Our goal in this project is to examine the effects of local applications of the statin simvastatin for its capacity to enhance bone formation in a defect model of bone regeneration and in a model of fracture repair. Determination of usefulness in these circumstances will lead to this compound being a potential therapy for these important localized causes of bone loss. PROPOSED COMMERCIAL APPLICATIONS: Delayed fracture repair and osseous bone defects are major causes of disability. An agent which would hasten repair of fractures or the healing of bone defects would be a major advance for these problems. We have found that the statin simvastatin causes profound increases in normal bone formation when applied locally. This project aims to confirm these effects in several standard preclinical models to determine potential efficacy as a therapeutic local bone growth stimulant.