SERUM IMMUNOREACTIVE BONE SIALOPROTEIN AS A NEW MARKER OF BONE TURNOVER IN METABOLIC AND MALIGNANT BONE-DISEASE

Bone sialoprotein (BSP) is a phosphorylated glycoprotein with a M(r) o f 70-80 kDa that accounts for approximately 5-10% of the noncollagenou s proteins of bone. Due to its relatively restricted distribution to m ineralized tissues, BSP may serve as a potential marker of bone metabo lism. Employing a recently developed RIA, serum BSP was measured in 13 3 healthy subjects, aged 20-80 yr, and in patients with primary hyperp arathyroidism (pHPT; n = 26), Paget's disease of bone (PD; n = 14), un treated multiple myeloma (MM; n = 32), and breast cancer with bone met astases (BC; n = 19). Results were compared to clinical and laboratory data, including serum total alkaline phosphatase as a marker of bone formation, and the urinary cross-links pyridinoline (PYD) and deoxypyr idinoline (DPD) as markers of bone resorption. In healthy adults, seru m BSP values ranged between 5.0-21.6 ng/mL (5-95% interval), with a me dian of 10.5 ng/mL, (total group). In healthy females, a linear correl ation was found between serum BSP and age (r = 0.51; P < 0.001), with significantly higher values in postmenopausal than in premenopausal wo men (13.3 +/- 4.8 vs. 9.0 +/- 3.8; P < 0.01). In the healthy group, BS P values did not change with body mass index, lumbar bone mineral dens ity, serum calcium, serum creatinine, or serum total alkaline phosphat ase levels. In contrast, a weak, but significant, correlation was obse rved between serum BSP and the urinary excretion of PYD and DPD. Compa red to those in healthy controls, serum BSP levels were significantly higher in patients with pHPT, PD, MM, or BC (P < 0.01 for all groups). These differences remained after analyses were adjusted for age and s ex. In pHPT, serum BSP levels mere closely correlated to urinary PYD a nd DPD (r = 0.87 and 0.83, respectively; P < 0.01), whereas in PD, no correlation was observed between any of the bone markers. Serum BSP le vels were highest in patients with MM, and there was a significant dif ference between early and advanced stages of the disease (30.2 +/- 8.0 vs. 64.3 +/- 6.8; P < 0.01). In a subgroup of 15 patients with metast atic BC, iv bisphosphonate treatment resulted in a rapid reduction of serum BSP levels to 40% of the baseline values within 4 days of treatm ent. In conclusion, BSP appears to be a sensitive marker of bone turno ver, and the present data suggest that its serum levels predominantly reflect processes related to bone resorption.