ObjectiveDisturbances in high-density lipoprotein cholesterol (HDL-c) metabolic pathways can affect bone metabolism, which may rely on the particle function of apolipoprotein rather than HDL-c levels. This study aimed to evaluate the correlation of serum HDL-c and apolipoprotein A1 (APOA1) with bone metabolism in Chinese postmenopausal women with type 2 diabetes mellitus (T2DM).MethodA total of 1,053 participants with complete data were enrolled and separated into three groups based on the HDL-c and APOA1 tertiles. The trained reviewer collected demographic and anthropometric information. Bone turnover markers (BTMs) were determined by standard methods. Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry.ResultsOverall, the prevalence of osteoporosis was 29.7%. Groups with higher APOA1 have a remarkably more elevated level of osteocalcin (OC), L1-L4 BMD, andT-score across the APOA1 tertiles. APOA1 presented a positive correlation with OC (r= 0.194,p< 0.001), L1-L4 BMD (r= 0.165,p< 0.001), andT-score (r= 0.153,p< 0.001) rather than HDL-c. Meanwhile, APOA1 remained independently associated with OC (β= 0.126,p< 0.001), L1-L4 BMD (β= 0.181,p< 0.001), andT-score (β= 0.180,p< 0.001) after adjustment for confounding factors. APOA1 is also shown to be independently correlated with osteoporosis after adjustment for confounding factors, and the OR (95%CI) was 0.851 (0.784–0.924). In contrast, there was no significant association between HDL-c and osteoporosis. Furthermore, APOA1 seemed to have the largest areas under the curve (AUC) for osteoporosis. The AUC (95% CI) of APOA1 identifying osteoporosis was 0.615 (0.577–0.652). The optimal cut-off value of APOA1 was 0.89 g/L (sensitivity: 56.5%, specificity: 67.9%).ConclusionAPOA1 is independently associated with OC, L1-L4 BMD, and osteoporosis rather than HDL-c in Chinese postmenopausal women with T2DM.