[Abstract] Objective To analyze the relationships between the drinking water fluoride and bone mineral density (BMD), and serum osteocalcin (BGP), and to explore the feasibility that the BMD and serum BGP as a significant early screening biomarkers for fluorosis, especially for early bone damage in endemic fluomsis areas. Methods Wamiao (severe endemic fluorosis area, as fluoride exposed group) and Xinhuai (non endemic fluorosis area, as control group) Village were selected in 2006. 146 objects were chosen from 2 villages (103 in Wamiao, 43 in Xinhui) according the drinking water fluoride in their household shallow well. The sex, age, body height, body weight, drinking water fluoride in each object’s household well, BMD，and serum BGP were investigated, and the dose-response relationships were analyzed between the drinking water fluoride and BMD, and serum BGP. CurveExport 1.3 Software was used to fit the dose—response relationships between the rate of abnormal BMD, the rate of abnormal serum BGP, and the drinking water fluoride. Results The levels of drinking water fluoride in males’ and females’ families in Wamiao village were [(2.38±0.68), (2.62±0.91) mg/L] significant higher than that in Xinhuai [(0.35±0.08), (0.36±0.07) mg/L], the difference being statistically significant (t value were 14.27 and 11.08, and P<0.01, respectively). BMD in males in Wamiao village [(0.78±0.07)g/cm²] was significant lower than that in Xinhuai [(0.83±008)g/cm²], the difference being statistically significant (t=2.37, P<0.05). Serum BGP in males and females in Wamiao [(4.17±0.67), (4.1l±0.57) μg/L] were significant higher than that in Xinhuai [(1.48±0.40), (1.44±0.39) μg/L], the difference being statistically significant (t values were 17.64 and 19.40, and P<0.01, respectively]. BMD in the group with drinking water fluoride ≥2.92 mg/L [(0.66±0.15)g/cm²] was significant lower than that in the group with drinking water fluoride < 0.42 mg/L [(0.76±0.12)g/cm²], the difference being statistically significant (P<0.01). The levels of serum BGP in the groups with the drinking water 0.42 ~, 2.05~, ≥2.92 mg/L[(3.83±1.07), (4.22±0.72), (3.99±0.63) μg/L] were significant higher than that in the group with the drinking water <0.42mg/L[(1.44±0.37) μg/L], the difference being statistically significant (P<0.01). The equation for the dose—response relationship between the drinking water fluoride and the rate of abnormal BMD was y=(0.284-0.058x)^-1.260, r=0.99994; and y=100.05/(1+78.62e^-4.55x), r=0.99999 for the drinking water fluoride and the rate of abnormal serum BGP. Conclusions There were significant dose-response relationships between drinking water fluoride and BMD and serum BGP. It indicated that BMD and BGP might be considered as early screening biomarkers for endemic fluorosis，especially for the bone damage.

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