J Oral Maxillofac Surg 66:2233-2238, 2008 Effects of Simvastatin on Mandibular Distraction Osteogenesis Erdem Kılıç, DDS, PhD,* I ˙ lker Özeç, DDS, PhD,† Hasan Yeler, DDS, PhD,‡ Adnan Korkmaz, MD,§ Bülent Ayas, MD, and Cesur Gümüs ¸, MD¶ Purpose: The aim of this study was to evaluate the effects of local and systemic simvastatin application on distraction osteogenesis. Materials and Methods: Eighteen New Zealand white rabbits underwent unilateral mandibular dis- traction osteogenesis. After 7 days of neutral fixation, 0.4 mm twice per day, distraction was performed for 10 days. Simvastatin was applied locally during the osteotomy phase with a gelatin sponge carrier and systemically during the distraction osteogenesis period by oral gavage. All animals were killed at the end of the consolidation period of 14 days. The distracted mandibles were harvested and evaluated by plain radiography, by peripheral quantitative computed tomography, and with histomorphometry. Results: Radiographic evaluation with peripheral quantitative computed tomography showed that the area of the regenerate increased by 9.6% in the local simvastatin group and by 19.3% in the systemic simvastatin group as compared with the control group. In both experimental groups the density of the regenerate increased by 6.7% as compared with the control group. Statistical evaluation of radiographic data showed that all of these changes were not significant. Histomorphometric evaluation determined that there was no statistical difference among groups with regard to the ratios of bone tissue volume to fibrous tissue volume and bone tissue volume to marrow tissue volume. Conclusions: The results of this study suggest that simvastatin’s effect on enhancing distraction regenerate is limited with the applied doses and methods. © 2008 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 66:2233-2238, 2008 Distraction osteogenesis is the biologic process of new bone formation between gradually separated bone segments by incremental traction. Bone forma- tion occurs in response to tension forces on the cal- lus. Local growth factors that stimulate osteoblast activity are potential regulators of this process, and it has been shown that the most potent of the osteoin- ductive factors, bone morphogenetic protein (BMP) 2, is strongly expressed during the distraction osteo- genesis period. 1-4 The major problem with distraction osteogenesis is the length of time required for treatment. The entire process of distraction osteogenesis in the craniofacial bone takes from 2 to 4 months, and the patient has discomfort during this period. Longer periods also increase the possibility of complications. Shortening the distraction osteogenesis period by enhancing bone regeneration will shorten the morbid period for patients and also will decrease the complication rate. 5,6 Statins (including simvastatin), which are used to lower cholesterol levels, are competitive inhibitors of 3-hydroxy-3-methylglutaryl– coenzyme A reductase and its upstream metabolites, such as mevalonate. In attempts to identify small–molecular weight bone an- abolic compounds, attention has focused on the growth regulatory factors responsible for the control of normal bone remodeling, and it has been found that statins stimulate bone formation both in vitro and *Assistant Professor, Department of Oral and Maxillofacial Sur- gery, Dental School, Erciyes University, Kayseri, Turkey. †Assistant Professor, Department of Oral and Maxillofacial Sur- gery, Dental School, Cumhuriyet University, Sivas, Turkey. ‡Associate Professor, Department of Oral and Maxillofacial Sur- gery, Dental School, Cumhuriyet University, Sivas, Turkey. §Professor, Department of Histology and Embryology, Medical School, Ondokuz Mayıs University, Samsun, Turkey. Assistant Professor, Department of Histology and Embryology, Medical School, Ondokuz Mayıs University, Samsun, Turkey. ¶Assistant Professor, Department of Radiology, Medical School, Cumhuriyet University, Sivas, Turkey. Address correspondence and reprint requests to Dr Özeç: Cum- huriyet U ¨ niversitesi, Dis ¸hekimlig ˘i Fakültesi, ADÇH ve Cerrahisi AD, 58140, Sivas, Turkey; e-mail: iozec@cumhuriyet.edu.tr © 2008 American Association of Oral and Maxillofacial Surgeons 0278-2391/08/6611-0006$34.00/0 doi:10.1016/j.joms.2008.05.362 2233