Objective To investigate the age-related changes of osseous metabolic markers and their relationships to bone mineral density (BMD) in females. Methods A total of 309 females with different ages (25-84 years) were enrolled. The total collagen type I amino-terminal extension peptide (TPⅠNP) and beta collagen specific sequences (β-CTX) were measured by electrochemical luminescence method. 25-hydroxy vitamin D(25-OH-VitD) and tartrate-resistant acid phosphatase-5b(TRACP-5b) were measured using ELISA. BMD of femoral neck, lumbar spine 1-4 were measured with a bone densitometer (GE Lunar Prodigy dual energy X-ray absorptiometry, DXA). The differences among different age and BMD groups were compared by two-sample t test, one-way analysis of variance, χ2 test with SPSS 17.0 software. Results The serum TPⅠNP, β-CTX levels in the 45-54 years group were higher than those in the 35-44 years group: (55.63±19.24) μg/L vs (40.90±14.63) μg/L, (597.10±198.70) ng/L vs (404.79±147.22) ng/L (t=4.156, 5.319, both P<0.01), and decreased slightly with increasing age. The serum 25-OH-VitD level decreased with increasing age. The serum TRACP-5b in the 45-54 years group increased significantly compared to that in the 35-44 years group (t=5.934, P<0.01); and it reached the highest level of (5.05±1.63) U/L in the 55-64 years group, then decreased slightly. The serum levels of TPⅠNP, β-CTX, 25-OH-VitD, TRACP-5b in osteopenic and osteoporosis groups were significantly different from those in the normal group (F=225.908, 253.208, 252.927, 313.265, all P<0.01). The specificities and positive predictive values of all four osseous metabolic markers were all over 95% for the diagnosis of abnormal BMD. The sensitivities of both serum 25-OH-VitD and TRACP-5b levels were higher than those of TPⅠNP(91.47%(193/211), 88.15%(186/211) vs 65.40%(138/211); χ2=42.381, 30.621, both P<0.01) and β-CTX(51.66%(109/211); χ2=82.164, 66.783, both P<0.01). Negative predictive values of both serum 25-OH-VitD and TRACP-5b levels were higher than those of TPⅠNP(χ2=23.103, 15.367, both P<0.01) and β-CTX(χ2=38.126, 28.514, both P<0.01). Conclusions The osseous metabolic markers might be closely related to the changes of BMD and age in females. It was important to measure the bone metabolism markers in the early diagnosis of osteoporosis. Key words: Bone density; Age factors; Female; Type Ⅰ amino-terminal extention peptide; Beta collagen specific sequences; Calcifediol; Tartrate-resistant acid phosphatase