reductase (HMG-CoA), reducing the synthesis of cholesterol, which is required for the conversion of HMG-CoA to mevalonate. Thus, by acting to reduce the synthesis of mevalonate, they interfere with the proliferation and activities of cells [15]. One study demonstrated that statins stimulate bone formation associated with increased expression of the BMP-2 gene in bone cells and that they act as markers in enhanced gene expression for vascular endothelial growth factor (VEGF) [19].…”