Critical size defects for bone regeneration experiments in rabbit calvariae: systematic review and quality evaluation using ARRIVE guidelines

Abstract

Objectives: To perform a systematic review of studies that report the healing of critical size defects (CSDs) in rabbit calvaria and to determine the quality of the studies according to ARRIVE guidelines.

Materials and methods: An Internet search was made in duplicate between December 2011 and August 2013 using MEDLINE, PubMed and Google Scholar (without restrictions on date of publication) for rabbit studies reporting the healing of CSD in the calvaria. Animal Research Reporting in Vivo Experiment (ARRIVE) guidelines (a list of 20 aspects to score and to ensure comparison between different experimental studies in animals) were used to evaluate the quality of the selected works.

Results: Twenty-five manuscripts were evaluated. Case-control studies predominated (92.59%). Animal age was not stated in 70.37% of the studies; weight was not reported in 29.62%; most animals weighed 3.5 kg (26.31%). A CSD dimension of 15 mm was common (51.61%), generally located centrally (51.85%), followed by bilateral locations (48.14%). Circular (66.66%), rectangular (14.81%), square (14.81%) and ovoid (1.48%) geometries were used. Histomorphometric data showed incomplete healing in all CSDs and higher percentages of healing in smaller defects (<10 mm). The longer the healing time allowed, the more bone healing took place, for both smaller and larger defects (>15 mm). Minimum quality grades were assigned to ARRIVE items study design (6), experimental animals (8), housing and husbandry (9), sample size (10), allocation (11), statistics (13), results-baseline data (14), numbers analyzed (15), adverse events (17) and funding (20).

Conclusions: Data on CSDs in rabbit calvariae lack homogeneity. Smaller defects can be considered critical depending on the time of sacrifice. When new diagnostic technologies are used in addition to histomorphometry, these should be applied with caution to facilitate future comparison with other research. The ARRIVE guidelines should be followed in any animal research protocol to improve the homogeneity, comparison and reproducibility between studies.

Keywords: bone healing; calvaria; cranial; critical size defect; rabbits; skull; systematic review.