Abstract
Introduction: Polymorphisms within genes encoding bone regulatory cytokines influence individuals’ susceptibility to osteolysis after THA. We aimed to determine whether single nucleotide polymorphisms (SNPs) within these genes influence the severity of these osteolytic lesions in 272 patients with established aseptic loosening.
Methods: Assessment of osteolytic lesions was made from pre-revision radiographs in conjunction with direct visualisation in those subjects undergoing surgery. Osteolytic lesions were defined as linear (AAOS pelvic and femoral osteolysis classification grade 0) or expansile, in the presence of segmental or cavitary defects (AAOS grade 1 or greater). We analysed 11 SNPs in the pro-inflammatory cytokines IL-1A, IL-1B, IL-1RA, IL-6 and TNF; 2 SNPs within the FRZB gene, which modulates osteoblast function; and 6 SNPS in the RANK/RANKL/OPG pathway, that modulates osteoclast function.
Results: Femoral Osteolysis: Carriage of the IL-6 −174C allele was 60% in the expansile osteolysis group versus 80% in the linear osteolysis group (χ2 test p=0.007). Carriage of the OPG −163G allele was 34% in the expansile osteolysis group versus 18% in the linear group (χ2 test p=0.03). The odds ratios for expansile osteolysis associated with carriage of IL-6-174G and OPG −163G were 2.7 (1.3 to 5.7, p=0.008) and 2.3 (1.1 to 5.0, p=0.03) respectively.
Acetabular Osteolysis: No differences in SNP genotype were found between osteolysis groups.
Discussion: The IL-6-174G allele and the OPG-163G allele are over-represented in subjects with expansile femoral versus linear osteolysis, but do not relate to severity of pelvic osteolysis. These differences in association may reflect differences in the mechanism of osteolysis between the bone sites, however, replication of the results are required to confirm this differential association.
Correspondence should be addressed to BHS c/o BOA, at the Royal College of Surgeons, 35–43 Lincoln’s Inn Fields, London, WC2A 3PE, England.
