ObjectiveTo evaluate the influence of nicotine intake on bone microstructure, bone biomechanics, and oxidative stress state in rats. MethodsThirty-six 6-week-old male Sprague Dawley rats (weight, 160-180 g) were randomly divided into control group, low dose group, and high dose group, 12 rats each group. The rats in high dose group and low dose group were given respectively 6.0 mg/kg and 0.4 mg/kg nicotine gavage intervention for 12 months; no intervention was made in the control group. The survival of rats was observed during experiment, and the weight of rats was measured every month. At 12 months after modeling, the L1 vertebral body was harvested to measure the bone mineral density (BMD), bone volume fraction (BVF), trabecular thickness (TT), trabecular number (TN), and trabecular spacing (TS) by Micro-CT three-dimensional reconstruction; the left femur was harvested for biomechanical tests of maximal load, stiffness, and the maximal fracture energy; and arterial blood was extracted to measure the malonyldialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and cotinine. ResultsDuring the experiment, two rats and one rat were added in the high dose group and the low dose group because of death, and no death in the control group. The body weight of the rats in the high and low dose groups gradually decreased with time when compared with one in the control group, and significant difference was found between two dose groups and the control group at 8-12 months (P < 0.05); the body weight of the high dose group was significantly lower than that of the low dose group at 11 and 12 months (P < 0.05). At 12 months after modeling, BMD, BVF, TT, and TN were significantly lower in the high dose group than the control group and the low dose group, but TS was significantly increased (P < 0.05). Difference in BVF, TN, and TS was significant between the low dose group and the control group (P < 0.05). The maximal load, stiffness, and maximal fracture energy of femoral shaft were significantly lower in the high dose group than the control group and the low dose group, and in the low dose group than the control group (P < 0.05). Compared with the control group, the levels of cotinine and MDA were significantly increased, and the levels of CAT and SOD were significantly decreased in the high and low dose groups (P < 0.05), and there were significant differences between the high and low dose groups (P < 0.05). ConclusionNicotine intake can cause micro-structural changes of the bone, decreased bone mechanical properties, and imbalance of oxidation-antioxidant levels in rats. High-dose nicotine intake may be one of the causes of osteoporosis.