Can the Combination of Simvastatin and Melatonin Create a Synergistic Effect on Bone Regeneration?

Purpose: The present study evaluated the potential bone regeneration capacity of combining melatonin and simvastatin, with a goal of producing more osteogenic bone substitutes. Materials and Methods: A total of 48 male Wistar rats were randomly divided into 4 groups. The following were administered into critical-sized calvarial defects of the rats: Group I–human allograft; Group II–human allograft + 10 mg melatonin; Group III–human allograft + 0.1 mg simvastatin; and Group IV–human allograft + 10 mg melatonin + 0.1 mg simvastatin. Histopathologic, histomorphometric, and microcomputed tomographic evaluations were performed postprocedurally at 4 and 8 weeks. A P value < .05 was considered significant for all evaluations. Results: Groups II and III had significantly superior regeneration compared to Group I at weeks 4 and 8. Group III had significantly superior regeneration compared to Group II, particularly in week 4. Group IV had significantly superior regeneration compared to all groups at week 8. Conclusions: The local administration of melatonin and simvastatin resulted in increased new bone mass and quality of bone microstructure than was seen in the control group. Simvastatin shortened the defect regeneration time more effectively than melatonin did. The combined use of melatonin and simvastatin provided a synergic effect on bone regeneration, particularly in the late phase of healing.