Optimal Timing for Intermittent Administration of Parathyroid Hormone (1-34) for Distraction Osteogenesis in Rabbits

BackgroundTo date, the usefulness of parathyroid hormone (PTH (1-34)) in distraction osteogenesis has been reported in several studies. We aimed to determine the optimal timing of PTH (1-34) administration in a rabbit distraction osteogenesis model.MethodsThe lower hind leg of a Japanese white rabbit was externally fixed, and tibial osteotomy was performed. One week after the osteotomy, bone lengthening was carried out at 0.375 mm/12 h for two weeks. After five weeks, the lower leg bone was collected. Bone mineral density (BMD), peripheral quantitative computed tomography (pQCT), micro-computed tomography (micro-CT), and mechanical tests were performed on the distracted callus. The rabbits were divided into three groups according to the timing of PTH administration: four weeks during the distraction and consolidation phases (group D+C), two weeks of the distraction phase (group D), and the first two weeks of the consolidation phase (group C). A control group (group N) was administered saline for four weeks during the distraction and consolidation phases. Furthermore, to obtain histological findings, lower leg bones were collected from each rabbit at two, three, and four weeks after osteotomy, and tissue sections of the distracted callus were examined histologically.ResultsThe BMD was highest in group C and was significantly higher than group D. In pQCT, the total cross-sectional area was significantly higher in groups D+C, D, and C than group N, and the cortical bone area was highest in group C and was significantly higher than group D. In micro-CT, group C had the highest bone mass and number of trabeculae. Regarding the mechanical test, group C had the highest callus failure strength, and this value was significantly higher compared to group N. There was no significant difference between groups D and N. The histological findings revealed that the distracted callus mainly consisted of endochondral ossification in the distraction phase. In the consolidation phase, the chondrocytes were almost absent, and intramembranous ossification was the main type of ossification.ConclusionWe found that the optimal timing of PTH (1-34) administration is during the consolidation phase, which is mainly characterized by intramembranous ossification.