Bone Sialoprotein (BSP), synthesized by osteoblasts and osteoclasts, is a highly glycosylated and phosphorylated protein, accounting for approximately 5-10% of noncollagenous proteins of bone extracellular matrix. The present study investigates possible correlations between serum values of immunoreactive Bone Sialoprotein in relation to established bone turnover markers like osteocalcin (OC), bone alkaline phosphatase (B-ALP) and the c-terminal extension peptide of type-I-Procollagen (PICP) in 170 osteoporosis patients (female n = 144, male n = 26) in order to evaluate the usefulness of BSP in the diagnosis of bone disease. Fasting venous blood samples were collected from our osteoporosis outpatients in the morning and stored at -80 degrees C until processing. Serum levels of BSP were determined by RIA, OC and B-ALP were measured by IRMA, and PICP was assessed employing an ELISA technique. A significant correlation was found between BSP serum values and B-ALP (r = 0.532, p = 0.0001). Median serum BSP levels were 8.0 micrograms/l, median B-ALP values were 22.39 U/ml in these patients. Also a significant correlation was observed between BSP and OC (r = 0.588, p = 0.0001), more pronounced in the female patient group (r = 0.632, p < 0.0001). A weak association between BSP and PICP in the female group was detected (r = 0.398, p = 0.0001). In the female group BSP was inversely related to serum estradiol levels (r = -0.274, p = 0.002) as to BMD (DEXA) at the lumbar spine and femoral neck. In conclusion, BSP might be a useful marker of non-collagenous organic bone matrix in laboratory assessment of bone turnover, being inversely related to BMD at lumbar spine and femoral neck and showing significant correlations to established markers of bone turnover like B-ALP and OC.