The aim of this study was to investigate generalized osteoarthritis (GOA) by combining X-ray grading of the knee, spine and hand using biochemical markers for arthritis, such as YKL-40 and urinary pyridinoline (Pyr). One hundred and thirty postmenopausal women with primary knee osteoarthritis (OA) aged 55-92 years were included. Knee X-rays were taken in all patients. Spinal X-rays and hand X-rays were taken in 101 and 102 patients, respectively, and both spine and hand X-rays were taken in 86 patients. The degree of OA was graded using the Kellgren-Lawrence grading scale. Blood and urine were collected from all patients. Serum YKL-40 was measured using an ELISA kit and Pyr was measured using high-performance liquid chromatography directly linked to an automated sample preparation with extraction columns system. The knee X-ray grades were most related to YKL-40 and Pyr. A combination of knee and spinal OA grades revealed a significant relation to changes in both YKL-40 and Pyr, and a combination of hand OA and knee OA grades to YKL-40. Although OA of the three joints was related to YKL-40, hand OA alone was not related to either of the biochemical markers. We concluded that Pyr and YKL-40 as biochemical markers of arthritis did not discriminate GOA defined by hand OA alone. Overall observation in the combination of three joint sites indicated that the site to discriminate GOA, from the most useful to the least, was the knee, the spine and the hand, and knee OA was the most closely related to Pyr and YKL-40.