Quantitative ultrasound (QUS) measurement was shown to have the ability to predict the principal structural orientation (PSO) with a spherical bone model. It is hypothesized that with a cubic bone model, integrated transmission-reflection QUS measurement can predict the PSO and therefore improved the correlation with the mechanical and structural parameters. Twelve trabecular bone cubes were harvested from bovine distal femur. Compression testing and µCT of 30 µm resolution were performed to obtain the mechanical and structural parameters. QUS measurement was performed on the transverse plane in a range of angles, from -30̊ to 30̊ to medial-lateral orientation at 5̊ increment. For each angle, reflection mode was used to measure the thickness of the sample in the specific scanning angle. Then, the sample thickness was used to normalize the transmission mode measurement in the same angle. The thickness measured by reflection mode QUS was highly correlated to the results measured by caliber (slope = 0.99, R2 = 0.85). Compared to the traditional transmission mode, the correlation coefficients (R2) between transmission-reflection mode ultrasound velocity versus mechanical and structural parameters were improved (elastic modulus, 0.62 to 0.73; SMI, 0.74 to 0.90; BV/TV, 0.75 to 0.85; Tb.N, 0.60 to 0.75; Tb.Sp, 0.66 to 0.73).