While the need for employing subject-specific computational biomechanics models for treatment planning in orthopaedics is being increasingly voiced, it has not been clear when such specificity is essential and for which questions simpler models might be adequate. This study uses a novel modelling approach to generate finite element models to examine the influence of subject-specificity in the treatment of distal femur fractures. Three subject-specific finite element models are created from clinical CT scans, and the proposed approach is employed to impose identical fractures and locking plate treatments upon them. Additionally, the performance of the generic two-material model based on a Sawbones fourth generation femur is also evaluated. Interfragmentary motions, plate stresses, and strains at the screw-bone interface are examined due to a physiological loading at different stages of healing. The study finds that subject-specificity has a major effect on strains in the bone at the screw-bone interface. However, interfragmentary motions at the far cortex and plate stresses show minimal sensitivity to subject-specific factors, while near-cortical and shear interfragmentary motions are influenced by them. The influence of subject-specificity decreases as healing progresses. These results indicate that while generic approaches may be sufficient to calculate global assembly responses, material heterogeneity and subject-specific bone stock variations have a large impact on the interaction between the screws and bone. The study also shows that the proposed method, which enables manipulating bone geometry while retaining subject-specific properties, can be used to evaluate the influence of subject-specificity for other orthopaedic simulations.