Associations of Osteocalcin Forms with Metabolic Syndrome and Its Individual Components in Older Men: The Health in Men Study

Context: The osteoblast-derived polypeptide, osteocalcin (OC), has been associated with lower risk of type 2 diabetes and metabolic syndrome (MetS) in several epidemiological studies. Animal studies have indicated the undercarboxylated form of OC (ucOC) drives its association with metabolic outcomes. Objective: We compared associations of ucOC and carboxylated OC (cOC) with MetS and its components in older men. Methods: A cross-sectional analysis of 2575 men aged ≥70 years and older resident in Perth, Western Australia. ucOC was assayed using a hydroxyapatite-binding method, and cOC calculated by subtracting ucOC from total OC. Main outcome measures were MetS and its components. Results: Both lower serum ucOC and cOC levels, and the proportion of cOC (%cOC) were associated with less favorable metabolic parameters (higher waist circumference, triglyceride, glucose, blood pressure, and lower high-density lipoprotein cholesterol), whereas inverse associations were found with %ucOC. Men in the lowest quintile of ucOC had higher risk of MetS compared to men in the highest quintile (Q1≤7.7 vs Q5>13.8 ng/mL; OR=2.4; 95% CI, 1.8-3.2). Men in the lowest quintile of cOC had higher risk of MetS compared to those in the highest quintile (≤5.8 vs>13.0 ng/mL; OR=2.4; 95% CI, 1.8-3.2). Conclusion: Lower concentrations of serum ucOC or cOC were associated with less favorable metabolic parameters and a higher risk of MetS. In contrast, a lower proportion of ucOC was associated with better metabolic parameters and lower MetS risk. Further research is warranted to determine whether ucOC and cOC are suitable biomarkers for cardiometabolic risk in men.