{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T08:24:10Z","timestamp":1786955050758,"version":"build-2736575974"},"reference-count":127,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Older adults with comparable bone mineral density or fracture-risk estimates may nevertheless differ markedly in fracture occurrence, repair kinetics and functional recovery. This heterogeneity suggests that skeletal fragility reflects, at least in part, ageing of the bone\u2013immune\u2013haematopoietic system rather than bone mass alone. Here, we synthesise evidence linking the aged osteoimmune niche to inflammatory bone loss and impaired fracture repair. We focus on four interrelated processes: CHIP-associated amplification of myeloid inflammation, shaped by driver mutation and clone size; age-related skewing of T- and B-cell compartments; persistent cellular senescence and senescence-associated secretory signalling; and failure of macrophage- and regulatory T-cell-mediated inflammatory resolution. Among CHIP drivers, direct skeletal evidence is strongest for DNMT3A-mutant clones in inflammatory bone loss. Bone-specific evidence for TET2 remains limited, whereas evidence for ASXL1 is largely absent. In fracture repair, the most direct preclinical evidence concerns cellular senescence and age-altered macrophage function, while the ability of CHIP to predict delayed union has not been validated. We define immune resilience as the capacity to mount a proportionate acute response, clear damaged cells and debris, actively resolve inflammation, and transition to reparative and remodelling states. Current evidence is insufficient to support routine immune-guided fracture care. The immediate priority is to determine, in prospective fracture cohorts, whether phase-resolved local and circulating measures explain variation in repair beyond bone mineral density, frailty, fracture characteristics, biological sex and treatment exposure.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1913480","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T07:29:21Z","timestamp":1786951761000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune ageing in skeletal fragility: clonal haematopoiesis and failure of inflammatory resolution during fracture repair"],"prefix":"10.3389","volume":"17","author":[{"given":"Yong","family":"He","sequence":"first","affiliation":[{"name":"Longhua Hospital, Shanghai University of Traditional Chinese Medicine","place":["Shanghai, 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