A combined study using finite element analysis technique and a long term experimental animal study was undertaken to investigate the differences in long bone remodeling when internal fixation plates with large differences in bending and axial stiffness are applied. The results of the numerical analysis indicate that internal fixation plates of higher rigidity prevent the underlying bone from carrying the normal physiological stress and thus may be a causal factor for the bone to remodel into a weaker structure following Wolff's law. The experimental study using adult mongrel dogs supports the stress analysis results. Prolonged application of a more rigid internal fixation plate to an intact long bone results in cortical bone atrophy directly beneath the plate. In the contralateral bone where a less rigid internal fixation plate is applied, significantly less effect of plate-induced osteopenia is found. The biomechanical and histological evaluations show that the more rigidly and less rigidly plated bones have similar material properties, but different structural properties.