The endochondral skeleton evolved over 300 million years ago when the first animals colonized land. Survival of terrestrial vertebrates in this new environment required wholesale adaptations in their anatomy and physiology. A larger musculoskeletal system enabled ambulation against increased gravitational forces and new strategies evolved to regulate extracellular mineral ion levels. The upgraded musculoskeletal system provided a storage site for scarce minerals essential for life, but also increased overall fuel requirements and altered global energy balance, prompting the evolution of endocrine networks to coordinate energy expenditure.
Bone forming osteoblasts require a constant supply of fuel bone matrix production. When fuel demands are not met, bone quality and strength is compromised. Recent studies suggest that key developmental signaling pathways are coupled to bioenergetic programs to accommodate changes in energy requirements at different stages in the osteoblast lifecycle. In vivo studies in genetically altered mice have confirmed a link between bone cells and global metabolism, and have led to the identification of hormonal interactions between the skeleton and other tissues. These observations have prompted new questions regarding the nature of the mechanisms of fuel sensing and processing in the osteoblast and their contribution to overall energy utilization and homeostasis. Answers to such questions should advance our understanding of metabolic diseases and may ultimately improve management of patients with diabetes and osteoporosis.