Compressive loading of the murine tibia reveals site-specific micro-scale differences in adaptation and maturation rates of bone

Osteoporos Int. 2017 Mar;28(3):1121-1131. doi: 10.1007/s00198-016-3846-6. Epub 2016 Dec 5.


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.

Introduction: 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.

Methods: 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).

Results: 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.

Conclusion: 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.

Keywords: Loading; RPI; Raman spectroscopy; SAXS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / physiology*
  • Animals
  • Calcification, Physiologic / physiology
  • Collagen / analysis
  • Compressive Strength / physiology
  • Female
  • Mice, Inbred C57BL
  • Spectrum Analysis, Raman / methods
  • Tibia / chemistry
  • Tibia / diagnostic imaging
  • Tibia / physiology*
  • Weight-Bearing / physiology*
  • X-Ray Microtomography / methods


  • Collagen