Bone Abstracts

Our understanding of skeletal biology has revealed bone as a tissue under complex regulatory control, with numerous systems influencing bone development and remodeling. In contrast, the regulatory output from bone tissue is very minimal. However, skeletal research is currently undergoing a period of marked expansion. One aspect in particular is the relationship between bone and fat metabolism. In addition to well-defined responses to weight bearing, emerging evidence indicates that bone and adipose tissue are co-regulated and interdependent. Signals from fat cells are known to regulate bone mass, with prominent adipokines such as leptin and adiponectin. Interestingly, signals produced by bone cells are now being identified that are capable of regulating fat cells, both directly and through central hypothalamic signalling, thereby providing feedback from bone to the regulatory elements of energy homeostasis, within the adipocyte and the brain.

Osteocalcin, a protein secreted by osteoblasts, has emerged as a bone-specific endocrine signal, capable of feedback control of energy homeostasis. Osteocalcin null mice are obese, hyperglycaemic, glucose intolerant and hypoinsulinaemic. Importantly, opposing changes were evident following treatment with exogenous Ocn. Increasing Ocn levels reduced fat mass and improved insulin sensitivity in wild type mice. In subsequent studies investigating energy and glucose homeostasis, osteocalcin has been demonstrated to beneficially regulate energy metabolism through secretion of the undercarboxylated form of osteocalcin (ucOC), acting to increase the insulin sensitising adipokines adiponectin, and directly increasing insulin production in the beta cell. Recently, our laboratory has produced data suggesting a novel central loop for OC signalling, also capable of regulating adipose and glucose homeostasis. To date human data are emerging with varied results, with several recent studies in children conflicting with this view.

In conclusion, the link between energy and bone homeostasis is far more complex than a response to weigh bearing, with multiple axes of control, involving both central and direct signalling pathways. Feedback signals must exist for this bone/fat cross talk to be controlled, and osteocalcin has emerged as a candidate for that role. Further research, particularly in children, is required to define this novel axis.