Low-Dose Bone Morphogenetic Protein Use in Spinal Fusion : Rethinking Clinical Efficacy

In spinal fusion surgery, autogenous bone grafting remains the gold standard for achieving optimal bone fusion; however, challenges such as donor site morbidity and limited graft availability have prompted active research into alternative options. Recombinant human bone morphogenetic protein-2 (rhBMP-2) exhibits excellent osteoinductive properties. Using rhBMP-2 was anticipated to promote early and effective fusion, particularly in challenging surgical scenarios involving elderly patients, those with low bone density, or individuals with multiple comorbidities, although in these populations, the biological response to rhBMP-2 may be attenuated and the risk of complications increased. This review provides a comprehensive overview of the development, characteristics, and dose-related adverse reactions of rhBMP-2 in spinal fusion, based on extensive clinical and experimental findings. Factors contributing to the decline in rhBMP-2 usage are also discussed. Furthermore, this review proposes a safer carrier with reduced rhBMP-2 doses to optimize delivery and minimize complications. Emphasis is placed on the critical role of carriers in improving bioavailability control, minimizing side effects, and better aligning with natural bone healing processes.