Simvastatin and its impact on healing of craniofacial bone and cartilage: A systematic review

Aims and objectives: Many bone regeneration techniques have been introduced in dentistry in order to address lacking of bone tissue. Besides autogenous bone, considered the gold standard, many biomaterials have been involved, such as bone substitutes, barrier membranes, autologous and recombinant growth factors, stem cells and, lately, osteo-promotive pharmacological compounds, such as BMPs, teriparatide, statins, and others. Preclinical and clinical studies, systematic reviews and meta-analyses have investigated the potential of simvastatin in enhancing bone formation. This review aimed at assessing the relevance of simvastatin in bone regeneration, focusing on clinical and histological outcomes in oral surgery. Methodology: The PICO question was “Is the adjunctive use of simvastatin beneficial respect to control for bone regeneration in dentistry?” An electronic search was performed on MEDLINE, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL) using a combination of keywords. A hand search was undertaken on seven oral surgery Journals: Previous systematic reviews were considered for further potential eligible studies. No limitation of language and publication year was placed. Both animal and clinical comparative studies were considered. After inclusion, data on methodology, efficacy and safety were extracted. Included studies underwent risk of bias assessment. Results: One randomized clinical study and 23 studies on animal models (rats, pigs, dogs, rabbits) were included. Simvastatin was tested in different oral applications, such as: periodontal disease, distraction osteogenesis, temporomandibular joint disease, socket preservation, orthodontics. In the range 0.5-1mg and 2.2-2.5mg simvastatin was associated with higher bone formation rate and decreased osteoclastic activity as compared to control. Immunohistochemistry revealed the increased activity of TRAP, MMP-1 and BMP and decreased activity of RANKL when using simvastatin. The outcomes were unrelated to the administration route (local or systemic). Conclusion: This review provided a detailed insight into the osteopromotive effects of simvastatin through clinical, histological and immunohistochemical markers associated with bone regeneration.