Significant deterioration in nanomechanical quality occurs through incomplete extrafibrillar mineralization in rachitic bone: Evidence from in-situ synchrotron X-ray scattering and backscattered electron imaging
Copyright policy )Significant deterioration in nanomechanical quality occurs through incomplete extrafibrillar mineralization in rachitic bone: Evidence from in-situ synchrotron X-ray scattering and backscattered electron imaging
Abstract Bone diseases such as rickets and osteoporosis cause significant reduction in bone quantity and quality, which leads to mechanical abnormalities. However, the precise ultrastructural mechanism by which altered bone quality affects mechanical properties is not clearly understood. Here we demonstrate the functional link between altered bone quality (reduced mineralization) and abnormal fibrillar-level mechanics using a novel, real-time synchrotron X-ray nanomechanical imaging method to study a mouse model with rickets due to reduced extrafibrillar mineralization. A previously unreported N-ethyl-N-nitrosourea (ENU) mouse model for hypophosphatemic rickets (Hpr), as a result of missense Trp314Arg mutation of the phosphate regulating gene with homologies to endopeptidase on the X chromosome (Phex) and with features consistent with X-linked hypophosphatemic rickets (XLHR) in man, was investigated using in situ synchrotron small angle X-ray scattering to measure real-time changes in axial periodicity of the nanoscale mineralized fibrils in bone during tensile loading. These determine nanomechanical parameters including fibril elastic modulus and maximum fibril strain. Mineral content was estimated using backscattered electron imaging. A significant reduction of effective fibril modulus and enhancement of maximum fibril strain was found in Hpr mice. Effective fibril modulus and maximum fibril strain in the elastic region increased consistently with age in Hpr and wild-type mice. However, the mean mineral content was ∼21% lower in Hpr mice and was more heterogeneous in its distribution. Our results are consistent with a nanostructural mechanism in which incompletely mineralized fibrils show greater extensibility and lower stiffness, leading to macroscopic outcomes such as greater bone flexibility. Our study demonstrates the value of in situ X-ray nanomechanical imaging in linking the alterations in bone nanostructure to nanoscale mechanical deterioration in a metabolic bone disease. © 2012 American Society for Bone and Mineral Research.
- Imperial College London United Kingdom
- University of Queensland Australia
- University of Sheffield United Kingdom
- Queensland University of Technology Australia
- Queen Mary University of London United Kingdom
Small Angle, Male, genotype, Inbred C57BL, Scattering, X chromosome, Mice, bone stress, mineralization, Biomechanics, article, Genetic Diseases, X-Linked, Biomechanical Phenomena, Diabetes and Metabolism, 2712 Endocrinology, X-linked hypophosphatemic rickets, female, Phenotype, N-ethyl-N-nitrosurea, bone mineral, Female, Familial Hypophosphatemic Rickets, in vitro study, bone structure, Genotype, animal experiment, Molecular Sequence Data, DNA sequence, Mutation, Missense, Hypophosphatemic Rickets, Electrons, Stress, Bone and Bones, Calcification, animal tissue, in vivo study, ethylnitrosourea, 2732 Orthopedics and Sports Medicine, Calcification, Physiologic, male, 616, bone matrix properties, Animals, Amino Acid Sequence, Physiologic, deterioration, X-Linked Dominant, X-Rays, animal model, gene mapping, Mechanical, PHEX Phosphate Regulating Neutral Endopeptidase, nanomechanical imaging, elastic fiber, Nanostructures, bone deformation, Mice, Inbred C57BL, Radiography, in situ synchrotron small angle X-ray scattering, bone mineralization, Ethylnitrosourea, Mutation, elasticity, femur, Missense, collagen fibril, Synchrotrons
Small Angle, Male, genotype, Inbred C57BL, Scattering, X chromosome, Mice, bone stress, mineralization, Biomechanics, article, Genetic Diseases, X-Linked, Biomechanical Phenomena, Diabetes and Metabolism, 2712 Endocrinology, X-linked hypophosphatemic rickets, female, Phenotype, N-ethyl-N-nitrosurea, bone mineral, Female, Familial Hypophosphatemic Rickets, in vitro study, bone structure, Genotype, animal experiment, Molecular Sequence Data, DNA sequence, Mutation, Missense, Hypophosphatemic Rickets, Electrons, Stress, Bone and Bones, Calcification, animal tissue, in vivo study, ethylnitrosourea, 2732 Orthopedics and Sports Medicine, Calcification, Physiologic, male, 616, bone matrix properties, Animals, Amino Acid Sequence, Physiologic, deterioration, X-Linked Dominant, X-Rays, animal model, gene mapping, Mechanical, PHEX Phosphate Regulating Neutral Endopeptidase, nanomechanical imaging, elastic fiber, Nanostructures, bone deformation, Mice, Inbred C57BL, Radiography, in situ synchrotron small angle X-ray scattering, bone mineralization, Ethylnitrosourea, Mutation, elasticity, femur, Missense, collagen fibril, Synchrotrons
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