title: Compressive loading of the murine tibia reveals site-specific micro-scale differences in adaptation and maturation rates of bone.
abstract: Loading increases bone mass and strength in a site-specific manner; however, possible effects of loading on bone matrix composition have not been evaluated. Site-specific structural and material properties of mouse bone were analyzed on the macro- and micro/molecular scale in the presence and absence of axial loading. The response of bone to load is heterogeneous, adapting at molecular, micro-, and macro-levels.
  
  
  
  Osteoporosis is a degenerative disease resulting in reduced bone mineral density, structure, and strength. The overall aim was to explore the hypothesis that changes in loading environment result in site-specific adaptations at molecular/micro- and macro-scale in mouse bone.
  
  
  
  Right tibiae of adult mice were subjected to well-defined cyclic axial loading for 2 weeks; left tibiae were used as physiologically loaded controls. The bones were analyzed with μCT (structure), reference point indentation (material properties), Raman spectroscopy (chemical), and small-angle X-ray scattering (mineral crystallization and structure).
  
  
  
  The cranial and caudal sites of tibiae are structurally and biochemically different within control bones. In response to loading, cranial and caudal sites increase in cortical thickness with reduced mineralization (-14 and -3%, p < 0.01, respectively) and crystallinity (-1.4 and -0.3%, p < 0.05, respectively). Along the length of the loaded bones, collagen content becomes more heterogeneous on the caudal site and the mineral/collagen increases distally at both sites.
  
  
  
  Bone structure and composition are heterogeneous, finely tuned, adaptive, and site-specifically responsive at the micro-scale to maintain optimal function. Manipulation of this heterogeneity may affect bone strength, relative to specific applied loads.
authors.affiliation: Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: I
authors.initials: I
authors.lastname: Bergström
authors.affiliation: UCL Institute of Orthopedics and Musculoskeletal Science, Royal National Orthopedic Hospital, London, UK.|Lancaster Medical School, Faculty of Health and Medicine, Lancaster University, Lancaster, LA1 4YG, UK.
authors.forename: J G
authors.initials: JG
authors.lastname: Kerns
authors.affiliation: Rheumatology and Bone Diseases Unit, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, EH4 2XU, UK.
authors.forename: A E
authors.initials: AE
authors.lastname: Törnqvist
authors.affiliation: Department of Biomedical Engineering and Department of Orthopedics, Lund University, Lund, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Perdikouri
authors.affiliation: Department of Biomedical Engineering and Department of Orthopedics, Lund University, Lund, Sweden.
authors.forename: N
authors.initials: N
authors.lastname: Mathavan
authors.affiliation: Institute of Cancer and Translational Medicine, Department of Anatomy and Cell Biology, MRC Oulu, University of Oulu, Oulu, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Koskela
authors.affiliation: Department of Orthopedics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.|Department of Orthopedics, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: H B
authors.initials: HB
authors.lastname: Henriksson
authors.affiliation: Institute of Cancer and Translational Medicine, Department of Anatomy and Cell Biology, MRC Oulu, University of Oulu, Oulu, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Tuukkanen
authors.affiliation: Department of Laboratory Medicine, Division of Pathology, Karolinska University Hospital, Karolinska Institutet, Huddinge, Stockholm, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Andersson
authors.affiliation: Department of Biomedical Engineering and Department of Orthopedics, Lund University, Lund, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Isaksson
authors.affiliation: UCL Institute of Orthopedics and Musculoskeletal Science, Royal National Orthopedic Hospital, London, UK.|Centre for Comparative and Clinical Anatomy, School of Veterinary Science, University of Bristol, Bristol, UK.
authors.forename: A E
authors.initials: AE
authors.lastname: Goodship
authors.affiliation: Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. sara.windahl@gu.se.
authors.forename: S H
authors.initials: SH
authors.lastname: Windahl
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D002113:Calcification, Physiologic / Q000502:physiology; D003094:Collagen / Q000032:analysis; D019245:Compressive Strength / Q000502:physiology; D005260:Female; D008810:Mice, Inbred C57BL; D013059:Spectrum Analysis, Raman / Q000379:methods; D013977:Tibia / Q000737:chemistry / Q000000981:diagnostic imaging / Q000502:physiology*; D016474:Weight-Bearing / Q000502:physiology*; D055114:X-Ray Microtomography / Q000379:methods
chemical_list: D003094:Collagen
keywords: Loading; RPI; Raman spectroscopy; SAXS