Safety and Efficacy of Recombinant Human Bone Morphogenetic Protein-2 in Multilevel Posterolateral Lumbar Fusion in a Prospective, Randomized, Controlled Trial

Abstract

Objective: This study is an investigator-initiated, prospective, randomized, controlled study to evaluate the efficacy and safety of the combined use of recombinant human BMP-2 (rhBMP-2) and a hydroxyapatite (HA) carrier in multilevel fusion in patients with adult spinal deformity (ASD).Methods: Thirty patients underwent posterolateral fusion for lumbar spinal deformities at 3 to 5 segments between L1 and S1. The patients received rhBMP-2+HA or HA on the left or right side of the transverse processes. They were followed up regularly at 1, 3, 6, and 12 months postoperatively. Fusion was defined according to the bone bridging on computed tomography scans. The fusion rate per segment was subanalyzed. Function and quality of life as well as pain in the lower back and lower extremities were evaluated.Results: The union rate for the rhBMP-2+HA group was 100% at 6 and 12 months. The union rate for the HA group was 77.8% (21 of 27) at 6 months and 88.0% (22 of 25) at 12 months (p = 0.014 at 6 months; not significant at 12 months). All segments were fused at 6 and 12 months in the rhBMP-2+HA group (p < 0.001). In the HA group, 108 of 115 segments (93.5%) were fused at 6 months and 105 of 109 segments (96.3%) at 12 months. Other clinical parameters (visual analogue scale, 36-item Short Form Health Survey, and Scoliosis Research Society-22 scores) improved compared to baseline.Conclusion: Combining rhBMP-2 and an HA carrier is a safe and effective method to achieve multilevel fusion in patients with ASD.

Multi-modulation of immune-inflammatory response using bioactive molecule-integrated PLGA composite for spinal fusion

“…Therefore, gene technology was used to develop rhBMP, which effectively increases bone fusion rates after lumbar surgery and leads to reductions in pseudoarthrosis and iliac bone harvesting. In 2002, the US Food and Drug Administration approved use of rhBMP-2 for anterior lumbar interbody fusion surgery, including one-level degenerative disc disease and spondylolisthesis [ 11 ].…”

“…Recombinant human BMP-2 (rhBMP-2) is commercially available, has US Food and Drug Administration approval, and is widely used in spinal fusion surgery due to the high potency of the fusion process. However, use of this product can lead to serious complications, such as heterotopic ossification and soft tissue inflammation [ 10 , 11 ]. Therefore, researchers and clinicians have worked to develop efficient and safe non-stationary materials.…”

Vertebral Primary Bone Lesions: Review of Management Options

“…The application of recombinant human bone morphogenic proteins (BMP) in such decompressive spinal surgeries has recently captured clinical interest. BMPs are growth factors believed to induce both bone and cartilage formation [ 91 ]. Evidence indicates that these factors can significantly enhance bone deposition at needed fusion sites following lumbar decompression [ 92 ].…”

Concentration-Dependent Efficacy of Recombinant Human Bone Morphogenetic Protein-2 Using a HA/β-TCP Hydrogel Carrier in a Mini-Pig Vertebral Oblique Lateral Interbody Fusion Model

“…Bone morphogenetic proteins (BMPs) are multifunctional growth factors belonging to the transforming growth factor-β superfamily that were discovered during the demineralization process of cortical bone, and are potent factors that induce bone and cartilage formation and bone regeneration [1][2][3][4][5]. BMP is currently used in various applications, such as the treatment of degenerative spinal disease and vertebral fractures, spine fusion, dental surgery, and facial surgery.…”

“…The ambivalence of the bone metabolism regulation mechanism of BMP-2 suggests that an elaborate regulatory system exists in vivo to prevent excessive bone formation. Indeed, clinical trials using supraphysiological doses of recombinant human BMP-2 (rhBMP-2) in milligrams for anterior lumbar interbody fusion have demonstrated bone fusion rates superior to those achieved with standard iliac bone grafts [3,13,14]. Therefore, using small amounts of BMP-2 may be sufficiently effective, as the use of high doses of rhBMP-2 cause side effects including inflammation, soft tissue edema, intestinal edema, and unintended ectopic bone formation, which could impair its extensive clinical application [15,16].…”