Osteoprotegerin Polymorphisms in a Mexican Population with Rheumatoid Arthritis and Generalized Osteoporosis: A Preliminary Report.

Bone disease in rheumatoid arthritis (RA) is a complex phenomenon where genetic risk factors have been partially evaluated. The system formed by receptor activator for nuclear factor-κB (RANK), receptor activator for nuclear factor-κB ligand (RANKL), and osteoprotegerin (OPG): RANK/RANKL/OPG is a crucial molecular pathway for coupling between osteoblasts and osteoclasts, since OPG is able to inhibit osteoclast differentiation and activation. We aim to evaluate the association between SNPs C950T (rs2073617), C209T (rs3134069), T245G (rs3134070) in the TNFRSF11B (OPG) gene, and osteoporosis in RA. We included 81 women with RA and 52 healthy subjects in a cross-sectional study, genotyped them, and measured bone mineral density (BMD) at the lumbar spine and the femoral neck. Mean age in RA was 50 ± 12 with disease duration of 12 ± 8 years. According to BMD results, 23 (33.3%) were normal and 46 (66.7%) had osteopenia/osteoporosis. We found a higher prevalence of C allele for C950T SNP in RA. Polymorphisms C209T and T245G did not reach statistical significance in allele distribution. Further studies including patients from other regions of Latin America with a multicenter design to increase the sample size are required to confirm our findings and elucidate if C950T SNP could be associated with osteoporosis in RA.

PADI4 haplotypes in association with RA Mexican patients, a new prospect for antigen modulation.

Peptidyl arginine deiminase IV (PAD 4) is the responsible enzyme for a posttranslational modification called citrullination, originating the antigenic determinant recognized by anti-cyclic citrullinated peptide antibodies (ACPA). Four SNPs (single nucleotide polymorphisms) have been described in PADI4 gene to form a susceptibility haplotype for rheumatoid arthritis (RA); nevertheless, results in association studies appear contradictory in different populations. The aim of the study was to analyze if the presence of three SNPs in PADI4 gene susceptibility haplotype (GTG) is associated with ACPA positivity in patients with RA. This was a cross-sectional study that included 86 RA patients and 98 healthy controls. Polymorphisms PADI4_89, PADI4_90, and PADI4_92 in the PADI4 gene were genotyped. The susceptibility haplotype (GTG) was more frequent in RA patients; interestingly, we found a new haplotype associated with RA with a higher frequency (GTC). There were no associations between polymorphisms and high scores in Spanish HAQ-DI and DAS-28, but we did find an association between RARBIS index and PADI4_89, PADI4_90 polymorphisms. We could not confirm an association between susceptibility haplotype presence and ACPA positivity. Further evidence about proteomic expression of this gene will determine its participation in antigenic generation and autoimmunity.

Performance of risk indices for identifying low bone mineral density and osteoporosis in Mexican Mestizo women with rheumatoid arthritis.

OBJECTIVE: We evaluated the utility of 6 generic and 2 specific risk indices for identifying low bone mineral density (BMD) or osteoporosis in women with rheumatoid arthritis (RA); and their correlation with 10-year probability of fractures as assessed with the World Health Organization fracture risk assessment (FRAX) tool. METHODS: Mexican Mestizo women with RA were evaluated in this cross-sectional study using 6 generic indices [Simple Calculated Osteoporosis Risk Estimation (SCORE); Osteoporosis Risk Assessment Instrument (ORAI); Osteoporosis Self-Assessment Tool; Age, Body Size, No Estrogen; Osteoporosis Index of Risk (OSIRIS); and Guidelines of the US National Osteoporosis Foundation], 2 specific indices (Amsterdam and modified Amsterdam), and FRAX. BMD results on dual-energy x-ray absorptiometry (DEXA) at the lumbar spine and femoral neck were considered the "gold standard." Sensitivity, specificity, and predictive values (PV) of the indices and their correlations with FRAX results were estimated. RESULTS: Among 191 patients, 46 had osteoporosis (24.1%) and 119 had low BMD (62.3%). For predicting osteoporosis, SCORE showed the highest sensitivity (96%), whereas OSIRIS (87%) and ORAI (82%) showed the highest specificities. OSIRIS also had the greatest positive PV (92%). The specific indices had low sensitivity and low specificity (Amsterdam, 50% and 79%, respectively; modified Amsterdam, 56% and 70%). All the indices had a low but significant correlation with FRAX. CONCLUSION: These findings support the use of some generic indices to identify patients with RA who should undergo DEXA testing. Currently available specific indices did not perform satisfactorily. New specific risk indices for osteoporosis in RA should be developed to increase sensitivity and specificity for predicting osteoporosis.