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Cortical reaming and intramedullary nail insertion injure the medullary vascular system. Little attention has been directed toward quantitative assessment of bone injury and repair after locked intramedullary nailing of long-bone fractures with and without reaming. The effects of reamed versus unreamed locked intramedullary nailing on cortical porosity and new bone formation were compared in a sheep fractured tibia model.After creation of a standardized spiral fracture by three-point bending with torsion, each tibia was stabilized by insertion of a locked intramedullary nail. Ten sheep were randomized into two groups, one that had reaming before nail insertion and one that did not. Fluorochromes were given 2 weeks (xylenol orange), 6 weeks (calcein green), and 12 weeks (tetracycline) postoperatively. All animals were killed at 12 weeks postoperatively. Cortical porosity and new bone formation were determined for the proximal diaphysis, fracture site, and distal diaphysis.Overall cortical porosity was greater with reamed nails than with unreamed nails (p = 0.02). Porosity in the inner cortex (18.3% (reamed) vs. 14.3% (unreamed); p = 0.09) and outer cortex (16.8% (reamed) vs. 12.2% (unreamed); p = 0.04) was greater in the reamed group. With reamed nails only, there was less new bone formation at 2 (p = 0.04) and 12 (p = 0.05) weeks in the inner cortex compared with the central cortex and outer cortex. Overall, there was no difference between reamed and unreamed nails in the amount of new bone formation at 2, 6, or 12 weeks.This study demonstrates that greater injury or overall cortical porosity is associated with reamed nail insertion. There is no difference, however, between the amount of new bone formation after reamed and unreamed nail insertion. Nail insertion without reaming may be initially advantageous when tibial cortical vascularity is compromised, by limiting further injury to cortical bone. This may be important with open tibial fractures in which there is a significant risk of infection after injury. Between 2 and 12 weeks after injury, neither reamed nor unreamed nail insertion seems to have a significant advantage with respect to the amount of new bone formation that occurs.