Objective To observe and compare the changes of vertebral bone mineral density (BMD) in the early stages of spinal Mycobacterium tuberculosis infection. Methods Patients who underwent spinal surgery at Xiangya Hospital, Central South University from January 1 to December 31, 2023 were continuously enrolled (spinal tuberculosis group), based on gender matching, non-spinal tuberculosis surgical patients treated for spinal stenosis were selected as the control group. Dual-energy X-ray scans were performed on the enrolled patients, difference in vertebral BMD between two groups of patients was compared. An animal model of spinal Mycobacterium tuberculosis infection (referred to as the animal model) was constructed, differences in microstructure of trabecular bone between spinal tuberculosis group and control group was compared, and the bone volume/tissue volume (BV/TV), the thickness of trabecular bone (Tb.Th), the number of trabecular bone (Tb.N), and sparse density of trabecular (Tb.Sp) were used as evaluation indexes to further analyze the bone quality differences between the diseased vertebrae and the neighboring vertebrae. Results 69 patients were included in the spinal tuberculosis group and the control group, respectively. The BMD of patients in the spinal tuberculosis group (0.793 ［0.712, 0.869］ g/cm²) was lower than that of the control group (0.907 ［0.800, 1.020］ g/cm²), difference was statistically significant (P<0.05). Microstructure of trabecular bone BV/TV (［18.4±5.4］%), Tb.Th (［0.124±0.010］ mm) in the spinal tuberculosis group of animal model were significantly altered compared with BV/TV (［22.6±3.2］%), Tb.Th (［0.160±0.017］ mm) in the control group (both P<0.05). In the spinal tuberculosis group, microstructure of diseased vetebral trabecular bone BV/TV (［25.5±6.7］%) and Tb.N (［1.871±0.443］/mm) were significantly lower than BV/TV (［26.6±6.8］%) and Tb.N (［1.969±0.454］/mm) in the neighboring vertebrae, both with statistically difference (both P<0.05). Conclusion In the early stages of spinal Mycobacterium tuberculosis infection, microstructure of vertebral trabecular bone can be altered, leading to a decrease in BMD.