Abstract
SummaryLoading increases bone mass and strength in a site-specific manner; however, possible effects of loading on bone matrix composition have not been evaluated. Site-specific structural and material properties of mouse bone were analyzed on the macro- and micro/molecular scale in the presence and absence of axial loading. The response of bone to load is heterogeneous, adapting at molecular, micro-, and macro-levels.IntroductionOsteoporosis is a degenerative disease resulting in reduced bone mineral density, structure, and strength. The overall aim was to explore the hypothesis that changes in loading environment result in site-specific adaptations at molecular/micro- and macro-scale in mouse bone.MethodsRight tibiae of adult mice were subjected to well-defined cyclic axial loading for 2 weeks; left tibiae were used as physiologically loaded controls. The bones were analyzed with μCT (structure), reference point indentation (material properties), Raman spectroscopy (chemical), and small-angle X-ray scattering (mineral crystallization and structure).ResultsThe cranial and caudal sites of tibiae are structurally and biochemically different within control bones. In response to loading, cranial and caudal sites increase in cortical thickness with reduced mineralization (−14 and −3%, p < 0.01, respectively) and crystallinity (−1.4 and −0.3%, p < 0.05, respectively). Along the length of the loaded bones, collagen content becomes more heterogeneous on the caudal site and the mineral/collagen increases distally at both sites.ConclusionBone structure and composition are heterogeneous, finely tuned, adaptive, and site-specifically responsive at the micro-scale to maintain optimal function. Manipulation of this heterogeneity may affect bone strength, relative to specific applied loads.
Highlights
Bone mineral density is a major parameter influencing bone material properties, stiffness, and elastic modulus
Ex vivo mechanical strain measurement during dynamic axial loading of tibia The magnitude of axial mechanical strain applied to the tibia during loading was established ex vivo as previously described [17]
Previous studies have shown that this region corresponds to the site of greatest osteogenic response to axial loading, and the 37% site is often used as a representative part of this region [16, 24, 25]
Summary
Bone mineral density is a major parameter influencing bone material properties, stiffness, and elastic modulus. Bone Bquality^ includes all factors contributing to the strength of the bone and is characterized by a combination of the geometry, micro-architecture (three-dimensional organization), bone turnover, micro-damage, and bone matrix chemistry (mineral and collagen content) [1, 2]. The organic component of bone is composed of up to 90% type I collagen and, together with the mineral component, governs the biomechanical properties, strength, toughness, and functional integrity of the tissue [4, 5]. Collagen has a mechanical function in all connective tissues contributing to tensile strength and structural integrity. Several studies indicate that the collagen component has a substantial role in the toughness of bone (capacity to absorb energy), while the mineral content mainly determines the stiffness of bone [1]. Bone strength is affected by both the relative amounts and the geometric organization of the bone matrix and the specific chemistry of the organic and inorganic components
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