title: Decreased collagen organization and content are associated with reduced strength of demineralized and intact bone in the SAMP6 mouse.
abstract: To examine the link between bone material properties and skeletal fragility, we analyzed the mechanical, histological, biochemical, and spectroscopic properties of bones from a murine model of skeletal fragility (SAMP6). Intact bones from SAMP6 mice are weak and brittle compared with SAMR1 controls, a defect attributed to reduced strength of the bone matrix. The matrix weakness is attributed primarily to poorer organization of collagen fibers and reduced collagen content.
  
  
  BACKGROUND
  The contribution of age-related changes in tissue material properties to skeletal fragility is poorly understood. We previously reported that bones from SAMP6 mice are weak and brittle versus age-matched controls. Our present objectives were to use the SAMP6 mouse to assess bone material properties in a model of skeletal fragility and to relate defects in the mechanical properties of bone to the properties of demineralized bone and to the structure and organization of collagen and mineral.
  
  
  METHODS
  Femora from 4- and 12-month-old SAMR1 (control) and SAMP6 mice were analyzed using bending and torsional mechanical testing of intact bones, tensile testing of demineralized bone, quantitative histology (including collagen fiber orientation), collagen cross-links biochemistry, and Raman spectroscopic analysis of mineral and collagen.
  
  
  RESULTS
  Intact bones from SAMP6 mice have normal elastic properties but inferior failure properties, with 60% lower fracture energy versus SAMR1 controls. The strength defect in SAMP6 bones was associated with a 23% reduction in demineralized bone strength, which in turn was associated with poorer collagen fiber organization, lower collagen content, and higher hydroxylysine levels. However, SAMP6 have normal levels of collagen cross-links and normal apatite mineral structure.
  
  
  CONCLUSIONS
  Bones from SAMP6 osteoporotic mice are weak and brittle because of a defect in the strength of the bone matrix. This defect is attributed primarily to poorer organization of collagen fibers and reduced collagen content. These findings highlight the role of the collagen component of the bone matrix in influencing skeletal fragility.
authors.affiliation: Department of Orthopaedic Surgery, Barnes-Jewish Hospital at Washington University, St Louis, Missouri 63110, USA. silvam@wustl.edu
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Silva
authors.forename: Michael D
authors.initials: MD
authors.lastname: Brodt
authors.forename: Brigitte
authors.initials: B
authors.lastname: Wopenka
authors.forename: Stavros
authors.initials: S
authors.lastname: Thomopoulos
authors.forename: Derek
authors.initials: D
authors.lastname: Williams
authors.forename: Maurice H M
authors.initials: MH
authors.lastname: Wassen
authors.forename: Mike
authors.initials: M
authors.lastname: Ko
authors.forename: Nozomu
authors.initials: N
authors.lastname: Kusano
authors.forename: Ruud A
authors.initials: RA
authors.lastname: Bank
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D003094:Collagen / Q000378:metabolism*; D005269:Femur / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D010024:Osteoporosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D013718:Tensile Strength
chemical_list: D003094:Collagen