We evaluated the effect of nicotine on osteoinduction by recombinant human bone morphogenetic protein-2 (rhBMP-2). Five micrograms of rhBMP-2 was implanted into the calf muscle of 10-week-old Wistar rats. For 14 days after implantation, nicotine was continuously administered subcutaneously in a dose of 0.1 (group L), 1.0 (group M), or 10.0 (group H) mg/kg/day. In the control group (group C), only physiological saline was administered. On day 21 after implantation, soft radiographs were obtained, and histological and biochemical analyses were performed. The results suggested that a high dose of nicotine pre ents bone formation.
In addition, we investigated the effect of nicotine on osteoinduction. For 14 days after rhBMP-2 implantation, nicotine was continuously administered in the dose used in group M. The control group was given only physiological saline. On days 3, 7, 14, and 21 after implantation, soft radiographs were obtained after the injection of contrast media, and histological and biochemical analyses were performed. In the radiographic study with contrast media, there were fewer small capillaries in the rhBMP-2-implanted muscle in the nicotine group than in the control group. Histologically, nicotine reduced new bone and cartilage formation and decreased the number of capillaries. On quantitative biochemical analysis, indices of bone formation in the nicotine group were significantly lower than those in control. These results suggest that the prevention of bone formation by nicotine may be caused by a reduced blood supply to rhBMP-2-implanted muscle.