Osteocalcin: a new link between bone and energy metabolism. Some evolutionary cluesFernández-Real, Jose M; Ricart, WifredoCurrent Opinion in Clinical Nutrition & Metabolic Care: July 2011 - Volume 14 - Issue 4 - p 360–366 doi: 10.1097/MCO.0b013e328346df4e Carbohydrates: Edited by Luc Tappy and Bettina Mittendorfer Abstract Author Information Purpose of review: Recent findings suggest that the bone is an active regulator of energy and glucose metabolism. The purpose of this review is to summarize current evidence in humans. Recent findings: Both cross-sectional and longitudinal studies support osteocalcin as an active regulator of carbohydrate metabolism in humans, being the muscular load of physical activity one of the possible links between the osteoblast and the insulin axis. This axis could also have been involved in the modulation of nonalcoholic steatohepatitis. The osteoblast-to-insulin axis seems to act paradoxically in patients with increased growth hormone (acromegaly) and during bone repair. Some possible evolutionary implications are suggested. Summary: Osteocalcin may have a role in the regulation of systemic energy metabolism, given the common origin of the osteoblast with the two other cells implicated (adipocytes and muscle cells). Bioactivity of circulating human carboxylated and uncarboxylated osteocalcin should be characterized in depth, especially in those patients with increased concentrations (renal failure). Osteocalcin is one of the clues in the interaction between calcium and glucose metabolism, and the discovery of the osteocalcin receptor will aid in the study of these relationships. Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomédica de Girona (IdIBGi) CIBER Fisiopatología de la Obesidad y Nutrición CB06/03/010, Girona, Catalonia, Spain Correspondence to Jose M. Fernandez-Real, MD, PhD, Unit of Diabetes, Endocrinology and Nutrition, Hospital de Girona ‘Dr Josep Trueta’, Ctra. França s/n, E-17007 Girona, Catalonia, Spain Tel: + 34 972 94 02 00; fax: +34 972 227 443; e-mail: firstname.lastname@example.org © 2011 Lippincott Williams & Wilkins, Inc.