Bone and glucose metabolism: a two-way street

Abstract

Evidence from rodent models indicates that undercarboxylated osteocalcin (ucOC), a product of osteoblasts, is a hormone affecting insulin production by the pancreas and insulin sensitivity in peripheral tissues, at least in part through enhanced secretion of adiponectin from adipocytes. Clinical research to test whether this relationship is found in humans is just beginning to emerge. Cross-sectional studies confirm associations between total osteocalcin (OC), ucOC and glucose metabolism but cannot distinguish causality. To date, longitudinal studies have not provided a consistent picture of the effects of ucOC or OC on fasting glucose and insulin sensitivity. Further exploration into the physiological and mechanistic effects of ucOC and OC, in rodent models and clinical studies, is necessary to determine to what extent the skeleton regulates energy metabolism in humans.

Figure 1. Proposed regulation of Esp expression and osteocalcin carboxylation in mice

Abbreviations: HA, hydroxyapatite; K, vitamin K; SNS, sympathetic nervous system; OC, osteocalcin; ucOC, uncarboxylated osteocalcin.

Figure 2. Regulation of glucose metabolism by bone

In mouse models, undercarboxylated osteocalcin (ucOC) produced by osteoblasts increases insulin production and sensitivity and decreases fat mass, and diabetes risk. Increases in adiponectin accompany increased ucOC, suggesting that adiponectin is a pathway for the effect of ucOC on insulin sensitivity.