Osteoimmunology: Effects of Standard Orthopaedic Interventions on Inflammatory Response and Early Fracture Healing.

Achieving fracture union is highly dependent on the initial inflammatory phase of fracture healing, which is influenced by both the local and systemic inflammatory environments. The rapidly emerging field of osteoimmunology involves the study of the interactions between the immune system and the skeletal system. Recent research has advanced the current state of knowledge regarding the effects of the surrounding soft-tissue injury, fracture hematoma, and the method of fracture fixation on the inflammatory phase of fracture healing. Acute systemic inflammation, as seen in patients with polytrauma, and chronic systemic inflammation, as seen in patients with diabetes or rheumatoid arthritis, affects the inflammatory phase of fracture healing. The use of NSAIDs can influence early fracture healing. Understanding the effects of standard orthopaedic interventions on the local and systemic inflammatory responses and early fracture healing is important for optimizing fracture union.

Osteoimmunology: The Conceptual Framework Unifying the Immune and Skeletal Systems.

The immune and skeletal systems share a variety of molecules, including cytokines, chemokines, hormones, receptors, and transcription factors. Bone cells interact with immune cells under physiological and pathological conditions. Osteoimmunology was created as a new interdisciplinary field in large part to highlight the shared molecules and reciprocal interactions between the two systems in both heath and disease. Receptor activator of NF-κB ligand (RANKL) plays an essential role not only in the development of immune organs and bones, but also in autoimmune diseases affecting bone, thus effectively comprising the molecule that links the two systems. Here we review the function, gene regulation, and signal transduction of osteoimmune molecules, including RANKL, in the context of osteoclastogenesis as well as multiple other regulatory functions. Osteoimmunology has become indispensable for understanding the pathogenesis of a number of diseases such as rheumatoid arthritis (RA). We review the various osteoimmune pathologies, including the bone destruction in RA, in which pathogenic helper T cell subsets [such as IL-17-expressing helper T (Th17) cells] induce bone erosion through aberrant RANKL expression. We also focus on cellular interactions and the identification of the communication factors in the bone marrow, discussing the contribution of bone cells to the maintenance and regulation of hematopoietic stem and progenitors cells. Thus the time has come for a basic reappraisal of the framework for understanding both the immune and bone systems. The concept of a unified osteoimmune system will be absolutely indispensable for basic and translational approaches to diseases related to bone and/or the immune system.