Osteocalcin is secreted from osteoblasts and might affect metabolic regulation. A study in mice shows that disruption of glucocorticoid signalling specifically in osteoblasts prevents the development of insulin resistance, glucose intolerance and weight gain, which are common adverse consequences of glucocorticoid therapy. Additionally, following glucocorticoid treatment, these adverse effects were attenuated in mice expressing carboxylated and undercarboxylated osteocalcin in the liver. These results suggest that the adverse metabolic effects of glucocorticoid therapy are mediated via effects on the skeleton.