Serrum immunoreactive bone sialoprotein (BSP) is a non collageneous protein of bone and although it is mainly synthesized by osteoblasts, it is believed that its quantification represents processes preferentially linked to bone resorption. This effect may be due to the protein’s role in cell matrix adhesion processes in attachment of osteoclasts to bone. To determine the physiological and pathological variability, serum levels of BSP (by RIA) were studied in: ① 54 healthy children aged 0-20 years (M/F: 30/24); ② healthy males (n=74); ③healthy pre (n=91) and postmenopausal (n=71) females; ④ patients with renal (RF; n=20) and hepatic (HF; n=20) failure In a subgroup of 10 healthy adults aged 23-39 years (M/F: 5/5),day to day variability (one measurement on 10 consecutive days), and the circadian variation (measurements at 08, 10, 12, 14, 16, 18, 20, 24, 04, and 08 years) were evaluated. Serum BSP was compared with serum C terminal crosslinked telopeptide of type I collagen (CTX; by ELISA), and urinary total deaxypyridiniline (DPD; by HPLC). In children, the highest values were found during early childhood and the pubertal growth spurt. Postmenopausal females had significantly higher mean BSP levels than premenopausal females (9.22±4.94 vs 7.82±3.30; P < 0.05), with the highest values soon after the menopause. No significant correlations were found between serum BSP and weight, height, or body mass index (IBM), in any of the groups of healthy individuals. The day to day variability of BSP ranged between 7.3% and 14.8% (mean 9.6%). Circadian variation showed a maximum amplitude of approx. ±20% at a mean BSP concentration of 10.4?ng/ml with peak values between 04 and 08 hours, followed by a steady decline until noon time. RF was associated with higher levels of serum BSP and CTX, and of urinary DPD. Both BSP ( r =-0.67, P < 0.001) and CTX ( r =-0.59, P <0.001) showed an inverse correlation with the creatinine clearance. HF patients had higher levels of BSP, CTX, and DPD, but no correlations were found between these markers and parameters of liver function. In conclution, serum BSP reflects physiologic changes of bone turnover with age(i.e. the pubertal growth spurt in adolescents, accelerated bone turnover soon after the menopause), but is not associated with other anthropometric variables (weight, height). The day to day variability of BSP is in acceptable range, and diurnal variation is attenuated. In the absence of RF or HF, serum BSP provides a valid index of bone metabolism and may improve the routine assessment of skeletal disorders. Serum immunoreactive bone sialoprotein (BSP) is a non collageneous protein of bone and although it is primarily synthesized by osteoblasts, it is believed that its quantification says processes preferentially linked to bone resorption. This effect may be due to the protein’s role in cell matrix adhesion processes in attachment of osteoclasts to bone. To determine the physiological and pathological variability, serum levels of BSP (by RIA) were studied in: ① 54 healthy children aged 0-20 years (M / F: 30/24); ② healthy males (n = 20) and hepatic (HF; n = 20) failure in a subgroup of 10 healthy adults (n = 74); (3) aged 23-39 years (M / F: 5/5), day to day variability (one measurement on 10 consecutive days), and the circadian variation (measurements at 08, 10, 12, 14, 16, 18, 20, 24 , 04, and 08 years) were evaluated. Serum BSP was compared with serum C terminal crosslinked telopeptide of type I collag In children, the highest values ​​were found during early childhood and the pubertal growth spurt. Postmenopausal females had a significantly higher BSP levels than premenopausal females (9.22 ± 4.94 vs 7.82 ± 3.30; P <0.05), with the highest values ​​soon after the menopause. No significant correlations were found between serum BSP and weight, height, or body mass index (IBM), in any of the groups of healthy individuals. The day to day variability of BSP ranged between 7.3% and 14.8% (mean 9.6%). Circadian variation showed a maximum amplitude of approx. ± 20% at a mean BSP concentration of 10.4 ng / ml with peak values ​​between 04 and 08 hours, followed by a steady decline until noon time. RF was associated with higher levels of serum BSP and CTX, and of urinary DPD. Both BSP (r = -0.67, P <0.001) and CTX (r = -0.59, 0.001) showed an inverse correlation with the creatinine clearance. HF patient s had higher levels of BSP, CTX, and DPD, but no correlations were found between these markers and parameters of liver function. In conclution, serum BSP represented physiologic changes of bone turnover with age (ie the pubertal growth spurt in adolescents, accelerated bone turnover soon after the menopause), but is not associated with other anthropometric variables (weight, height). The day to day variability of BSP is in an acceptable range, and diurnal variation is attenuated. In the absence of RF or HF, serum BSP provides a valid index of bone metabolism and may improve the routine assessment of skeletal disorders.