The effect of HIF stabilizer on distraction osteogenesis.

ABSTRACT

OBJECTIVE: The aim of this study was to investigate the effect of an orally applicable hypoxia-inducible factor (HIF) stabilizer on distraction osteogenesis (DO) in a rat model. METHODS: The study included 24 Wistar albino rats undergoing osteotomy of the left tibia diaphysis. Rats were divided equally into experiment and control groups. Tibias were fixed using an external fixator. HIF stabilizer was administered to the experiment group. On the 5th postoperative day, distraction with increased rate (0.4 mm twice a day) was commenced and continued for 10 days. Histological and immunohistochemical evaluation was performed. RESULTS: Vascular endothelial growth factor levels of the experiment group were higher than those of the control group (p<0.05). The experiment group had slightly better intramembranous ossification quality than the control group on both Day 16 and 30. Endochondral ossification rates were better in the experiment group on Day 16. CONCLUSION: Vascular endothelial growth factor levels increased and stimulated angiogenesis in the presence of HIF pathway activation by oral administration of HIF stabilizer during DO. The biomechanical features of the distraction and angiogenesis should be coupled to achieve adequate bone homeostasis.