Bone-seeking nanomaterials for rebalancing bone remodeling in osteoporosis

Osteoporosis is a prevalent skeletal disorder characterized by reduced bone mass and microarchitectural deterioration, primarily resulting from an imbalance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Although current anti-osteoporosis drugs can slow bone loss or stimulate bone formation, their clinical effectiveness is often limited by poor bone specificity, systemic side effects, and insufficient restoration of physiological bone remodeling. Recently, bone-seeking nanomaterials have emerged as a promising strategy to enhance therapeutic precision in osteoporosis. By integrating bone-targeting ligands with engineered nanocarriers, these systems enable preferential accumulation in mineralized tissues and improve the local delivery of therapeutic agents. In addition to conventional anti-resorptive and anabolic drugs, nanoplatforms have been developed to deliver nucleic acids, growth factors, and immunomodulatory molecules that regulate the complex cellular networks governing bone remodeling. This review summarizes recent advances in bone-targeted nanomaterial design, discusses their roles in modulating osteoclasts, osteoblasts, osteocytes, and osteoimmune interactions, and highlights key challenges and future opportunities for the clinical translation of nanomedicine in osteoporosis therapy. Distinct from prior reviews that often emphasize nanocarrier composition or individual payload classes, this review is organized around the concept of rebalancing bone remodeling and integrates osteoclast, osteoblast, osteocyte, and osteoimmune regulation with emerging translational considerations.