Abstract:A partial review is proposed on the existing literature for the research performed in orthopedic implant used as drug delivery system. In the first part, an evaluation is given on the clinical need to deliver a drug in the surrounding of an implant. Secondly, a review of the clinical situation is developed for implants already used as drug delivery system. Experimental works performed for local delivery are reported. In particular, a description is given on the in vitro and in vivo studies where the implant is coated with different proteins or drugs. Finally, a conclusion is proposed on the next step in the development of orthopedic implant as drug delivery system mentioning also the industrial situation.Keywords: Orthopedic implant, local delivery, drug, bone remodelling.
IS THERE A CLINICAL NEED FOR LOCAL DELIVERY OF DRUG AROUND ORTHOPEDIC IMPLANT?Orthopedic practice recently enters a new area by considering use of drugs to enhance the fixation of implants. The rational behind this approach is to keep the bone around the implant as the trend observed clinically is a peri-implant bone resorption for hip or knee implants. Studies over the past 2 decades have strongly implicated osteoclasts as the major cause of the bone lysis leading to implant failure [1,2]. Different activation pathways of osteoclasts have been identified and in particular the RANKL/OPG/RANK pathway has been given much interest [3]. Decreasing the catabolic bone activity would then be a good strategy to avoid peri-implant bone loss. The drug of choice so far is of bisphosphonate type and several clinical trials have been performed and effectively show a reduction of peri-implant bone loss in treated groups [4][5][6]. Systemic injections of a drug may then be potentially interesting to control the bone remodeling around orthopedic implant, however this mode of delivery may not be optimal.The failure of an orthopedic implant is strongly correlated to its bone fixation [7]. When an implant is used without cement, stability immediately after the surgery must be obtained, a process called primary fixation, followed by a long-term fixation, a process called secondary fixation. A race on fixation quality is then engaged with the concept that the faster the secondary implant fixation is obtained, the better will be the implant outcome. The primary fixation being insured by the press-fit technique, the drug should then target the secondary fixation with the goal of reducing the bone loss. We should not be mislead by the term secondary fixation which is indeed already happening during the first months following the surgery. This has been shown in a clinical study where up to 14% bone loss arose during the first three months after total hip arthroplasties [8]. In parallel, rapid early migrations have been detected by roentgen stereophotogrammetry in many asymptotic hips, often as early as four months postoperatively [9]. The migrations have been found to predict an increased risk of clinical loosening.Systemic delivery of bisphosphonate by sever...