BACKGROUND: Although local application of statins stimulates bone formation, high dose of simvastatin induces inflammation. OBJECTIVE: A study was conducted to test the hypothesis that maximum bone regeneration with less inflammation would be achieved by combining an optimal dose of simvastatin with alpha-tricalcium phosphate (alpha-TCP), which is an osteoconductive biomaterial capable of releasing the drug gradually. MATERIAL AND METHODS: Bilateral 5-mm-diameter calvarial defects were created in adult Wistar rats and filled with preparations of different doses of simvastatin (0, 0.01, 0.1, 0.25 and 0.5 mg) combined with alpha-TCP particles or left empty. The animals were sacrificed at 2, 4 and 8 weeks and analyzed radiologically and histologically. Half of the animals of 4 and 8 weeks were labeled with fluorescence dyes and histomorphometrically analyzed. RESULTS: Simvastatin doses of 0.25 and 0.5 mg caused inflammation of the soft tissue at the graft site whereas control and other doses did not. The micro-CT analysis revealed that the alpha-TCP with 0.1 mg simvastatin (TCP-0.1) group yielded significantly higher bone volumes than untreated control group at all three time points (249%, 227% and 266% at 2, 4 and 8 weeks, respectively). The percentage of defect closure, bone mineral content and bone mineral density were also higher in the TCP-0.1 group than in the other groups. CONCLUSION: When combined with alpha-TCP particles, 0.1 mg simvastatin is the optimal dose for stimulation of the maximum bone regeneration in rat calvarial defects without inducing inflammation and it could be applied as an effective bone graft material.
BACKGROUND: Although local application of statins stimulates bone formation, high dose of simvastatin induces inflammation. OBJECTIVE: A study was conducted to test the hypothesis that maximum bone regeneration with less inflammation would be achieved by combining an optimal dose of simvastatin with alpha-tricalcium phosphate (alpha-TCP), which is an osteoconductive biomaterial capable of releasing the drug gradually. MATERIAL AND METHODS: Bilateral 5-mm-diameter calvarial defects were created in adult Wistar rats and filled with preparations of different doses of simvastatin (0, 0.01, 0.1, 0.25 and 0.5 mg) combined with alpha-TCP particles or left empty. The animals were sacrificed at 2, 4 and 8 weeks and analyzed radiologically and histologically. Half of the animals of 4 and 8 weeks were labeled with fluorescence dyes and histomorphometrically analyzed. RESULTS:Simvastatin doses of 0.25 and 0.5 mg caused inflammation of the soft tissue at the graft site whereas control and other doses did not. The micro-CT analysis revealed that the alpha-TCP with 0.1 mg simvastatin (TCP-0.1) group yielded significantly higher bone volumes than untreated control group at all three time points (249%, 227% and 266% at 2, 4 and 8 weeks, respectively). The percentage of defect closure, bone mineral content and bone mineral density were also higher in the TCP-0.1 group than in the other groups. CONCLUSION: When combined with alpha-TCP particles, 0.1 mg simvastatin is the optimal dose for stimulation of the maximum bone regeneration in rat calvarial defects without inducing inflammation and it could be applied as an effective bone graft material.
Authors: F Camacho-Alonso; C Martínez-Ortiz; L Plazas-Buendía; A M Mercado-Díaz; C Vilaplana-Vivo; J A Navarro; A J Buendía; J J Merino; Y Martínez-Beneyto Journal: Clin Oral Investig Date: 2020-01-11 Impact factor: 3.573
Authors: Vishnu Priya Murali; Tomoko Fujiwara; Caleb Gallop; Yongmei Wang; Jack A Wilson; Matthew Thomas Atwill; Mallesh Kurakula; Joel D Bumgardner Journal: Int J Pharm Date: 2020-05-17 Impact factor: 5.875
Authors: Jiordanne Araújo Diniz; Davi da Silva Barbirato; Eduarda Helena Leandro do Nascimento; Andrea Dos Anjos Pontual; Ana Cláudia Amorim Gomes Dourado; José Rodrigues Laureano Filho Journal: Clin Oral Investig Date: 2022-01-22 Impact factor: 3.573