Basic and patient-oriented research
Effects of Simvastatin on Mandibular Distraction Osteogenesis

https://doi.org/10.1016/j.joms.2008.05.362Get rights and content

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 distraction 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.

Section snippets

Materials and Methods

A total of 18 New Zealand rabbits, weighing about 2 kg, were used as experimental animals. The animals were kept in cages and fed a solid diet and given water ad libitum. The protocol of the experiment was approved by the Animal Care and Use Committee at Cumhuriyet University, Sivas, Turkey.

The animals were divided into 3 study groups, and a unilateral mandibular distraction osteogenesis procedure was applied to all animals. In group 1 (local application) a simvastatin gelatin sponge was

Results

The experimental procedures were well tolerated by all animals. Rabbits were able to feed normally. Malocclusion occurred in all rabbits, and the lower incisors elongated markedly. Superficial pinhole infection was observed in some of the animals. Gross examination of the distracted mandible indicated bony union across the distraction zone at the time of death. No adverse effects were observed in any of the animals because of simvastatin treatment.

Plain radiographic evaluation showed

Discussion

Physiologic strain plays a key role in the growth and maintenance of the skeletal system, and distraction osteogenesis is a method of producing bone by mechanical distraction forces. The molecular mechanism that translates the mechanical forces into cellular events is not fully understood, but it has been determined that distraction osteogenesis stimulates the production of osteoinductive growth factors. The studies on molecular biology of distraction osteogenesis showed that BMPs are central

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