Bone morphogenetic proteins: types, signaling mechanisms, clinical applications, and reported complications

Abstract

Background. Bone morphogenetic proteins (BMPs) are essential regulators of bone and cartilage formation, tissue repair, and embryogenesis, with BMP-2, BMP-7, and BMP-9 being the most studied for osteogenic activity. Material and methods A narrative review of literature from 2010–2025 was performed, including clinical trials, systematic and narrative reviews, and preclinical studies. Data was extracted on BMP types, signaling mechanisms, clinical applications, benefits, and complications, with separation of clinical and preclinical evidence. Results Recombinant human BMP-2 (rhBMP-2) and BMP-7 (rhBMP-7) are well-supported clinically for spinal fusion, long-bone fracture repair, and dental/maxillofacial applications, achieving high union rates and reducing donor-site morbidity versus autografts. RhBMP-2 complications include ectopic bone formation, localized edema, seroma, and rare neurological deficits, while rhBMP-7 complications are less frequent but limited by cost and regulatory factors. Preclinical studies show BMP-9 has superior osteogenic potential to BMP-2, mediated by canonical SMAD-dependent and non-canonical ALK1/ActR2A/B signaling, suggesting promise for fracture healing and bone regeneration. Regulatory BMPs such as Noggin, Chordin, and Gremlin are crucial for maintaining tissue homeostasis and preventing pathological ossification. Discussion Clinical and preclinical evidence highlights a hierarchy: rhBMP-2 and rhBMP-7 are established therapies, whereas BMP-9 is an emerging candidate. Optimized delivery, precise dosing, and careful surgical technique are critical to maximize benefit and minimize complications. Conclusions BMPs offer significant therapeutic potential in bone regeneration. RhBMP-2 and rhBMP-7 remain the mainstays of clinical practice, with BMP-9 poised for future translation pending human safety studies and optimized clinical protocols.