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FRONTIERS IN TOTAL JOINT REPLACEMENT

Joshua J. Jacobs, M.D.

Crown Family Professor of Orthopaedic Surgery

Rush University Medical Center

Chicago, IL

Total joint arthroplasty is one of the success stories of modern medicine and has led to relief of suffering for millions of people with end stage disease involving major joints of the upper and lower extremities.  While overall this procedure has been very successful, there is a finite incidence of prosthesis-related complications, the most prevalent of which are osteolysis and aseptic loosening.  These complications are more commonly observed in the so-called high-demand patient population.  That is, young active individuals with life expectancies exceeding two decades.  Unfortunately, currently available modalities for monitoring prosthetic performance in this at-risk population are generally limited to patient questionnaires, radiographs, and physical examination.  These are relatively crude tools that are helpful for diagnosing implant-related problems only at relatively advanced stages. 

Over the last two decades, orthopedic researchers have developed a far more detailed understanding of the molecular pathways involved in osteolysis and aseptic loosening.  As these pathways are elucidated, potential therapeutic targets as well as systemic biomarkers are identified. If the appropriate clinical correlates can be established, these biomarkers may herald the onset of osteolysis and aseptic loosening at relatively early stages, prior to clinical symptomatology and/or radiographic changes.  The development and validation of such biomarkers would have tremendous impact on orthopedic clinical practice in that individuals can be identified that may benefit from closer surveillance and/or therapeutic intervention to prevent the progression of the osteolytic and loosening processes.  Furthermore, this line of research may facilitate the development of preoperative screening tools to identify those patients at risk for prosthetic failure and those patients who may be susceptible to certain materials or material combinations. 

Potential biomarkers of prosthetic performance include serum and urine metal ion levels, serum cytokines, serum and/or urine collagen degradation products, vitamin D metabolites, osteoclast activators, chemokines, matrix metalloproteinases, peripheral blood lymphocyte responsiveness, and gene microarrays.  There is a developing literature on each of these potential biomarkers. However, at the present time none are sufficiently validated for routine clinical use.  Further research correlating prosthetic performance and outcome with the systemic concentration of these biomarkers will help establish their role in the armamentarium of the orthopedic surgeon monitoring patients with total joint replacements.