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This study investigated the effect of locally immobilized bisphosphonates and systemic estrogen replacement therapy on fixation of hydroxyapatite-coated screws in ovariectomized rats.Twelve weeks after being ovariectomized, each of the 20 rats received 2 hydroxyapatite-coated screws in the proximal tibia, with or without immobilized bisphosphonates. Half of the animals also received subcutaneous injections of 17β-estradiol. Thus, there were 4 groups: control, estrogen, bisphosphonates, and estrogen plus bisphosphonates. Tibiae with screws were measured by microscopic computerized tomography and push-out test 12 weeks after implantation.Combined treatment had the strongest effects, with the bone volume ratio around screws and the percentage of osteointegration significantly increased by 2.3-fold and 1.9-fold and the push-out force by 3.3-fold compared with untreated control samples. Monotherapy also enhanced the fixation of screws, although less.Systemic estrogen replacement therapy and locally immobilized bisphosphonates had additive effects on fixation of hydroxyapatite-coated screws in ovariectomized rats.