Use of OP-1 (rhBMP-7) in posterolateral lumbar arthrodesis

Posterolateral fusion is a common treatment for lumbar spondylolisthesis (1). Most often, autologous bone from the iliac crest is used for arthrodesis. However, failure of fusion remains a common complication following this procedure (2-4). In addition to pseudoarthrosis, another concern is donor site morbidity related to iliac bone graft harvest, which may complicate as many as 25% of cases (5-7). There has hence been interest in the development and use of bioactive molecules capable of inducing bone regeneration in hopes of achieving higher fusion rates, while also avoiding the morbidity of autograft harvest. Marshall Urist in 1965 identified proteins from bone matrix responsible for ectopic bone formation, later termed bone morphogenetic proteins (BMPs) (8). BMPs exert an osteoinductive effect by stimulating differentiation of mesenchymal stem cells into mineral-depositing osteoblasts (9,10). Further efforts led to cloning of BMP-2 and BMP-7 (OP-1), members of the transforming growth factor-beta (TGF-beta) superfamily, and expression of recombinant human forms of these proteins (11,12). Both rhBMP-2 and rhOP-1 demonstrated efficacy in inducing bone formation in preclinical animal studies, which has spurred clinical investigation of their efficacy as bone graft substitute (13-16). Moreover, other investigators have suggested that BMPs, including OP-1, may show promise in promoting fusion in patients with high-risk adverse medical conditions (17).