<p>Serum C-terminal telopeptide of type I collagen (CTX-I) is a key bone turnover biomarker in osteoporosis, and its elevated levels are indicative of increased bone resorption. Current techniques for CTX-I measurement suffer from high operational requirements, complex procedures, and high costs. This study focuses on a novel strategy for detecting serum CTX-I concentration to predict the occurrence and severity of osteoporosis. Using silver-capped Fe₃O₄ (Fe₃O₄@Ag) as the substrate material, an artificial antibody for CTX-I was prepared via magnetic core-shell molecularly imprinted polymers (MIPs), and surface-enhanced Raman scattering (SERS) was used as a signal output device. With crystal violet (CV) at 10⁻⁴ M as the reporter molecule, the proposed biosensor exhibited a good linear response over the range of 10 pg/mL to 2 ng/mL (R² = 0.986, LOQ = 4.79 pg/mL), covering the normal reference range required for identifying bone turnover. Moreover, the biosensing platform demonstrated resistance to matrix interference in real serum and urine samples. After six reuse cycles, the SERS intensity of CV decreased by only 10.5%, and after 15 days of storage at 4&#xa0;°C, it decreased by 15.7%. The Fe₃O₄@Ag-MIPs were used to detect CTX-I with excellent uniformity (RSD = 4.1%) and repeatability (RSD = 2.7%), and the overall analysis time was 30&#xa0;min. The proposed biosensing platform was applied to analyze known real serum samples obtained from human. The proposed biosensor was validated using enzyme-linked immunosorbent assay (ELISA), and the developed biosensor showed good correlation with ELISA. The experimental results indicate that the proposed novel biosensing platform is a fast, low-cost, and reliable tool for the rapid detection of the bone biomarker CTX-I in serum or urine.</p> Graphical abstract <p></p>