This study was designed to compare the compressive mechanical properties of filler materials, Wood’s metal, dental stone, and polymethylmethacrylate (PMMA), which are widely used for performing structural testing of whole vertebrae. The effect of strain rate and specimen size on the mechanical properties of the filler materials was examined using standardized specimens and mechanical testing. Because Wood’s metal can be reused after remelting, the effect of remelting on the mechanical properties was tested by comparing them before and after remelting. Finite element (FE) models were built to simulate the effect of filler material size and properties on the stiffness of vertebral body construct in compression. Modulus, yield strain, and yield strength were not different between batches (melt-remelt) of Wood’s metal. Strain rate had no effect on the modulus of Wood’s metal, however, Young’s modulus decreased with increasing strain rate in dental stone whereas increased in PMMA. Both Wood’s metal and dental stone were significantly stiffer than PMMA (, , and , respectively). PMMA had greater yield strength than Wood’s metal ( and ). All materials exhibited size-dependent modulus values. The FE results indicated that filler materials, if not accounted for, could cause more than 9% variation in vertebral body stiffness. We conclude that Wood’s metal is a superior moldable bonding material for biomechanical testing of whole bones, especially whole vertebrae, compared to the other candidate materials.