Aging, Osteocytes, and Mechanotransduction

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Ageing is leading to alterations in murine cortical bone microporosity

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Aging, Osteocytes, and Mechanotransduction

PURPOSE OF REVIEW: The 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 FINDINGS: Several 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. Though 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.status: publishe

Age-related changes in the 3D microstructural mouse cortical bone using high resolution desktop micro-CT system

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Variation in osteocyte lacunar size and shape in rapidly forming cortical bone due to mechanical loading

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Three-dimensional visualization and quantification of mouse cortical bone porosity at submicron resolution using desktop micro-CT

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Alterations in osteocyte lacunar morphology affect local bone tissue strains

Osteocytes are capable of remodeling their perilacunar bone matrix, which causes considerable variations in the shape and size of their lacunae. If these variations in lacunar morphology cause changes in the mechanical environment of the osteocytes, in particular local strains, they would subsequently affect bone mechanotransduction, since osteocytes are likely able to directly sense these strains. The purpose of this study is to quantify the effect of alterations in osteocyte lacunar morphology on peri-lacunar bone tissue strains. To this end, we related the actual lacunar shape in fibulae of six young-adult (5-month) and six old (23-month) mice, quantified by high-resolution micro-computed tomography, to microscopic strains, analyzed by micro-finite element modeling. We showed that peak effective strain increased by 12.6% in osteocyte cell bodies (OCYs), 9.6% in pericellular matrix (PCM), and 5.3% in extra cellular matrix (ECM) as the lacunae volume increased from 100-200 μm3 to 500–600 μm3. Lacunae with a larger deviation (>8°) in orientation from the longitudinal axis of the bone are exposed to 8% higher strains in OCYs, 6.5% in PCM, 4.2% in ECM than lacunae with a deviation in orientation below 8°. Moreover, increased lacuna sphericity from 0 to 0.5 to 0.7–1 led to 25%, 23%, and 13% decrease in maximum effective strains in OCYs, PCM, and ECM, respectively. We further showed that due to the presence of smaller and more round lacunae in old mice, local bone tissue strains are on average 5% lower in the vicinity of lacunae and their osteocytes of old mice compared to young. Understanding how changes in lacunar morphology affect the micromechanical environment of osteocytes presents a first step in unraveling their potential role in impaired bone mechanoresponsiveness with e.g. aging

Correlation Between Cone-Beam Computed Tomography and High-Resolution Peripheral Computed Tomography for Assessment of Wrist Bone Microstructure

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.status: publishe

Accuracy and reproducibility of mouse cortical bone microporosity as quantified by desktop microcomputed tomography

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.status: publishe