Serum osteocalcin and bone mineral density at various skeletal sites: a study performed with three different assays

The purposes of this study were threefold: (1) to compare values obtained by three conventional radioimmunoassays for serum bone-gla-protein (BGP) in a population of normal women, (2) to study the relationship between serum BGP and bone mineral density (BMD) measured at four different skeletal sites (lumbar spine, proximal femur, proximal and ultradistal radius), and (3) to compare the results obtained by the three assays with conventional markers of bone turnover. Ninety-seven normal women (age range 25 to 75 years, mean +/- 1 SD = 54.3 +/- 10.9 years) were studied. Three independent assays were used to measure serum osteocalcin levels: a heterologous radioimmunoassay (RIA) (A) (Incstar Co., Stillwater, Minn.), a homologous RIA (B) (Nichols Institute, San Juan Capistrano, Calif.), and a two-site immunoradiometric assay (C) (Cis Biointernational, Gif-sur-Yvette, France). Mean +/- SD values of serum osteocalcin in the group as a whole were 4.05 +/- 1.37 microg/L by assay A, 6.03 +/- 2.90 microg/L by assay B, and 22.67 +/- 7.52 microg/L by assay C. Serum osteocalcin levels increased linearly with age; however, no correlation between serum BGP (whatever the assay used) and age was observed when only postmenopausal women were taken into account. When the effect of age was held constant by means of partial correlation analysis, only serum BGP levels measured by assays B and C were still inversely related with lumbar spine and ultradistal radius BMD; the latter assay was also weakly correlated with Ward's triangle BMD. After all the biochemical and clinical variables taken into consideration were introduced in a multiple regression equation, serum BGP still represented an important predictor of ultradistal radius and lumbar spine BMD only. Regarding relationships with other markers of bone turnover, the assay C in general showed the highest r values. In conclusion, our results indicate that commercially available BGP assays differ analytically and clinically; furthermore for the first time they show the existence of an inverse correlation between serum osteocalcin levels (which reflects bone turnover at the time of examination) and bone mass (which at a given time represents the balance of all previous metabolic events), after the influence of aging is excluded.