title: Reference point indentation is not indicative of whole mouse bone measures of stress intensity fracture toughness.
abstract: Bone fragility is a concern for aged and diseased bone. Measuring bone toughness and understanding fracture properties of the bone are critical for predicting fracture risk associated with age and disease and for preclinical testing of therapies. A reference point indentation technique (BioDent) has recently been developed to determine bone's resistance to fracture in a minimally invasive way by measuring the indentation distance increase (IDI) between the first and last indentations over cyclic indentations in the same position. In this study, we investigate the relationship between fracture toughness KC and reference point indentation parameters (i.e. IDI, total indentation distance (TID) and creep indentation distance (CID)) in bones from 38 mice from six types (C57Bl/6, Balb, oim/oim, oim/+, Phospho1(-/-) and Phospho1 wild type counterpart). These mice bone are models of healthy and diseased bone spanning a range of fracture toughness from very brittle (oim/oim) to ductile (Phospho1(-/-)). Left femora were dissected, notched and tested in 3-point bending until complete failure. Contralateral femora were dissected and indented in 10 sites of their anterior and posterior shaft surface over 10 indentation cycles. IDI, TID and CID were measured. Results from this study suggest that reference point indentation parameters are not indicative of stress intensity fracture toughness in mouse bone. In particular, the IDI values at the anterior mid-diaphysis across mouse types overlapped, making it difficult to discern differences between mouse types, despite having extreme differences in stress intensity based toughness measures. When more locations of indentation were considered, the normalised IDIs could distinguish between mouse types. Future studies should investigate the relationship of the reference point indentation parameters for mouse bone in other material properties of the bone tissue in order to determine their use for measuring bone quality.
authors.affiliation: Department of Bioengineering, Imperial College London, London SW7 2AZ, UK. Electronic address: a.carriero@imperial.ac.uk.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Carriero
authors.affiliation: Department of Bioengineering, Imperial College London, London SW7 2AZ, UK.
authors.forename: Jan L
authors.initials: JL
authors.lastname: Bruse
authors.affiliation: The Roslin Institute and Royal School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK.
authors.forename: Karla J
authors.initials: KJ
authors.lastname: Oldknow
authors.affiliation: Sanford Children's Health Research Center, Sanford-Burnham Medical Research Institute, La Jolla, CA 92037, USA.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Millán
authors.affiliation: The Roslin Institute and Royal School of Veterinary Studies, The University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK.
authors.forename: Colin
authors.initials: C
authors.lastname: Farquharson
authors.affiliation: Department of Bioengineering, Imperial College London, London SW7 2AZ, UK.
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Shefelbine
mesh_terms: D000818:Animals; D001847:Bone Diseases / Q000175:diagnosis*; D019937:Diagnostic Techniques and Procedures; D004195:Disease Models, Animal; D050723:Fractures, Bone; D051379:Mice; D012307:Risk Factors
keywords: BioDent; Bone fracture; Bone quality; Bone toughness; Mouse bone; Reference point indentation