Bone metastases at the nutrition–bone–immune interface: implications for immune checkpoint blockade

Bone metastases develop within a mineralized and hematopoietic environment shaped by continuous skeletal remodeling, immune-cell trafficking, and systemic host physiology. This specialized niche can restrict immune checkpoint blockade, but the factors governing its responsiveness remain incompletely defined. Evidence linking nutritional status and related endocrine or metabolic factors to bone-specific immunity is fragmented across osteoimmunology, tumor immunology, nutrition, endocrinology, and translational oncology. We distinguish direct nutritional exposures from host-state indices, mineral endocrine regulators, and microbiome-derived metabolites. Mechanistic studies identify osteoclast-associated pathways, including RANK–RANKL signaling and osteopontin, as direct links between skeletal remodeling, impaired T-cell recruitment, and experimental resistance to checkpoint blockade. By contrast, albumin-based indices, cachexia, anemia-related measures, glucocorticoid exposure, thyroid dysfunction, and microbiome features generally provide prognostic, treatment-related, or associative evidence across heterogeneous cancer cohorts. They do not establish ICI-specific prediction, causal reversibility, or therapeutic benefit. Clinical evidence for combining checkpoint inhibitors with antiresorptive, nutritional, endocrine, or microbiome interventions remains inconsistent or preliminary. We therefore use the nutrition–bone–immune axis as a conceptual, evidence-organizing framework, not as a clinically validated unified causal pathway. Clinical translation will require prospective bone-specific cohorts, paired systemic and lesion-level profiling, rigorous temporal definitions, treatment-interaction analyses, and randomized trials integrating skeletal, immune, and oncological endpoints.