THU0143 LOW-ENERGY FRACTURES IN RHEUMATOID ARTHRITIS – ASSOCIATIONS WITH GENES AND CLINICAL CHARACTERISTICS
Authors: Lotta Ljung, Kristina Wiberg, Lisbeth Ärlestig, Solbritt Rantapää Dahlqvist
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Patients with rheumatoid arthritis (RA) have increased risk of osteoporosis and low-energy fractures. Several genes associated with bone mineralization, osteoporosis or risk of fracture in the general population have been identified. <h3>Objectives:</h3> To analyse the association between nine selected SNPs and the risk of low-energy fracture, taking clinical patient characteristics into account. <h3>Methods:</h3> We identified a cohort of patients (n=896, 70% women, age at inclusion 60.0±14.8 years) with RA according to ACR criteria from the catchment area of the register of Umeå injury database, Umeå, Sweden, which enabled identification of low-energy fractures (n=254). The follow-up (mean 8.8±6.1 years, total 7928 person-years) started two years after RA diagnosis but not earlier than January 1, 1993 and ended at the first of December 31, 2011, death or the first low-energy fracture. Nine SNPs were analysed in all patients with available DNA-samples (n=667) using KASPTM genotyping assays (LGC genomics Ltd, Hoddesdon, UK): rs3801387 (WNT16), rs6666455 (SOAT), rs3736228 (LRP5), rs4796995 (FAM210A), rs4792909 (SOST), rs2062377 (TNFRSF11B/OPG), rs884205 (TNFRSF11A/RANK), rs9533090 (TNFSF11/RANKL), and rs1373004 (DKK1). Anti-CCP was analysed and clinical patient characteristics (duration of RA, ever smoking, disease activity the first two years after RA diagnosis, and joint erosions) were extracted from patient files. Associations between the risk of fracture and risk alleles in the cohort were evaluated using Kaplan-Meier curves (K-M) and Cox proportional hazards models: crude, adjusted for age and sex, and for clinical patient characteristics. <h3>Results:</h3> The SNPs: rs1373004, rs4792909, and rs2062377 were associated with the risk of fracture in K-M analyses (Figure 1). For the other genes no significant associations were observed. Patients carrying the risk allele of rs1373004 (22.6% of the patients), or who were homozygous for the risk allele of SNP rs4792909 (38.6%), had a &gt;50% higher risk of low-energy fracture compare to other patients, irrespectively of disease characteristics (Table 1). The association between rs2062377 and the risk of fracture was not independent of clinical patient characteristics (Table 1). *Hazard ratio (HR)1=crude model, HR2= adjusted for age at inclusion and sex, HR3=adjusted for age at inclusion, sex, duration of RA, anti-CCP positivity, ever smoking, disease activity the first two years after RA diagnosis, and erosive disease. <h3>Conclusion:</h3> Genes related to bone metabolism may have a considerable contribution to the already high risk of low-energy fractures in RA. <h3>References:</h3> [1] Estrada K, et al. Nat Genet2012 [2] Baron R &amp; Kneissel M. Nat Med2013 <h3>Disclosure of Interests:</h3> Lotta Ljung: None declared, Kristina Wiberg: None declared, Lisbeth Ärlestig: None declared, Solbritt Rantapää Dahlqvist Consultant for: Member of the advisory board, Lipum AB, Umeå, Sweden.