Advances in the biology of spinal fusion: growth factors and gene therapy

Abstract

The rate of failure to obtain a solid bone fusion in spine arthrodesis may be as high as 45%, and the incidence of morbidity associated with autogenous iliac crest bone graft harvest may approach 30%. Extensive work is currently underway to improve the healing success and decrease the morbidity associated with conventional bone-grafting material of autogenous iliac crest. Several in vivo studies with various bone morphogenetic proteins have yielded promising results, but substantially higher doses of protein have been required in nonhuman primates and in limited human trials. Problems with delivery vehicles for BMP-based bone graft substitutes have limited their application for spinal fusion. Alternative osteoinductive proteins and new delivery methods are currently under investigation to circumvent this problem. Recently, local gene therapy for spine fusion with the complementary DNA of novel osteoinductive proteins has shown some promise in stimulating expression of the genes needed to initiate the cascade of osteoinduction. Advances in local gene therapy may lead to a minimally invasive technique for the induction of bone formation and hopefully improved treatment for patients with a variety of spine disorders. The studies reviewed herein examine these novel biologic and genetic modalities and their possible role in spinal fusion.