The following is a two-part study. Part A evaluates biomechanically intramedullary (IM) nails vs. locking plates for fixation of femoral fractures in osteoporotic bone. Part B of this study introduces a deterministic finite element model of each construct type and investigates the probability of periprosthetic fracture of the locking plate compared with the retrograde IM nail using Monte Carlo simulation. For Part A, an extra-articular, metaphyseal wedge fracture pattern was created in 11 osteoporotic fourth-generation composite femurs. Fixation was performed with a locking plate or a retrograde IM nail. Axial, torsion and bending cyclic loading to simulate post-operative damage accumulation were performed followed by ramped load to failure. Locking plates proved to be more stable (using stiffness as the determining factor) in osteoporotic bone as observed under low load cycle conditions. However, some of these advantages were offset by a greater incidence of sudden periprosthetic fracture observed under ramped loading conditions. Cadaveric, osteoporotic femurs included as a case study also exhibited periprosthetic fracture, but failure was accompanied by catastrophic comminution of the cortex. Periprosthetic failure at the implant end including bone comminution is difficult to salvage with revision fixation. The weakened trabecular matrix and thinned cortex of osteoporotic bone may increase the incidence of periprosthetic fracture. It is, therefore, essential for the surgeon to consider all possible loading scenarios when recommending an ideal implant for the osteoporotic patient.