Several new serum markers for bone metabolism have recently become available and are being applied to clinical practice. Their clinical usefulness in predialysis patients with chronic renal failure (CRF), however, has not yet been determined. Serum levels of three bone formation markers-bone alkaline phosphatase (BAP), osteocalcin (OC), and N-terminal propeptide of type I collagen (PINP)-and three bone resorption markers-type I collagen cross-linked N-telopeptide (NTx), deoxypyridinoline (DPD), and pyridinoline (PYD)-were measured simultaneously in 85 predialysis CRF patients (serum creatinine 3.5 +/- 1.9 mg/dl, 61.0 +/- 10.9 years old, 54 males and 31 females, 36 diabetics and 49 nondiabetics) to examine the relationships between these markers and bone mineral density (BMD) of the distal radius, as measured by peripheral quantitative computed tomography (pQCT). Trabecular BMD, which is strongly affected by bone metabolism, was significantly negatively correlated with each of the bone formation markers (r=-0.341, p=0.0016, for OC; r=-0.314, p=0.0036, for PINP; r=-0.238, p=0.0315, for BAP), but there was no significant correlation between BMD and any of the bone resorption markers. In multivariate regression analyses (adjusted by age, sex, presence of diabetes, glomerular filtration rate, intact parathyroid hormone, calcium, phosphate, and 1,25-dihydroxyvitamin D), OC and PINP were significantly associated with a decrease in BMD, but BAP was not. In conclusion, we demonstrated that in predialysis CRF patients, BMD of the distal radius, particularly of trabecular bone, is associated with serum OC and PINP levels. OC and PINP are suggested to be possible parameters for the clinical evaluation of the effect of bone metabolism on BMD.