In clinical applications, ultrasound parameters are measured as an average value over a region of interest (ROI) or as a value at a single measurement point. Due to natural adaptation to loading conditions, trabecular bone is structurally, compositionally and mechanically heterogeneous and anisotropic. Thus, spatial variation of ultrasound parameters within ROI may contain valuable information on the mechanical integrity of trabecular bone. However, this issue has not been thoroughly investigated. In the present study, we aimed at investigating the significance of the spatial variation of ultrasound parameters for the prediction of mechanical properties of human trabecular bone. For this aim, parametric maps of apparent integrated backscattering (AIB), integrated reflection coefficient (IRC), speed of sound (SOS), average attenuation (AA) and normalized broadband ultrasound attenuation (nBUA) were calculated for femoral and tibial bone cylinders (n = 19–20). Further, the effect of time window length on the AIB, variation of AIB within ROI and association between AIB and bone mechanical properties were characterized. Based on linear correlation analysis, spatial variation of AIB, assessed as standard deviation of measurements within ROI, was a strong predictor of bone ultimate strength (r = −0.82, n = 19, p < 0.01). Further, the time window length affected absolute values of AIB and strength of correlation between AIB and bone ultimate strength. Interestingly, linear combination of mean IRC and spatial variation of AIB within ROI was the strongest predictor of bone ultimate strength (r = 0.92, n = 19, p < 0.01). In conclusion, our findings suggest that the measurement of two-dimensional parametric maps of ultrasound parameters could yield information on bone status not extractable from single point measurements. This highlights the potential of parametric imaging in osteoporosis diagnostics.