Frontiers in Immunology · Nov 7, 2026
Senescence-Associated Osteoimmune Communication in Osteoporosis: Bone Marrow Niche Remodeling and Therapeutic Targeting
By Jing Luo, Li Li, Zhongkai Ji et al.
Osteoporosis develops within an immune-active skeletal niche in which stromal, skeletal, vascular, adipose-lineage, and immune cells exchange signals. Cellular senescence can sustain remodeling imbalance, but broad anti-inflammatory activity is distinct from modification of a validated senescent source. This Review organizes the evidence around source-cell identity, mediator, recipient response, skeletal outcome, and therapeutic perturbation. Soluble secretory factors, extracellular vesicles, metabolic cues, and receptor-ligand interactions provide different routes through which cellular dysfunction may spread or protective niche support may be lost. Their roles depend on lineage and disease context: estrogen withdrawal can cause senescence-independent bone loss, senolytics can impair osteoprogenitors, and a randomized human trial did not meet its primary bone-resorption endpoint. We compare senolytic, senomorphic, immune-pathway, and delivery-based interventions as investigational adjuncts to established osteoporosis care. Mechanistic plausibility, preclinical skeletal benefit, human target engagement, and clinical efficacy require separate judgments. Translation depends on demonstrating that modification of a defined source or mediator produces durable skeletal benefit while preserving progenitor reserve, immune function, and repair.