Hybrid movement strategies in orthopedic oncology: Mechanistic integration of musculoskeletal and tumor-host interactions.

Exercise is widely recommended in oncology; however, its role in orthopedic oncology remains insufficiently defined within a clinical context where tumor biology, skeletal fragility, muscle loss, systemic therapy, and reconstructive biomechanics converge. Existing rehabilitation frameworks primarily emphasize functional recovery, while the biological integration between mechanical loading and tumor-host systems remains incompletely characterized in clinical decision-making contexts. This narrative review synthesizes mechanistic evidence across tumor mechanobiology and its integration with bone-muscle endocrine crosstalk, marrow niche regulation, immunometabolism, and vascular-metabolic adaptation. Key pathways, including integrin-FAK/Src signaling, RhoA/ROCK dynamics, YAP/TAZ and β-catenin transcriptional regulation, Piezo-mediated mechanosensing, and load-sensitive RANKL/OPG balance, are examined within hybrid movement strategies that integrate aerobic, resistance, neuromotor, isometric, eccentric, and blood flow-restricted modalities. Emerging evidence indicates that mechanical stimuli may be associated with coordinated changes in extracellular matrix organization, perfusion dynamics, and immune cell trafficking, with secondary effects on mitochondrial function and marrow adiposity. These effects appear to remain context-dependent, with implications for fracture risk, cachexia, neuropathy, and treatment tolerance. However, the boundary between adaptive remodeling and pro-invasive signaling remains incompletely defined, supporting a threshold-dependent rather than linear dose-response relationship. Accordingly, this review proposes a safety-calibrated, phase-sensitive framework for translational movement dosing in orthopedic oncology. Future research should prioritize biomarker-driven clinical trials and temporally resolved dosing strategies to clarify how structured movement may support musculoskeletal integrity while remaining aligned with oncologic treatment constraints.