Current and future clinical applications of bone morphogenetic proteins in orthopaedic trauma surgery

Abstract

Forty years after the discovery by Marshal R. Urist of a substance in bone matrix that has inductive properties for the development of bone and cartilage, there are now 15 individual human bone morphogenetic proteins (BMPs) that possess varying degrees of inductive activities. Two of these, BMP-2 and BMP-7, have become the subject of extensive research aimed at developing therapeutic strategies for the restoration and treatment of skeletal conditions. This has led to three different therapeutic preparations, each for a distinct clinical application. Non-union, open tibial fractures and spinal fusions are the three conditions for which there is clinical approval for use of BMPs. This article reviews the evidence supporting the therapeutic applications of BMPs as they are presently available and suggests future applications based on current research. Among the future directions discussed are percutaneous injections, protein carriers, advances in gene transfer technology and the use of BMPs to engineer the regeneration of skeletal parts.

Fig. 1

a–f Use of OP-1 in the treatment of a 10-month-old, infected, supracondylar femoral non-union in a 40-year-old woman with insulin-dependent diabetes who had undergone prior irrigation, debridement and open reduction and internal fixation followed by allogeneic bone grafting and supplementation with demineralised bone matrix. The presence of drains in the preoperative radiographs indicate recent surgical efforts to manage the wound infection. Preoperative antero-posterior (a) and lateral (b) radiographs showing no evidence of union. Immediate postoperative anteroposterior (c) and lateral (d) radiographs showing implantation of allogeneic bone chips in combination with demineralised bone matrix and OP-1. Anteroposterior (e) and lateral (f) radiographs, made 3 months postoperatively, showing healing of the non-union. (Radiographs courtesy of Paul Tornetta III, Boston University Medical Center)

Fig. 2

a–b Mould of a rat femur cast using inert silicone rubber and bivalved to allow placement of the muscle flap (a). Resultant bone in the shape of a femoral head obtained following removal for the mould 10 days later (b). Note the femoral vessel pedicle at the inferior portion of the flap [9]

Fig. 3

a–g Three-dimensional CT scan of size defect (a) and CAD plan of ideal mandibular transplant (b). Titanium cage filled with bone mineral block infiltrated with recombinant human BMP7 and bone-marrow mixture (c). Dorsal view of mandibular replacement 3 weeks after implantation (d). Skeletal scintigraphy of implant (e). Three-dimensional CT scan after transplantation of the bone replacement with enhancement of soft tissue (f) and repeat skeletal (g) scintigraphy with tracer enhancement showing continued bone remodelling and mineralisation (arrows) [22]