Background: Osteocalcin (OC), an osteoblast-specific secreted protein expressed by mature osteoblasts is used in clinical practice and in research as a marker of bone turnover. OC, has two major forms carboxylated (cOC) and undercarboxylated (ucOC) and each form has a different biological function including bone remodelling and glucose metabolism. Reference ranges for cOC and ucOC across the adult lifespan are not clear and current reference intervals for ucOC are limited to older men. Given the different physiological roles of cOC and ucOC, development of reference ranges of the total OC (tOC) and different forms may help to identify people who are at risk for future bone or metabolic conditions.
Methods: Blood was collected in the morning after an overnight fast from 236 community dwelling men (18 to 92 years old). Participants did not have a history of diabetes, antiresorptive, warfarin or glucocorticoid use. Serum was analysed for tOC and the ucOC fraction using the hydroxyapatite binding method. cOC, ucOC/OC and cOC/OC ratios were calculated. Reference intervals were established by polynomial quantile regression analysis.
Results: The normal range for our reference population of young men (≤30 years), was: tOC 17.9-56.8 ng/mL, ucOC 7.1- 22.0 ng/mL, cOC 8.51-40.3 ng/mL (mean and 95% CI). Aging had a significant effect on tOC, ucOC and cOC which reflected a “U” shape pattern. The ucOC/OC ratio increases with increasing age while cOC/OC ratio decreases with age. Body mass index (BMI) explained 4% of the variance in the ratios, while age explained 31% of the variance.
Conclusions: We have defined reference ranges for the OC-forms across the adult male lifespan and demonstrated OC-ratios better reflect the effects of aging on OC-forms.