Bone remodeling is a key player for attaining and maintaining the integrity of bone-implant systems. Remodeling is mechanically controlled and external mechanical stimulation can be conceived as an effective therapy to improve bone quality. However, in the complex context of bone regeneration following implant insertion, it is not clear whether the ability of bone to respond to mechanical loading is maintained. Here we investigated the response of implanted bone to local application of external mechanical stimulation. In vivo micro-computed tomography (micro-CT) was used to assess load-induced changes in bone remodeling and architecture following implantation in a mouse model for low bone mass. We focused on the mechanobiological response of caudal vertebrae in ovariectomized female C57BL/6J mice: special needle-shape implants were inserted into the sixth caudal vertebra (CV6) and two pins were placed in CV5 and CV7 for the application of load according to a well-established protocol (8N, 10 Hz, 15 minutes/week). Time-lapse in vivo micro-CT scans were performed weekly during the 4-week loading regime. Bone formation and resorption were assessed by registering two consecutive scans (Figure 1). Image-based micro-finite element (micro-FE) models were solved to characterize the time evolution of bone strength and to understand mechano-regulation of the implanted bone by linking local mechanical environment (characterized by strain energy density) with remodeling events. Mechanical stimulation was capable, even in the presence of the implant, of increasing bone formation and decreasing bone resorption, resulting in a net increase in bone mass and strength. The effect of mechanical loading was reduced (albeit still present) in the peri-implant region. There, the mechanical control of bone resorption was dysregulated, probably due to the need of removing microdamage caused by implant insertion. The proposed framework can be used in future studies to design and optimize loading protocols to promote peri-implant bone regeneration in osteoporotic conditions.