The periosteum as an endocrine organ: historical foundations and new insights

Anatomists have recognized the periosteum as essential for bone growth and repair, and yet its broader physiological roles have remained underappreciated. Emerging evidence now positions the periosteum not only as a structural membrane, but also as a dynamic interface that integrates mechanical load, nutritional status, metabolic cues and systemic hormones to regulate skeletal homeostasis. In this review, we trace the historical foundations that first revealed periosteal function and synthesize modern insights into the cellular and molecular pathways that enable this tissue to sense and respond to its environment. We highlight nutrient- and energy-sensing mechanisms, alongside classical endocrine pathways. We also discuss mechanical load sensing, neural, vascular and immune signals within the periosteum. By uniting historical observations with single-cell and spatial omics datasets, we propose a modern framework in which the periosteum is reconsidered as an endocrine organ with implications for bone growth, homeostasis and regeneration.