THE EFFECT OF NICOTINE ON INCORPORATION OF CANCELLOUS BONE-GRAFT IN AN ANIMAL-MODEL

Study Design. A basic science study using a rabbit model of bone graft revascularization in the distal femoral metaphysis. Objectives. The goal of the present study was to determine the effect of nicotine on the revascularization and incorporation of autogenous iliac crest bone graft implanted in an orthotopic location. Summary of Background Data. Although nicotine is the major toxin in cigarettes, it has not been confirmed as the primary factor affecting bone metabolism, and although the effects of smoking on bone homeostasis have been well studied, the effect of nicotine on new bone formation and neovascularization in the setting of bone graft transplantation has not been well studied. Methods. Twenty-four New Zealand white rabbits were randomly divided into two groups to be exposed to nicotine or saline control. A cancellous iliac crest bone graft was harvested and implanted in the lateral distal femur. Mini-osmotic pumps were used to deliver continuous serum levels of nicotine. The animals were killed at the following intervals: 1 week (n = 6), 2 weeks (n = 120, and 4 weeks (n = 6). The vascular tree was injected with Microfil silicone rubber solution, and the degree of revascularization was determined with a semiautomated image analysis system to determine the area of vascularization for each specimen. Results. All seven of the control (no nicotine) animals harvested at 1 or 2 weeks had over 50% bony vascular ingrowth, whereas only four of the nine nicotine-exposed animals showed over 50% bony vascular ingrowth. These differences were statistically significant (P = 0.03) using the Fischer exact test. By the fourth week(after nicotine levels in experimental animals had diminished), the revascularization of the nicotine-exposed grafts was indistinguishable from that of grafts in the animals that were not exposed to nicotine. Conclusions. We conclude the following. 1) Uniform dosages of nicotine in the rabbit model decreases the vascular ingrowth into autogenous cancellous bone graft. 2) The inhibitory effect of nicotine varies between animals, suggesting predisposition in some. 3) The vascular effects are reversible within 2 weeks of elimination of nicotine, although late bony resorption continues beyond the time of high serum nicotine levels.