Involvement of CGRP-Positive Nerve Fibers in Consolidation Stage of Distraction Osteogenesis

To investigate the temporal and spatial distribution of calcitonin gene-related peptide (CGRP) positive nerve fibers during the consolidation stage of distraction osteogenesis (DO), twenty New Zealand white rabbits were used for unilateral DO. Distraction started at the 7 th day after osteotomy with 1 mm of length per day. The lengthening lasted for 10 days. Four rabbits were sacrificed at each of the following time point at 7-day, 14-day, 21-day, 28-day and 42-day post-distraction. The entire distraction callus and 2 mm of neighboring cortical bone on the proximal and distal sides was removed en bloc for assessments. The results showed that CGRP-positive nerve fibers were observed in the periosteal, intercortical and endocortical regions at 7-day post-distraction. After that, CGRP-positive nerve fibers were mainly found in the fibrous tissue of periosteal region and bone marrow of bony callus. Moreover, the density of CGRP innervations was significantly higher at 21-day post-distraction than that of other time point. In conclusion, the observed spatial and temporal distribution of CGRP-positive nerve fibers during consolidation stage of DO suggested CGRP innervation is associated with DO.