Genetska podloga aseptičke nestabilnosti totalne endoproteze zgloba kuka [Genetic background of aseptic instability after total hip arthroplasty]

Kolundžić, Robert and Trkulja, Vladimir and Orlić, Dubravko (2012) Genetska podloga aseptičke nestabilnosti totalne endoproteze zgloba kuka [Genetic background of aseptic instability after total hip arthroplasty]. Liječnički vjesnik, 134 (7-8). pp. 218-223. ISSN 0024-3477

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Abstract

Total hip arthroplasty (THA) has dramatically improved the treatment of an entire range of hip joint diseases. On the other hand, however, it has favored the development of a new disease - periprosthetic osteolysis with a consequent instability of THA. Aseptic instability is the major late complication of THA and the main reason of its malfunction. Molecular and cellular mechanisms of this complication have been thoroughly studied. The importance of prosthetic materials and design have been clearly demonstrated. However, existence of individual susceptibility to development of this complication that is determined neither by endoprothesis properties nor by demographic or morbidity characteristics of a patient has also been recognized. In the recent years, several smaller studies have tried to define the "genetic background of the individual susceptibility" towards the development of aseptic instability. All these studies followed the same logic - they searched for a link between the complication and genes coding for mediators of inflammation and/or bone remodeling, particularly those with known polymorphisms that influence expression/activity. Several associations have been found indicating, at least theoretically, a potential of developing a system of relatively reliable individual risk prediction, which in turn could result in individualized choice of prosthetic material, postoperative therapy programs and medication therapy. However, this research is at an early stage and future efforts should be focused on a) identification of genetic markers - reliable predictors and b) identification of functional links between particular genetic markers and aseptic instability. It is impossible to meet these goals without application of techniques of proteomic analysis.

Abstract in Croatian

Ugradnja totalne endoproteze zgloba kuka dramatično je unaprijedila liječenje niza bolesti zgloba, no ta je metoda, s druge strane, pogodovala nastanku nove bolesti – periprostetske osteolize s posljedičnom aseptičkom nestabilnosti endoproteze. Aseptička nestabilnost najčešća je kasna komplikacija ugradnje endoproteze i glavni uzrok njezine nestabilnosti, odnosno nefunkcionalnosti. Molekularni i stanični mehanizmi ove komplikacije vrlo su opsežno istraženi i jasno je pokazana važnost protetskog materijala i oblikovanja u njezinu nastanku. No, prepoznata je i činjenica da postoji određena individualna sklonost njezinu nastanku koja nije određena ni svojstvima endoproteze ni demografskim ili morbiditetnim svojstvima bolesnika. Posljednjih je godina provedeno nekoliko manjih studija koje su pokušale definirati »genetsku podlogu individualne sklonosti« aseptičkoj nestabilnosti. Sve su slijedile istu logiku – tražena je veza između komplikacije i gena koji kodiraju za medijatore upale i/ili koštanog remodeliranja, posebice onih s poznatim polimorfizmima koji utječu na ekspresiju/aktivnost. Do sada su pronađene neke združenosti, što ovom pristupu daje, barem teorijski, potencijal da rezultira sustavom razmjerno pouzdanog predviđanja individualnog rizika, koji bi pak mogao utjecati na individualizaciju u odabiru protetskih materijala, programa postoperativne terapije ili terapije lijekovima. Međutim ova su istraživanja u ranoj fazi. Budući napori trebali bi biti usmjereni prema a) definiranju genskih markera – pouzdanih prediktora i b) definiranju funkcionalnih veza između određenih genskih markera i aseptičke nestabilnosti. Ti su ciljevi neostvarivi bez primjene tehnika proteomske analize.

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