A systematic review and meta-analyses on animal models used in bone adhesive research

Currently, steel implants are used for osteosynthesis of (comminuted) fractures and intra-articular bone defects. These osteosyntheses can sometimes be complicated procedures and can have several drawbacks including stress shielding of the bone. A bone glue might be a safe and effective alternative to current materials. Despite numerous animal studies on bone adhesives, no such material is clinically applied yet. We have conducted a systematic review to summarize the evidence in experimental animal models used in research on bone adhesive materials for trauma and orthopedic surgery. Additionally, we analysed the efficacy of the different bone adhesives for different experimental designs. A heterogeneity in experimental parameters including animal species, defect types, and control measurements resulted in a wide variety in experimental models. In addition, no standard outcome measurements could be identified. Meta-analysis on bone regeneration between adhesive treatment and nonadhesive treatment showed a high heterogeneity and no statistically significant overall effect (M: -0.71, 95% confidence interval [CI]: -1.63-0.21, p = 0.13). Besides, currently there is not enough evidence to draw conclusions based on the effectiveness of the individual types of adhesives or experimental models. A positive statistically significant effect was found for the adhesive treatment in comparison with conventional osteosynthesis materials (M: 2.49, 95% CI: 1.20-3.79, p = 0.0002). To enhance progression in bone adhesive research and provide valuable evidence for clinical application, more standard experimental parameters and a higher reporting quality in animal studies are needed. Statement of Clinical Significance: Current materials restoring anatomical alignments of bones have several drawbacks. A (biodegradable) adhesive for fixating bone defects can be a treatment breakthrough. Although numerous bone adhesives have been researched, most seemed to fail at the preclinical stage. An overview in this field is missing. This systematic review highlights the relevant parameters for design of experimental bone adhesive studies. It demonstrates evidence regarding benefit of bone adhesives but also that the quality of reporting and the risk of bias in studies need to be improved. The results will aid in designing better quality animal studies for bone adhesive research with higher translational value