Abstract

Dynamic processes modify bone micro-structure to adapt to external loading and avoid mechanical failure. Age-related cortical bone loss is thought to occur because of increased endocortical resorption and reduced periosteal formation. Differences in the (re)modeling response to loading on both surfaces, however, are poorly understood. Combining in-vivo tibial loading, in-vivo micro-tomography and finite element analysis, remodeling in C57Bl/6J mice of three ages (10, 26, 78 week old) was analyzed to identify differences in mechano-responsiveness and its age-related change on the two cortical surfaces. Mechanical stimulation enhanced endocortical and periosteal formation and reduced endocortical resorption; a reduction in periosteal resorption was hardly possible since it was low, even without additional loading. Endocortically a greater mechano-responsiveness was identified, evident by a larger bone-forming surface and enhanced thickness of formed bone packets, which was not detected periosteally. Endocortical mechano-responsiveness was better conserved with age, since here adaptive response declined continuously with aging, whereas periosteally the main decay in formation response occurred already before adulthood. Higher endocortical mechano-responsiveness is not due to higher endocortical strains. Although it is clear structural adaptation varies between different bones in the skeleton, this study demonstrates that adaptation varies even at different sites within the same bone.

Highlights

  • Bone structure and material properties have presumably adapted to meet evolutionary pressures, balancing the contradictory needs of stiffness and toughness

  • We investigated the reaction to mechanical stimulation of cortical bone at both the endocortical and periosteal surfaces of young (10 week old), adult (26 week old), and elderly (78 week old) female C57Bl/6J mice subjected to in-vivo loading

  • With aging there is an increase in endocortical resorption leading to cortical thinning, so far it remains unknown whether a change in the response to mechanical stimulation of the endocortical or periosteal surfaces occurs that might contribute to this reduction of cortical thickness

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Summary

Introduction

Bone structure and material properties have presumably adapted to meet evolutionary pressures, balancing the contradictory needs of stiffness and toughness. Periosteal apposition, derived from measurements of increases in bone diameter, remains constant in elderly men[5] and decreases in postmenopausal women[6,7] This long-term structural development of the cortex is well documented, much less clear are the reasons for this different behavior of the endocortical and periosteal surfaces. Randomized control trials incorporating high-intensity, impact and resistance exercise have shown marked age-dependent outcomes[12,13] It remains unclear how this loss in responsiveness to mechanical loading may contribute to age-related cortical thinning by altering formation and resorption on the endocortical and periosteal surfaces. While the above-mentioned age-related structural changes occur over months in mice (and years in humans), the response to mechanical simulation happens much faster within a few weeks This ability of mechanical stimulation to move the endocortical and periosteal surfaces due to bone apposition and resorption was studied in mice of different ages. To support the interpretation of the obtained results, the mechanical environment at both surfaces was determined using finite element analysis

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