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.

骨骼对全身稳态的调节是由其分泌内分泌信号分子的能力介导的。尽管骨源性激素具有多种适应性益处，但它们的生理功能也需要权衡取舍，从而最终导致疾病。在这份手稿中，我们在进化背景下讨论了两种研究最充分的骨骼介质，成纤维细胞生长因子 23 和骨钙素的起源和功能。此外，我们提供了一个理论框架，试图解释这两种激素在羊膜生理学中的广泛参与以及它们促进疾病发展和进展的潜力。反之亦然，我们概述了哪些扰动可能适合操纵这些系统，并讨论骨骼内分泌研究中的局限性和持续挑战。最后，