The Effects of Simvastatin on Bone Healing in Mandible Fractured Rats

ABSTRACT

PURPOSE: The hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) are widely used in the treatment of dyslipidemia for lowering of cholesterol level. And the studies in simvastatins have shown to enhance bone formation in vitro and in vivo in rodents. But some other researchers have reported that simvastatins' anabolic effect on bone does not exist. The peripheral distribution beyond the liver represents a small fraction of an orally administered dose. We hypothesized that this poor peripheral distribution is the likely reason that simvastatins, yield ambiguous results as anabolic agents. We therefore investigated whether the effects of simvastatins on bone may be enhanced by subcutaneous administration, providing better peripheral delivery of these drugs. METHODS: 36 rat unilaterally mandible fractured models were prepared and divided into two groups. The simvastatin treated group where 1mg/kg of simvastatin was daily injected subcutaneously. The same dose of normal saline was injected on the control group. And 3 rats in each group were sacrificed and taken bone samples in each week. Bone sample was evaluated with tensile strength and histological morphology after 1, 2, 3, 4, 5 and 6 weeks. RESULTS: In simvastatin treated group, the fracture healing process, chondrocyte aggregation, collagen formation and trabecular bone formation was rapidly proceeded than the control group histologically. The tensile strength in the simvastatin treated group was measured as 1.02, 2.25, 3.95, 4.42, 5.49 and 6.00 N/mm2 each week, while it was 0.60, 1.05, 2.17, 3.75, 4.15 and 5.17 N/mm2 in the control group. The average tensile strength was higher by 1.04N/mm2 in simvastatin treated group. CONCLUSION: The currently available data on the effects of simvastatin on bone confirms that simvastatin helps fracture healing. And the potential for simvastatin to be used as anabolic agents for bone when delivered by the subcutaneous route.