Apoptotic bodies in bone homeostasis and skeletal disease: biology and therapeutic implications

Bone is among the most apoptotically active tissues in the body. During remodeling, repair, and disease, dying osteoclasts, osteoblast-lineage cells, osteocytes, mesenchymal stem/stromal cells, and injury-associated cells release apoptotic bodies (ABs) that retain parent-cell-derived cargo and surface ligands. These vesicles are increasingly viewed not only as debris for efferocytic clearance but also as source-specific signalling units that shape skeletal cell fate, immune activity, mineralization, and repair. This review integrates current evidence for ABs across skeletal homeostasis and disease. We first define ABs within the broader extracellular vesicle landscape, emphasizing vesicle heterogeneity, isolation and characterization challenges, and terminology boundaries. We then examine AB sources and recipient interfaces, including osteoclasts, osteoblast-lineage cells, osteocytes, mesenchymal stem/stromal cells, platelet-derived ABs in injury repair, macrophages, osteoclast phagocytes, chondrocytes, and bone lining cells. We further discuss how dysregulated AB signalling contributes to osteoporosis, osteoarthritis, and bone metastasis, as well as alveolar bone destruction, aging-related bone loss, osteochondral mineralization, and bone injury repair. We highlight therapeutic implications, including AB-based or AB-inspired strategies, the cathepsin K (CTSK)-responsive self-assembling peptide nanoparticle OsteoSAVE for in vivo generation of osteoclast-derived ABs, and the hypothesis that antiresorptive therapies may reshape osteoclast-derived AB (OC-AB) production. We also identify unresolved translational questions, including AB lifespan, circulation, source attribution, and direct human validation.