BackgroundChanges over time in the callus during intermittent administration of parathyroid hormone (PTH) were studied in rabbit distraction osteogenesis models.MethodModels of distraction osteogenesis in Japanese white rabbits were created, and distraction osteogenesis (total length: 10.5 mm) was performed for 2 weeks. Simultaneously with the start of distraction, 30 rabbits received 4 weeks of subcutaneous administration of 30 μg/kg of PTH(1–34), teriparatide, (P-group: n = 15) or saline (N-group: n = 15) every other day. The tibias of five rabbits were dissected at 6, 8, and 10 weeks after surgery to perform bone mineral density (BMD), peripheral quantitative computed tomography (pQCT), and mechanical testing.ResultsThe mean BMD had no significant differences over time at 6, 8, and 10 weeks after surgery between the P-group and the N-group. On pQCT, the P-group had significant increases in total bone cross-sectional area of the callus compared to the N-group at 8 and 10 weeks after surgery. On mechanical testing, the P-group’s absorption energy had not changed at 6 weeks after surgery compared to the N-group, but it had significantly increased at 8 weeks. At 10 weeks after surgery, the N-group’s absorption energy rapidly increased, and the difference between the two groups disappeared.ConclusionThe intermittent administration of PTH(1–34), teriparatide, for 4 weeks every other day from the start of distraction had the potential to shorten the callus maturation period in the rabbit distraction osteogenesis models.
Background To 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. Methods The 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 2 weeks. After 5 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 (1–34) administration: 4 weeks during the distraction and consolidation phases (group D + C), 2 weeks of the distraction phase (group D), and the first 2 weeks of the consolidation phase (group C). A control group (group N) was administered saline for 4 weeks during the distraction and consolidation phases. Furthermore, to obtain histological findings, lower leg bones were collected from each rabbit at 2, 3, and 4 weeks after osteotomy, and tissue sections of the distracted callus were examined histologically. Results The 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. Conclusion We found that the optimal timing of PTH (1–34) administration is during the consolidation phase, which is mainly characterized by intramembranous ossification.
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