title: Cortical bone resorption following muscle paralysis is spatially heterogeneous.
abstract: Mechanical loading of the skeleton, as induced by muscle function during activity, plays a critical role in maintaining bone homeostasis. It is not understood, however, whether diminished loading (and thus diminished mechanical stimuli) directly mediates the bone resorption that is associated with disuse. Our group has recently developed a murine model in which we have observed rapid and profound bone loss in the tibia following transient paralysis of the calf muscles. As cortical bone loss is achieved via rapid endocortical expansion without alterations in periosteal morphology, we believe this model holds unique potential to explore the spatial relation between altered mechanical stimuli and subsequent bone resorption. Given the available literature, we hypothesized that endocortical resorption following transient muscle paralysis would be spatially homogeneous. To test this hypothesis, we first validated an image registration algorithm that quantified site-specific cortical bone alterations with high precision and accuracy. We then quantified endocortical expansion in the tibial diaphysis within 21 days following transient muscle paralysis and found that, within the analyzed mid-diaphyseal region (3.15 mm), site-specific bone loss was focused on the anterior surface in the proximal region but shifted to the posterior surface at the distal end of the analyzed volume. This site-specific, and highly repeatable biologic response suggests active osteoclast chemotaxis or focal activation of osteoclastic resorption underlies the spatially consistent endocortical resorption induced by transient muscle paralysis. Clarifying this relation holds potential to yield unique insight into how the removal of factors critical for bone homeostasis acutely precipitates local modulation of cellular responses within bone.
authors.affiliation: Orthopaedics and Sports Medicine, University of Washington, Seattle, WA 98104-2420, USA. bjausk@u.washington.edu
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: Ausk
authors.forename: Philippe
authors.initials: P
authors.lastname: Huber
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Poliachik
authors.forename: Steven D
authors.initials: SD
authors.lastname: Bain
authors.forename: Sundar
authors.initials: S
authors.lastname: Srinivasan
authors.forename: Ted S
authors.initials: TS
authors.lastname: Gross
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000473:pathology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000503:physiopathology*; D010243:Paralysis / Q000503:physiopathology*; D013977:Tibia / Q000033:anatomy & histology* / Q000473:pathology*; D055114:X-Ray Microtomography / Q000379:methods