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The mechanical behavior of long bones and fractures has been under investigation for many decades due to its complexity and clinical relevance. In this paper, we report a new subject-specific methodology to predict and analyze the mechanical behavior of the soft tissue at a bone interface with the intent of identifying the presence and location of bone abnormalities with high accuracy, spatial resolution, and contrast. The proposed methodology was tested on both intact and fractured rabbit femur samples with finite element-based 3-D simulations, created from actual femur computed tomography data, and ultrasound elastography experiments. The results included in this study demonstrate that elastographic strains at the bone/soft tissue interface can be used to differentiate fractured femurs from the intact ones on a distribution level. These results also demonstrate that coronal plane axial shear strain creates a unique contrast mechanism that can be used to reliably detect fractures (both complete and incomplete) in long bones. Kruskal–Wallis test further demonstrates that the contrast measure for the fracture group (simulation: 2.1286±0.2206; experiment: 2.7034 ± 1.0672) is significantly different from that for the intact group (simulation: 0 ± 0; experiment: 1.1540±0.6909) when using coronal plane axial shear strain elastography ($p$ < 0.01). We conclude that: 1) elastography techniques can be used to accurately identify the presence and location of fractures in a long bone and 2) the proposed model-based approach can be used to predict and analyze strains at a bone fracture site and to better interpret experimental elastographic data. [ABSTRACT FROM AUTHOR]