Everything You Need To Know About Role Of BMP In Lumbar Spine Surgery.
Fusion or arthrodesis remains gold standard for treating various acquired and degenerative conditions of the spine. Autogenous iliac crest bone grafting (ICBG) between decorticated surfaces remains the gold standard for spine fusion surgery. Successful fusion is contingent upon multiple host and graft characteristics. Low bone density, alcohol abuse, cigarette smoking, and long fusions are known risk factors for nonunion. To augment spinal fusion, bone graft is often used, and bone graft material must have sufficient osteoconductive and osteoinductive activities to promote healing. For healing to occur, osteogenic cells lay down new bone on an acceptable scaffolding (osteoconductivity) and stimulate differentiation of stem cells or osteoprogenitor cells into osteoblasts (osteoinduction). Given the critical role graft materials play in driving successful fusion, substantial research efforts have focused upon methods to augment this biologic process in order to achieve stable fusion in circumstances which otherwise would be unfeasible.
Since Marshal R Urist’s initial discovery in 1960s, BMPs have been the subject of extensive basic science and animal and clinical research as a potential therapeutic modality to induce fracture healing and to promote bone fusion. BMPs have been in use since 2002 which are of equivalent or superior efficacy to autogenous ICBG in the specific treatment of certain spinal conditions. Until now at least 7 structurally related BMPs have been isolated, purified, and characterized using recombinant DNA techniques. Currently, there are only two BMPs that have received FDA approval for clinical use. Re-combinant human bone morphogenic protein-2 (rhBMP-2), carried on an absorbable collagen sponge, trademarked as INFUSE Bone Graft (Medtronic Sofamor Danek, Memphis, TN), is commercially available and FDA approved when used with a lumbar tapered fusion cage (LT-CAGE, Medtronic) for one-level anterior lumbar interbody fusion for degenerative disc disease. rhBMP-7, trademarked as Osteogenic Protein-1 (OP-1 Putty, Stryker Biotech, Inc., Hopkinton, MA, USA) is FDA approved as a humanitarian device exemption (HDE) for revision posterolateral lumbar spinal fusion. The early results from several completed prospective, randomized clinical trials have demonstrated rhBMP-2 and -7 to be equivalent or superior to autologous ICBG in both fusion rate and clinical outcome.
Application of either rhBMP-2 or OP-1 to raw decorticated bony surfaces leads to osteogenesis, which is desirable in the inter-transverse or inter-body regions of the spine. However, new bone formation also may occur if rhBMP-2 or OP-1 comes in contact with laminectomy sites or decompressed neuroforamina, and may lead to re-stenosis. Inadvertent placement of either rhBMP-2 or OP-1 in the spinal canal leads to formation of bone. Leakage of rhBMP-2 or OP-1 outside the fusion area may lead to adjacent-level fusion. Accurate placement of these factors and adequate retention by their carrier are highly important factors in minimizing these problems. Subdural bone formation occurs if OP-1 is implanted directly beneath the dura. Systemic and local toxicity, significant adverse effects, and harmful effects on distant organs have not been observed in either human or animal studies on rhBMP-2 and OP-1. The benign safety profile of rhBMP-2 may result from its rapid systemic clearance, which results in very little systemic exposure. Systemic exposure to OP-1 also is low. No reproductive toxicity has been observed with either rhBMP-2 or OP-1. However, there is no human safety data. The interaction of anti-BMP or anti-collagen antibodies in patients with autoimmune disorders, collagen vascular disorders, or a history of malignancy is unknown. Because of these potential safety concerns, rhBMP-7 is contraindicated in pregnant women, skeletally immature patients, patients with a history of malignancy, and patients with a known hypersensitivity to BMPs or collagen.
The risk of uncontrolled bone formation, BMP antibody formation, bone resorprtion, immunogenicity, urethrogenital complications, and malignancies have yet to be fully characterized.
More judicious use of rhBMP-2 in spinal surgery in augmentation options when auto-graft from the iliac crest is either unavailable or the side effects of the procedure are unwanted by the patients.
The decision-making process around BMP for spinal fusion in 2021 is primarily a cost–benefit analysis. There is mounting experience, and a little bit of evidence, suggesting that smaller doses are effective. With all its potential benefits in one hand, the high costs of BMPs preclude its use in routine clinical use. Therefore, one must analyse the cost-benefit model for their patients who really need BMP for spinal fusion.