Article: Jepsen, KJ; Silva, MJ; Vashishth, D; Guo, XE; van der Meulen, MCH; (2015) “Establishing Biomechanical Mechanisms in Mouse Models: Practical Guidelines for Systematically Evaluating Phenotypic Changes in the Diaphyses of Long Bones”, Journal of Bone and Mineral Research, 30(6):951-966
Abstract: Mice are widely used in studies of skeletal biology, and assessment of their bones by mechanical testing is a critical step when evaluating the functional effects of an experimental perturbation. For example, a gene knockout may target a pathway important in bone formation and result in a low bone mass phenotype. But how well does the skeleton bear functional loads; eg, how much do bones deform during loading and how resistant are bones to fracture? By systematic evaluation of bone morphological, densitometric, and mechanical properties, investigators can establish the biomechanical mechanisms whereby an experimental perturbation alters whole-bone mechanical function. The goal of this review is to clarify these biomechanical mechanisms and to make recommendations for systematically evaluating phenotypic changes in mouse bones, with a focus on long-bone diaphyses and cortical bone.
Further, minimum reportable standards for testing conditions and outcome variables are suggested that will improve the comparison of data across studies. Basic biomechanical principles are reviewed, followed by a description of the cross-sectional morphological properties that best inform the net cellular effects of a given experimental perturbation and are most relevant to biomechanical function. Although morphology is critical, whole-bone mechanical properties can only be determined accurately by a mechanical test. The functional importance of stiffness, maximum load, postyield displacement, and work-to-fracture are reviewed.
Because bone and body size are often strongly related, strategies to adjust whole-bone properties for body mass are detailed. Finally, a comprehensive framework is presented using real data, and several examples from the literature are reviewed to illustrate how to synthesize morphological, tissue-level, and whole-bone mechanical properties of mouse long bones. (c) 2015 American Society for Bone and Mineral Research.
Funding Acknowledgement: National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health [AR44927, AR065424, AR047867, AR057235, AR058004, AR052461, AR049635, AR064034]
Funding Text: The work reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Numbers AR44927 (KJJ), AR065424 (KJJ), AR047867 (MJS), AR057235 (MJS), AR058004 (XEG), AR052461 (XEG), AR049635 (DV), and AR064034 (MCHM). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We thank Lauren Smith and Erin Bigelow for their roles in acquiring the mechanical and morphological data used to illustrate the systematic phenotypic analyses.