Figure 2. Energy metabolism endocrine systems calibrate the balance between bone quality and energy conservation.

Bone remodeling is the lifelong creation and destruction of bone tissue that preserves bone quality. Because bone is one of the largest organs in the body and because bone remodeling is one of the only healthy biological processes that requires the active destruction of tissue, bone remodeling is one of the largest consumers of energy in bony vertebrates. For these reasons and others, it was proposed that there would be a coordinated regulation of organismal energy metabolism and bone remodeling. This concept stimulated the discovery that leptin inhibits bone formation and stimulates bone resorption by signaling through the brain to activate the sympathetic nervous system, which then signals through the β-adrenergic receptor in osteoblasts. Over the subsequent two decades, a host of energy metabolism hormones and metabolites, listed in this figure, have been shown to influence bone remodeling and, as hypothesized, help calibrate the balance between bone quality and energy conservation.