Hierarchical\nPorous Microspheres-Assisted Serum Metabolic\nProfile for the Early Diagnosis and Surveillance of Postmenopausal\nOsteoporosis

With the aging global population, the incidence of osteoporosis\n(OP) is increasing, putting more individuals at risk. Since postmenopausal\nosteoporosis (PMOP) often remains asymptomatic until a fracture occurs,\nmaking the early clinical diagnosis of PMOP particularly challenging.\nIn this work, the AuNPs-anchored hierarchical porous ZrO<sub>2</sub> microspheres (Au/HPZOMs) is designed to assist laser desorption/ionization\nmass spectrometry (LDI-MS) for the requirement of serum metabolic\nfingerprints of PMOP, postmenopausal osteopenia (PMON), and healthy\ncontrols (HC) and realize the early diagnosis and surveillance of\nPMOP. With its large surface area, suitable surface roughness, and\nenhanced UV absorbance, the LDI efficiency of Au/HPZOMs is significantly\nenhanced. Combining machine learning, PMOP and non-PMOP (HC and PMON)\nare clearly distinguished with the area under the receiver operating\ncharacteristic curves reaching up to 1.000. Furthermore, seven key <i>m</i>/<i>z</i> features are identified, facilitating\nthe specific detection of PMON and two stages of PMOP. The precision\nof distinguishing PMON and PMOP at different stages based on these\nfeatures exceeds 86.5% in both the training and validation sets, aiding\nin the early diagnosis and monitoring of PMOP. This work sheds light\non the metabolic profile for large-scale screening, early detection,\nand monitoring of PMOP, which will promote the application of fluid\nmetabolism-driven precision medicine into practical clinical use.