engleski

New insights into aseptic loosening of the total hip arthroplasty: an emerging role of genetics and proteomic

Introduction of the total hip arthroplasty (THA) techniques has revolutionized the treatment of a number of states resulting in hip dysfunction by conveying considerable improvements in patients’ ability and quality of life. As in the case of any medical procedure, patients undergoing THA may experience complications - early (e.g., infections, dislocations) or late. Aseptic loosening of the stem or the acetabular cup, or both, is the major late complication of THA. It is a consequence of the so-called particle disease: implant wear debris accumulating at the prosthesis interface due to friction activates phagocytes and induces an aseptic inflammation mediated by a number of cellular and humoral factors that eventually results in bone demineralization, prosthesis instability, dysfunction and pain. Whilst the early complications of THA are largely preventable by adherence to the principles of good clinical practice, attempts to prevent aseptic instability by suppressing inflammation and/or by preventing/improving bone loss have not been successful. The actual incidence of aseptic instability and “survival” of THA implants has not been uniformly estimated. It is more likely to occur earlier after arthroplasty with certain types of prosthetic devices/materials (e.g., uncoated cups or stems), with less experienced surgeons, in patients suffering from developmental hip dysplasia or complications of the femoral neck facture (vs. primary osteoarthritis), in obese patients, in men vs. women, in younger patients, in cases with more pronounced debris accumulation. However, all these factors cumulatively explain only a minor portion of variability of occurrence (and timing) of aseptic instability after THA – it may occur with any type of prosthetic material, in any age group, irrespective of surgeon's skill or underlying disease and with minimum accumulated debris (whereas THA may be perfectly stable despite a considerable debris accumulation). Consequently, “individual susceptibility” to aseptic loosening determined by factors other than demographic or morbidity characteristics has been well recognized. During the past five years several smaller studies appeared that tried to define the “genetic background” of “individual susceptibility” to aseptic loosening. They all followed the same logic – genes encoding for mediators of inflammation and/or bone remodeling, and particularly those with known polymorphisms affecting expression/activity, appear to be good candidates in this respect. So far, several significant associations have been found and the approach apparently has a great potential – at least theoretically, it might result in ability of reliable individual risk predictions that might influence the choice of prosthetic materials, post-surgical recovery programs or pharmacological treatments. However, the work is at very early stages and future efforts should: a) define the best genetic predictors (strength of association) ; b) provide evidence of consistency (different populations, different combinations of genetic, morbidity, demographic characteristics and prosthetic materials) ; c) define functional links between genetic markers and aseptic instability (biological plausibility). The rapidly developing techniques of proteomic analysis are likely to be useful in this respect – they may help to identify the best candidate genes and to recognize functional relationships.

total hip arthroplasty (THA)

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