The bone–immune interface shapes skeletal regeneration

The bone–immune interface is increasingly recognized as a central regulator of skeletal regeneration. In addition to its structural and metabolic functions, bone contains specialized immunological niches that shape the composition and behavior of adaptive and innate immune cells. Recent advances in osteoimmunology demonstrate that the dynamics of immune cells — particularly the balance between pro-inflammatory effector responses and their regulatory mechanisms — critically influence the course of fracture healing. Dysregulated adaptive immunity can prolong early inflammation and impair the function of osteogenic progenitors, thereby disrupting the coordinated progression of the repair process. This Perspective synthesizes emerging evidence on how immunological memory, inflammatory kinetics and adaptive immune heterogeneity interact to shape skeletal repair. It highlights the growing potential of immune profiling for early risk stratification, alongside preclinical and early clinical data supporting targeted immunomodulatory strategies aimed at restoring a pro-regenerative inflammatory environment. Together, these developments support a conceptual shift from purely mechanical models of fracture healing toward biologically informed, precision‑guided approaches with the potential to improve outcomes in patients at increased risk of regenerative failure. • Bone–immune crosstalk is a key regulator of skeletal regeneration • Adaptive immune composition influences individual healing outcomes • Immune profiling enables early risk stratification in fracture healing • CD8⁺ effector responses can impair osteogenesis and delay callus formation • Targeted immunomodulation offers new strategies to improve bone repair.