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Introduction  Patients with rheumatoid arthritis (RA) have a higher prevalence of osteoporosis and hip fracture than healthy individuals. Multiple genetic loci for osteoporotic fracture were identified in recent genome-wide association studies. The purpose of this study was to identify genetic variants associated with the occurrence of hip fracture in Japanese patients with RA.    Methods  DNA samples from 2,282 Japanese patients with RA were obtained from the DNA collection of the Institute of Rheumatology Rheumatoid Arthritis cohort (IORRA) study. Six single nucleotide polymorphisms (SNPs) that have been reported to be associated with fractures in recent studies were selected and genotyped. Forty hip fractures were identified with a maximum follow-up of 10 years. The genetic risk for hip fracture was examined using a multivariate Cox proportional hazards regression model.    Results  The risk analyses revealed that patients who are homozygous for the major allele of SNP rs6993813, in the  OPG  locus, have a higher risk for hip fracture (hazard ratio [95% CI]  = 2.53 [1.29–4.95],  P   = 0.0067). No association was found for the other SNPs.    Conclusions  Our results indicate that an  OPG  allele is associated with increased risk for hip fracture in Japanese patients with RA.

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An Osteoprotegerin Gene Polymorphism Is Associated with an Increased Risk of Hip Fracture in Japanese Patients with Rheumatoid Arthritis: Results from the IORRA Observational Cohort Study