A Review on Multiscale Bone Damage: From the Clinical to the Research Perspective
Abstract
:1. Introduction
2. Imaging Techniques for Multiscale Damage Assessment and Prediction
2.1. Macro- and Meso-Scale Imaging
2.2. Micro- and Nano-Scale Imaging
3. Bone Damage Physical Principle
4. Multiscale Computational Damage Models
5. Validation Approaches to Multiscale Computational Damage Models
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Macro- and Meso-Scale Imaging Technique | Brief Description of the Technique | Invasiveness | Outcomes | Spatial Resolution | 2D or 3D | Advantages | Disadvantages |
---|---|---|---|---|---|---|---|
In Vitro/In Vivo Application | |||||||
Radiography | Based on the interaction between a beam of photons (X-rays) directed from a source to a receptor. The atoms of the body prevent, in a percentage dependent on their atomic number, some photons from reaching the receptor, reproducing a “negative” image of the body | No Radiation dose: 40–50 times lower, if compared to computed tomography (CT) scans (e.g., radiographs of the abdomen → 0.25 mGy) [39] | Estimation of density variation (fracture risk prediction) by means of two indexes: Singh index [40] for proximal femur and cortical–medullary index [41] for hand radiographs | 0.17 mm/pixel → The size of the monitor screens used in digital radiography is sufficient for 35 × 43 cm2 radiographs to be displayed at a resolution of 2048 × 2560 pixels [42] | 2D | Clear identification of distal radius fractures [43] | Difficult detection of hip and spine fractures Insensitive to changes in Bone Mineral Density (BMD)until 20 to 40% of bone mass lost [43] |
In vivo | |||||||
Dual-energy X-ray Absorptiometry (DXA) | Involves the emission of two X-ray beams with different energy levels, that collide with the body of the patient. Once the absorption of the soft tissue has been subtracted, it is possible to determine the absorption of the beam by the bone and therefore the BMD | No Low radiation dose (0.001–0.003 mGy for L-spine, to 0.004 mGy for total body) [37] | Determination of areal BMD in g/cm2 Calculation of bone mineral content (BMC = BMD × area) Calculation of T-score and Z-score (negative for values under the average BMD), that are numerical indexes for the evaluation of osteoporosis. | 1 pixel → ≃ 0.56 × 0.56 mm2. (for a Hologic system) [44] | 2D | Ease of use of the equipment Standardization Short examination time [45] | No bone architecture detection (no difference between cortical and trabecular bone) Sampling errors Incorrect evaluation in obese patients [37] |
In vivo | |||||||
Vertebral Fracture Assessment (VFA) | Special DXA analysis that permits the detection of spinal fractures from a lateral image of the spine | No Lower radiation exposure with respect to spine radiography [46] | Spinal fracture detection [47] | Low spatial resolution | 2D | Possibility to add a VFA scan after areal BMD assessment High sensitivity High specificity [48] | Low spatial resolution |
In vivo | |||||||
Quantitative Computed Tomography (QCT) | X-ray-based technique that measures BMD. It produces cross-sectional images of X-ray absorption coefficient (measured in Hounsfield units) calibrated to water. It is used to evaluate fracture risk primarily at the lumbar spine and at the hip [49] | Medium–high invasiveness Medium–high radiation dose (0.2–0.4 mGy for a spine exam) [50] | True measurement of BMD assessment (areal BMD does not predict if an individual patient will eventually fracture) | 100× higher resolution with respect to conventional radiologic imaging [51] | 3D (multiple slices are obtained and then reconstructed) | Fracture risk prediction in patients with scoliosis, obesity, etc. without having artificially high BMD values, as in DXA [52] High reproducibility Assessment of cortical and trabecular bone Good accuracy and precision [37] | Relevant radiation dose Low accessibility High cost [53] |
In vivo | |||||||
Magnetic Resonance Imaging (MRI) | MRIs employ a magnetic field that forces protons in the body to align with that field. When a radiofrequency current is pulsed through the patient, the protons are strained against the pull of the magnetic field. When the radiofrequency field is turned off, the MRI sensors detect the released energy as the protons realign with the magnetic field. The time it takes for the protons to realign, as well as the amount of energy released, changes depending on the environment and the chemical nature of the molecules | No MRI does not use ionizing radiation | Bone fracture detection Parameters: T2* [54] (effective transverse relaxation time) → a function of the density and orientation of the trabeculae [55] R2* → rate constant of the free induction signal (lower with respect to the control in osteoporotic women’s bone marrow [56]) | MRI scanners used for medical purposes could reach typical resolutions of around 1.5 × 1.5 × 4 mm3 [57] | 3D | Useful in age-related fracture detection (marrow fat increases with age and in osteoporosis, allowing better contrast with the trabecular bone) Investigation of cortical water content [43] | Presence of a magnetic field (risk for patients with pacemakers and all implants containing iron) Noise up to 120 dB Use of contrast agents Claustrophobia side effect |
In vivo |
Micro- and Nano-Scale Imaging Technique | Brief Description of the Technique | Invasiveness | Outcomes | Spatial Resolution | 2D or 3D | Advantages | Disadvantages |
---|---|---|---|---|---|---|---|
In Vitro/In Vivo Application | |||||||
Stereomicroscopy Based on Histological Sections | Histology from the bone tissue is obtained and then the sample is properly treated (fixation, dehydration and clearing, embedding, sectioning, staining and mounting). The histological section is then observed by means of an optical microscope | Yes | Traditional technique for the visualization of bone microarchitecture | ~1.6 µm [58] | 2D | Bone remodeling assessment [59] | Destructive and invasive technique Limitations related to the bidimensional output images: the three-dimensional features are lost. High-resolution images (at least 1.4 µm or better) are required to identify and measure individual resorption cavities in the process of bone remodeling [59] |
In vitro | |||||||
Micro-Computed Tomography (Micro-CT) and Nano-Computed Tomography (Nano-CT) | Micro- and nano-CT scans use radiographs to generate cross-sections of bone, that are generally processed (image reconstruction) to generate a virtual 3D model without destroying the original bone sample | No Generally, the samples are obtained from surgical wastes that derive from prosthetic treatment | Microarchitectural 3D data for both the cortical and the trabecular sections (tissue volume, bone volume, bone surface, bone volume fraction, bone surface to tissue volume, trabecular/cortical thickness, degree of anisotropy, cortical porosity, etc.) [37]. Local and global parameters related to the lacunar network are obtained [36] | 1.2 µm (micro-CT) ~50–150 nm (nano-CT) | 3D | Large number of obtainable outputs (morphological parameters at different scales) Detailed finite element 3D models could be implemented by using micro-CT images | Static evaluation of micro-scale features Not suitable for in vivo human evaluation due to the high radiation dose No detection of the canalicular network (insufficient resolution for the micro-CT scans) Nano-CT |
In vitro | |||||||
Peripheral QCT (pQCT) and High-Resolution pQCT (HR-pQCT) | Dedicated CT scanners for the forearm (radius and ulna) and leg (tibia and fibula) | No Low radiation dose (≈0.003 mGy) [37] | Analysis of the trabecular and cortical sections (BMD, bone mineral content and bone geometrical parameter calculation). Acquisition of biomechanical parameters, such as the cross-sectional moment of inertia. Evaluation of the functional muscle–bone unit [60]. | Isotropic voxel size of 82 μm with HR-pQCT | 3D | High precision and accuracy Low radiation dose Applicable for the study of a large number of diseases, especially pediatric (useful in applications where trabecular and cortical sections are affected in a different way) | Evaluation restricted to the appendicular bone Only transversal data are available for fracture risk prediction Low spatial resolution |
In vivo | |||||||
Synchrotron Radiation Imaging (SR) | A high-intensity white beam travels around a fixed closed loop. It permits a high level of detail in bone visualization (ultra-structural porosity detection) | No Generally, the samples are obtained from surgical wastes that derive from prosthetic treatment | Morphological analysis of ultra-structural porosities | Voxel size of 0.9 μm for the white beam [61] | 3D | Visualization of the lacunar and canalicular network Phase contrast permits the clear detection of micro-cracks | Reduced field of view |
In vitro | |||||||
Micro-MRI and nano-MRI | The technique generates images by exploiting the nuclear magnetic behavior of different atoms in a sample tissue placed in a magnetic field | No | Structural parameters, such as trabecular bone thickness and mean bone volume fraction, associated with bone biomechanical properties and fracture resistance | Spatial resolution up to 25 µm (micro-MRI) and ~10 nm for the nano-MRI | 3D | Non-destructive technique Good special resolution Good contrast resolution [62] | Long acquisition times High costs [62] |
In vivo | |||||||
Laser Scanning Confocal Microscopy (LSCM) | LSCM employs lasers at proper wavelengths to excite fluorochromes that are used to stain bone sections | Yes | Correlation between micro-crack parameters and bone matrix toughness Comparison among damage morphologies [13] | 180 nm laterally and 500 nm axially [63] | 2D/3D images of consecutive planes can be reconstructed into a 3D image in vitro. | Evaluation of bone microdamage | Axial resolution in depth impaired by spherical aberration [63] High costs |
Scanning Electon Microscopy (SEM) | SEM produces images of the bone sample by scanning the surface with a focused beam of electrons | Yes | Quantitative analysis of fracture surfaces Visualization of microdamage morphology, fiber bridging and interlamellar separation [13] | ~1 nm | 3D In vitro | Significant information related to sub-micro-scale damage | Destructive technique (sample surfaces should be conductive → bone needs to be coated with conductive materials) |
Atomic Force Microscopy (AFM) | The deflections of a cantilever on the surface of the bone sample are transduced into electrical signals | Yes | Topographical parameters of fractured bone surfaces (mineral particle sizes) Identification of sacrificial bonding | Vertical resolution → up to 0.1 nm Lateral resolution → ~30 nm | 3D In vitro | Versatile imaging technique for the visualization of fracture surfaces High accuracy Non-destructive technique [64] | Small dimensions of the single scan image size (150 × 150 µm, compared with mm for SEM) Slow scan time [64] |
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Buccino, F.; Colombo, C.; Vergani, L.M. A Review on Multiscale Bone Damage: From the Clinical to the Research Perspective. Materials 2021, 14, 1240. https://doi.org/10.3390/ma14051240
Buccino F, Colombo C, Vergani LM. A Review on Multiscale Bone Damage: From the Clinical to the Research Perspective. Materials. 2021; 14(5):1240. https://doi.org/10.3390/ma14051240
Chicago/Turabian StyleBuccino, Federica, Chiara Colombo, and Laura Maria Vergani. 2021. "A Review on Multiscale Bone Damage: From the Clinical to the Research Perspective" Materials 14, no. 5: 1240. https://doi.org/10.3390/ma14051240
APA StyleBuccino, F., Colombo, C., & Vergani, L. M. (2021). A Review on Multiscale Bone Damage: From the Clinical to the Research Perspective. Materials, 14(5), 1240. https://doi.org/10.3390/ma14051240