Increases in lacuna size also led to increased lacunar strains. Lacunar strains were lower for the osteocytes aligned along the loading axis compared to those aligned perpendicular to axis. Overall, lacunar strains decreased by 14% in the cell body, 15% in the fluid space region and 25% in the perilacunar space as the perilacunar modulus increased, indicating a stress shielding effect. Finally, 3-D lacunar models were created using confocal image stacks from mouse femurs to determine the theoretical strain in the lacunae represented by realistic geometries. Secondly, a nanoscale FE model was built using known osteocyte dimensions to determine the predicted strains in the perilacunar matrix, fluid space, and cell body regions. A parametric analysis was performed by steadily increasing the perilacunar modulus (5, 10, 15, and 20В GPa). In this study, a multi-scale computational approach was used to first create an osteocyte FE model at the microscale level to examine both the theoretical lacunar and perilacunar strain responses based on two parameters: 1) lacunar orientation and 2) lacunar size. The number of osteocytes in the 3D confocal scan models ranged from five to seventeen. However, all the FE models in this preliminary study consist of multiple osteocytes. The osteocytes in our microscale and nanoscale models have an idealized oval shape and some are based on confocal scans.

We hypothesized that variation in size and orientation of the osteocyte lacunae within bone would give rise to micro heterogeneity in the strain fields that could better explain the observed patterns of osteocyte activation following load. Finite element models by other groups included more details, such as canaliculi, but all were done on models consisting of a single osteocyte. Several studies have investigated the strain responses of osteocyte lacunae using finite element (FE) models, but many were limited by the use of idealized geometries (e.g., ellipsoids) and analysis of a single osteocyte. However, this process of osteocyte activation appears heterogeneous since it occurs in sub-populations of osteocytes, even within regions predicted to be experiencing similar global strain magnitudes determined based on traditional finite element modeling approaches.

In response to changing mechanical loads (strain) the osteocytes signal to cells on the bone surface. Osteocytes initiate intracellular responses including activating the Wnt/ОІ-catenin signaling pathway after experiencing mechanical forces. Osteocytes are thought to be the primary mechanosensory cells within bone, regulating both osteoclasts and osteoblasts to control load induced changes in bone resorption and formation.

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