Biologic immunomodulators and spinal fusion: evidence, mechanisms, and perioperative considerations

Purpose Biologic immunomodulators are increasingly used across autoimmune, inflammatory, oncologic, and metabolic diseases, resulting in a growing population of patients undergoing spinal fusion while receiving these agents. Because immune pathways targeted by biologic therapies play essential, time-dependent roles in bone graft incorporation, this review examines how pharmacologic modulation of these pathways may affect fusion outcomes and perioperative risk.Methods We synthesized mechanistic, translational, and clinical evidence examining the impact of major classes of biologic immunomodulators on spinal fusion biology. Preclinical, translational, and available clinical data were reviewed with attention to drug class, timing of exposure, and host factors.Results Preclinical and translational studies consistently demonstrate that disruption of cytokine signaling, immune cell activation, or osteoblast-osteoclast coupling can impair angiogenesis, progenitor recruitment, and graft remodeling. Clinical data, while limited and heterogeneous, suggest variable associations with postoperative complications and fusion outcomes depending on the specific agent and timing of exposure. Perioperative management strategies for biologic therapies remain heterogeneous across spine surgery practice.Conclusion Biologic immunomodulators have the potential to dysregulate normal bone healing, particularly when exposure occurs during early or transitional phases of fusion. This review provides a biologically grounded framework to inform perioperative risk stratification and management in patients receiving these agents who undergo spinal fusion.