The use of prosthetic implants for joint replacement is one of the most significant successes of orthopaedic surgery and led to improvement of the quality of life of may patients. It is however known that these implants are not built to last forever. One of the main complications occurring in the long term after, for example, hip replacement surgery, is aseptic loosening. This occurs because of periprosthetic osteolysis and, although a few prognostic risk factors have been identified, most of them show inconsistent results.
A few in vitro studies on experimental aseptic loosening suggested that some genetic factors may be important as prognostic markers. The authors of the study presented here, started with the evidence that some polymorphisms such as those that influence the expression of IL6, and TNFα, influence the susceptibility to total hip replacement failure. Bachman and colleagues focused on a protein involved in signal transduction downstream of many receptors including IL6 and the parathyroid hormone. This protein is the ubiquitously expressed G-protein Gαs whose signal transduction function is to increase intracellular cAMP levels. The Gαs/cAMP pathways play a major role in regulating osteoblastogenesis and are implicated in many aspects of bone physiology and pathology.
The hypothesis of the author was that a common single nucleotide polymorphism (SNP) in the GNAS1 gene could affect the time to aseptic loosening after hip replacement. Caucasian patients were genotyped for the GNAS1 T393C polymorphism. The time parameters related to the occurring of aseptic loosening were measured and analyzed for dependency on GNAS1 genotypes. Bachman and co-workers report that both time and median time to aseptic loosening were not significantly associated with genotypes however a significant gender effect was revealed when data were stratified. The TT genotype was associated with significantly longer time (p<0.048) as well as median time ( p<0.022) to aseptic loosening in female patients. In contrast male patients with a TT genotype had significantly shorter time and median time to the occurring of aseptic loosening. The complex statistical analysis revealed that in comparison to TT genotype carriers the male patients carrying the CC genotype had an 11-fold lower risk of aseptic loosening. This study therefore suggest that there is a significant gender-dependent role of the T393C polymorphism in aseptic loosening and the results in men and women suggest that the GNAS1 T393C is an interesting target for further investigations in bone diseases.