Gantenbein, Benjamin; Oswald, Katharina A. C.; Bigdon, Sebastian F.; Erbach, Georg F.; Croft, Andreas S.; Bermudez-Lekerika, Paola; Strunz, Franziska; Rutsch, Niklas; Albers, Christoph E. (2023). The Bone Morphogenetic Protein L51P Enhances Spinal Fusion in Combination with BMP2 - An In Vivo Rat Spinal Fusion Model of the Elderly. In: 31st Annual Meeting of the European Orthopaedic Research Society. 27-29 September.
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Non-union and pseudoarthrosis remain major complications after spinal fusion surgery, resulting in unsatisfactory outcomes and high socio-economic costs. Several biomaterials and osteo-biologics have been used to improve spinal fusion, including bone morphogenetic protein (BMP) 2. However, its necessary high dose application often leads to adverse effects. L51P, a BMP-2 analogue and inhibitor of BMP antagonists, has been shown to augment BMP-induced bone formation and lower the required doses. The current study therefore aimed to demonstrate the effects of L51P and BMP-2 on spinal fusion in vivo. 46 elderly Wistar rats (~12 months, 52% female, 423±78g) underwent a two-step spinal fusion surgery [1]. Firstly, a custom external fixator was applied in the proximal tail. Secondly, discectomy and disc replacement with a β tri-calcium-phosphate (β-TCP) carrier were conducted. Carriers were loaded with the study compounds based on random and blinded allocation into seven groups: Phosphate-buffered-saline (PBS) as material control, 1µg and 10µg BMP-2, 10µg L51P, 1µg BMP-2 + 1/5/10µg L51P. Digital X-rays were performed on day zero, at six weeks, and twelve weeks postoperatively. After twelve weeks, high-resolution µCT scans and histology were obtained. Results. At twelve weeks, 10µg BMP-2, 1µg BMP-2 + 5µg L51P and 1µg BMP-2 + 10µg L51P showed significantly higher fusion rates compared to the PBS control in X-ray analysis. µCT analysis showed significantly higher fusion rates for all groups compared to the control group. 1µg BMP-2 + 1µg L51P demonstrated significantly higher fusion rates than 1µg BMP2 alone and equivalent ossification compared to 10µg BMP-2; higher doses of L51P did not lead to a better fusion outcome. Histological analysis confirmed the radiographical results. Combining low doses of L51P and BMP-2 enhances spinal fusion equivalent to high-dose BMP-2 and may reduce BMP-2 doses and side effects at similar to higher efficacy in clinical application.
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