A critical review of the methodology of ovine lumbar interbody fusion studies and recommendations for future study design.

Aims: Interbody fusion stabilizes the spine by promoting bony growth between vertebrae. Large animal models have physiological and biomechanical similarities to human spines that can provide safety and efficacy data before human use. Sheep models are well validated and are the model of choice to improve understanding of fusion processes by allowing post-mortem analyses of tissues unavailable in human studies. They should be consistently designed to allow appropriate translation of the results into clinical practice. This paper investigates the methodological rigour of ovine lumbar interbody fusion (LIF) studies, and proposes recommendations for researchers designing future studies. Methods: PubMed and the Cochrane library were searched up to 20 December 2024. The search terms were 1) lumbar AND ("in vivo" OR "animal model") AND "fusion" AND (interbody OR cage OR anterior) and 2) (lumbar AND ("in vivo" OR "animal model") AND (spine OR intervertebral disc) AND (sheep OR ovine) AND fusion). Results: A total of 323 papers were identified; 48 studies were included after rejection of non-spinal references, duplicates, and non-English-language papers. Data regarding 993 animals and 1,668 fusion levels were examined. Animal ages varied from six months to nine years. Cages were used in 88% of studies, with a wide range of sizes. The commonest assessments included radiography, histology, and mechanical testing. The in-life phase of the studies varied from one week to three years. High risk of bias was evident in all papers, especially considering 1) treatment allocation sequences, 2) housing randomization, 3) blinding of caregivers, and 4) outcome assessment randomization. Conclusion: This review demonstrates variability in the design of ovine LIF studies, highlights features likely to limit the translatability of results into clinical practice (sheep age and interbody cage size), shows high risk of bias in the published literature, and makes recommendations for future studies.