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A GC polymorphism associated with serum 25-hydroxyvitamin D level is a risk factor for hip fracture in Japanese patients with rheumatoid arthritis: 10-year follow-up of the Institute of Rheumatology, Rheumatoid Arthritis cohort study.

ABSTRACT: Vitamin D deficiency has been reported to be common in patients with rheumatoid arthritis (RA) who have a higher prevalence of osteoporosis and hip fracture than healthy individuals. Genetic variants affecting serum 25-hydroxyvitamin D (25(OH)D) concentration, an indicator of vitamin D status, were recently identified by genome-wide association studies of Caucasian populations. The purpose of this study was to validate the association and to test whether the serum 25(OH)D-linked genetic variants were associated with the occurrence of hip fracture in Japanese RA patients.DNA samples of 1,957 Japanese RA patients were obtained from the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort DNA collection. First, five single nucleotide polymorphisms (SNPs) that were reported to be associated with serum 25(OH)D concentration by genome-wide association studies were genotyped. The SNPs that showed a significant association with serum 25(OH)D level in the cross-sectional study were used in the longitudinal analysis of hip fracture risk. The genetic risk for hip fracture was determined by a multivariate Cox proportional hazards model in 1,957 patients with a maximum follow-up of 10 years (median, 8 years).Multivariate linear regression analyses showed that rs2282679 in GC (the gene encoding group-specific component (vitamin D binding protein)) locus was significantly associated with lower serum 25(OH)D concentration (P?=?8.1 × 10??). A Cox proportional hazards model indicated that rs2282679 in GC was significantly associated with the occurrence of hip fracture in a recessive model (hazard ratio (95% confidence interval)?=?2.52 (1.05-6.05), P?=?0.039).A two-staged analysis demonstrated that rs2282679 in GC was associated with serum 25(OH)D concentration and could be a risk factor for hip fracture in Japanese RA patients.

SUBMITTER: Yoshida S

PROVIDER: S-EPMC4060202 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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A GC polymorphism associated with serum 25-hydroxyvitamin D level is a risk factor for hip fracture in Japanese patients with rheumatoid arthritis: 10-year follow-up of the Institute of Rheumatology, Rheumatoid Arthritis cohort study.

Yoshida Shinji S Ikari Katsunori K Furuya Takefumi T Toyama Yoshiaki Y Taniguchi Atsuo A Yamanaka Hisashi H Momohara Shigeki S

Arthritis research & therapy 20140320 2

<h4>Introduction</h4>Vitamin D deficiency has been reported to be common in patients with rheumatoid arthritis (RA) who have a higher prevalence of osteoporosis and hip fracture than healthy individuals. Genetic variants affecting serum 25-hydroxyvitamin D (25(OH)D) concentration, an indicator of vitamin D status, were recently identified by genome-wide association studies of Caucasian populations. The purpose of this study was to validate the association and to test whether the serum 25(OH)D-li ...[more]

PMID: 24646907

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Project description:The association between serum 25-hydroxyvitamin D level and post-fracture mortality indicates beneficial relatively high serum 25-hydroxyvitamin D concentrations. A 1-year cohort study on 245 hip fracture patients in Finland indicated the lowest 3-year mortality and highest survival among patients with serum 25-hydroxyvitamin D level of 50-74 nmol/L.PurposeTo explore pre-fracture serum 25-hydroxyvitamin D level as a factor associated with post-fracture survival among a cohort of hip fracture patients in Finland.MethodsA prospectively collected cohort of hip fracture patients (n = 245, 70% women) from two hospitals was followed for 3.2 post-hip fracture years. Serum 25-hydroxyvitamin D was measured in admission to the hospital and classified: < 50, 50-74, 75-99, and ≥ 100 nmol/L. Survival was analyzed with a Bayesian multivariate model. Relative survival was explored with the life table method according to serum 25-hydroxyvitamin D. Mortality according to serum 25-hydroxyvitamin D level and to the hospital was calculated.ResultsMortality in the patients with serum 25-hydroxyvitamin D level of 50-74 nmol/L was significantly lower than in all other patients together at every post-fracture year. The most important factors for survival were age under 85 years; living in an actual/private home; serum 25-hydroxyvitamin D level of 50-74 nmol/L, followed by 75-99 nmol/L; ASA classes 1-2 and 3; and female sex. The mean age of patients with serum 25-hydroxyvitamin D level of 50-99 nmol/L was significantly higher than in other levels. Relative survival was highest in men, women, and patients in hospital B with serum 25-hydroxyvitamin D level of 50-74 nmol.ConclusionThe highest 3-year survival and the lowest mortality in this cohort appeared in patients with pre-fracture serum 25-hydroxyvitamin D level of 50-74 nmol/L. This result differs from similar studies and is lower than the recommended level of 25-hydroxyvitamin D among hip fracture patients. The results should be examined in future research with larger data.

Project description:ObjectivesThe impact of immunosuppression on postoperative outcomes has primarily been studied in patients undergoing joint replacement surgery. We aimed to evaluate the impact of biologics and glucocorticoids on outcomes after other major surgeries.MethodsThis retrospective cohort study used Medicare data 2006-2015 to identified adults with rheumatoid arthritis undergoing hip fracture repair, abdominopelvic surgery (cholecystectomy, hysterectomy, hernia, appendectomy, colectomy) or cardiac surgery (coronary artery bypass graft, mitral/aortic valve). Logistic regression with propensity-score-based inverse probability weighting compared 90-day mortality and 30-day readmission in patients receiving methotrexate (without a biologic or targeted synthetic disease-modifying antirheumatic drug (tsDMARD)), a tumour necrosis factor inhibitor (TNFi) or a non-TNFi biologic/tsDMARD <8 weeks before surgery. Similar analyses evaluated associations between glucocorticoids and outcomes.ResultsWe identified 10 777 eligible surgeries: 3585 hip fracture, 5025 abdominopelvic and 2167 cardiac surgeries. Compared with patients receiving methotrexate, there was no increase in the risk of 90-day mortality or 30-day readmission among patients receiving a TNFi (mortality adjusted OR (aOR) 0.83 (0.67 to 1.02), readmission aOR 0.86 (0.75 to 0.993)) or non-TNFi biologic/tsDMARD (mortality aOR 0.78 (0.49 to 1.22), readmission aOR 1.02 (0.78 to 1.33)). Analyses stratified by surgery category were similar. Risk of mortality and readmission was higher with 5-10 mg/day of glucocorticoids (mortality aOR 1.41 (1.08 to 1.82), readmission aOR 1.26 (1.05 to 1.52)) or >10 mg/day (mortality aOR 1.64 (1.02 to 2.64), readmission aOR 1.60 (1.15 to 2.24)) versus no glucocorticoids, although results varied when stratifying by surgery category.ConclusionsRecent biologic or tsDMARD use was not associated with a greater risk of mortality or readmission after hip fracture, abdominopelvic or cardiac surgery compared with methotrexate. Higher dose glucocorticoids were associated with greater risk.

Project description:BackgroundPreclinical data suggest that tofacitinib would protect bone health in patients with rheumatoid arthritis (RA).ObjectiveTo assess fracture risk in tofacitinib RA clinical trials.DesignPost hoc analysis.MethodsWe analyzed pooled data of phase I/II/III and long-term extension studies ('P123LTE cohort'), pooled data of placebo-controlled portions of phase III studies (phase III placebo-controlled cohort), and data from ORAL Surveillance [phase IIIb/IV randomized, open-label trial evaluating tofacitinib 5/10 mg twice daily (BID) vs tumor necrosis factor inhibitor (TNFi) in patients ⩾ 50 years with ⩾ 1 additional cardiovascular risk factor].ResultsIn the phase III placebo-controlled cohort, incidence rates (IRs) [95% confidence interval (CI)] of fracture were 2.11 (1.09-3.68), 2.56 (1.23-4.71), and 4.43 (1.78-9.12) per 100 patient-years (PYs) for tofacitinib 5 mg BID, tofacitinib 10 mg BID, and placebo, respectively [tofacitinib 5 mg BID vs placebo: hazard ratio (HR) (95% CI) = 0.55(0.18-1.65); tofacitinib 10 mg BID vs placebo: HR (95% CI) = 0.72 (0.26-2.01)]. In P123LTE, IRs (95% CI) were 2.62 (2.29-2.99) and 2.26 (2.02-2.52) per 100 PY for average tofacitinib 5 and 10 mg BID, respectively. In ORAL Surveillance, IRs (95% CI) were 2.79 (2.34-3.30), 2.87 (2.40-3.40), and 2.27 (1.87-2.74) per 100 PY for tofacitinib 5 mg BID, tofacitinib 10 mg BID, and TNFi, respectively. In ORAL Surveillance, the risk of fracture was numerically higher than TNFi for tofacitinib 5 mg BID [HR (95% CI) = 1.23 (0.96-1.58)] and tofacitinib 10 mg BID [HR (95% CI) = 1.26 (0.97-1.62)]. In ORAL Surveillance, independent predictors of all and osteoporotic fractures with tofacitinib or TNFi included age ⩾ 65, female sex, history of fracture/osteoporosis, and baseline oral corticosteroid use.ConclusionThis post hoc analysis showed numerically lower fracture risk with tofacitinib versus placebo and numerically greater risk versus TNFi. We did not identify any tofacitinib-specific predictors of fractures, and predictors of fracture were generally aligned with prior literature in the general population and patients with RA. Patients with fracture risk factors should be adequately monitored and treated.Clinical trial registrationNCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385, NCT01039688, NCT02187055, NCT02831855, NCT00413699, NCT00147498, NCT00413660, NCT00550446, NCT00603512, NCT00687193, NCT00661661, NCT01164579, NCT00976599, NCT01059864, NCT01359150, NCT01262118, NCT01484561, NCT02281552, NCT02147587, NCT02092467.

Project description:BackgroundSerum 25-hydroxyvitamin D3 levels are generally lower in chronic hepatitis C patients than in healthy individuals. The purpose of this study is to clarify the factors which affect serum 25-hydroxyvitamin D3 levels using data obtained from Japanese chronic hepatitis C patients.MethodsThe subjects were 619 chronic hepatitis C patients. Serum 25-hydroxyvitamin D3 levels were measured by using double-antibody radioimmunoassay between April 2009 and August 2014. Serum 25-hydroxyvitamin D3 levels of 20 ng/mL or less were classified as vitamin D deficiency, and those with serum 25-hydroxyvitamin D3 levels of 30 ng/mL or more as vitamin D sufficiency. The relationship between patient-related factors and serum 25-hydroxyvitamin D3 levels was analyzed.ResultsThe cohort consisted of 305 females and 314 males, aged between 18 and 89 years (median, 63 years). The median serum 25-hydroxyvitamin D3 level was 21 ng/mL (range, 6-61 ng/mL). On the other hand, the median serum 25-hydroxyvitamin D3 level in the healthy subjects was 25 ng/mL (range, 7-52), being significantly higher than that those in 80 chronic hepatitis C patients matched for age, gender, and season (p = 1.16 × 10(-8)). In multivariate analysis, independent contributors to serum 25-hydroxyvitamin D3 deficiency were as follows: female gender (p = 2.03 × 10(-4), odds ratio = 2.290, 95 % confidence interval = 1.479-3.545), older age (p = 4.30 × 10(-4), odds ratio = 1.038, 95 % confidence interval = 1.017-1.060), cold season (p = 0.015, odds ratio = 1.586, 95 % confidence interval = 1.095-2.297), and low hemoglobin level (p = 0.037, odds ratio = 1.165, 95 % confidence interval = 1.009-1.345). By contrast, independent contributors to serum 25-hydroxyvitamin D3 sufficiency were male gender (p = 0.001, odds ratio = 3.400, 95 % confidence interval = 1.635-7.069), warm season (p = 0.014, odds ratio = 1.765, 95 % confidence interval = 1.117-2.789) and serum albumin (p = 0.016, OR = 2.247, 95 % CI = 1.163-4.342).ConclusionsSerum 25-hydroxyvitamin D3 levels in chronic hepatitis C Japanese patients were influenced by gender, age, hemoglobin level, albumin and the season of measurement.

Dataset Information

A GC polymorphism associated with serum 25-hydroxyvitamin D level is a risk factor for hip fracture in Japanese patients with rheumatoid arthritis: 10-year follow-up of the Institute of Rheumatology, Rheumatoid Arthritis cohort study.

Publications

A GC polymorphism associated with serum 25-hydroxyvitamin D level is a risk factor for hip fracture in Japanese patients with rheumatoid arthritis: 10-year follow-up of the Institute of Rheumatology, Rheumatoid Arthritis cohort study.

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