A good fixation of osteosynthesis implants is crucial for a successful bone healing but often difficult to achieve in osteoporotic patients. One possible solution to this issue is the local delivery of bisphosphonates in direct proximity to the implants, A critical aspect of this method, that has not yet been well investigated, is the time course of the implant fixation following the drug release. Usual destructive mechanical tests require large numbers of animals to produce meaningful results. Therefore, a micro-finite element (microFE) approach was chosen to analyze implant fixation. In vivo micro computed tomography (microCT) scans were obtained, first weekly and later bi-weekly, after implantation of polymeric screws in the femoral condyles of ovariectomized rats. In one half of the animals, Zoledronate was released from a hydrogel matrix directly in the peri-implant bone stock, the other animals were implanted only with screws as control. The time course of the implant fixation was investigated with linear elastic microFE models that were created based on in vivo microCT scans. The numerical models were validated against experimental pullout-tests measurements in an additional cadaver study. The microFE analysis revealed a significant increase in force at yield of the Zoledronate treated group compared to the control group. The force of the treated group was 28% higher after 17 days of screw implantation, 42% higher after 31 days. The significant difference persisted until the end of the in vivo study at day 58 (p<0.01). The early onset and prolonged duration of the implant anchorage improvement that was found in this study indicates the great potential of Zoledronate-loaded hydrogel for an enhancement of osteosynthesis implant fixation in impaired bone.