PURPOSE: The relationship of CAN and BMD, fracture risk is still unclear in T2DM. The aim of the present study is to investigate the correlation between heart rate variability (HRV) and BMD in T2DM. METHODS: The study included 276 patients with T2DM aged >/= 50 years, and Cardiovascular Autonomic Reflex Tests (CARTs) were applied to divide patients into two groups: CAN ( +/-). 24 h Ambulatory ECG was assessed for HRV, BMD was measured by dual-energy X-ray bone densitometry, and FRAX scores were calculated for 10-year hip fracture risk (HF(1)) and major osteoporotic fracture risk (MOF). Adjusted regression analysis was performed to investigate influence factors for BMD and fracture risk. ROC curve was used to analyze the optimal cut-off point of LF/HF for screening osteoporosis. RESULTS: Baseline data showed significant differences in the duration of T2DM, insulin resistance index (HOMA-IR), 25-hydroxyvitamin D[25(OH)D], femoral neck BMD, hip BMD, lumbar BMD, HF(1), and MOF between the CAN ( +) and CAN (-) groups. The proportion of patients with osteoporosis increased as the degree of CAN lesion increased. Correlation analysis showed that LF/HF was significantly correlated with BMD, especially with hip (r = - 0.534, p < 0.001). Regression analysis showed that LF/HF was a risk factor for reduced BMD and increased fracture risk. The optimal cut-point value for LF/HF to predict osteoporosis by ROC curve analysis was 3.17. CONCLUSIONS: CAN is associated with reduced BMD and increased fracture risk in patients with T2DM, and LF/HF may have the potential to be a predictor of diabetic osteoporosis and have some clinical value in early diagnosis of diabetic osteoporosis and non-traumatic fractures in T2DM.