ucOC

Uncarboxylated osteocalcin (ucOC) is a circulating form of osteocalcin, a small protein produced by osteoblasts in bone. Osteocalcin is normally secreted in a carboxylated form, a modification that requires vitamin K and promotes binding to hydroxyapatite in bone. During bone remodeling, some osteocalcin that escapes this carboxylation becomes undercarboxylated and is released into the bloodstream as ucOC. The balance between carboxylated and uncarboxylated osteocalcin reflects vitamin K status and bone turnover.

In mammals, ucOC is thought to act as a hormone that influences energy metabolism. In mice, ucOC acts on pancreatic beta cells via the GPRC6A receptor to promote insulin secretion, and on adipocytes to raise adiponectin and energy expenditure; in male mice, it increases testosterone production by Leydig cells. In humans, associations exist between ucOC levels and metabolic parameters, but causality is not established and findings are inconsistent.

Measurement and interpretation: ucOC is typically measured in serum by immunoassays that target the undercarboxylated epitope. Levels are influenced by vitamin K intake and status, time of day, age, renal function, and bone turnover. Distinguishing ucOC from carboxylated and total osteocalcin is important for interpreting results.

Current status: The idea of ucOC as a bone-derived hormone is supported by animal studies but remains debated in humans. Evidence for metabolic effects is largely observational, and interventional data are limited. Ongoing research aims to clarify causal roles, mechanisms, and clinical relevance.