Bone as an endocrine regulator of lipid and energy metabolism

Bone has long been viewed as a structural organ with essential roles in mechanical support and mineral homeostasis. However, accumulating evidence shows that the skeleton is also an active endocrine organ that contributes to the regulation of systemic energy metabolism. Bone remodeling requires substantial energy, and skeletal cells, including osteoblasts, osteocytes, and bone marrow adipocytes, secrete endocrine factors that influence adipose tissue plasticity, glucose homeostasis, insulin sensitivity, and energy expenditure. In this Review, we summarize current knowledge of bone-derived endocrine factors, or osteokines, and their roles in lipid and energy metabolism. We discuss how signals from osteoblasts, osteocytes, and marrow adipose tissue link skeletal state to peripheral metabolic adaptation. We highlight key osteokines, including osteocalcin, adiponectin, sclerostin, FGF23, PTHrP, lipocalin-2, and components of the RANKL-OPG axis, and summarize evidence for their systemic metabolic effects. Collectively, these findings identify bone as an active regulator of whole-body energy homeostasis rather than a passive target of metabolic signals. Understanding how skeletal endocrine programs interact with adipose tissue and other metabolic organs may offer new ideas and therapeutic opportunities for metabolic diseases.