TNF-α modulation in spinal fusion: high-dose TNF-α is associated with failed arthrodesis, while etanercept is associated with successful fusion in a rat model.
Publication/Presentation Date
7-17-2026
Abstract
BACKGROUND CONTEXT: TNF-α has been studied in fracture healing; modulation of its activity, either by supraphysiologic exposure or pharmacologic inhibition, may alter the likelihood of pseudarthrosis in spinal fusion.
PURPOSE: Our main objective is to determine the effects of high- and low-dose tumor necrosis factor-α (TNF-α) and the TNF-α inhibitor Etanercept on spinal fusion outcomes.
STUDY DESIGN: Laboratory study.
METHODS: Seventy-five Wistar rats underwent L4-L5 posterolateral fusion with demineralized bone matrix and received either high-dose TNF-α, low-dose TNF-α, local Etanercept, systemic Etanercept, or carrier alone. At 2, 4, and 28 days, serum and local fusion masses were analyzed with ELISA for IGF-1 and VEGF. Fusion was assessed at 4 weeks by manual palpation and microCT. The study was funded by Rothman Orthopaedic Institute , no study specific conflicts of interest to report.
RESULTS: In vivo, high-dose TNF-α significantly elevated local IGF-1 (22.1 ± 2.1 ng/mg) and VEGF (539 ± 177 pg/mg) at day 2 compared with controls (IGF-1: 6.2 ± 1.2; VEGF: 112 ± 12; p< .001). By day 28, only VEGF was reduced in all treatment groups compared with controls (p< .001). At 4 weeks, fusion was present in 4/5 controls, 0/5 high-dose TNF-α animals (p=.048), 5/5 low-dose TNF-α, 3/5 local Etanercept, and 4/5 systemic Etanercept. MicroCT demonstrated bilateral fusion in 5/5 systemic Etanercept animals, 2/5 controls, and 0/5 high-dose TNF-α (p=.016).
CONCLUSION: High-dose TNF-α impaired fusion and was consistently associated with pseudarthrosis despite early increases in growth factor expression. Low-dose TNF-α and Etanercept, administered locally or systemically, did not compromise fusion, with systemic Etanercept showing the highest bilateral fusion rate. These findings indicate that TNF-α modulation significantly influences spinal fusion, and that TNF-α inhibition does not adversely affect arthrodesis.
CLINICAL SIGNIFICANCE: Modulating TNF-α appears to affect fusion success and implementing anti-TNF-α could decrease pseudoarthrosis rates among patients who have elevated TNF-α disease states.
ISSN
1878-1632
Published In/Presented At
Koerner, J. D., Ng, M. K., Dalton, J., Eichbaum, Y. K., Banko, S. J., Vaccaro, A. R., Markova, D. Z., & Kepler, C. K. (2026). TNF-α modulation in spinal fusion: high-dose TNF-α is associated with failed arthrodesis, while etanercept is associated with successful fusion in a rat model. The spine journal : official journal of the North American Spine Society, S1529-9430(26)00586-3. Advance online publication. https://doi.org/10.1016/j.spinee.2026.07.012
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
42468831
Department(s)
Administration and Leadership
Document Type
Article