Neuropeptide Y innervation during fracture healing and remodeling: A study of angulated tibial fractures in the rat

BACKGROUND AND PURPOSE: Autonomic neuropeptide Y (NPY) is involved in local bone remodeling via the central nervous system. However, the role of peripheral neuronal NPY in fracture healing is not known. We investigated the relationship between bone healing and side-specific occurrence of NPY in angular and straight fractures. METHODS: Tibial fractures in Sprague-Dawley rats were fixed with intramedullary pins in straight alignment and anterior angulation. The samples were analyzed by radiography, histology, and immunohistochemistry (IHC) between 3 and 56 days postfracture. RESULTS: In the angular fractures, radiography and histology showed a 3.5-fold increase in callus thickness on the concave side compared to the convex side at day 21, whereas a 0.2-fold reduction in callus thickness was seen on the convex side between days 21 and 56. IHC showed regenerating NPY fibers in the callus and woven bone in both fractures at day 7. In angular fractures, a 5-fold increase in NPY fibers was observed on the concave side compared to the convex side at 7 days, whereas a 6-fold increase in NPY fibers was seen on the convex side between 21 and 56 days; only a 0.1-fold increase in NPY fibers was seen on the concave side during the same time period. In straight fractures, similar bony and neuronal changes were observed on both sides. INTERPRETATION: The increase in NPY innervation on the convex side appears to correlate with the loss of callus thickness on the same side in angular fractures. Our results highlight the probable function of the peripheral NPY system in local bone remodeling.