Osteocalcin is one of the major proteins in the osseous matrix. To evaluate the determinants and thus the physiological control of osteocalcin production in normal and osteoporotic subjects, the serum levels of osteocalcin, 25-hydroxycholecalciferol (25-OH-D3), and insulin-like growth factor I (IGFI) were measured by radioimmunoassay in 44 subjects over 60 years old. Circulating osteocalcin, 25-OH-D3, and IGFI were 0.28 +/- 0.10 nmol/L (1.65 +/- 0.96 ng/mL), 70.5 +/- 25.1 nmol/L (28.3 +/- 10.1 ng/mL), and 23.8 +/- 12.0 nmol/L in 27 healthy controls respectively, as compared with 0.09 +/- 0.09 nmol/L (0.52 +/- 0.52 ng/mL), 48.2 +/- 19.9 nmol/L (19.35 +/- 7.91 ng/mL), and 16.56 +/- 6.96 nmol/L in 17 patients with spinal fractures. Significant correlation was found between osteocalcin and 25-OH-D3 level, as well as between osteocalcin and IGFI. The results show that IGFI and 25-OH-D3 are important determinants for serum concentration of osteocalcin in elderly subjects with and without spinal fractures.