TY - JOUR

T1 - Compressive loading of the murine tibia reveals site-specific micro-scale differences in adaptation and maturation rates of bone

AU - Bergström, Ingrid

AU - Kerns, Jemma Gillian

AU - Törnqvist, Anna

AU - Perdikouri, Cristina

AU - Mathavan, Neashan

AU - Koskela, Antti

AU - Henriksson, Helena

AU - Tuukkanen, Juha

AU - Andersson, Goran

AU - Isaksson, Hanna

AU - Goodship, Allen

AU - Windahl, Sara

PY - 2017/3

Y1 - 2017/3

N2 - Summary: 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. Purpose/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 two 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.

AB - Summary: 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. Purpose/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 two 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.

KW - Loading

KW - Raman spectroscopy

KW - RPI

KW - SAXS

U2 - 10.1007/s00198-016-3846-6

DO - 10.1007/s00198-016-3846-6

M3 - Journal article

VL - 28

SP - 1121

EP - 1131

JO - Osteoporosis International

JF - Osteoporosis International

SN - 0937-941X

IS - 3

ER -