Abstract
abstract Osteogenesis imperfecta (OI) is an inheritable, genetic, and collagen‐related disorder leading to an increase in bone fragility, but the origin of its “brittle behavior” is unclear. Because of its complex hierarchical structure, bone behaves differently at various length scales. This study aims to compare mechanical properties of human OI bone with healthy control bone at the extracellular matrix (ECM) level and to quantify the influence of the degree of mineralization. Degree of mineralization and mechanical properties were analyzed under dry conditions in 12 fixed and embedded transiliac crest biopsies (control n = 6, OI type I n = 3, OI type IV n = 2, and OI type III n = 1). Mean degree of mineralization was measured by microcomputed tomography at the biopsy level and the mineral‐to‐matrix ratio was assessed by Raman spectroscopy at the ECM level. Both methods revealed that the degree of mineralization is higher for OI bone compared with healthy control. Micropillar compression is a novel technique for quantifying post‐yield properties of bone at the ECM level. Micropillars (d = 5 μm, h = 10 μm) were fabricated using focused ion beam milling and quasi‐statically compressed to capture key post‐yield properties such as ultimate strength. The qualitative inspection of the stress–strain curves showed that both OI and healthy control bone have a ductile response at the ECM level. The quantitative results showed that compressive strength is not reduced in OI bone and is increasing with OI severity. Nanoindentation measurements revealed that OI bone tends to have a higher Young's modulus, hardness, and dissipated energy compared with healthy bone. Micropillar strength and indentation modulus increased linearly and significantly (p < .0001) with mineral‐to‐matrix ratio. In conclusion, this study indicates that compressive mechanical properties of dry OI bone at the iliac crest are not inferior to healthy control at the ECM level and increase with mineralization. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Highlights
Osteogenesis imperfecta (OI), known as brittle bone disease, is a rare genetic disorder
The tissue bone mineral density (TMD) value of μCT is increased for all OI groups compared with healthy control
Roschger and colleagues showed that the mineral-to-matrix ratio correlates linearly with calcium weight fraction (R2 = 0.75).(29) OI bone shows a significantly higher mineralization level than healthy bone (Table 2), as measured by Raman spectroscopy, which confirms the literature.[6,7,8,9] The TMD of cortical shell measured with μCT for healthy control and OI bone in the present study are in agreement with values reported in the literature (control: 988(6) and 1032(7) mgHA/cm3; OI: 1103(6) and 1131(7) mgHA/cm3)
Summary
Osteogenesis imperfecta (OI), known as brittle bone disease, is a rare genetic disorder. OI is caused by mutations in genes encoding type I collagen (COL1A1 and COL1A2), leading to increased bone fragility. These OI types can be categorized according to disease severity into type I (mild), type II (perinatally lethal), type III (severe), and type IV (moderate).(1) Individuals with OI have high rates of bone fracture, especially during growth,(2) as well as an abnormal multiscale bone structure and composition. With the increasing use of high-resolution quantitative peripheral computed tomography (HR-pQCT) to assess bone structure and strength in clinical trials, bone material property measurements from the OI population are needed. The material properties are used as inputs in computational models for n 1364 INDERMAUR ET AL
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