The osteocyte lacunar-canalicular system (LCS) serves as a mechanotransductive core where external loading applied to the skeleton is transduced into mechanical signals (e.g., fluid shear) that can be sensed by mechanosensors (osteocytes). The fluid velocity and shear stress within the LCS are affected by various loading parameters. However, the interactive effect of distinct loading parameters on the velocity and shear stress in the LCS remains unclear. To address this issue, we developed a multiscale modeling approach, combining a poroelastic finite element (FE) model with a single osteocytic LCS unit model to calculate the flow velocity and shear stress within the LCS. Next, a sensitivity analysis was performed to investigate individual and interactive effects of strain magnitude, strain rate, number of cycles, and intervening short rests between loading cycles on the velocity and shear stress around the osteocyte. Lastly, we developed a relatively simple regression model to predict those outcomes. Our results demonstrated that the strain magnitude or rate alone were the main factors affecting the velocity and shear stress;​ however, the combination of these two was not directly additive, and addition of a short rest between cycles could enhance the combination of these two related factors. These results show highly interactive effects of distinct loading parameters on fluid velocity and shear stress in the LCS. Specifically, our results suggest that an enhanced fluid dynamics environment in the LCS can be achieved with a brief number of load cycles combined with short rest insertion and high strain magnitude and rate.