Purpose of ReviewThe bone is able to adapt its structure to mechanical signals via the bone remodeling process governed by mechanosensitive osteocytes. With aging, an imbalance in bone remodeling results in osteoporosis. In this review, we hypothesized that changes in lacunar morphology underlie the decreased bone mechanoresponsiveness to mechanical loading with aging.Recent FindingsSeveral studies have reported considerable variations in the shape of osteocytes and their lacunae with aging. Since osteocytes can sense matrix strain directly via their cell bodies, the variations in osteocyte morphology may cause changes in osteocyte mechanosensitivity. As a consequence, the load-adaptive response of osteocytes may change with aging, even when mechanical loading would remain unchanged.SummaryThough extensive quantitative data is lacking, evidence exists that the osteocyte lacunae are becoming smaller and more spherical with aging. Future dedicated studies might reveal whether these changes would affect osteocyte mechanosensation and the subsequent biological response, and whether this is (one of) the pathways involved in age-related bone loss.

Bone's microporosity plays important roles in bone biology and bone mechanical quality. In this study, we explored the accuracy and reproducibility of nondestructive desktop μCT for 3D visualization and subsequent morphometric analysis of mouse cortical bone microporosity including the vascular canal network and osteocyte lacunae. The accuracy of measurements was evaluated in five murine fibula using confocal laser scanning microscopy (CLSM) in conjunction with Fluorescein isothiocyanate (FITC) staining as the reference method. The reproducibility of μCT-derived cortical bone microstructural indices was examined in 10 fibulae of C57Bl/6J male mice at a nominal resolution of 700 nanometer. Three repeated measurements were made on different days. An excellent correlation between μCT and CLSM was observed for both mean lacuna volume (r = 0.98, p = 0.002) and for mean lacuna orientation (r = 0.93, p = 0.02). Whereas the two techniques showed no significant differences for these parameters, the mean lacuna sphericity acquired from μCT was significantly higher than CLSM (p = 0.01). Reproducibility was high, with precision errors (PE) of 1.57–4.69% for lacuna parameters, and of 1.01–9.45% for vascular canal parameters. Intraclass correlation coefficient (ICC) showed a high reliability of the measurements, ranging from 0.998–1.000 for cortical parameters, 0.973–0.999 for vascular canal parameters and 0.755–0.991 for lacuna parameters. In conclusion, desktop μCT is a valuable tool to quantify the 3D characteristics of bone vascular canals as well as lacunae which can be applied to intact murine bones with high accuracy and reproducibility. Thus, μCT might be an important tool to improve our understanding of the physiological and biomechanical significance of these cannular and lacunar structure in cortical bone.

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Hormonal changes during lactation are associated with profound changes in bone cell biology, such as osteocytic osteolysis, resulting in larger lacunae. Larger lacuna shape theoretically enhances the transmission of mechanical signals to osteocytes. We aimed to provide experimental evidence supporting this theory by comparing the mechanoresponse of osteocytes in the bone of lactating mice, which have enlarged lacunae due to osteocytic osteolysis, with the response of osteocytes in bone from age-matched virgin mice. The osteocyte mechanoresponse was measured in excised fibulae that were cultured in hormone-free medium for 24 h and cyclically loaded for 10 min (sinusoidal compressive load, 3000 µε, 5 Hz) by quantifying loading-related changes in Sost mRNA expression (qPCR) and sclerostin and β-catenin protein expression (immunohistochemistry). Loading decreased Sost expression by ~ threefold in fibulae of lactating mice. The loading-induced decrease in sclerostin protein expression by osteocytes was larger in lactating mice (55% decrease ± 14 (± SD), n = 8) than virgin mice (33% decrease ± 15, n = 7). Mechanical loading upregulated β-catenin expression in osteocytes in lactating mice by 3.5-fold (± 0.2, n = 6) which is significantly (p < 0.01) higher than the 1.6-fold increase in β-catenin expression by osteocytes in fibulae from virgin mice (± 0.12, n = 4). These results suggest that osteocytes in fibulae from lactating mice with large lacunae may respond stronger to mechanical loading than those from virgin mice. This could indicate that osteocytes residing in larger lacuna show a stronger response to mechanical loading.Electronic supplementary materialThe online version of this article (10.1007/s00223-018-0463-8) contains supplementary material, which is available to authorized users.

Bone continuously adapts to its mechanical environment by structural reorganization to maintain mechanical strength. As the adaptive capabilities of bone are portrayed in its nano-and microstructure, the existence of dark and bright osteons with contrasting preferential collagen fiber orientation (longitudinal and oblique-angled, respectively) points at a required tissue heterogeneity that contributes to the excellent fracture resistance mechanisms in bone. Dark and bright osteons provide an exceptional opportunity to deepen our understanding of how nanoscale tissue properties influence and guide fracture mechanisms at larger length scales. To this end, a comprehensive structural, compositional, and mechanical assessment is performed using circularly polarized light microscopy, synchrotron nanocomputed tomography, focused ion beam/scanning electron microscopy, quantitative backscattered electron imaging, Fourier transform infrared spectroscopy, and nanoindentation testing. To predict how the mechanical behavior of osteons is affected by shifts in collagen fiber orientation, finite element models are generated. Fundamental disparities between both osteon types are observed: dark osteons are characterized by a higher degree of mineralization along with a higher ratio of inorganic to organic matrix components that lead to higher stiffness and the ability to resist plastic deformation under compression. On the contrary, bright osteons contain a higher fraction of collagen and provide enhanced ductility and energy dissipation due to lower stiffness and hardness.

High‐resolution peripheral quantitative computed tomography (HR‐pQCT) is considered as the best technique to measure bone microarchitecture in vivo. However, a breakthrough for medical applications is inhibited because of the restricted field of view (∼9 mm) and a relatively long acquisition time (∼3 minutes). The goal of this study was to compare the accuracy of cone‐beam computed tomography (CBCT) and HR‐pQCT and to determine the agreement between CBCT and HR‐pQCT in quantifying bone structural parameters. Nineteen trapezia of arthritic patients were scanned four times ex vivo: 1) CBCT (NewTom 5G, Cefla, at 75 μm); 2) HR‐pQCT (XTremeCT‐I, Scanco, at 82 μm); 3) HR‐pQCT (XTremeCT‐II, Scanco, at 60.7 μm); and 4) microCT (SkyScan1172, Bruker, at 19.84 μm). XTremeCT‐I and XtremeCT‐II were reconstructed, segmented, and analyzed following the manufacturer's guidelines. CBCT was reconstructed with in‐house developed software and analyzed twice: once with an adaptive segmentation technique combined with a direct analysis method (AT‐DM) and once with a Laplace‐Hamming filtering technique combined with an indirect analysis method (LH‐IM). Parameters of interest included bone volume fraction (BV/TV) and trabecular thickness (Tb.Th), separation (Tb.Sp), and number (Tb.N). The analyses of the CBCT data showed that the AT‐DM analysis correlated better with microCT for BV/TV, Tb.Sp, and Tb.N, whereas the LH‐IM technique correlated better for Tb.Th. Evaluated over all parameters, the coefficient of determination for XtremeCT‐I, XtremeCT‐II, and CBCT were higher as R2 = 0.68, 0.72, and 0.67, respectively. For CBCT, the correlations improved when three samples with very thin trabeculae close to each other were excluded and became similar to those for XtremeCT‐I and XtremeCT‐II. Interesting for clinical practice is that those bones could be identified automatically with the CBCT scanner. We conclude that CBCT produced similar accuracy as HR‐pQCT in bone morphometric analyses of trapezia. The broader range of application, larger field of view, and shorter acquisition time make CBCT a valuable alternative to HR‐pQCT. © 2019 American Society for Bone and Mineral Research.

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