Filling the Spinal Fracture Treatment Gap: An Osteoporotic Rabbit Model of Vertebral Augmentation

Hemmerla, A. J.; Grisolano, A. R.; Kimes, A. D.; Wray, J. T.; Huddleston, S. E.; Ramachandra, S.; Schultz, R. E.; Moore, D. K.; Lim, J.-H.; Ulery, B.

doi:10.64898/2025.12.18.695239

bioRxiv · 10.64898/2025.12.18.695239

Filling the Spinal Fracture Treatment Gap: An Osteoporotic Rabbit Model of Vertebral Augmentation

Hemmerla, A. J.·Grisolano, A. R.·Kimes, A. D.·Wray, J. T.·Huddleston, S. E.·Ramachandra, S.·Schultz, R. E.·Moore, D. K.·Lim, J.-H.·Ulery, B.

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Abstract

Background contextVertebral compression fractures (VCFs) are the most common osteoporotic fracture, yet current vertebral augmentation (VA) approaches rely exclusively on poly(methyl methacrylate) (PMMA), a non-resorbable cement that is associated with significant clinical drawbacks. Preclinical models are essential for evaluating novel injectable, bioactive alternatives, but existing small- and large-animal systems have translational limitations. PurposeThe purpose of this study was to develop and validate a reproducible osteoporotic rabbit model that integrates controlled osteoporosis induction with a surgically accessible, fluoroscopically guided VA procedure suitable for preclinical evaluation of novel injectable biomaterials. Study designThis study employed a basic science, preclinical method-development approach using an adult female New Zealand White rabbit model of osteoporosis combined with lumbar VA. MethodsAdult female New Zealand White rabbits underwent bilateral ovariectomy followed by glucocorticoid treatment to establish osteoporosis as confirmed by qCT-derived reductions in bone mineral density and T-scores [≤] -2.5. A novel open dorsal surgical approach was optimized ex vivo and applied in vivo to access the lumbar vertebrae (L4 - L5) for bilateral cortical decortication and PMMA injection. Structural changes were assessed by quantitative CT before and after VA. ResultsThe induction protocol produced consistent, reversible, and re-inducible osteoporotic phenotypes, with significant reductions in trabecular and cortical density as well as thinning of cortical microarchitecture. The surgical workflow achieved reproducible, fluoroscopically-confirmed cement delivery into the vertebral cancellous compartment while minimizing leakage. Post-VA imaging demonstrated stable trabecular and cortical parameters, with expected reductions in bone surface metrics attributable to surgical access and cement filling. ConclusionThis study establishes the technical feasibility and reproducibility of a combined osteoporotic and VA rabbit model that integrates disease-relevant bone degeneration with a clinically aligned surgical workflow. Clinical significanceThis model bridges a critical translational gap between rodent and large-animal systems and provides a robust preclinical platform for evaluating next-generation injectable, bioactive, and biodegradable materials aimed at improving safety and regenerative outcomes in osteoporotic VCF repair.

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Hemmerla, A. J., Grisolano, A. R., Kimes, A. D., Wray, J. T., Huddleston, S. E., Ramachandra, S., Schultz, R. E., Moore, D. K., Lim, J.-H., Ulery, B.. 2025-12-22. Filling the Spinal Fracture Treatment Gap: An Osteoporotic Rabbit Model of Vertebral Augmentation. https://doi.org/10.64898/2025.12.18.695239

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