Gender dimorphism and lack of day/night variation or effects of energy deprivation on undercarboxylated osteocalcin levels in humans.

Objective: Undercarboxylated osteocalcin (ucOC) is a bone marker with potent metabolic effects. Leptin regulates Esp gene expression and osteocalcin carboxylation in animal models. We aim to elucidate day/night patterns of ucOC levels, whether short-term and/or chronic energy deprivation alters ucOC levels, and whether leptin may mediate these changes in humans.

Methods: Twelve healthy males and females were studied for 72 h in the fed state to study day/night pattern of ucOC. The six female subjects were also studied in a crossover interventional study in the fasting state for 72 h with administration of either placebo or metreleptin in physiological doses. Blood samples were obtained hourly from 0800 a.m. on day 3 until 0800 a.m. on day 4. In a separate study, eleven obese subjects who underwent bariatric surgery were followed for 24 weeks to examine the effects of postsurgery weight loss on ucOC levels.

Results: Males have higher ucOC levels compared to females. There is no day/night variation pattern of circulating ucOC in humans. Short-term and chronic energy deprivation or leptin administrations do not alter ucOC levels.

Conclusions: The hypothesis that ucOC plays a role in energy homeostasis or of leptin in regulating ucOC in humans is not supported.