Copyright © 2009 Elsevier Inc. All rights reserved.
22. Low Dose Nicotine Exposure Improves Posterior Spinal Fusion in an In Vivo Rabbit Model
John France MD1, Scott Daffner MD1, Chad Smalley MD1, Stacey Waugh MS1, Timothy Norman PhD2, Nina Clovis1, Suzanne Smith BS1, Vincent Kish PA1 and Nilay Mukherjee PhD1
1West Virginia University, Morgantown, WV, USA
2Cedarville University, Cedarville, OH, USA

Available online 12 October 2009.

BACKGROUND CONTEXT: A previous pilot study by our group demonstrated that nicotine administration via transdermal nicotine patch showed consistent serum nicotine levels whereas administration via the more commonly utilized mini-osmotic pump resulted in large variations in serum levels of nicotine of rabbits. In other work, we have previously demonstrated that nicotine delivered via a transdermal patch enhanced posterior spinal fusion rates in rabbits. This is contrary to studies published by other groups where nicotine administration decreased fusion rates. Hence, there may be a dose-dependent effect of nicotine on posterior spinal fusion outcomes.
PURPOSE: To determine if a dose-dependent effect of nicotine could be shown in an in vivo rabbit spinal fusion model.
STUDY DESIGN/SETTING: In vivo rabbit model of spinal fusion.
PATIENT SAMPLE: 24 New Zealand White Rabbits.
OUTCOME MEASURES: Serum nicotine levels, radiographic fusion, manual palpation, biomechanical testing.
METHODS: 24 adult New Zealand white rabbits were randomly divided into four groups. All groups received a single level posterolateral, intertransverse process fusion at L5-L6 with autologous iliac crest bone. One group served as controls and only underwent the spine fusion surgery. Three groups received 5.25 mg, 10.5 mg and 21 mg nicotine patches, respectively for 5 weeks. Serum nicotine levels were recorded for each group. All animals were sacrificed five weeks post-operatively and spinal fusions were evaluated radiographically, by manual palpation, and via biomechanical testing. Statistical analysis evaluated dose response effect of outcomes variables and nicotine dosage.
RESULTS: Average serum levels of nicotine from the different patches were: 7.8.±1.9 ng/mL for the 5.25 mg patch group; 99.7.±17.7 ng/mL for the 10.5 mg patch group; and 149.1.±24.6 ng/mL for the 21 mg patch group. The doses positively correlated with serum concentrations of nicotine (correlation coefficient =0.8410, p=0.001). The 5.25 mg group provided the best fusion rate, trabeculation, and stiffness. The fusion rates, based on the palpation tests, were: control (50%), 5.25 mg (80%), 10.5 mg (50%) and 21 mg (42.8%); this neared significance for the 5.25 mg group (p=0.16). Radiographic assessment of trabeculation and bone incorporation and biomechanical analysis of bending stiffness ratio was also greatest in the 5.25 mg group. Radiographic evaluation showed a significant (p=0.0446) quadratic effect of nicotine dose on spinal fusion.
CONCLUSIONS: The effects of nicotine on spinal fusion are complex, may be dose dependent and may not always be detrimental. The uniformly negative effects of smoking reported on patients undergoing spinal fusion may possibly be attributed to the other components of cigarette smoke.
FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs.


The Spine Journal
Volume 9, Issue 10, Supplement 1, October 2009, Page 12S
Proceedings of the 24rd Annual Meeting of the North American Spine Society, NASS 24th Annual Meeting