Comparison of remote ischemic preconditioning and intermittent hypoxia training in fracture healing

Fracture healing in elderly patients is an emerging public health concern. As non-drug treatments, intermittent hypoxia training (IHT) and remote ischemic preconditioning (RIPC) are considered to have substantial advantages and to aid fracture healing in elderly patients. The purpose of the present study was to evaluate and compare the effects of IHT and RIPC on fracture healing. Micro-computed tomography (micro-CT) and biomechanical testing were used to assess the morphology and structural properties of bone callus dissected from aged rats with tibial fractures. In addition, hypoxia-inducible factor-1 (HIF-1) and its target gene, associated with the healing process, were investigated by reverse transcription-quantitative polymerase chain reaction and western blot analyses. The micro-CT-based parameters, including bone mineral density and trabecular number, were measured, and significant differences were identified between the experimental and control groups. The IHT group exhibited superior bone formation and mineralization rates compared with the RIPC group. The biomechanical testing revealed that the ultimate loading and stiffness values were significantly higher in the IHT group compared with those in the RIPC group. In accordance with previous studies, RIPC exerted a similar effect in increasing the expression of HIF-1, and its downstream genes, throughout the course of healing. In addition, the IHT group exhibited increased expression levels of HIF-1 compared with the RIPC group. Taken together, the results suggested that IHT and RIPC significantly enhanced fracture healing; however, IHT exhibited superior bone formation and healing effects compared with RIPC.