The Bone Morphogenetic Protein 2 Analogue L51P Enhances Spinal Fusion in Combination with BMP2 in an In Vivo Rat Tail Model

Gantenbein, Benjamin; Oswald, Katharina AC; Erbach, Georg F; Croft, Andreas S; Bermudez Lekerika, Paola; Strunz, Franziska; Bigdon, Sebastian; Albers, Christoph (2024). The Bone Morphogenetic Protein 2 Analogue L51P Enhances Spinal Fusion in Combination with BMP2 in an In Vivo Rat Tail Model (Unpublished). In: 50th International Society for the Study of the Lumbar Spine Annual Meeting 2024. Milano, Italy. 31 May 2024.

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INTRODUCTION

Non-union and pseudoarthrosis remain major complications after spinal fusion surgery, resulting in unsatisfactory outcomes and high socio-economic costs [1,2]. Several biomaterials and osteobiologics have improved 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.

METHODS

46 elderly Wistar rats (~12 months, 52% female, 423±78g) underwent a two-step spinal fusion surgery [3,4]. 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: g 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, 10 µg BMP-2, 1 µg BMP-2 + 5 µg L51P and 1 µg BMP-2 + 10 µg 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 than the control group. 1 µg BMP-2 + 1 µg L51P demonstrated significantly higher fusion rates than 1 µg BMP2 alone and equivalent ossification compared to 10 µg BMP-2; higher doses of L51P did not lead to a better fusion outcome. Histological analysis confirmed the radiographical results. Figure 1 provides representative images of the seven experimental groups for each investigated read-outs, i.e., 2D X-rays, µCT and histology.

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