Bone morphogenetic proteins and spinal fusion

Abstract

<jats:p>Bone morphogenetic proteins (BMPs) have increasingly become a focus of research in the laboratory, with animal models, and in human clinical trials for the treatment of spinal disorders. Basic science research has elucidated the putative mechanism of action of BMPs, and the efficacy of BMPs in inducing bone formation has been evaluated in multiple animal models of anterior and posterior spinal fusion. Not only has BMP been shown to improve the quality and amount of bone formation when used as a supplement to autograft, it has also been shown to promote superior fusion in the absence of autograft, even in high-risk fusion models involving the use of nicotine or nonsteroidal antiinflam-matory agents. Both completed and ongoing clinical trials have demonstrated the efficacy of recombinant BMP, leading to the first BMP product being approved for clinical use earlier this year.</jats:p> <jats:p>Animal models and clinical trials have also been used to evaluate the safety of BMPs. Although few complications have been reported, BMPs can induce heterotopic bone formation, especially when placed adjacent to exposed neural elements. Potentially more serious, antibody formation has been seen in up to 38% of patients in some clinical trials. No clinical sequelae have been reported despite the development of antibodies against BMP, a naturally occurring human protein implicated in processes other than osteoinduction.</jats:p> <jats:p>The future directions of biological manipulation of the osteoinduction process include further understanding of the interactions of the BMP subtypes, the interactions of BMP with its receptors, and exploring other molecules capable of osteoinduction.</jats:p>

Human Perivascular Stem Cells Show Enhanced Osteogenesis and Vasculogenesis with Nel-Like Molecule I Protein

“…36,37,39,43 From a bone tissue engineering standpoint, osteogenic specificity is essential for reducing the potential for adverse clinical effects of a differentiation factor. 36,44 This is a significant concern, as the dose of BMP-2 required for successful osteogenesis in humans is associated with life-threatening cervical swelling, severe inflammation, increased adipogenesis, osseous overgrowth, and other complications. 36,[45][46][47][48] In addition, NELL-1 has significant effects on vascularization.…”

Angiogenesis: A new factor on the block —A preliminary observation

“…Bone morphogenetic proteins (BMP) have gained prominence in the healing of fractures and in spinal fusion [16][17][18][19]. BMPs, which are part of the transforming growth factor-beta (TGF-b) family, are known to elicit their effects at the cellular level by inducing heteromeric complexes [20,21].…”

Novel Wnt Regulator NEL-Like Molecule-1 Antagonizes Adipogenesis and Augments Osteogenesis Induced by Bone Morphogenetic Protein 2

“…16,17 Notably, BMP2 has species-specific dosing responses in which the required BMP2 concentration for osteogenesis increases with phylogenetic complexity. 18 The BMP2 concentration for consistent bone formation in nonhuman primates is 0.75 to 2.0 mg/mL, but in rodents is only 0.02 to 0.4 mg/mL. 19 Based on data from nonhuman primates, the minimum effective human BMP2 concentration was initially set at 1.5 mg/mL (total dose, 4.2 to 12 mg) in pilot and pivotal trials in humans and is currently the approved concentration for clinical use.…”