Introduction:Limb-salvage surgery using endoprosthetic replacements (EPRs) is frequently used to reconstruct segmental bone defects, but the reconstruction longevity is still a major concern. In EPRs, the stem-collar junction is the most critical region for bone resorption. We hypothesised that an in-lay collar would be more likely to promote bone ongrowth in Proximal Femur Reconstruction (PFR), and we tested this hypothesis through validated Finite Element (FE) analyses simulating the maximum load during walking.Methods:We simulated three different femur reconstruction lengths (proximal, mid-diaphyseal, and distal). For each reconstruction length one in-lay and one traditional on-lay collar model was built and compared. All reconstructions were virtually implanted in a population-average femur. Personalised Finite Element models were built from Computed Tomography for the intact case and for all reconstruction cases, including contact interfaces where appropriate. We compared the mechanical environment in the in-lay and on-lay collar configurations, through metrics of reconstruction safety, osseointegration potential, and risk of long-term bone resorption due to stress-shielding.Results:In all models, differences with respect to intact conditions were localized at the inner bone-implant interface, being more marked in the collar-bone interface. In proximal and mid-diaphyseal reconstructions, the in-lay configuration doubled the area in contact at the bone-collar interface with respect to the on-lay configuration, showed less critical values and trends of contact micromotions, and consistently showed higher (roughly double) volume percentages of predicted bone apposition and reduced (up to one-third) percentages of predicted bone resorption. In the most distal reconstruction, results for the in-lay and on-lay configurations were generally similar and showed overall less favourable maps of the bone remodelling tendency.Discussion:In summary, the models corroborate the hypothesis that an in-lay collar, by realising a more uniform load transfer into the bone with a more physiological pattern, creates an advantageous mechanical environment at the bone-collar interface, compared to an on-lay design. Therefore, it could significantly increase the survivorship of endo-prosthetic replacements.