Surface-Engineered Phytochemical Nanomedicines for Postmenopausal Osteoporosis: Skeletal Targeting, Imaging-Supported Evaluation, and Therapeutic Performance

Postmenopausal osteoporosis (PMOP) is a metabolic bone disease driven by estrogen deficiency and a major contributor to fragility fractures, yet long-term use of current antiresorptive and anabolic agents remains constrained by tolerability and adherence. Plant-derived bioactive compounds—including flavonoids, isoflavones, curcuminoids, and stilbenes—show bone-protective activity in ovariectomized (OVX) models but share common delivery barriers: poor aqueous solubility, low oral bioavailability, rapid metabolic clearance, and limited skeletal targeting. Conventional nanonization improves systemic pharmacokinetics but cannot by itself address the spatial heterogeneity of skeletal target sites. This review focuses on surface-engineered phytochemical nanomedicines, in which mineral-affinity, cell-affinity, and pathology-responsive modules are introduced at the carrier interface to enhance bone-associated distribution, local retention, and microenvironment-responsive release. Organized around nanocarrier platforms, it summarizes cross-platform surface/interfacial engineering strategies and discusses how whole-body, ex vivo, and bone-section imaging can be combined with quantitative exposure assessment, micro-computed tomography (micro-CT), bone turnover markers, and histology to characterize carrier- or probe-associated distribution, spatial localization, and therapeutic performance, respectively. It then considers translational issues, including formulation reproducibility, ligand-density effects, model relevance, and long-term safety. The review aims to provide a framework for surface-engineered phytochemical strategies and a reference approach for multimodal, imaging-based evaluation of therapeutic outcomes.