Background Vitamin D has been shown to have significant immunomodulatory effects. Its actions are mediated by the ubiquitous vitamin D receptor (VDR). In one study, BsmI VDR gene polymorphism was associated with an early onset of rheumatoid arthritis (RA). Additionally, TT genotype of the FokI VDR gene polymorphism was established as a genetic susceptibility marker for RA in French and Tunisian populations. Objectives To determine the degree of association of BsmI and FokI VDR gene polymorphisms with disease activity in patients with established RA. Methods Clinical features and peripheral blood samples were collected from a monitoring visit. The Portuguese version of HAQ and the disease activity scores (DAS28 (4v; ESR), DAS28 (3v; ESR), DAS 28 (4v; CRP), DAS28 (3v; CRP)) were obtained. We measured the following acute phase reactants: ESR and CRP. Genomic DNA was extracted from blood and genotyped for the BsmI (A/G) (rs1544410) and FokI (T/C) (rs 2228570) SNPs by PCR-RFLPs analysis. A multivariate analysis model was used for statistical analysis (IBM SPSS Statistics 21). Results We evaluated 208 RA patients, 166 (80%) women, 65 (31%) premenopausal women, age 54±12 years, disease duration 14±10 years, mean DAS28 (4v) of 4.25±1.33 and a mean HAQ of 1.254±0.709. In our sample, 107 (51%) were under biologics, 87 (42%) under anti-TNFalpha agents and 42 (20%) under vitamin D supplements. Genotype frequencies were determined for the two distinct VDR polymorphisms: BsmI (GG 37%, 44% AG, AA 19%) and FoKI (CC 42%, TC 46%, TT 12%). GG genotype of the BsmI VDR gene polymorphism was associated with higher DAS28 (4v; ESR), DAS28 (3v; ESR), DAS 28 (4v; CRP) and DAS28 (3v; CRP) scores (p<0.001). Additionally, TT genotype of the FokI VDR gene polymorphism was associated with higher DAS28 (4v; ESR), DAS28 (3v; ESR), DAS 28 (4v; CRP) and DAS28 (3v; CRP) scores (p<0.001). In the subgroup of patients without vitamin D supplements, the previously observed associations remained significant (p<0.001). All these associations were found after adjusting for age, disease duration, current HAQ, time under DMARDs therapy, current average daily dose of prednisone and years of corticosteroid use. Conclusions In our RA population, the BsmI GG and the FokI TT genotypes of the VDR gene were related with disease severity. In the future, VDR gene polymorphisms could be useful in establishing RA prognosis. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3913

Background Low bone mineral density (BMD) is highly prevalent in patients with systemic lupus erythematosus (SLE). However, determinants of BMD changes in SLE are still largely unknown. Objectives The aim of this study was to describe the clinical characteristics of SLE patients submitted to a dual energy X-ray absorptiometry (DEXA), evaluating the prevalence of osteopenia/osteoporosis and searching for possible predictors of bone loss in these patients. Methods Retrospective observational study of 160 SLE patients of our Rheumatology department, was performed. Demographic, clinical data and BMD measurements (g/cm2) of the lumbar spine (LS) and total hip (TH) were collected. The DEXA results were classified according to WHO criteria for osteoporosis. Statistical analyses was performed using t-test, Mann-Whitney U-test, and Spearman correlation (SPSS 21.0). Results Out of 160 SLE patients, 148 (92,5%) were female with a mean age 44,23±12,5 years. The median SLEDAI was 2 [0-23], median SLICC was 0,2 [0-5]. 74 (56%) patients were taking vitamin D supplements, 56 (35%) were taking calcium supplements and 24 (15%) received bisphosphonate therapy. Only 81 (50,6%) had a DEXA done. Patients with DEXA were older (47.28±12.7 vs 41.09±11.8 years, p<0.01), had a longer disease duration (13.8±9 vs. 10.6±8 years, p=0.02), high SLICC score (2,0 vs 0,0 p=0,04) and were taking a higher dose of steroids (7 vs 5; p=0,01). No significant differences were found between gender, SLEDAI, serum vitamin D, complement levels, erythrocyte sedimentation rate or c-reactive protein. Of the 81 patients with DEXA, 34 (42%) had osteopenia, 13 (16%) had osteoporosis and 34 (42%) had normal BMD. The mean lumbar spine BMD was 0.96±0.12 g/cm2 and the mean total hip BMD was 0.87±0.13 g/cm2. Statistically significantly correlation was found between age and lumbar spine BMD (r=-0,256; p=0,02), age and total hip BMD (r=-0,262; p=0,02), SLICC score and lumbar spine DMO (r=-0,230; p=0,04) and SLICC score and total hip BMD (r=-0,279; p=0,04). Conclusions In our cohort, SLE patients referred for a DEXA have more traditional risk factors, take a higher dose of corticosteroids and have a higher disease damage access by SLICC score. The prevalence of osteopenia and osteoporosis in our SLE-patients was greater than in general population. In addition to age, disease damage access by SLICC score was associated with low BMD. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4635

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Background Rheumatoid arthritis (RA) is characterized by a localized bone resorption at the hands, namely, and generalized osteoporosis. LRP5 gene is related to rare metabolic bone diseases and several LRP5 polymorphisms have been associated with bone mineral density (BMD) in healthy populations. Objectives To determine the association of three LRP5 gene polymorphisms with bone density and metabolism in patients with established rheumatoid arthritis (RA) Methods Clinical features and peripheral blood samples were collected. The Portuguese version of HAQ, DAS28 (4v)), tender (out of 68) and swollen (out of 66) joint counts were obtained. Several laboratory parameters were measured: ESR, CRP, serum β-C-telopeptides of type 1 collagen cross-links (β-CTX1), osteocalcin, Dkk-1 (ELISA, Biomedica), sclerostin (ELISA TECOmedical), RANKL (ELISA, Cusabio) and OPG (ELISA, Biomedica). BMD was assessed by DXA (Lunar Expert ® 1320) at lumbar spine, total hip, femoral neck, Wards triangle, hands and second proximal phalanges. A multivariate analysis model was used for statistical analysis (PASW Statistics 18). Results We evaluated 208 RA patients, 166 (80%) women, 65 (31%) premenopausal women, age 54 ± 12 years, disease duration 14 ± 10 years, mean DAS28 (4v) of 4.25 ± 1.33 and a mean HAQ of 1.254 ± 0.709. In our sample, 107 (51%) were under biologics, 87 (42%) under anti-TNFalpha agents, 69 (33%) under bisphosphonates and 42 (20%) under vitamin D supplements, Genotypic frequencies were determined: V667M (GG 89%, 11% AG, AA: 1%), N740N (CC 69%, 27% TC, TT 4%) and A1330V (CC 72% TC 24%; TT 4%). The AG genotype (V667M LRP5), the TT genotype (N740N LRP5) and TT genotype (A1330V LRP5) were associated with lower BMD at the hip, femoral neck, Wards triangle, hands and second proximal phalanges (p <0.001). In the analysis by therapeutic subgroups, these associations remained, particularly at femoral level. The same genotypes were associated with higher sclerostin levels (p <0.001) and lower RANKL (p <0.05). The genotype TT (A1330V polymorphism) was also associated with higher serum OPG (p <0.05). Whether in the subgroup of patients on biologics, whether under classical DMARDs, only the associations with sclerostin levels remained significant. All these associations were found even after adjusting for age, disease duration, body mass index, DAS28 (4v), current HAQ, current average daily dose of prednisolone and years of corticosteroid use. Conclusions In a rheumatoid arthritis population, the genotypic frequencies of the V667M, N740N and A1330V polymorphisms in LRP5 gene proved to be similar to healthy populations, correlating with femoral and hands bone mass in these patients. The association of these polymorphisms to high serum levels of sclerostin can justify the major lack of bone formation and bone repair in rheumatoid arthritis patients. Disclosure of Interest None Declared