Regulation of Bone Remodeling by Metal–Phenolic Networks for the Treatment of Systemic Osteoporosis

Osteoporosis is a systemic metabolic disease that impairs bone remodeling by favoring osteoclastic resorption over osteoblastic formation. Nanotechnology-based therapeutic strategies focus on the delivery of drug molecules to either decrease bone resorption or increase bone formation rather than regulating the entire bone remodeling process, and osteoporosis interventions suffer from this limitation. Here, we present a multifunctional nanoparticle based on metal–phenolic networks (MPNs) for the treatment of systemic osteoporosis by regulating both osteoclasts and osteoblasts. In the osteoporotic microenvironment, the MPN nanoparticles degrade and trigger the release of bioactive metals (strontium ions, Sr^II) to promote osteogenesis and functionalized phenols (epigallocatechin gallate, EGCG) to suppress osteoclastogenesis. Injecting these nanoparticles into the tail vein of an ovariectomized mouse model, trabecular bone loss has been significantly prevented in the femoral head and vertebrae, along with increased trabecular bone volume and decreased trabecular bone separation. Overall, this work represents a versatile approach to explore MPN nanomaterials for the treatment of systemic osteoporosis and related orthopedic diseases.