Bone and glucose metabolism: A two-way street

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. ► Bone effects on glucose metabolism in mice and humans. ► Undercarboxylated osteocalcin (ucOC) promotes insulin secretion and sensitivity in mice. ► Lower OC and insulin resistance associated in cross-sectional clinical studies. ► Longitudinal studies needed to determine if OC affects glucose metabolism in humans.