Healing of extraction socket following local application of simvastatin: A split mouth prospective study

Evaluation of the Efficacy of Simvastatin in Bone Regeneration after Surgical Removal of Bilaterally Impacted Third Molars—A Split-Mouth Randomized Clinical Trial

“…15,20 Many investigators have reviewed the role of statins in switching on genes for osseous formation, with great potential in bone grafting in the craniofacial region. The emphasis was shifted to their osteoinductive properties by the research of Gutierrez et al 4,15 Simvastatin has been proved to stimulate osteoblastic differentiation and mineralization in nontransformed osteoblastic cells in vitro and in vivo in rats and rabbits. It also markedly increases mRNA expression for alkaline phosphatase, type I collagen, bone sialoprotein, and osteocalcin in nontransformed osteoblastic cells and decreases gene expression for collagenase-1 and collagenase-3.…”

“…It also markedly increases mRNA expression for alkaline phosphatase, type I collagen, bone sialoprotein, and osteocalcin in nontransformed osteoblastic cells and decreases gene expression for collagenase-1 and collagenase-3. 6,15,18 Some studies have found that simvastatin suppresses osteoclasts, thus promoting bone repair. 7 Vascular endothelial growth factor (VEGF) is not only an intense angiogenic factor but also a vital particle for bone development, suggesting that statin-actuated VEGF could assume a part in angiogenesis and osteogenesis.…”

“…Conversely, local administration was suggested to deliver simvastatin directly in therapeutic concentrations for bone formation with virtually no side effects. 6,15 In this trial, a dosage of 10 mg was standardized for all participants and no adverse effects were observed.…”

“…Gutierrez et al 4 concluded that topical application of statin was 50 times more active in bone formation in rats than oral administration. In addition, several studies have used simvastatin with carriers, such as the gelatin sponge, 6,9,10,15 collagen sponge, 11 collagen matrix, 23 poly(lactic-co-glycolic acid), 13,19,24 methyl cellulose gel, 13,25 a-tricalcium phosphate rods, 1,8 and biodegradable hydrogel, 26 for successful local delivery.…”

“…1,3,[7][8][9][10][11][12] Almost all the trials reported positive results not only for intraoral sites but also for extraoral sites, such as cranial defects and femur fractures. Trials also have been carried out in humans for periodontal defects, 13 periapical cystic lesions, 14 extracted premolar sockets 15 and osteoporosis in women. 16 In vitro studies also have been initiated to determine the exact mechanism of action.…”