ABSTRACT: This study aimed to explore the risk factors attributed to osteoporosis in newly type 2 diabetes mellitus (T2DM) patients. This study aimed to recruit 244 T2DM patients and 218 non-diabetic controls. We collected demographic characteristics, medical history, bone mineral density and biomarkers including bone specific alkaline phosphatase (BALP), osteocalcin, N-terminal peptide of type I procollagen (P1NP), tartrate-resistant acid phosphatase 5b (TRCAP-5b), β-Cross Laps of type I collagen-containing cross-linked C-telopeptide (β-CTX), 25-hydroxyvitamin D, parathyroid hormone were recorded or detected. Bone mineral density (BMD) was our primary outcome. Based on the result of BMD, we divided both the control group and T2DM group into three subgroups: normal bone mass, osteopenia and osteoporosis. In control group, we found age, sex, menopausal status, BMI, P1NP, BALP, TRACP-5b, osteocalcin, and corrected serum calcium are differential among three subgroups. In T2DM group, we found age, sex, menopausal status, drinking status, BMI, HbA1c, TRACP-5b and OC were differential among three subgroups. In T2DM and control groups, age, female, postmenopausal status, BALP, TRACP-5b and osteocalcin were positively correlated while BMI was negatively correlated with osteoporosis. In control group, β-CTX was positively correlated with osteoporosis. In T2DM group, HbA1c and corrected serum calcium concentration were positively correlated with osteoporosis. After further adjustment of age, BMI in male, TRACP-5b was positively correlated with the risk of osteoporosis in newly diagnosed T2DM. After adjusted of age, BMI and menopausal status in female, OC was positively correlated with the risk of osteoporosis in newly diagnosed T2DM and controls. In female T2DM, BALP and P1NP were positively correlated with the risk of osteoporosis. In conclusion, age, BMI and menopausal status are common risk factors for osteoporosis in diabetic and non-diabetic patients, however TRACP-5b, BALP and osteocalcin are special risk factors for osteoporosis in newly diagnosed T2DM patients but not non-diabetic patients, which may be applied to identify osteoporosis risk in T2DM patients, but this result needs to be proven with fracture data.