Normal carboxylation of circulating osteocalcin (bone Gla-protein) in Paget's disease of bone

Serum osteocalcin (bone Gla-protein), a specific marker of osteoblastic activity, is only moderately increased in patients with active Paget's disease of bone, despite biochemical evidence of increased bone turnover. Because pagetic bone has an abnormal texture, such a discrepancy could be due to an abnormal carboxylation of osteocalcin. To test this hypothesis, we measured the fraction of decarboxylated osteocalcin in the serum of 11 patients with active Paget's disease of bone by the hydroxyapatite binding technique and the data were compared to those obtained in 10 controls and in 10 patients on vitamin K antagonist therapy. In contrast to the decreased decarboxylated fraction of osteocalcin in warfarin-treated patients (27 +/- 2.2%, P less than 0.01 vs controls), the fraction of decarboxylated osteocalcin was normal in pagetic patients (8.9 +/- 2.2% vs 6.5 +/- 1.7% in controls, n.s.). These data suggest that there is no abnormality of the osteocalcin carboxylation in Paget's disease. The disproportionate levels of circulating osteocalcin compared to the marked elevation of alkaline phosphatase in that disease could be due to other factors such as an increased binding of the protein to the woven bone matrix.