Compressive Strength of Iliac Bone ECM Is Not Reduced in Osteogenesis Imperfecta and Increases With Mineralization

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-tomatrix 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.

Mineralized Collagen Fibrils: An Essential Component in Determining the Mechanical Behavior of Cortical Bone

“…By contrast, higher Young’s modulus, hardness, and dissipated energy of bone at the extracellular matrix level are observed in the iliac crest of human OI patients than in healthy bone. The compressive strength of iliac bone at the extracellular matrix level does not show dramatic decrease compared to healthy bone . Mineralized fibrils in healthy murine bone show strain-rate dependent stiffening.…”

“…The compressive strength of iliac bone at the extracellular matrix level does not show dramatic decrease compared to healthy bone. 99 Mineralized fibrils in healthy murine bone show strain-rate dependent stiffening. By contrast, the fibrillar stiffening mechanism is absent in the steroid induced osteoporosis murine model.…”

Nanoscale Imaging and Analysis of Bone Pathologies

“…Numerous studies have reported modified whole-bone-level mechanics of OI bone, including decreased compressive elastic modulus, reduced bending strength, increased compressive strength, increased hardness, and, most notably, heightened brittleness compared to healthy counterparts [142,143,152,153]. For smaller length scales, an increased compressive modulus was found in the extracellular matrix of OI bone compared to WT using FIB-machined micropillar samples, and the magnitude of increase appeared to correlate with the degree of bone mineralization and disease severity (Figure 5c) [46]. In another recent study, by subjecting OIM bone to ex-situ micropillar compression tests and through finite element modeling, Maghsoudi-Ganjeh et al proposed the possible mechanical behavior of OI bone at the fibrillar level [153].…”

“…Compressive strength of bone was found to increase with OI severity. Figures reprinted with permission from [46].…”

“…One of the disease manifestations is an impairment in bone mechanics, leading to greater susceptibility to fracture. For example, osteoporotic bone possesses compromised strength, and there is reduced hardness in bone with osteogenesis imperfecta pathology [45,46]. Since the functional link of bone structure and mechanics starts at the nanoscale, bulk mechanical techniques examining whole bone samples will fall short in isolating the effect of molecular-and fibrillar-level modifications on bone mechanics.…”