Overview of Bone Morphogenetic Proteins

STUDY DESIGN: A literature review was conducted. OBJECTIVES: To review the discovery of the bone morphogenetic proteins and describe the bone morphogenetic protein products that will or may be available for clinical use. SUMMARY OF BACKGROUND DATA: Bone morphogenetic proteins comprise the osteoinductive component of several tissue engineering products in late-stage development as replacements for autogenous bone graft, and for bone augmentation and repair. METHODS: The literature on bone morphogenetic proteins was reviewed. RESULTS: Bone morphogenetic proteins were discovered originally on the basis of their presence in osteoinductive extracts of bone matrix. Molecular cloning of bone morphogenetic proteins demonstrated that they are a family of related differentiation factors, each capable of inducing the formation of new bone tissue when implanted. Two of the molecules in clinical use, recombinant human bone morphogenetic protein-2 and recombinant human bone morphogenetic protein-7 (OP-1) are produced in a biotechnology process using recombinant deoxyribonucleic acid technology that offers unlimited supply and substantial control over purity and reproducible activity. A third material, bovine bone morphogenetic protein extract, is extracted from bone, and contains a mixture of bone morphogenetic protein molecules. Each of these molecules, although osteoinductive in vivo, has different physiologic roles and biologic activities in vivo and in vitro. Successful development of a product for use in spinal fusion involves selecting the osteoinductive molecule, the amount of the bone morphogenetic protein required, and the method of delivery, as well as conducting subsequent preclinical and clinical studies to evaluate its efficacy and safety. CONCLUSIONS: On the basis of the data provided in this issue of Spine, some of these bone morphogenetic protein-based products provide for revolutionary therapies in orthopedic practice.