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J Orthop Trauma. 2012 Dec;26(12):724-7. doi: 10.1097/BOT.0b013e318270466f.

The effect of transdermal nicotine on fracture healing in a rabbit model.

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Department of Orthopedic Surgery, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.



Cigarette smoking inhibits fracture healing and places the patient at a higher risk of delayed union and nonunion. Nicotine has been implicated as the primary ingredient responsible for these effects. However, an analysis of current published investigations reveals conflicting data, with some evidence that nicotine alone does not significantly affect healing. We undertook an animal study of the effects of transdermal nicotine on fracture healing.


Twenty-two adult male New Zealand white rabbits were randomly assigned to the nicotine group or the control group. A midshaft tibial osteotomy was performed on the left tibiae of all 22 rabbits. The nicotine rabbits were exposed using a 10.5-mg transdermal patch applied daily to the ear. Radiographs were obtained, and the area of fracture callus was assessed. Rabbits were euthanized at 21 days. Fractures were stressed to failure, and load/deformation curves were recorded.


The average area of callus formation was greater in the control group (


0.158 cm, Nicotine: 0.124 cm), but the difference was not statistically significant (P = 0.30). There was a significant difference between the 2 groups for mean normalized torque to failure (Nicotine: 36% of nonfractured side,


69% of nonfractured side, P = 0.028). The control group mean normalized stiffness was significantly greater than that for the nicotine rabbits (


87%, Nicotine: 43%, P = 0.036). There were 3 nonunions in the nicotine group (27%) compared with none in the control group (P = 0.062).


In a rabbit model of fracture healing, transdermal nicotine exposure resulted in decreased mechanical strength of healing fractures at 21 days and a higher rate of nonunion at 21 days compared with that of controls.

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