Bone Morphogenetic Proteins and Other Bone Growth Factors

Abstract

Dr. Marshall Urist's discovery of the osteoinductive properties of bone morphogenetic proteins (BMPs) nearly 40 years ago marked the beginning of a new era in bone biology that has bridged the gap from bench to bedside. BMPs have the potential to greatly advance the fi elds of orthopaedic, oral/maxillofacial and craniofacial plastic surgery, as well as dentistry. Numerous BMPs have now been identified; of these, recombinant human BMP-2 and BMP-7 (OP-1) are the best characterized. These BMPs exert their effects via serine/threonine receptor-activated Smad signaling. Mutations that alter BMP regulation at the cellular level have been shown to result in various skeletal disorders. Animal studies in which BMPs are tested in sites that would otherwise not support bone formation have demonstrated the osteoinductive properties of several of the BMPs, and studies assessing the use of BMPs in orthotopic sites have provided great insight into optimal BMP delivery methods. Currently, BMP-2 and BMP-7 are approved for specifi c human orthopaedic applications. It is becoming clear that clinical use of BMPs requires application-specifi c testing to determine correct dosing and delivery kinetics. Autologous growth and angiogenic factors are also being explored for use in orthopaedics and will also likely play important roles in enhancing BMP delivery. Long-term effects, especially in developing bone, will need to be probed before BMP treatment can be expanded to more general clinical use. Bone morphogenetic proteins have great clinical potential; however, further investigations into their applied biology are necessary for safe and effective therapeutic applications.