Computational model for the underlying mechanisms regulating bone loss by mechanical unloading and estrogen deficiency

The objective of this paper is to investigate the different effects of disuse and estrogen deficiency on bone loss and the underlying mechanisms. A mechanical-biological factors coupled computational model was built to simulate different patterns of bone loss induced in female rats by hind limb unloading, ovariectomy, or both in an animal study. A remodeling analysis was performed on a representative cross section of 6 mm of cancellous bone in the distal femoral metaphysis of the rats. The BMU activation frequency, the refilling rate, and the principal compressive strain in the state of mechanical unloading and estrogen deficiency were simulated to interpret the underlying mechanisms. Simulated bone loss patterns due to mechanical unloading, estrogen deficiency, or both all corresponded with the experimental observations. The results show that mechanical unloading and estrogen deficiency cause different bone loss patterns; moreover, mechanical unloading induces a greater degree of bone loss than estrogen deficiency, which can lead to improved treatment and prevention strategies for osteoporosis.