title: Hyperlipidemia affects multiscale structure and strength of murine femur.
abstract: To improve bone strength prediction beyond limitations of assessment founded solely on the bone mineral component, we investigated the effect of hyperlipidemia, present in more than 40% of osteoporotic patients, on multiscale structure of murine bone. Our overarching purpose is to estimate bone strength accurately, to facilitate mitigating fracture morbidity and mortality in patients. Because (i) orientation of collagen type I affects, independently of degree of mineralization, cortical bone׳s micro-structural strength; and, (ii) hyperlipidemia affects collagen orientation and μCT volumetric tissue mineral density (vTMD) in murine cortical bone, we have constructed the first multiscale finite element (mFE), mouse-specific femoral model to study the effect of collagen orientation and vTMD on strength in Ldlr(-/-), a mouse model of hyperlipidemia, and its control wild type, on either high fat diet or normal diet. Each µCT scan-based mFE model included either element-specific elastic orthotropic properties calculated from collagen orientation and vTMD (collagen-density model) by experimentally validated formulation, or usual element-specific elastic isotropic material properties dependent on vTMD-only (density-only model). We found that collagen orientation, assessed by circularly polarized light and confocal microscopies, and vTMD, differed among groups and that microindentation results strongly correlate with elastic modulus of collagen-density models (r(2)=0.85, p=10(-5)). Collagen-density models yielded (1) larger strains, and therefore lower strength, in simulations of 3-point bending and physiological loading; and (2) higher correlation between mFE-predicted strength and 3-point bending experimental strength, than density-only models. This novel method supports ongoing translational research to achieve the as yet elusive goal of accurate bone strength prediction.
authors.affiliation: Department of Orthopaedic Surgery, University of California, Los Angeles, CA 90095, USA. Electronic address: mgascenzi@mednet.ucla.edu.
authors.forename: Maria-Grazia
authors.initials: MG
authors.lastname: Ascenzi
authors.affiliation: Continental Tire Company, Hannover, Germany. Electronic address: andre.lutz@hotmail.de.
authors.forename: Andre
authors.initials: A
authors.lastname: Lutz
authors.affiliation: Department of Orthopaedic Surgery, University of California, Los Angeles, CA 90095, USA. Electronic address: duxia1992721@ucla.edu.
authors.forename: Xia
authors.initials: X
authors.lastname: Du
authors.affiliation: Ostesys, 115 rue Claude Chappe, 29280 Plouzané, France. Electronic address: laureen.klimecky@hotmail.fr.
authors.forename: Laureen
authors.initials: L
authors.lastname: Klimecky
authors.affiliation: Department of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, CA 90404, USA. Electronic address: nealkawas@ucla.edu.
authors.forename: Neal
authors.initials: N
authors.lastname: Kawas
authors.affiliation: Department of Orthopaedic Surgery, University of California, Los Angeles, CA 90095, USA. Electronic address: talia1434@ucla.edu.
authors.forename: Talia
authors.initials: T
authors.lastname: Hourany
authors.affiliation: Department of Orthopaedic Surgery, University of California, Los Angeles, CA 90095, USA. Electronic address: jojahng@gmail.com.
authors.forename: Joelle
authors.initials: J
authors.lastname: Jahng
authors.affiliation: Department of Orthopaedic Surgery, University of California, Los Angeles, CA 90095, USA. Electronic address: jessywchin@gmail.com.
authors.forename: Jesse
authors.initials: J
authors.lastname: Chin
authors.affiliation: Department of Medicine, University of California, Los Angeles, CA 90095, USA. Electronic address: ytintut@mednet.ucla.edu.
authors.forename: Yin
authors.initials: Y
authors.lastname: Tintut
authors.affiliation: Institute of Mechanics and Computational Mechanics, Leibniz University Hannover, 30167 Hannover, Germany. Electronic address: nackenhorst@ibnm.uni-hannover.de.
authors.forename: Udo
authors.initials: U
authors.lastname: Nackenhors
authors.affiliation: Department of Radiological Sciences, Medical Sciences I, Bldg 811, Room B140, University of California, Irvine, CA 92697, USA. Electronic address: jhkeyak@uci.edu.
authors.forename: Joyce
authors.initials: J
authors.lastname: Keyak
mesh_terms: D000818:Animals; D015519:Bone Density; D003094:Collagen / Q000737:chemistry; D055119:Elastic Modulus; D005269:Femur / Q000502:physiology / Q000503:physiopathology*; D020342:Finite Element Analysis; D050723:Fractures, Bone / Q000000981:diagnostic imaging; D006949:Hyperlipidemias / Q000503:physiopathology*; D008027:Light; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D013314:Stress, Mechanical; D014057:Tomography, X-Ray Computed
chemical_list: D003094:Collagen
keywords: Collagen type I; High fat diet; Hyperlipidemia; Mouse bone; Multiscale finite element