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Synchrotron X-ray phase nano-tomography-based analysis of the lacunar–canalicular network morphology and its relation to the strains experienced by osteocytes in situ as predicted by case-specific finite element analysis

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Abstract

Osteocytes are hypothesized to regulate bone remodeling guided by both biological and mechanical stimuli. Morphology of the lacunar–canalicular network of osteocytes has been hypothesized to be strongly related to the level of mechanical loading and to various bone diseases. Finite element modeling could help to better understand the mechanosensation process by predicting the physiological strain environment. The aims of this study were to (i) quantify the lacunar–canalicular morphology in the cortex of the human femur; (ii) predict the in situ local deformations around and in osteocytes by means of case-specific finite element models; and (iii) investigate the potential relationship between morphology and deformations. Human femoral cortical bone samples were imaged using synchrotron X-ray phase nano-tomography with 50 nm voxel size. Rectangular volumes of interest were selected to contain single osteocyte lacunae and the surrounding matrix. Lacunar–canalicular morphology was quantified and the cell geometry was artificially reconstructed based on a priori assumptions. Finite element models of the volumes of interest were generated, containing the extracellular matrix, osteocyte and peri-cellular matrix, and subjected to uniaxial compression. The morphological analysis revealed that canalicular number was dictated by lacunar size, that the spacing of canaliculi fell within a narrow range, suggesting that these pores are well distributed throughout the bone matrix and indicated the trend that lacunae at the outer osteon boundary were less elongated than others. No apparent relationship was found between the morphological parameters and the predicted strains. The globally applied strain was amplified locally by factors up to 10 and up to 70 in the extracellular matrix and the in cells, respectively. Cell deformations were localized mainly at the body–dendrite junctions, with magnitudes reaching the in vitro stimulatory threshold reported for osteocytes.

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Acknowledgments

The authors acknowledge the European Synchrotron Radiation Facility for allocating the beam time on ID22-NI within the experiment MD672. We thank Dr. Peter Cloetens for his excellent support during these measurements. We thank Dr. Enrico Dall’Ara for his help with sample preparation. PV gratefully acknowledges the European Union for providing funding through the grant PCIG09-GA-2011-293419. BH and NM are thankful for being supported by the BSRT. This work has been conducted within the European Associated Laboratory ‘Ultrasound Based Assessment of Bone’ and was partially supported by the Deutsche Forschungsgemeinschaft (SPP1420, grant Ra1380/7), by the LabEX PRIMES (‘Physics Radiobiology Medical Imaging and Simulation’) of the Universit de Lyon and by the French Agence Nationale de la Recherche.

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  1. Julius Wolff Institute, Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 , Berlin, Germany

    Peter Varga, Bernhard Hesse, Susanne Schrof, Nils Männicke & Kay Raum

  2. European Synchrotron Radiation Facility, Grenoble, France

    Bernhard Hesse, Max Langer, Heikki Suhonen, Alexandra Pacureanu & Françoise Peyrin

  3. Creatis CNRS 5220, Inserm U1044, INSA-Lyon, UCB, Université de Lyon, Lyon, France

    Max Langer & Françoise Peyrin

  4. Centre for Image Analysis and Science for Life Laboratory, Uppsala University, Uppsala, Sweden

    Alexandra Pacureanu

  5. Institute of Lightweight Design and Structural Biomechanics, Vienna University of Technology, Vienna, Austria

    Dieter Pahr

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  1. Peter Varga
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Varga, P., Hesse, B., Langer, M. et al. Synchrotron X-ray phase nano-tomography-based analysis of the lacunar–canalicular network morphology and its relation to the strains experienced by osteocytes in situ as predicted by case-specific finite element analysis. Biomech Model Mechanobiol 14, 267–282 (2015). https://doi.org/10.1007/s10237-014-0601-9

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