Intermittent hypoxia retards mandibular growth and alters RANKL expression in adolescent and juvenile rats

Objectives: Chronic intermittent hypoxia (IH), a common state experienced in obstructive sleep apnoea (OSA), retards mandibular growth in adolescent rats.The aim of this study was to elucidate the differential effects of IH on mandibular growth in different growth stages. Materials and methods: Three-week-old (juvenile stage) and 7-week-old (adolescent stage) male Sprague-Dawley rats underwent IH for 3 weeks. Age-matched control rats were exposed to room air. Mandibular growth was evaluated by radiograph analysis, micro-computed tomography, real-time polymerase chain reaction and immunohistology. Tibial growth was evaluated as an index of systemic skeletal growth. Results: IH had no significant impact on the general growth of either the juvenile or adolescent rats. However, it significantly decreased the total mandibular length and the posterior corpus length of the mandible in the adolescent rats and the anterior corpus length in the juvenile rats. IH also increased bone mineral density (BMD) of the condylar head in adolescent rats but did not affect the BMD of the tibia. Immunohistological analysis showed that the expression level of receptor activation of nuclear factor-kappa B ligand significantly decreased (in contrast to its messenger ribonucleicacid level) in the condylar head of adolescent rats with IH, while the number of osteoprotegerin-positive cells was comparable in the mandibles of adolescent IH rats and control rats. Limitations: The animal model could not simulate the pathological conditions of OSA completely and there were differences in bone growth between humans and rodents. Conclusions: These results suggest that the susceptibility of mandibular growth retardation to IH depends on the growth stage of the rats.