Bone Substitute Containing a Drug: Application to a Tooth Socket

Objectives: In 1999, Mundy and his collaborators reported that statins, inhibitors of cholesterol synthesis, enhance BMP2 expression in osteoblasts and that oral administration of simvastatin, one of statins, exerts therapeutic effect in ovariectomized rats, which mimics post-menoposal osteoporosis. Alveolar ridge atrophy after tooth extraction is a clinical problem and we speculated that we could prevent this atrophy by applying statins to the tooth socket after tooth extraction. Methods: We developed bone substitute, which contained beta-TCP, PLGA, CaCO3 and simvastatin. After lower incisor extraction of rats, we applied our bone substitute to the tooth socket and radiographically measured bone amount at the extracted site and examined histologically. Furthermore, we applied our bone substitute to critical size segmental defect (15mm) of rabbit ulna. Results: Alveolar bone around the socket, where our bone substitute was applied, extremely thickened and appearance of newly formed bone in the socket was prominent. In rabbit ulna defect, our bone substitute stimulated the bone healing and the defect was completely fused. Conclusions: Simvastatin is chemically stable and inexpensive compared to recombinant proteins such as BMPs and FGFs. It is unlikely that local application of simvastatin elicits serious side effects. Thus, although further studies are required, our bone substitute containing simvastatin could be clinically applied in dental and orthopedic fields in the near future.