Abstract
Bone morphogenetic proteins are low molecular weight proteins which have extensive similarity in structure and function to the transforming growth factor beta factors. They bind receptors on the surface of osteoprogenitor stem cells and activate intracellular signal transduction cascades resulting in the osteoblastic differentiation of pluripotential stem cells.
Bone morphogenetic proteins (BMP) are being increasingly used in orthopaedic surgery including spinal fusion. These small molecules are capable of inducing bone formation when delivered in the appropriate concentration and on the appropriate scaffold. Recombinant BMP usually is combined with an osteoconductive carrier to form a composite graft. The osteoconductive carrier not only supports cellular adhesion but restricts the diffusion of these soluble factors away from the fusion site increasing local concentration of BMP. There is currently no consensus as to the ideal carrier but the optimal carrier may be dependent upon the specific clinical application for which it is used. In addition osteogenic cells that are able to respond to these osteoinductive signals must also be present for a successful spinal fusion to occur.
Not all BMPs are equally effective. Over 15 BMPs have been identified and there are currently only two Food and Drug Administration (FDA)-approved BMPs (BMP-2 with a full PMA approval and BMP-7 with an HDE approval).
Recombinant BMPs have been used successfully in anterior lumbar interbody fusions. Multiple animal studies have shown recombinant human BMP to be superior to autograft in the cervical, thoracic and lumbar spine, while human clinical trials have also shown recombinant human BMP-2 to be superior to autograft for anterior fusion. Similarly, multiple animal studies and clinical trials have shown that recombinant human BMPs result in equivalent or superior fusion rates for posterior spinal fusion compared to autograft. The use of BMPs may obviate the need for decortication and overcome the negative effects of nicotine and anti-inflammatories
In all studies, the concentration of BMPs necessary to produce successful spinal fusion was substantially greater than physiological levels, raising several potential safety concerns including bony overgrowth and bone formation which may lead to neural compression or unintended extension of the fusion. There are also the risks of local toxicity and a host immunologic response. These potential complications related to off-label use of BMPs need to be understood. For this reason, it is essential to determine the appropriate dose for each clinical application and develop efficient carrier systems.
There are economic concerns associated with the use of this new technology. A single treatment of recombinant human BMP is expensive but may be cost effective if clinical outcomes are improved or other costs are avoided. The increased cost of BMP may offset the complications associated with harvesting autograft bone. When used properly, these molecules have the potential to eliminate the need for iliac crest bone graft harvest and improve the speed and success of spinal fusion.
The abstracts were prepared by Assoc Prof Bruce McPhee. Correspondence should be addressed to him at the Division of Orthopaedics, The University of Queensland, Clinical Sciences Building, Royal Brisbane Hospital, Herston, Brisbane, 4029, Australia.
