Abstract
Bone is a strong and tough material composed of apatite mineral, organic matter, and water. Changes in composition and organization of these building blocks affect bone's mechanical integrity. Skeletal disorders often affect bone's mineral phase, either by variations in the collagen or directly altering mineralization. The aim of the current study was to explore the differences in the mineral of brittle and ductile cortical bone at the mineral (nm) and tissue (µm) levels using two mouse phenotypes. Osteogenesis imperfecta model, oim(-/-) , mice have a defect in the collagen, which leads to brittle bone; PHOSPHO1 mutants, Phospho1(-/-) , have ductile bone resulting from altered mineralization. Oim(-/-) and Phospho1(-/-) were compared with their respective wild-type controls. Femora were defatted and ground to powder to measure average mineral crystal size using X-ray diffraction (XRD) and to monitor the bulk mineral to matrix ratio via thermogravimetric analysis (TGA). XRD scans were run after TGA for phase identification to assess the fractions of hydroxyapatite and β-tricalcium phosphate. Tibiae were embedded to measure elastic properties with nanoindentation and the extent of mineralization with backscattered electron microscopy (BSE SEM). Results revealed that although both pathology models had extremely different whole-bone mechanics, they both had smaller apatite crystals, lower bulk mineral to matrix ratio, and showed more thermal conversion to β-tricalcium phosphate than their wild types, indicating deviations from stoichiometric hydroxyapatite in the original mineral. In contrast, the degree of mineralization of bone matrix was different for each strain: brittle oim(-/-) were hypermineralized, whereas ductile Phospho1(-/-) were hypomineralized. Despite differences in the mineralization, nanoscale alterations in the mineral were associated with reduced tissue elastic moduli in both pathologies. Results indicated that alterations from normal crystal size, composition, and structure are correlated with reduced mechanical integrity of bone.
Highlights
Cortical bone is a tough material; bone’s ability to resist fracture often deteriorates because of aging and/or skeletal diseases
Reductions in calcium to phosphate (Ca/P) ratio have been reported in human osteogenesis imperfecta bone[51] and in osteoporotic bone.[52,53] Our results further indicate that pathologic bone mineral tends to be less stoichiometric.[23,29] Heating the samples to different temperatures before X-ray diffraction (XRD) measurements brings out differences in composition of pathologic bones not readily evident from XRD
The mineral phase of brittle and ductile bones was compared at the nano- and microscale
Summary
Cortical bone is a tough material; bone’s ability to resist fracture often deteriorates because of aging and/or skeletal diseases. At the tissue level (microscale), lamellar bone is built up of collagen fibers, which are composed of collagen fibrils and mineral crystals (nanoscale). The constituent elements of bone material include apatite mineral, primarily impure forms of hydroxyapatite (HA); organic matter, composed of collagen and noncollagenous proteins; and water, which resides on the surface, within mineral crystals, and between collagen fibers. Because of this complex hierarchical structure, there are many determinants of bone’s fracture toughness. The composite nature of mineralized collagen fibrils and, the mineral and collagen as well as the interaction between them contribute to bone-toughening mechanisms.[5,6] collagen is accepted to play a major role in bone toughness,(5–7)
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