The Intraosseous Environment: Physiological Parameters, Regulatory Mechanisms, and Emerging Insights in Bone Biology

The intraosseous environment is a dynamic and intricate system integral to bone health, encompassing vascular, cellular, and biochemical interactions that drive key processes such as hematopoiesis, bone remodeling, and systemic mineral regulation. This review examines the structural composition of the bone matrix, the diverse cellular landscape, and the interconnected vascular and nervous networks, highlighting their roles in preserving bone function and responding to pathological changes. Recent studies reveal regulatory mechanisms involving oxygen tension, ionic balance, signaling molecules, and mechanotransduction pathways that shape bone metabolism and its adaptation to mechanical forces. Insights into the bone microenvironment’s metabolic shifts in cancer and its interaction with inflammation underscore its pivotal role in disease progression and therapeutic innovation. Additionally, advances in imaging techniques and biomaterials fuel progress in bone regeneration and understanding its microenvironment. Exploring the intricate physiochemical dynamics and regulatory networks within the intraosseous system unlocks potential clinical applications in bone diseases, tissue engineering, and systemic metabolic disorders. This comprehensive review bridges fundamental science with translational research, offering insights into the complex yet essential intraosseous environment. © 2025 Elsevier B.V., All rights reserved.