title: An investigation of the mineral in ductile and brittle cortical mouse bone.
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.
authors.affiliation: Department of Bioengineering, Imperial College London, London, UK.
authors.forename: Naiara
authors.initials: N
authors.lastname: Rodriguez-Florez
authors.forename: Esther
authors.initials: E
authors.lastname: Garcia-Tunon
authors.forename: Quresh
authors.initials: Q
authors.lastname: Mukadam
authors.forename: Eduardo
authors.initials: E
authors.lastname: Saiz
authors.forename: Karla J
authors.initials: KJ
authors.lastname: Oldknow
authors.forename: Colin
authors.initials: C
authors.lastname: Farquharson
authors.forename: José Luis
authors.initials: JL
authors.lastname: Millán
authors.forename: Alan
authors.initials: A
authors.lastname: Boyde
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Shefelbine
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D001857:Bone Matrix / Q000187:drug effects / Q000378:metabolism; D002113:Calcification, Physiologic / Q000187:drug effects; D002130:Calcium Phosphates / Q000494:pharmacology; D003460:Crystallization; D004548:Elasticity / Q000187:drug effects; D051379:Mice; D008903:Minerals / Q000378:metabolism*; D011208:Powders; D013818:Thermogravimetry; D013977:Tibia / Q000187:drug effects / Q000502:physiology*; D014961:X-Ray Diffraction
chemical_list: D002130:Calcium Phosphates; D008903:Minerals; D011208:Powders; C485817:beta-tricalcium phosphate
keywords: GENETIC ANIMAL MODELS; MATRIX MINERALIZATION; OSTEOGENESIS IMPERFECTA