Background and HypothesisMorphologic analysis of the proximal humerus has been performed to provide information about regions of best bone quality for stemless implant fixation. However, implant design-related bone analysis regarding primary fixation strength has not been reported. The purpose of this study was to investigate bone volume fraction (BV/TV) and bone mineral density (BMD) in the spatial vicinity of humeral implant fixation and biomechanical performance following placement of two different stemless RSA designs. It was hypothesized that peripheral expandable implant fixation (PEF) would result in residual peri-implant bone with higher BMD and BV/TV and higher fixation strength compared to a central-hexagonal impaction fixation (CHIF) design. MethodsOverall 25 human cadavers were prepped for stemless RSA using either a CHIF (n = 5) or PEF design (n = 20). Micro computed tomography scans were obtained post-preparation to analyze overall BV/TV and BMD in the anchoring region of 2 stemless implant designs. Bone volumes of paired specimens (each group n = 5) were further segmented and divided into three even planar subsections along the implantation direction with four additional radial sectors, each according to their anterior-posterior and medial-lateral direction. Following implantation, biomechanical testing was performed to evaluate ultimate failure load and stiffness of the 2 implants. ResultsPostpreparation paired humeral bone analysis revealed significantly greater residual peri-implant BMD (P< .026) and higher BV/TV for PEF. Overall linear correlation between residual BMD and BV/TV showed good coefficients of determination (R2 > 0.69) with significantly higher bone density for PEF (P= .003). Further division in proximal to distal planar subsections of paired specimens showed overall statistically higher BMD and BV/ TV for PEF (at least P< .002). Except from the posterior sector, BMD and BV/TV of overall and specific radial sectors within planar subvolumes were significantly higher for PEF. Biomechanical testing revealed increased ultimate loads (−818 ± 282 N vs. −535 ± 144 N; P= .081) and stiffness (898 ± 106 N/mm vs. 431 ± 121 N/mm; P< .001) with smaller tilting angles at failure for PEF compared to CHIF. A linear relationship between normalized failure load by the implant size and combined bone parameter (BV/TV*BMD) provided an accuracy in the order of R2 > 0.89 with significantly higher primary stability for PEF (P = .046). ConclusionImplant design in stemless RSA affects residual bone quality in the anchoring region and primary fixation strength. Peripheral implant anchoring along the insertion direction provides significantly higher residual peri-implant BMD and BV/TV to achieve improved primary fixation with a radial expandable anchoring implant compared to a central-hexagonal impacted design. Level of EvidenceBasic Science Study; Anatomy Study; Imaging; Biomechanics