25dkou275 10.3205/25dkou275 urn:nbn:de:0183-25dkou2751 Meeting Abstract Tian Tian Xinggui X

Carl Gustav Carus University Hospital, Dresden, Deutschland

author Schroeter Schroeter Paul P

Carl Gustav Carus University Hospital, Dresden, Deutschland

author Vater Vater Corina C

Carl Gustav Carus University Hospital, Dresden, Deutschland

author Pei Pei Xuan X

Carl Gustav Carus University Hospital, Dresden, Deutschland

author Schaser Schaser Klaus-Dieter KD author Disch Disch Alexander A

Carl Gustav Carus University Hospital, Dresden, Deutschland

author Zwingenberger Zwingenberger Stefan S

Carl Gustav Carus University Hospital, Dresden, Deutschland

author German Medical Science GMS Publishing House

Düsseldorf

610 20251031 engl This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). M0634 275 Deutsche Gesellschaft für Orthopädie und Unfallchirurgie Deutsche Gesellschaft für Orthopädie und Orthopädische Chirurgie Deutsche Gesellschaft für Unfallchirurgie Berufsverband für Orthopädie und Unfallchirurgie Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2025) Grundlagenforschung | Knochen & Implantate Berlin 20251028 20251031 AB40-4392 TextObjectives and questions: Spinal fusion in patients with osteoporosis is challenging . rhBMP-2 is the only FDA-approved osteoinductive agent but has high costs and side effects . KMN-159, a novel prostaglandin EP4 receptor agonist, promotes spinal fusion in healthy rats (Vater et al., 2024). Zoledronic acid (ZA) inhibits osteoclast activity and enhances fusion when locally administered with rhBMP-2 . This study examined whether local co-administration of a minimal effective dose of KMN-159 with ZA could improve osteoporotic spinal fusion. Material and methods: An osteoporotic spinal fusion model was created using 40–41-week-old female Wistar rats subjected to bilateral ovariectomy (OVX) for 18 weeks. A mineralized collagen matrix (MCM) scaffold was used for local drug delivery. Rats were divided into five groups: MCM, MCM + 20 µg rhBMP-2, MCM + 20 µg KMN-159, MCM + 10 µg ZA, and MCM + 20 µg KMN-159 + 10 µg ZA. At 3 and 6 weeks, 9 animals per group were euthanized for µCT and histological analysis. Statistical significance was set at p < 0.05.Results: µCT analysis showed that rhBMP-2 enhanced spinal fusion but caused heterotopic ossification. MCM alone or with KMN-159 did not induce fusion, while ZA, with or without KMN-159, promoted fusion. Histology confirmed rhBMP-2-induced bone formation, whereas ZA ± KMN-159 enhanced scaffold mineralization. Biomechanical testing showed improved stability in the rhBMP-2 and ZA ± KMN-159 groups at 6 weeks (Figure 1 ).Discussion and conclusions: rhBMP-2 was associated with significant ectopic bone formation, suggesting the need to develop safe alternatives in spinal fusion surgery. Local delivery of ZA facilitated spinal fusion through scaffold mineralization, presenting a promising alternative. While KMN-159 alone has shown efficacy in promoting bone growth in healthy rat models, its reduced effectiveness as monotherapy in this osteoporotic rat highlights the challenges of fusion in compromised bone environments. Although the particular combination of KMN-159 and ZA doses used here did not appear to produce synergistic effects, it is reasonable that a higher dose of KMN-159 in combination with ZA might be efficacious in an osteoporotic spinal fusion model and warrants further investigation. Park SB Chung CK Strategies of spinal fusion on osteoporotic spine 2011 J Korean Neurosurg Soc 317-22 Park SB, Chung CK. Strategies of spinal fusion on osteoporotic spine. J Korean Neurosurg Soc. 2011 Jun;49(6):317-22. DOI: 10.3340/jkns.2011.49.6.317 https://doi.org/10.3340/jkns.2011.49.6.317 Gillman CE Jayasuriya AC FDA-approved bone grafts and bone graft substitute devices in bone regeneration 2021 Mater Sci Eng C Mater Biol Appl 112466 Gillman CE, Jayasuriya AC. FDA-approved bone grafts and bone graft substitute devices in bone regeneration. Mater Sci Eng C Mater Biol Appl. 2021 Nov;130:112466. DOI: 10.1016/j.msec.2021.112466 https://doi.org/10.1016/j.msec.2021.112466 Tian X Vater C Raina DB Findeisen L Matuszewski LM Tägil M Lidgren L Winkler A Gottwald R Modler N Schaser KD Disch AC Zwingenberger S Co-delivery of rhBMP-2 and zoledronic acid using calcium sulfate/hydroxyapatite carrier as a bioactive bone substitute to enhance and accelerate spinal fusion 2024 Bioact Mater 256-71 Tian X, Vater C, Raina DB, Findeisen L, Matuszewski LM, Tägil M, Lidgren L, Winkler A, Gottwald R, Modler N, Schaser KD, Disch AC, Zwingenberger S. Co-delivery of rhBMP-2 and zoledronic acid using calcium sulfate/hydroxyapatite carrier as a bioactive bone substitute to enhance and accelerate spinal fusion. Bioact Mater. 2024 Mar 6;36:256-71. DOI: 10.1016/j.bioactmat.2024.02.034 https://doi.org/10.1016/j.bioactmat.2024.02.034 0

1 1 Figure 1: (A) micro-CT analysis at 3 and 6 weeks. (B-C) Histological staining and fluorescent labeling. (D) Biomechanical analysis at 6 weeks. Scale bar = 1,000 µm. *P < 0.05, **P < 0.01.

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