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Significant Differences in the Bone of an Isogenic Inbred Versus Nonisogenic Outbred Murine Mandible

A Study in Rigor and Reproducibility

Carey, Edward G. BA*; Deshpande, Sagar S. BS*; Urlaub, Kevin M.*; Zheutlin, Alexander R. BS*; Nelson, Noah S. BS*; Donneys, Alexis MD, MS*; Kang, Stephen Y. MD; Gallagher, Kathleen K. MD; Felice, Peter A. MD*; Tchanque-Fossuo, Catherine N. MD, MS§; Buchman, Steven R. MD*

Journal of Craniofacial Surgery: June 2017 - Volume 28 - Issue 4 - p 915–919
doi: 10.1097/SCS.0000000000003530
Original Articles

Inattention to differences between animal strains is a potential cause of irreproducibility of basic science investigations. Accordingly, the authors’ laboratory sought to ensure that cross-comparisons of results generated from studies of mandibular physiology utilizing the Sprague Dawley and Lewis rat strains are valid. The authors specifically investigated baseline histomorphometrics, bone mineral density, and biomechanical strength of the unaltered endogenous mandibles of the inbred, isogenic Lewis rat, and the outbred, nonisogenic Sprague Dawley rat to determine if they are indeed equal. The authors hypothesized that little difference would be found within these metrics.

The authors’ study utilized 20 male Lewis and Sprague Dawley rats, which underwent no manipulation other than final dissection and analysis. Ten rats from each strain underwent bone mineral density and biomechanical strength analysis. The remaining rats underwent histological analysis. Descriptive and bivariate statistics were computed and the P value was set at 0.05.

Lewis rats had a significantly greater number of empty lacunae. Sprague Dawley rats exhibited a significantly greater ratio of bone volume-to-total volume, bone mineral density, tissue mineral density, bone volume fraction, and total mineral content. No differences were found during biomechanical testing.

This study demonstrates that differences exist between the Lewis and Sprague Dawley rat within unaltered baseline mandibular tissue. However, these differences appear to have limited functional impact, as demonstrated by similar biomechanical strength metrics. Other specific differences not addressed in this manuscript may exist. However, the authors believe that researchers may confidently cross-compare results between the 2 strains, while taking into account the differences found within this study.

*Craniofacial Research Laboratory, Section of Plastic Surgery, University of Michigan, Ann Arbor, MI

Department of Otolaryngology—Head and Neck Surgery, The Ohio State University, Columbus, OH

Department of Otolaryngology—Head and Neck Surgery, Baylor College of Medicine, Waco, TX

§Department of Dermatology, University of California Davis, Sacramento, CA.

Address correspondence and reprint requests to Steven R. Buchman, MD, Pediatric Plastic Surgery Section, University of Michigan, 4-730 C.S. Mott Children's Hospital, 1540 E. Hospital Drive, Ann Arbor, MI 48109-0219; E-mail:

Received 25 September, 2016

Accepted 4 December, 2016

Funding was supported by the following grant from the National Institutes of Health: “Translational Optimization of Bone Regeneration in the Irradiated Mandible” (R01 CA12587-06) to SRB.

The authors report no conflicts of interest.

© 2017 by Mutaz B. Habal, MD.