en Orthopedic Surgery Orthopedic Surgery Original Research Original Research <p> <strong> Abstract </strong></p><p> <strong> Introduction: </strong>Inflammation and wear debris may be responsible for bone lysis </p><p>  and subsequent lost in aseptic arthroplasty. Prostaglandin E2, platelet activating factor, </p><p>  and histamine are important mediators of inflammatory cells. We studied </p><p>  histopathological changes of cement-bone interface after using specific antagonists </p><p>  of these mediators. </p><p> <strong> Methods: </strong>Left and right tibiae of 120 rats in ten groups were drilled. The left side </p><p>  was filled with polymethylmethacrylate and the right side was used as control. The </p><p>  first three groups respectively received 1mg/kg, 10mg/kg, and 25mg/kg of terfenadine, </p><p>  the second three groups respectively received 0.08mg/kg, 0.32mg/kg, and </p><p>  0.64mg/kg of alprazolam, and the third three groups respectively received 1mg/kg, </p><p>  5mg/kg, and 25mg/kg of naproxen. The tenth group received no drug and served as </p><p>  the control group. The animals were killed after 16 weeks and studied by one pathologist. </p><p> <strong> Results: </strong>Cellular reaction in the left side was significantly more than the right side </p><p>  in all cases. Medium and high doses of terfenadine and naproxen and high doses of </p><p>  alprazolam could also significantly decrease giant cells and histiocytes. </p><p> <strong> Conclusion: </strong>Increased cellular reaction in the cement-bone interface was suppressed </p><p>  by administration of PGE2, PAF, and histamine specific inhibitors. The use </p><p>  of these agents may induce retardation of the bone loss associated with early prosthetic </p><p>  loosening. </p><p>  </p> PMMA, arthroplasty, aseptic loosening, PGE2, PAF, histamine, terfenadine, alprazolam, 64 69 http://mjiri.iums.ac.ir/browse.php?a_code=A-10-1-34&slc_lang=en&sid=1 Hossein Farahini 20031947532846001790 20031947532846001790 No Rasool-e-Akram General Hospital, Iran University of Medical Sciences, Tehran, Iran. Mehdi Moghtadaei 20031947532846001791 20031947532846001791 No Rasule-Akram General Hospital, Iran University of Medical Sciences, Tehran, Iran. Ehsan Akbarian eakbarian@gmail.com 20031947532846001792 20031947532846001792 Yes Karolinska Institutet Stockholm, Sweden. Mohammad Reza Pazouki 20031947532846001793 20031947532846001793 No Department of Physiology, Iran University of Medical Sciences. Mahdi Zangi 20031947532846001794 20031947532846001794 No Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden. Pezhman Nayersabeti 20031947532846001795 20031947532846001795 No Rasule-Akram General Hospital, Iran University of Medical Sciences. Amir Shaghaghi 20031947532846001796 20031947532846001796 No Rasule-Akram General Hospital, Iran University of Medical Sciences.