Effects of the combination with α-tricalcium phosphate and simvastatin on bone regeneration

• Published in: Clinical oral implants research 2009-03, Vol.20 (3), p.280-287
• Main Authors: Nyan, Myat, Sato, Daisuke, Kihara, Hidemichi, Machida, Tetsu, Ohya, Keiichi, Kasugai, Shohei
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Anticholesteremic Agents - pharmacology; Biocompatible Materials - pharmacology; BMP-2; bone formation; bone regeneration; Bone Regeneration - drug effects; Calcium Phosphates - pharmacology; Dentistry; Dose-Response Relationship, Drug; Drug Carriers - pharmacology; Drug Combinations; Osteogenesis - drug effects; Rats; Rats, Wistar; simvastatin; Simvastatin - pharmacology; Skull - drug effects; Skull - surgery; α-TCP
• ISSN: 0905-7161; 1600-0501
• DOI: 10.1111/j.1600-0501.2008.01639.x

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 α‐tricalcium phosphate (α‐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 α‐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 α‐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 α‐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.