title: Strain energy density gradients in bone marrow predict osteoblast and osteoclast activity: a finite element study.
abstract: Huiskes et al. hypothesized that mechanical strains sensed by osteocytes residing in trabecular bone dictate the magnitude of load-induced bone formation. More recently, the mechanical environment in bone marrow has also been implicated in bone׳s response to mechanical stimulation. In this study, we hypothesize that trabecular load-induced bone formation can be predicted by mechanical signals derived from an integrative µFE model, incorporating a description of both the bone and marrow phase. Using the mouse tail loading model in combination with in vivo micro-computed tomography (µCT) we tracked load induced changes in the sixth caudal vertebrae of C57BL/6 mice to quantify the amount of newly mineralized and eroded bone volumes. To identify the mechanical signals responsible for adaptation, local morphometric changes were compared to micro-finite element (µFE) models of vertebrae prior to loading. The mechanical parameters calculated were strain energy density (SED) on trabeculae at bone forming and resorbing surfaces, SED in the marrow at the boundary between bone forming and resorbing surfaces, along with SED in the trabecular bone and marrow volumes. The gradients of each parameter were also calculated. Simple regression analysis showed mean SED gradients in the trabecular bone matrix to significantly correlate with newly mineralized and eroded bone volumes R(2)=0.57 and 0.41, respectively, p<0.001). Nevertheless, SED gradients in the marrow were shown to be the best predictor of osteoblastic and osteoclastic activity (R(2)=0.83 and 0.60, respectively, p<0.001). These data suggest that the mechanical environment of the bone marrow plays a significant role in determining osteoblast and osteoclast activity.
authors.affiliation: Institute for Biomechanics, ETH Zürich, Zürich, Switzerland.
authors.forename: Duncan
authors.initials: D
authors.lastname: Webster
authors.affiliation: Institute for Biomechanics, ETH Zürich, Zürich, Switzerland.
authors.forename: Friederike A
authors.initials: FA
authors.lastname: Schulte
authors.affiliation: Institute for Biomechanics, ETH Zürich, Zürich, Switzerland.
authors.forename: Floor M
authors.initials: FM
authors.lastname: Lambers
authors.affiliation: Institute for Biomechanics, ETH Zürich, Zürich, Switzerland.
authors.forename: Gisela
authors.initials: G
authors.lastname: Kuhn
authors.affiliation: Institute for Biomechanics, ETH Zürich, Zürich, Switzerland. Electronic address: http://www.biomech.ethz.ch.
authors.forename: Ralph
authors.initials: R
authors.lastname: Müller
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000502:physiology*; D005260:Female; D020342:Finite Element Analysis; D008810:Mice, Inbred C57BL; D008962:Models, Theoretical; D010006:Osteoblasts / Q000502:physiology*; D010010:Osteoclasts / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology; D013131:Spine / Q000502:physiology*; D013314:Stress, Mechanical; D016474:Weight-Bearing; D055114:X-Ray Microtomography
keywords: Finite element analysis; Marrow; Mechanical loading; Trabecular bone