title: The influence of age on adaptive bone formation and bone resorption.
abstract: Bone is a tissue with enormous adaptive capacity, balancing resorption and formation processes. It is known that mechanical loading shifts this balance towards an increased formation, leading to enhanced bone mass and mechanical performance. What is not known is how this adaptive response to mechanical loading changes with age. Using dynamic micro-tomography, we show that structural adaptive changes of trabecular bone within the tibia of living mice subjected to two weeks of in vivo cyclic loading are altered by aging. Comparisons of 10, 26 and 78 weeks old animals reveal that the adaptive capacity diminishes. Strikingly, adaptation was asymmetric in that loading increases formation more than it reduces resorption. This asymmetry further shifts the (re)modeling balance towards a net bone loss with age. Loading results in a major increase in the surface area of mineralizing bone. Interestingly, the resorption thickness is independent of loading in trabecular bone in all age groups. This data suggests that during youth, mechanical stimulation induces the recruitment of bone modeling cells whereas in old age, only bone forming cells are affected. These findings provide mechanistic insights into the processes that guide skeletal aging in mice as well as in other mammals.
authors.affiliation: Julius Wolff Institut, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Berlin-Brandenburg School for Regenerative Therapies GSC 203, Germany.
authors.forename: Annette I
authors.initials: AI
authors.lastname: Birkhold
authors.affiliation: Julius Wolff Institut, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; Berlin-Brandenburg School for Regenerative Therapies GSC 203, Germany.
authors.forename: Hajar
authors.initials: H
authors.lastname: Razi
authors.affiliation: Julius Wolff Institut, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Georg N
authors.initials: GN
authors.lastname: Duda
authors.affiliation: Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Weinkamer
authors.affiliation: Julius Wolff Institut, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Sara
authors.initials: S
authors.lastname: Checa
authors.affiliation: Julius Wolff Institut, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. Electronic address: bettina.willie@charite.de.
authors.forename: Bettina M
authors.initials: BM
authors.lastname: Willie
mesh_terms: D000222:Adaptation, Physiological; D000367:Age Factors; D000818:Animals; D015519:Bone Density; D016723:Bone Remodeling / Q000502:physiology*; D005260:Female; D007091:Image Processing, Computer-Assisted; D051379:Mice; D008810:Mice, Inbred C57BL; D010012:Osteogenesis / Q000502:physiology*; D015203:Reproducibility of Results; D013977:Tibia / Q000000981:diagnostic imaging; D014057:Tomography, X-Ray Computed
keywords: Adaptation; Aging; Bone remodeling; Image analysis; Microstructure