Serum osteocalcin in Paget's disease of bone: basal concentrations and response to bisphosphonate treatment

Serum osteocalcin concentrations were measured in 42 patients with Paget's disease of bone and elevated serum alkaline phosphatase (AP) levels. High serum osteocalcin levels were found in only 22 patients. Serum osteocalcin was significantly correlated with urinary hydroxyproline excretion (r = 0.747; P less than 0.001) and, to a lesser extent, with serum AP levels (r = 0.483; P less than 0.01). In 23 patients who were followed during treatment with iv (3-amino-1-hydroxypropylidene) 1,1-bisphosphonate (APD) for 10 days, a dissociation among these 3 biochemical parameters was found. Urinary hydroxyproline excretion fell significantly (P less than 0.001), serum AP levels decreased, but not significantly, and serum osteocalcin concentrations increased progressively (P less than 0.001). This increase was greater when initial levels were lower than expected for the activity of the disease. The rise in serum osteocalcin correlated significantly with the concomitant increase in serum 1,25-dihydroxyvitamin D concentrations. Three months after initiation of treatment, all 3 parameters, urinary OHP excretion, serum AP, and serum osteocalcin levels, were near or within the normal range. These results indicate that serum osteocalcin is not a clinically useful parameter for assessment of the activity of Paget's disease. Its basal concentrations lag behind those expected from the activity of the disease, suggesting defective osteocalcin production. It appears that the functions of osteocalcin and AP as well as their initial expression by the osteoblasts are different and that this difference may be important for the quality of bone formed in Paget's disease. APD can modulate the release of osteocalcin, possibly through stimulation of 1,25-dihydroxyvitamin D production, although other factors may be involved.