Chronic, low-grade metabolic acidosis due to Western diets may be a risk factor for osteoporosis. The severity can be determined in part by net endogenous acid production (NEAP). In a population-based study, a total of 1028 healthy men and women aged 20-72 years were evaluated for dietary intakes and NEAP estimates with a validated food frequency questionnaire. Dual-energy X-ray absorptiometry (DXA) was used to determine BMD of the lumbar spine (L2-L4), distal third of radius, and proximal femur. Serum CrossLaps, degradation products of the C-terminal telopeptides of type I collagen, and osteocalcin were measured by highly specific ELISA methods. Lower estimates of energy-adjusted rates of NEAP were associated with greater femoral neck BMD (p=0.01) in premenopausal women and with greater BMDs at the distal radius (p=0.001) and lumbar spine (p=0.04) in postmenopausal women. Compared with women in the highest quartile of the estimates of the energy-adjusted rates of NEAP, pre- and postmenopausal women in the lowest quartile had significantly greater means of osteocalcin [9.12 (SD+/-1.62) vs. 5.24 (SD+/-1.41) ng/ml, p=0.02 and 11.74 (SD+/-1.69) vs. 7.79 (SD+/-2.63) ng/ml, p=0.002, respectively]. Analysis by quartiles of the estimates of energy-adjusted rates of NEAP did not reveal a relationship between BMD and bone turnover markers in men. In conclusion, we found that a high energy-adjusted rate of NEAP was associated with a significantly lower BMD in women but not in men and the energy-adjusted rate of NEAP had a negative relationship with bone formation.