The aim of this study was to investigate determinants of reduced bone mineral density (BMD) in postmenopausal women with active rheumatoid arthritis (RA) and to evaluate whether there are common markers of bone loss. We evaluated BMD of the femoral neck using dual-energy X-ray absorptiometry, and the measured biochemical markers included serum bone-specific alkaline phosphatase (BALP), serum osteocalcin (OC), and serum cross-linked N-telopeptidases of type I collagen (NTx). Serum BALP and NTx concentrations were measured by enzyme-linked immunsorbent assay, and OC was measured using an immunoradiometric assay. One hundred and forty postmenopausal Japanese women who had not received treatment with bisphosphonates or hormone replacement therapy were entered into the study. Thirty-four patients (41.0%) had femoral osteopenia (T score -1 to -2.5) and 23 patients (27.7%) had osteoporosis (T < -2.5). The body mass index of patients with normal BMD (T score >or= -1.0) was significantly higher (P < 0.01) than in patients with osteoporosis at the femoral neck. The T score exhibited a significant negative correlation with age and the duration of RA disease. Serum BALP and serum OC, markers of osteoblast function, were negatively related to erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and matrix metalloproteinase-3 (MMP-3). However, serum NTx, a marker of resorptive function, exhibited a positive correlation with ESR, CRP, and MMP-3. From these results, this study suggests that generalized bone loss occurs in active RA and is characterized by evidence of bone resorption that is correlated with the high levels of inflammation. Body mass index, disease duration, and high serum NTx level were common risk factors in osteoporosis of postmenopausal women with RA.