Introduction The amputation of lower limbs and the subsequent use of a prosthesis require the adoption of new biomechanical patterns of load and gait by the patient, which may favor the onset of local or generalized bone mineral density loss. Osseo-anchored implants that allow distal weight bearing of the residuum may be able to mitigate bone mineral density loss related to amputation. The objective of this study is to determine the effect of the use of a distal weight-bearing implant on the bone mineral density of the amputated limb in relation to the nonamputated limb. Materials and Methods An interrupted time series clinical trial carried out in the Outpatient Department of Rehabilitation of the five participant hospitals. Thirteen patients with previous transfemoral amputations of traumatic, oncologic, and vascular etiology were enrolled. These patients underwent surgical implantation of an osseo-anchored implant with a distal spacer that allows a direct load on the residuum over the distal surface of the socket. Patients were followed for a 14-month period and assessed presurgically and postsurgically using dual-energy x-ray absorptiometry of the femur neck. Results The mean increase in bone mineral density for the amputated limb was 0.020 g/cm2, which represented a mean percentage increase of 3.0%. For the nonamputated limb, the mean increase in bone mineral density was 0.005 g/cm2 and the mean percentage increase was 0.5%, with eight patients showing improvements in bone mineral density. The mean percentage of bone mineral density of the amputated limb in comparison with the nonamputated limb was 70.6% preimplantation and 73.2% postimplantation, with an average increase of 2.6%. Conclusions The results of this study show an improvement in bone mineral density in individuals with transfemoral amputation 14 months after having received a distal weight-bearing implant.