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Aim We measured the levels of bone turnover markers (BTMs) in patients with early diabetic nephropathy from type 2 diabetes mellitus (T2DM), and investigated the associations of BTMs with adipokines, serum fibroblast growth factor-21 (FGF21) and osteonectin. Methods We included 159 males and 300 females with T2DM in this cross-sectional study. Clinical characteristics, BTMs and adipokines levels were measured. Results One-hundred and ninety-two (41.8%) patients presented with albuminuria. Patients with albuminuria had significantly higher levels of serum osteonectin ( P < 0.0001) and FGF21 ( P = 0.0125) than those with normoalbuminuria. Serum levels of P1NP were slightly lower among patients with albuminuria ( P = 0.031), but the difference disappeared after adjusting for FBG, PBG, and HbA1c. Serum FGF21 levels were independently and negatively related to eGFR (overall β = − 0.161, P = 0.001; albuminuria group β = − 0.240, P = 0.001) but not related to uACR. While Osteonectin was independently and positively related to uACR (overall β = 0.209, P = 0.001; albuminuria group β = 0.170, P = 0.021). The levels of serum FGF21 were independently inversely related with P1NP (overall β = − 0.192, P < 0.0001; albuminuria group β = − 0.195, P = 0.031). Conclusions Our results suggest that persistent hyperglycemia may inhibit bone formation. Both osteonectin and FGF21 were associated with early nephropathy in T2DM patients, albeit with different patterns. [ABSTRACT FROM AUTHOR]