  We propose a multiscale mechanobiological model of bone remodelling to
investigate the site-specific evolution of bone volume fraction across the
midshaft of a femur. The model includes hormonal regulation and biochemical
coupling of bone cell populations, the influence of the microstructure on bone
turnover rate, and mechanical adaptation of the tissue. Both microscopic and
tissue-scale stress/strain states of the tissue are calculated from macroscopic
loads by a combination of beam theory and micromechanical homogenisation.
  This model is applied to simulate the spatio-temporal evolution of a human
midshaft femur scan subjected to two deregulating circumstances: (i)
osteoporosis and (ii) mechanical disuse. Both simulated deregulations led to
endocortical bone loss, cortical wall thinning and expansion of the medullary
cavity, in accordance with experimental findings. Our model suggests that these
observations are attributable to a large extent to the influence of the
microstructure on bone turnover rate. Mechanical adaptation is found to help
preserve intracortical bone matrix near the periosteum. Moreover, it leads to
non-uniform cortical wall thickness due to the asymmetry of macroscopic loads
introduced by the bending moment. The effect of mechanical adaptation near the
endosteum can be greatly affected by whether the mechanical stimulus includes
stress concentration effects or not.
