A Systematic Review on the Critical Size Defect Model

Objectives: To systematically review the literature data regarding the critical size defect (CSD) in adult rat calvaria and to determine which defect dimensions could be considered as being critical size.

Material And Methods: A literature search was conducted at Ovid Medline and Embase up to July 2012. Studies presenting with at least one of the primary outcomes of interest (number of defects with complete closure and the percentage of new bone formation (%NBF) in rat calvaria) were included. Screening, data extraction and quality assessment were conducted independently and in duplicate.

Results: From 1461 citations, 257 full-text papers were screened and 61 papers were included in the analysis. Fourteen of 937 evaluated defects presented complete closure. Only 7 and 6 untreated sites in 5.0- and 6.0-mm-diameter defects, respectively, showed complete closure. A great variability among the preclinical models was seen, and the meta-analysis result showed a high heterogeneity regarding the mean %NBF. The mean %NBF according to the defect dimension was as follows: 18.29% and 21.44% for 5.0 mm central single defects at 1 and 3 months, respectively; 17.55%, 20.24% and 22.65% for 5.0 mm bilateral defects; 9.81%, 12.56% and 7.96% for 8.0 mm single defect; 11.18%, 9.48% and 26.24% for 9.0 mm single defects at 1, 2 and 3 months, respectively.

Conclusion: Calvarial defects with a diameter of 5.0 mm could be considered as a CSD. However, there is a necessity for further standardization of the rat calvaria model to enable more accurate comparison among future studies.