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The effects of bone cement placement, volume, and bone density on the degree of biomechanical reinforcement on cadaveric vertebral bodies were studied using experimentally calibrated detailed finite element models.To investigate the efficacy of prophylactic vertebroplasty on intact vertebral bodies with respect to biomechanical recovery and fracture risk reduction.Vertebroplasty is a potentially effective fracture prevention treatment, but the risk of complications due to cement leakage must be minimized. Therefore, the least amount of bone cement required to improve vertebral strengths to low fracture risk levels need to be determined.Six different polymethyl methacrylate volumes—1, 2.5, 3.5, 5, 7.5 and 9 cm3—were virtually implanted into previously validated vertebral body finite element models, following bipedicular and posterolateral vertebroplasty approaches. Stiffness and fracture load of the treated and untreated vertebral body models under uniaxial compression were determined.Greater augmentation effects were observed for vertebral bodies with average quantitative computed tomography densities below 0.1 g/cm3 injected with polymethyl methacrylate volumes higher than 20% compared to lower injection volumes and higher bone densities, as well as for the bipedicular approach versus posterolateral. Vertebral bodies at high risk of fracture required at least 20% fill of polymethyl methacrylate to improve the mechanical integrity of vertebral bodies to low fracture risk levels, whereas 5% to 15% polymethyl methacrylate volumes were needed for the medium-risk vertebral bodies.Prophylactic vertebroplasty can be effective in reducing fracture risk. However, for the polymethyl methacrylate volume (20%) required for the successful reinforcement of high-risk vertebral bodies, the risk of complications will be as high as that for current vertebroplasty procedure for fracture repair. Therefore, alternative materials have to be investigated for prophylactic vertebroplasty. Furthermore, bipedicular vertebroplasty is the recommended approach due to its higher strengthening effect and easier surgical access than the posterolateral case.