Demineralized Bone and BMPs: Basic Science and Clinical Utility

The clinical demand for bone void fillers led to the development of off-the-shelf banked bone and synthetic and biologic substitute materials to be used either alone or as bone graft volume extenders. Demineralized bone (DB) has a remarkable capacity to induce new bone formation even when implanted subcutaneously in experimental animals, a phenomenon termed "osteoinduction." DB products are now widely available through tissue bank procurement of bone from rigorously screened donors. When properly processed, DB products are useful in craniomaxillofacial, oral, hand, and orthopedic applications. The isolation of proteins believed to be responsible for the osteoinductive activity of DB, termed bone morphogenetic proteins (BMPs), led to the cloning of a family of genes and synthesis of recombinant human BMPs (rhBMPs). They have been approved for distribution and use in specific maxillofacial and orthopedic applications. Clinical trials and studies of orthopedic and craniofacial applications have indicated that supraphysiologic doses of a single recombinant protein are needed to promote bone repair. Information about the biology, chemistry, and actions of rhBMPs and DB has called into question whether a single recombinant BMP would result in clinically useful bone induction and morphogenesis. Compelling preclinical and specific clinical evidence has indicated the efficacy of DB and for rhBMPs either combined with autograft or compared with an autograft alone. In light of questions about potency and safety, however, additional high-level evidence is needed for specific clinical indications and appropriate patient populations that would benefit from their use.