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Variables Affecting Fusion Rates in the Rat Posterolateral Spinal Fusion Model with Autogenic/Allogenic Bone Grafts: A Meta-analysis

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Abstract

The rat posterolateral spinal fusion model with autogenic/allogenic bone graft (rat PFABG) has been increasingly utilized as an experimental model to assess the efficacy of novel fusion treatments. The objective of this study was to investigate the reliability of the rat PFABG model and examine the effects of different variables on spinal fusion. A web-based literature search from January, 1970 to September, 2015, yielded 26 studies, which included 40 rat PFABG control groups and 449 rats. Data regarding age, weight, sex, and strain of rats, graft volume, graft type, decorticated levels, surgical approach, institution, the number of control rats, fusion rate, methods of fusion assessment, and timing of fusion assessment were collected and analyzed. The primary outcome variable of interest was fusion rate, as evaluated by manual palpation. Fusion rates varied widely, from 0 to 96%. The calculated overall fusion rate was 46.1% with an I 2 value of 62.4, which indicated moderate heterogeneity. Weight >300 g, age >14 weeks, male rat, Sprague–Dawley strain, and autogenic coccyx grafts increased fusion rates with statistical significance. Additionally, an assessment time-point ≥8 weeks had a trend towards statistical significance (p = 0.070). Multi-regression analysis demonstrated that timing of assessment and age as continuous variables, as well as sex as a categorical variable, can predict the fusion rate with R 2 = 0.82. In an inter-institution reliability analysis, the pooled overall fusion rate was 50.0% [44.8, 55.3%], with statistically significant differences among fusion outcomes at different institutions (p < 0.001 and I 2 of 72.2). Due to the heterogeneity of fusion outcomes, the reliability of the rat PFABG model was relatively limited. However, selection of adequate variables can optimize its use as a control group in studies evaluating the efficacy of novel fusion therapies.

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Abbreviations

BMP:

Bone morphogenetic protein

MSC:

Mesenchymal stem cell

PFABG:

Posterolateral spinal fusion model with autogenic/allogenic bone graft

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

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Acknowledgments

This manuscript reflects the view of the authors and should not be construed to represent FDA’s views or policies. Although no funding was provided for this project, the senior author receives research materials from Eli Lilly and Co, as well as the Gordon and Marilyn Macklin Foundation.

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Associate Editor Mona Kamal Marei oversaw the review of this article.

Wataru Ishida and Benjamin D. Elder are co-first author and contributed equally to the work.

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Ishida, W., Elder, B.D., Holmes, C. et al. Variables Affecting Fusion Rates in the Rat Posterolateral Spinal Fusion Model with Autogenic/Allogenic Bone Grafts: A Meta-analysis. Ann Biomed Eng 44, 3186–3201 (2016). https://doi.org/10.1007/s10439-016-1701-8

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