A bone loading estimation algorithm was previously developed that provides
in vivo
loading conditions required for
in vivo
bone remodelling simulations. The algorithm derives a bone's loading history from its microstructure as assessed by high-resolution (HR) computed tomography (CT). This reverse engineering approach showed accurate and realistic results based on micro-CT and HR-peripheral quantitative CT images. However, its voxel size dependency, reproducibility and sensitivity still need to be investigated, which is the purpose of this study. Voxel size dependency was tested on cadaveric distal radii with micro-CT images scanned at 25 µm and downscaled to 50, 61, 75, 82, 100, 125 and 150 µm. Reproducibility was calculated with repeated
in vitro
as well as
in vivo
HR-pQCT measurements at 82 µm. Sensitivity was defined using HR-pQCT images from women with fracture versus non-fracture, and low versus high bone volume fraction, expecting similar and different loading histories, respectively. Our results indicate that the algorithm is voxel size independent within an average (maximum) error of 8.2% (32.9%) at 61 µm, but that the dependency increases considerably at voxel sizes bigger than 82 µm.
In vitro
and
in vivo
reproducibility are up to 4.5% and 10.2%, respectively, which is comparable to other
in vitro
studies and slightly higher than in other
in vivo
studies. Subjects with different bone volume fraction were clearly distinguished but not subjects with and without fracture. This is in agreement with bone adapting to customary loading but not to fall loads. We conclude that the
in vivo
bone loading estimation algorithm provides reproducible, sensitive and fairly voxel size independent results at up to 82 µm, but that smaller voxel sizes would be advantageous.