Cyclooxygenase-2 inhibitor reduces simvastatin-induced bone morphogenetic protein-2 and bone formation in vivo

Background and Objective: Simvastatin, a cholesterol‐lowering drug, also stimulates oral bone growth when applied topically, without systemic side‐effects. However, the mechanisms involved in vivo are not known. We hypothesized that bone morphogenetic protein‐2, nitric oxide synthase, and cyclooxygenase‐2 are involved, based on prior in vitro evidence. Material and Methods: A rat bilateral mandible model, where 0.5 mg of simvastatin in methylcellulose gel was placed on one side and gel alone on the other, was used to quantify nitric oxide, cyclooxygenase‐2 and bone morphogenetic protein‐2 (via tissue extraction, enzyme activity or immunoassay), and to analyze the bone formation rate (via undecalcified histomorphometry). Cyclooxygenase‐2 and nitric oxide synthase inhibitors (NS‐398 and L‐NAME, respectively) were administered intraperitoneally. Results: Simvastatin was found to stimulate local bone morphogenetic protein‐2, nitric oxide and the regional bone formation rate (p