Platelet-derived biomaterials in osteoporosis: mechanisms, evidence and translational prospects.

Osteoporosis is a systemic skeletal disorder characterized by impaired bone microarchitecture and reduced bone strength arising from dysregulated coupling between osteoclast-mediated resorption and osteoblast-driven formation. Estrogen deficiency, chronic inflammation, oxidative stress, and altered RANKL/OPG signaling amplify osteoclastogenesis while suppressing Wnt/β-catenin-dependent osteoblast differentiation, resulting in progressive trabecular thinning and cortical porosity. Although antiresorptive agents and anabolic therapies reduce fracture risk, they do not fully restore bone quality, microvascular integrity, or osteoimmune balance. Platelet-derived biomaterials (PDBs), including platelet-rich plasma, platelet-rich fibrin, platelet lysates, and platelet-based hydrogels, represent autologous bioactive systems enriched with platelet-derived growth factor, transforming growth factor-β, vascular endothelial growth factor, insulin-like growth factor-1, and bioactive lipid mediators. Upon activation, PDBs provide an early burst and sustained release of growth factors within a fibrin matrix that supports mesenchymal stem cell recruitment, RUNX2- and Osterix-mediated osteogenic differentiation, extracellular matrix deposition, and angiogenic coupling through VEGF-driven neovascularization. Concurrently, PDBs modulate osteoclast activity by influencing the RANKL/OPG axis, promoting macrophage polarization toward an M2 reparative phenotype, and attenuating inflammatory cytokine signaling. Integration of PDBs with osteoconductive scaffolds and nanostructured delivery platforms further enhances mechanical stability, local retention, and spatiotemporal biofactor presentation in osteoporotic bone defects. Preclinical evidence demonstrates improvements in bone mineral density, trabecular architecture, and fracture repair; emerging clinical applications in spinal fusion and fracture management suggest translational promise. However, variability in platelet concentration, activation protocols, and dosing standardization remains a barrier to widespread clinical adoption. PDB-based regenerative strategies therefore offer a mechanistically targeted and clinically adaptable approach to restoring skeletal integrity in osteoporosis.