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Combined Hind Limb Suspension and sRANK-L on Bone Strength in Mice by Finite Element Analysis: Effects of Anatomic Model Height

With commercial space travel on the horizon, it is important to understand how the microgravity environment of space effects bone strength. The reduction in skeletal loading is known to cause a rapid loss in bone density. How this corresponds to losses of bone strength is not well known, especially when combined with the osteoporotic effects of aging. In this study, a mouse model of hind limb suspension (HLS) was used to simulate the effects of gravitational unloading. This was combined with soluble receptor activator of nuclear factor kappa beta ligand (sRANK-L), which simulates age related osteoporosis. The proximal region of the tibia in mouse legs was scanned in-vivo pre-treatment as well as at the conclusion of the study with high resolution micro computed tomography (µCT). Subject specific finite element (FE) models were constructed from these 3D images to assess bone strength by simulating mechanical loading on these bone microstructures. Parameters indicative of bone strength obtained from the FE models were bone volume, stiffness, structural efficiency, and the 10th and 90th percentile nodal Von-Mises Stresses. Additionally, a model sensitivity analysis was performed to assess how these parameters varied with changes in anatomic model height. In regards to FE stiffness, HLS resulted in a 31% decline, sRANK-L resulted in a 16.8% decline, and HLS combined with sRANK-L (HLS+sRANK-L) resulted in a 38.6% decline. One interesting finding is that HLS caused a reduction in both bone stiffness and bone structural efficiency, while sRANK-L did not cause changes in bone structural efficiency, suggesting the importance of skeletal loading for maintaining bone health. In addition, sRANK-L combined with HLS caused an additional decline in bone stiffness, but did not further alter bone structural efficiency. In conclusion, this study shows that depending on the cause of osteoporosis, bone strength changes are not necessarily proportional to bone density changes. Thus, it is important to develop new clinical bone assessments beyond the current bone density measurement.Clinical Relevance— These parameters are associated with the microstructural mechanics of bone, and understanding how strength is decreased on a structural level may lead to the development of in-vivo bone strength testing clinically.