\begin{table}
\begin{tabular}{c c c} \hline \hline
**Characterization Techniques** & **Illustrative Examples of Information Acquired** \\ \hline _Structure/imaging_ & & \\ \hline Selected area electron diffraction (SAED) & \(\bullet\) & Poorly crystalline nature of apatite nanocrystals [10; 11] \\  & \(\bullet\) & Orientation of collagen fibrils [11] \\ \hline X-ray fiber diffraction & \(\bullet\) & In situ structure and supramolecular arrangement of type I collagen, showing quasi-hexagonal packing [12] \\ \hline  & \(\bullet\) & Acicular crystals of apatite with approximate dimensions of \(\sim\)20–30 nm by 5 nm [13] \\  & \(\bullet\) & Distinct calcium phosphate minerals morphologies in the bone extracellular matrix: dense granules, globular aggregates of needle-like apatites, and mature fibrous minerals [14; 15] \\ Transmission electron microscopy (TEM) and scanning transmission electron microscopy (STEM) & \(\bullet\) & Characteristic collagen banding pattern with a periodicity of \(\sim\)67 nm [16] \\  & \(\bullet\) & Gap zones and overlap zones in collagen fibrils [13] \\  & \(\bullet\) & Woven arrangement of aligned collagen fibrils in the ordered phase of trabecular bone [17] \\  & \(\bullet\) & Disorganized, entangled collagen fibrils without characteristic banding pattern in the disordered phase of trabecular bone [17] \\ \hline
3D S/TEM electron tomography & \(\bullet\) & Cross-fibrillar mineralization [10] \\ \hline  & \(\bullet\) & In situ formation of intracellular calcium phosphate minerals [18] \\ Cryogenic TEM & \(\bullet\) & Characteristic banding pattern of collagen in its hydrated state [19] \\ \hline Atomic force microscopy (AFM) & \(\bullet\) & In situ banding pattern of hydrated collagen and its D-spacing distribution [20; 21] \\ \hline  & \(\bullet\) & Osteons and cement line delineating osteonal and interstitial bones [22] \\ Scanning electron microscopy (SEM) & \(\bullet\) & Canalicular network with residing osteocytes [23] \\  & \(\bullet\) & Network organization in trabecular bone showing \\  & \(\bullet\) & topographical details [24] \\  & \(\bullet\) & Cross-sectional photomontage of an entire human rib bone [25] \\ \hline Environmental SEM (ESEM) & \(\bullet\) & In situ calcium phosphate mineralization in bone at \(\upmu\)m \\ \hline  & \(\bullet\) & Cross-fibrillar, contiguous mineral tessellation pattern [27] \\ Focused ion beam SEM (FIB-SEM) & \(\bullet\) & Differential collagen fibrillar alignments in lamellae and cement \\  & \(\bullet\) & Prolate, ellipsoidal mineral aggregates with \(\upmu\)m dimensions [29] \\  & \(\bullet\) & Extensive lacuno-canalicular network in mineralized bone [29] \\ \hline Polarized light microscopy & \(\bullet\) & Osteons showing birefringent lamellae [30] \\ \hline Scanning small-angle X-ray scattering (scanning SAXS) & \(\bullet\) & Ultrastruct organization and 3D orientation in trabecular bone at sub-mm scale [31] \\ \hline _Chemical analysis_ & \(\bullet\) & Spectral information (e.g., Ca L-edge, C K-edge, O K-edge, N K-edge, and P L-edge) and 1D elemental intensity profiles across, e.g., the collagen D banding [16; 32] \\ Electron energy-loss spectroscopy (EELS) & \(\bullet\) & Mapping of calcium, carbonate, carbonyl contents in bone minerals [14; 33] \\  & \(\bullet\) & Co-localization of N with bone minerals [14] \\  & \(\bullet\) & Elemental maps of proteinaceous vs. mineral contents of bone and the mineralization pattern at sub-\(\upmu\)m scale [34] \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Characterization of bone structure and chemistry from the nanoscale. Diseased bone possesses distinct structural and chemical alterations that cannot be recapitulated solely by a reduction in BMD. 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].