Bone as an endocrine organ relevant to diabetes.

There are well-established associations between diabetes and fracture risk and yet the mechanism underlying these associations are controversial. Guided by a series of mouse studies, a specific form of the bone protein, osteocalcin, was proposed to be the mechanistic link between these two chronic diseases. Translation to humans initially appeared elusive in part because serum concentrations of osteocalcin are a biomarker of bone turnover and not necessarily specific to the biology of this protein. The suitability of the mouse model for the study of osteocalcin as a therapeutic target also appears ambiguous. With greater discrimination of the different forms of osteocalcin present in circulation and inclusion of multiple measures of bone turnover, evidence currently does not support osteocalcin as a protein critical to the diabetes and fracture association in humans.