Lu, Li‐Chun

Abstract Senescent osteocytes are key contributors to age‐related bone loss and fragility; however, the impact of mechanobiological changes in these cells remains poorly understood. This study provides a novel analysis of these changes in primary osteocytes following irradiation‐induced senescence. By integrating subcellular mechanical measurements with gene expression analyses, we identified significant, time‐dependent alterations in the mechanical properties of senescent bone cells. Increases in classical markers such as SA‐β‐Gal activity and p16 Ink4a expression levels confirmed the senescence status post‐irradiation. Our key findings include a time‐dependent increase in cytoskeletal Young's modulus and altered viscoelastic properties of the plasma membrane, affecting the contractility of primary osteocytes. Additionally, we observed a significant increase in Sclerostin ( Sost ) expression 21 days post‐irradiation. These biophysical changes may impair osteocyte mechanosensation and mechanotransduction, contributing to bone fragility. This is the first study to time‐map senescence‐associated mechanical changes in the osteocyte cytoskeleton. Our findings highlight the potential of biophysical markers as indicators of cellular senescence, providing more specificity than traditional, variable biomolecular markers. We believe these results may support biomechanical stimulation as a potential therapeutic strategy to rejuvenate aging osteocytes and enhance bone health.

The spine is the most common site for secondary bone metastases, and clinical management for fractures is based on size and geometry of the defect. About 75% of the bone needs to be damaged before lesions are detectable, so clinical tools should measure changes in both geometry and material properties. We have developed an automated, user-friendly, Spine Cancer Assessment (SCA) image-based analysis method that builds on a platform designed for clinical practice providing failure characteristics of vertebrae. The objectives of this study were to (1) validate SCA predictions with experimental failure load outcomes; (2) evaluate the planning capabilities for prophylactic vertebroplasty procedures; and (3) investigate the effect of computed tomography (CT) protocols on predicted failure loads. Twenty-one vertebrae were randomly divided into two groups: (1) simulated defect without treatment (negative control) [ n = 9] and (2) with treatment [ n = 12]. Defects were created and a polymeric biomaterial was injected into the vertebrae in the treated-defect group. Spines were scanned, reconstructed with two algorithms, and analyzed for fracture loads. To virtually plan for prophylactic intervention, vertebrae with empty lesions were simulated to be augmented with either poly(methyl methacrylate) (PMMA) or a novel bone replacement copolymer, poly(propylene fumarate-co-caprolactone) [P(PF-co-CL)]. Axial rigidities were calculated from the CT images. Failure loads, determined from the cross section with the lowest axial rigidity, were compared with experimental values. Predicted loads correlated well with experimental outcomes ( R 2 = 0.73, p < 0.0001). Predictions from negative control specimens highly correlated with measured values ( R 2 = 0.90, p < 0.0001). Although a similar correlation was obtained using both algorithms, the smooth reconstruction (B30) tended to underestimate predicted failure loads by ∼50% compared with the ∼10% underestimate of the sharp reconstruction (B70). Percent increase in failure loads after virtual vertebroplasty showed a higher increase in samples with PMMA compared with those with copolymer. The SCA method developed in this study calculated failure loads from quantitative computed tomography scans in vertebrae with simulated metastatic lytic defects, with or without treatment, facilitating clinical applicability and providing more reliable guidelines for physicians to select appropriate treatment options. Furthermore, the analysis could accommodate augmentation planning procedures that aimed to determine the optimum material that would increase vertebral body failure load.