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

Abstract

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.

Keywords: Bone adhesive; animal model; bone defect; meta-analysis; systematic review.

Figure 1

Flow chart of search and screening process

Figure 2

Bar chart of animal species used in all included experiments, split into different defect models. Other defect types included scapula, ilium, and rotator cuff. Some experiment used more than one animal species [Color figure can be viewed at wileyonlinelibrary.com]

Figure 3

Bar chart of anatomical locations of created defects, split into different types of defect. Other defect types included scapula and ilium. Some experiment used more than one defect model [Color figure can be viewed at wileyonlinelibrary.com]

Figure 4

Bar chart of types of adhesive used in the included studies, split into different types of defect. Some experiment used more than one type of adhesive [Color figure can be viewed at wileyonlinelibrary.com]

Figure 5

Risk of bias analysis. The risk of bias was analysed using several signaling questions, using the SYRCLE's Risk of Bias Tool. Depicted results are the answers for all studies per question [Color figure can be viewed at wileyonlinelibrary.com]

Figure 6

(A) Percentage of studies in which randomization was reported in the article. (B) Percentage of studies in which blinding was reported in the article [Color figure can be viewed at wileyonlinelibrary.com]

Figure 7

(A) Forest plot of the results of bone area or volume after adhesive treatment in comparison with nonadhesive treatment. Random effect model was applied. (B) Forest plot of the results of bone strength after adhesive treatment in comparison with nonadhesive treatment. Random effect model was applied

Figure 8

(A) Forest plot of the results of bone area or volume after adhesive treatment in comparison with metal fixation materials. Random effect model was applied. Studies are subdivided per type of adhesive. (B) Forest plot of the results of bone strength after adhesive treatment in comparison with metal fixation materials. Random effect model was applied. Studies are subdivided per type of adhesive [Color figure can be viewed at wileyonlinelibrary.com]