Skeletal endocrinology: where evolutionary advantage meets disease

The regulation of whole-body homeostasis by the skeleton is mediated by its capacity to secrete endocrine signaling molecules. Although bone-derived hormones confer several adaptive benefits, their physiological functions also involve trade-offs, thus eventually contributing to disease. In this manuscript, we discuss the origins and functions of two of the best-studied skeletal mediators, fibroblast growth factor 23 and osteocalcin, in an evolutionary context. Moreover, we provide a theoretical framework seeking to explain the broad involvement of these two hormones in amniote physiology as well as their potential to fuel the development and progression of diseases. Vice versa, we outline which perturbations might be amenable to manipulation of these systems and discuss limitations and ongoing challenges in skeletal endocrine research. Finally, we summarize unresolved questions and potential future studies in this thriving field.

Automated summary

This article explores how the skeleton regulates whole-body homeostasis by secreting hormones and discusses the origins and functions of two common skeletal mediators in physiology and their potential disease associations. It provides a theoretical framework to explain the evolutionary roles of these hormones in amniote physiology and addresses limitations and challenges in research. Additionally, unresolved questions and potential future studies in this growing field are summarized.