Mechanism by which alendronate promotes rapid mandibular distraction osteogenesis in rabbits / 中国组织工程研究

ABSTRACT

BACKGROUND:Some studies have found that local application of alendronate can promote osteogenesis,but less is reported on the process of distraction osteogenesis. OBJECTIVE:To observe the promoting effect of alendronate on rapid mandibular distraction in a rabbit model and explore its possible mechanism. METHODS:Thirty-six male New Zealand white rabbits were randomly divided into groups A,B and C(n=12 per group)after operation and rapid distraction(3-day delay period followed by 3-day distraction at 1.5 mm/12 hours).At the 1st,3rd and 7th days of the consolidation period,animal were injected with 200 μg/kg alendronate in group A and 100 μg/kg alendronate in group B,while those in group C were treated as controls.CT scanning and dual energy X-ray bone mineral density measurement were performed at 4 and 8 weeks of the consolidation period.After the radionuclide scanning was completed at the 4th week,several animals were sacrificed and the samples were collected for western blot assay and tartrate resistant acid phosphatase staining.A three-point bending test was performed after the animals were sacrificed at the 8th week. RESULTS AND CONCLUSION:CT results showed that bone formation in the distraction space of group B was significantly better than that in groups A and C.At the 4th week,the bone mineral density in group B was(0.092±0.010)g/cm2,which was 1.26 times higher than that in group A(P＜0.001)and 1.28 times higher than that in group C(P＜0.001).At the 8th week,the bone mineral density in group B was(0.175±0.029)g/cm2,which was 1.38 times higher than that in group A(P＜0.001)and 1.45 times higher than that in group C(P＜0.001).Tartrate resistant acid phosphatase staining showed that the number of osteoclast-like cells in group C were 2.83 times more than that in group A(P＜0.001)and 2.21 times more than that in group B(P＜0.001).The radionuclide intensity was higher in group C than in groups A and B.Western blot assay results showed that the expression of Runx2 was significantly stronger in group B than in groups A and C.The maximum biomechanical load in group B was(158.48±23.21)N,which was 1.26 times higher than that in group A(P=0.007)and 1.31 times higher than that in group C(P=0.003).To conclude,the low concentration of alendronate may promote rapid distraction osteogenesis of the rabbit mandible by inhibiting osteoclast signals.