Advanced bone-targeted nanomaterials for the systemic treatment of osteoporosis

Abstract Osteoporosis is a systemic skeletal disorder marked by reduced bone density and microstructural deterioration, leading to increased fragility and fracture risk. Current clinical treatments, mainly pharmacological, are limited by inadequate efficacy at vertebral sites, unidirectional inhibition of osteoclasts, and systemic side effects. Nanotechnology offers a promising strategy to enhance drug delivery and bioavailability. Bone-targeted nanomaterial-based systems employing ligands such as bisphosphonates or peptides enable selective transport to bone tissue. Nanocarriers, including hydroxyapatite-based ones, can actively target osteoblasts or osteoclasts and support sustained release. This review synthesizes cellular-level insights into osteoporosis pathogenesis, critiques current therapeutic limitations, and highlights advances in targeted nanomedicines. Specifically, it focuses on bone-targeting polymeric nanoparticle systems, which promote bone repair through multiple mechanisms: targeted drug delivery, modulation of the bone microenvironment, dual regulation of osteoblasts and osteoclasts, stimulation of bioactive signals from internal organs, and restoration of mitochondrial homeostasis. By enhancing bone metabolism, these nanotherapeutic strategies present transformative potential for osteoporosis treatment and offer innovative directions for developing advanced regenerative biomaterials.