gms | German Medical Science

German Congress of Orthopaedics and Traumatology (DKOU 2023)

24. - 27.10.2023, Berlin

Calcium sulfate/hydroxyapatite mediated controlled co-delivery of BMP-2 and zoledronic acid enhances spinal fusion in a rat posterolateral spinal fusion model

Meeting Abstract

  • presenting/speaker Xinggui Tian - Universitätsklinikum Carl Gustav Carus, UniversitätsCentrum für Orthopädie, Unfall- und Plastische Chirurgie, Dresden, Germany
  • Corina Vater - Universitätsklinikum Carl Gustav Carus, UniversitätsCentrum für Orthopädie, Unfall- und Plastische Chirurgie, Dresden, Germany
  • Deepak Raina - Lund University, Department of Clinical Sciences, Orthopedics, Lund, Sweden
  • Lisa Findeisen - Universitätsklinikum Carl Gustav Carus, UniversitätsCentrum für Orthopädie, Unfall- und Plastische Chirurgie, Dresden, Germany
  • Lucas-Maximilian Matuszewski - Universitätsklinikum Carl Gustav Carus, UniversitätsCentrum für Orthopädie, Unfall- und Plastische Chirurgie, Dresden, Germany
  • Magnus Tägil - Lund University, Department of Clinical Sciences, Orthopedics, Lund, Sweden
  • Lars Lidgren - Lund University, Department of Clinical Sciences, Orthopedics, Lund, Sweden
  • Klaus-Dieter Schaser - Universitätsklinikum Carl Gustav Carus, UniversitätsCentrum für Orthopädie, Unfall- und Plastische Chirurgie, Dresden, Germany
  • Alexander C. Disch - Universitätsklinikum Carl Gustav Carus, UniversitätsCentrum für Orthopädie, Unfall- und Plastische Chirurgie, Dresden, Germany
  • Stefan Zwingenberger - Universitätsklinikum Carl Gustav Carus, UniversitätsCentrum für Orthopädie, Unfall- und Plastische Chirurgie, Dresden, Germany

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2023). Berlin, 24.-27.10.2023. Düsseldorf: German Medical Science GMS Publishing House; 2023. DocAB54-2784

doi: 10.3205/23dkou263, urn:nbn:de:0183-23dkou2631

Published: October 23, 2023

© 2023 Tian et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

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Objectives: Spinal fusion is the standard treatment of various spinal disorders, but pseudarthrosis following spinal fusion is still common, with an incidence of 5% to 35%. Our previous studies have proven that calcium sulfate/hydroxyapatite (CaS/HA) local co-delivery of bone morphogenetic protein 2 (BMP-2) and zoledronic acid (ZA) can obtain a higher bone volume in an ectopic muscle pouch model and in a femoral bone defect model. The aim of this study was to evaluate whether local application of BMP-2 and ZA released from a resorbable CaS/HA scaffold is favorable for posterolateral lumbar spinal fusion.

Methods: Based on the treatment and the implant type, 7 groups were set up in this study (CaS/HA, CaS/HA + BMP-2, CaS/HA + systemic ZA, CaS/HA + local ZA, CaS/HA + BMP-2 + systemic ZA, CaS/HA + BMP-2 + local ZA, SHAM (previous study of our group)). This in vivo study was performed on 132, 8-week-old male Wistar rats (n = 12 per group at 3 weeks and n = 10 per group at 6 weeks). A posterolateral intertransverse process spinal fusion at L4 to L5 was performed bilaterally by implanting group dependent scaffolds. At the time endpoints of 3 and 6 weeks, the animals were euthanized for µCT, histological staining, or mechanical testing.

Results and conclusion: µCT evaluation showed, that the CaS/HA + BMP-2 + local ZA group had the highest bone volume and bone mineral density at 6 weeks among all treated groups (Figure 1A). Biomechanical testing revealed significantly higher breaking force in CaS/HA + BMP + local ZA group than other groups at 6 weeks (Figure 1B). Histological staining results showed more newly formed bone in the CaS/HA + BMP-2 + local ZA group than any other group at 3 weeks. Staining for osteoclasts showed a reduced osteoclast activity within the scaffold when local ZA was present.

The CaS/HA-based biomaterial functionalized with the bioactive molecules rhBMP-2 and ZA enhanced bone formation and concomitant fusion outcome. The anabolic and anti-catabolic coupling effects of rhBMP-2 and ZA result in more net bone formation in spinal fusion surgery and may potentially lead to overall BMP-2 dose reduction. The carrier properties of the CaS/HA biomaterial are optimal for controlled co-delivery of both BMP-2 and ZA. All components in this study are already approved for clinical use. The treatment regime of combining CaS/HA biomaterial with co-delivery of BMP-2 and ZA may soon translate into clinical use as an alternative to autologous bone grafting for challenging procedures of posterolateral lumbar spinal fusion.