Evaluation of the osteoconductivity of α-tricalcium phosphate, β-tricalcium phosphate, and hydroxyapatite combined with or without simvastatin in rat calvarial defect

The purpose of this study is to evaluate the osteoconductivity of three different bone substitute materials: alpha-tricalcium phosphate (alpha-TCP), (beta-TCP), and hydroxyapatite (HA), combined with or without simvastatin, which is a cholesterol synthesis inhibitor stimulating BMP-2 expression in osteoblasts. We used 72 Wistar rats and prepared two calvarial bone defects of 5 mm diameter in each rat. Defects were filled with the particles of 500-750 mu m diameter combined with or without simvastatin at 0.1 mg dose for each defect. In the control group, defects were left empty. Animals were divided into seven groups: alpha-TCP, beta-TCP, HA, alpha-TCP with simvastatin, beta-TCP with simvastatin, HA with simvastatin, and control. The animals were sacrificed at 6 and 8 weeks. The calvariae were dissected out and analyzed with micro CT. The specimens were evaluated histologically and histomorphometrically. In a-TCP group, the amount of newly formed bone was significantly more than both HA and control groups but not significantly yet more than beta-TCP group. Degradation of alpha-TCP was prominent and beta-TCP showed slower rate while HA showed the least degradation. Combining the materials with Simvastatin led to increasing in the amount of newly formed bone. These results confirmed that alpha-TCP, beta-TCP, and HA are osteoconductive materials acting as space maintainer for bone formation and that combining these materials with simvastatin stimulates bone regeneration and it also affects degradability of alpha-TCP and b-TCP. Conclusively, alpha-TCP has the advantage of higher rate of degradation allowing the more bone formation and combining alpha-TCP with simvastatin enhances this property. (C) 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 98A: 488-498, 2011.