title: Bone adaptation to cyclic loading in murine caudal vertebrae is maintained with age and directly correlated to the local micromechanical environment.
abstract: The ability of the skeleton to adapt to mechanical stimuli (mechanosensitivity) has most often been investigated at the whole-bone level, but less is known about the local mechanoregulation of bone remodeling at the bone surface, especially in context of the aging skeleton. The aim of this study was to determine the local and global mechanosensitivity of the sixth caudal vertebra during cyclic loading (8 N, three times per week, for six weeks) in mice aged 15, 52, and 82 weeks at the start of loading. Bone adaptation was monitored with in vivo micro-computed tomography. Strain energy density (SED), assumed as the mechanical stimulus for bone adaptation, was determined with micro-finite element models. Mechanical loading had a beneficial effect on the bone microstructure and bone stiffness in all age groups. Mineralizing surface was on average 13% greater (p<0.05) in loaded than control groups in 15- and 82-week-old mice, but not for 52-week-old mice. SED at the start of loading correlated to the change in bone volume fraction in the following 6 weeks for loaded groups (r(2)=0.69-0.85) but not control groups. At the local level, SED was 14-20% greater (p<0.01) at sites of bone formation, and 15-20% lower (p<0.01) at sites of bone resorption compared to quiescent bone surfaces for all age groups, indicating SED was a stimulus for bone adaptation. Taken together, these results support that mechanosensitivity is maintained with age in caudal vertebrae of mice at a local and global level. Since age-related bone loss was not observed in caudal vertebrae, results from the current study might not be translatable to aged humans.
authors.affiliation: Institute for Biomechanics, ETH Zürich, Zürich, Switzerland. Electronic address: floor.lambers@gmail.com.
authors.forename: Floor M
authors.initials: FM
authors.lastname: Lambers
authors.affiliation: Institute for Biomechanics, ETH Zürich, Zürich, Switzerland. Electronic address: gakuhn@ethz.ch.
authors.forename: Gisela
authors.initials: G
authors.lastname: Kuhn
authors.affiliation: Institute for Biomechanics, ETH Zürich, Zürich, Switzerland. Electronic address: claudia.weigt@sl.ethz.ch.
authors.forename: Claudia
authors.initials: C
authors.lastname: Weigt
authors.affiliation: Institute for Biomechanics, ETH Zürich, Zürich, Switzerland. Electronic address: kathleen.m.koch@gmail.com.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Koch
authors.affiliation: Institute for Biomechanics, ETH Zürich, Zürich, Switzerland. Electronic address: fschulte@ethz.ch.
authors.forename: Friederike A
authors.initials: FA
authors.lastname: Schulte
authors.affiliation: Institute for Biomechanics, ETH Zürich, Zürich, Switzerland. Electronic address: ram@ethz.ch.
authors.forename: Ralph
authors.initials: R
authors.lastname: Müller
mesh_terms: D000222:Adaptation, Physiological; D000375:Aging; D000818:Animals; D001696:Biomechanical Phenomena; D016723:Bone Remodeling; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D013131:Spine / Q000000981:diagnostic imaging / Q000502:physiology*; D016474:Weight-Bearing; D055114:X-Ray Microtomography
keywords: Aging; Animal model; In vivo micro-computed tomography; Mechanical loading; Mechanosensitivity