Association between nanoscale strains and tissue level nanoindentation properties in age-related hip-fractures

Measurement of the properties of bone as a material can happen in various length scales in its hierarchical and composite structure. The aim of this study was to test the tissue level properties of clinically-relevant human bone samples which were collected from donors belonging to three groups: ageing donors who suffered no fractures (Control); untreated fracture patients (Fx-Untreated) and patient who experienced hip fracture despite being treated with bisphosphonates (Fx-BisTreated). Tissue level properties were assessed by (a) nanoindentation and (b) synchrotron tensile tests (STT) where strains were measured at the ‘tissue’, ‘fibril’ and ‘mineral’ levels by using simultaneous Wide-angle - (WAXD) and Small angle- X-ray diffraction (SAXD). The composition was analysed by thermogravimetric analysis and material level endo- and exo-thermic reactions by differential scanning calorimetry (TGA/DSC3+). Irrespective of treatment fracture donors exhibited significantly lower tissue, fibril and mineral strain at the micro and nanoscale respectively and had a higher mineral content than controls. In nanoindentation only nanohardness was significantly greater for Controls and Fx-BisTreated versus Fx-Untreated. The other nanoindentation parameters did not vary significantly across the three groups. There was a highly significant positive correlation (p < 0.001) between organic content and tissue level strain behaviour. Overall hip-fractures were associated with lower STT nanostrains and it was behaviour measured by STT which proved to be a more effective approach for predicting fracture risk because evidently it was able to demonstrate the mechanical deficit for the bone tissue of the donors who had experienced fractures

Association between nanoscale strains and tissue level nanoindentation properties in age-related hip-fractures

Measurement of the properties of bone as a material can happen in various length scales in its hierarchical and composite structure. The aim of this study was to test the tissue level properties of clinically-relevant human bone samples which were collected from donors belonging to three groups: ageing donors who suffered no fractures (Control); untreated fracture patients (Fx-Untreated) and patient who experienced hip fracture despite being treated with bisphosphonates (Fx-BisTreated). Tissue level properties were assessed by (a) nanoindentation and (b) synchrotron tensile tests (STT) where strains were measured at the 'tissue', 'fibril' and 'mineral' levels by using simultaneous Wide-angle - (WAXD) and Small angle- X-ray diffraction (SAXD). The composition was analysed by thermogravimetric analysis and material level endo- and exo-thermic reactions by differential scanning calorimetry (TGA/DSC3+). Irrespective of treatment fracture donors exhibited significantly lower tissue, fibril and mineral strain at the micro and nanoscale respectively and had a higher mineral content than controls. In nanoindentation only nanohardness was significantly greater for Controls and Fx-BisTreated versus Fx-Untreated. The other nanoindentation parameters did not vary significantly across the three groups. There was a highly significant positive correlation (p < 0.001) between organic content and tissue level strain behaviour. Overall hip-fractures were associated with lower STT nanostrains and it was behaviour measured by STT which proved to be a more effective approach for predicting fracture risk because evidently it was able to demonstrate the mechanical deficit for the bone tissue of the donors who had experienced fractures. [Abstract copyright: Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.

The changes in bone's nanostructure associated with bone fragility & bisphosphonate treatment

The contribution of the nanostructure to whole bone strength has long been debated. However the impact of the collagen-mineral matrix on whole bone mechanics has yet to be tested. At the start of the study, bone volume and microarchitecture were found to not entirely account for bone strength, even though new ITS techniques were included, and thus it seemed possible that the gap could be attributed to the nanostructure. State-of-the-art synchrotron imaging was used to compare nanomechanics between bones from ageing non-fracture donors and ageing fracture patients, half of whom had been prescribed bisphosphonate. Fracture patients exhibited with lower tissue, collagen and mineral strains than non-fracture patients, suggesting that their nanostructures were less deformable. In addition, the fracture patients exhibited with wider mineral crystals, providing for larger surface areas for interfacial bonding with collagen fibrils, and thus preventing the unwinding and sliding of the matrix during loading. The less deformable matrix may reduce macroscopic strength via a cascade effect by easier initiation and growth of microcracks in the collagen-mineral matrix and limiting the bone’s ability to bend and absorb energy during a trip or fall. This new knowledge of the importance of the nanoscale deformation to whole bone strength could fill gaps in current diagnostics and treatments, if it were possible to measure deformation properties in vivo. Nanoindentation was developed to measure such deformations, and as such, a benchtop system was used to measure material properties of the three groups, and the data was correlated with nanostrain data. However, nanoindentation material properties and fibril and mineral strains were not correlated. In addition to the lack of correlation to microstructure and macro level strength and stiffness, it seems that nanoindentation does not measure material properties accurately and thus other alternatives need to be looked into for in-vivo measurements at the nanoscale.  Open Acces

A Cross-Sectional Study of Bone Nanomechanics in Hip Fracture and Aging

Bone mechanics is well understood at every length scale except the nano-level. We aimed to investigate the relationship between bone nanoscale and tissue-level mechanics experimentally. We tested two hypotheses: (1) nanoscale strains were lower in hip fracture patients versus controls, and (2) nanoscale mineral and fibril strains were inversely correlated with aging and fracture. A cross-sectional sample of trabecular bone sections was prepared from the proximal femora of two human donor groups (aged 44–94 years): an aging non-fracture control group (n = 17) and a hip-fracture group (n = 20). Tissue, fibril, and mineral strain were measured simultaneously using synchrotron X-ray diffraction during tensile load to failure, then compared between groups using unpaired t-tests and correlated with age using Pearson’s correlation. Controls exhibited significantly greater peak tissue, mineral, and fibril strains than the hip fracture (all p p = 0.099) and mineral (p = 0.004) strain, but not fibril strain (p = 0.260). Overall, hip fracture and aging were associated with changes in the nanoscale strain that are reflected at the tissue level. Data must be interpreted within the limitations of the observational cross-sectional study design, so we propose two new hypotheses on the importance of nanomechanics. (1) Hip fracture risk is increased by low tissue strain, which can be caused by low collagen or mineral strain. (2) Age-related loss of tissue strain is dependent on the loss of mineral but not fibril strain. Novel insights into bone nano- and tissue-level mechanics could provide a platform for the development of bone health diagnostics and interventions based on failure mechanisms from the nanoscale up

Identification of Secondary Biomechanical Abnormalities in the Lower Limb Joints after Chronic Transtibial Amputation: A Proof-of-Concept Study Using SPM1D Analysis

SPM is a statistical method of analysis of time-varying human movement gait signal, depending on the random field theory (RFT). MovementRx is our inhouse-developed decision-support system that depends on SPM1D Python implementation of the SPM (spm1d.org). We present the potential application of MovementRx in the prediction of increased joint forces with the possibility to predispose to osteoarthritis in a sample of post-surgical Transtibial Amputation (TTA) patients who were ambulant in the community. We captured the three-dimensional movement profile of 12 males with TTA and studied them using MovementRx, employing the SPM1D Python library to quantify the deviation(s) they have from our corresponding reference data, using &ldquo;Hotelling 2&rdquo; and &ldquo;T test 2&rdquo; statistics for the 3D movement vectors of the 3 main lower limb joints (hip, knee, and ankle) and their nine respective components (3 joints &times; 3 dimensions), respectively. MovementRx results visually demonstrated a clear distinction in the biomechanical recordings between TTA patients and a reference set of normal people (ABILITY data project), and variability within the TTA patients&rsquo; group enabled identification of those with an increased risk of developing osteoarthritis in the future. We conclude that MovementRx is a potential tool to detect increased specific joint forces with the ability to identify TTA survivors who may be at risk for osteoarthritis