Osteocalcin: A bone protein with multiple endocrine functions

Bones are now recognised as endocrine organs with diverse functions. Osteocalcin, a protein primarily produced by osteoblasts, has garnered significant attention. Research into osteocalcin has revealed its impact on glucose metabolism and its unexpected endocrine role, particularly in its undercarboxylated form (ucOC). This form influences organs, affecting insulin sensitivity and even showing correlations with conditions like type 2 diabetes and cardiovascular diseases. However, analytical challenges are impeding advances in clinical research. Various immunoassays like RIA, EIA, ECLIA, IRMA, and ELISA have been developed to analyse osteocalcin. Recent innovations include techniques like OS-ELISA and OS phage Immuno-PCR, enabling fragment analysis. Advancements also encompass porous silicon for detection and ECLIA for rapid measurements. The limitations of immunoassays lead to ucOC measurement discrepancies, prompting the development of mass spectrometry-based techniques. Mass spectrometry increasingly quantifies carboxylated, undercarboxylated, and fragmented forms of osteocalcin. Mass spectrometry improves routine and clinical analysis accuracy. With heightened specificity, it identifies carboxylation status and serum fragmentations, boosting measurement reliability as a reference method. This approach augments analytical precision, advancing disease understanding, enabling personalised medicine, and ultimately benefiting clinical outcomes. In this review, the different techniques for the analysis of osteocalcin will be explored and compared, and their clinical implications will be discussed.