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Osteoporosis is a potential risk factor affecting implant stability following total joint arthroplasty. Bisphosphonates are potent inhibitors of osteoblastic bone resorption, and vitamin D is an important hormone involved in the regulation of calcium metabolism. We investigated the benefit of preoperative treatment with alendronate, vitamin D (calcitriol), or a combination of these substances on fixation of hydroxyapatite-coated implants in an ovariectomized rat model of osteoporosis.Of sixty-four female rats in the study, fifty-six underwent ovariectomy and eight, a sham operation. A hydroxyapatite-coated femoral implant and an uncoated implant were implanted in all rats seven months after the ovariectomy or the sham operation. Of the fifty-six rats that underwent ovariectomy, eight served as the control group. The remaining forty-eight were treated with alendronate, calcitriol, or a combination of these agents either starting eight weeks before implantation of the rod or starting immediately after implantation. The treatment was continued until four weeks after the implantation. Four weeks after the implantation, the total and cancellous bone mineral density at the proximal part of the tibia and the shear strength of the bone-implant interface were measured in all rats.Although total bone mineral density increased in all of the alendronate-treated groups, compared with that in the ovariectomized control group, cancellous bone mineral density increased only in the group pretreated with both alendronate and calcitriol. The implant stability in the ovariectomized control rats was significantly decreased compared with that in the sham-operation rats. While treatment with alendronate only or calcitriol only did not improve the stability of the implants, treatment with a combination of alendronate and calcitriol, starting preoperatively, significantly improved the stability of the hydroxyapatite-coated implants.Treatment with a combination of alendronate and calcitriol, starting preoperatively, can improve cancellous bone mineral density and the stability of hydroxyapatite-coated implants in an osteoporotic rat.Clinical Relevance: Patients who receive alendronate and vitamin D for the treatment of osteoporosis before cementless joint arthroplasty may have more stable fixation of the implants.