Anti-Mi-2 antibody-positive lung cancer-associated polymyositis.

After a 75-year-old man was diagnosed with lung cancer, proximal weakness and myalgia in the bilateral lower extremities developed, and the creatinine kinase (CK) level was elevated. The anti-Mi-2 antibody test was positive, muscle T2-weighted/fat-suppressed magnetic resonance imaging showed high intensity, and there were no skin lesions. Therefore, he was diagnosed with lung cancer-associated polymyositis (PM). The lung tumour shrank after chemotherapy, accompanied by gradual improvement of his PM-derived symptoms and CK level. Although positive anti-Mi-2 antibody tests rarely indicate PM and cancer, examining myositis-specific autoantibodies, including anti-Mi-2, should be considered if the CK level increases after a cancer diagnosis.

The Effect of S-Adenosylmethionine Treatment on Neurobehavioral Phenotypes in Lesch-Nyhan Disease: A Case Report.

Lesch-Nyhan disease (LND) is an X-linked recessive disorder caused by a deficiency in hypoxanthine-guanine phosphoribosyl transferase. Patients with LND experience involuntary movements, including dystonia, choreoathetosis, opisthotonos, ballismus, and self-injury. Alleviating these involuntary movements is important to improve the quality of life in patients with LND. Many clinicians have difficulty controlling these involuntary movements in their patients, and there are no established and effective treatments. A 6-month-old boy with LND presented with generalized dystonia and self-injury behavior that was alleviated after receiving S-adenosylmethionine (SAMe). His self-injury behavior completely resolved after he received SAMe and risperidone. Although he had often experienced inspiratory stridor because of laryngeal dystonia and frequently developed aspiration pneumonitis and bronchitis, no inspiratory stridor was noted after SAMe treatment. The patient is continuing to receive SAMe and risperidone. SAMe treatment alleviates dystonic movements and improves quality of life in pediatric patients with LND. Additional research is needed to determine the long-term safety and efficacy of SAMe and its appropriate dosage.

Shared epitope defines distinct associations of cigarette smoking with levels of anticitrullinated protein antibody and rheumatoid factor.

OBJECTS: Although the association of cigarette smoking (CS) with susceptibility to rheumatoid arthritis (RA) has been established, the impact of CS on anticitrullinated cyclic peptide/protein antibody (ACPA) and rheumatoid factor (RF) levels in RA has yet been clear, especially in relation to shared epitope (SE) alleles. METHODS: A total of 6239 subjects, the largest Asian study ever, from two independent Japanese cohorts were enrolled. Precise smoking histories, levels of ACPA and RF, and HLA-DRB1 allele status were withdrawn from databases. Associations between CS and high ACPA or RF levels, defined by the top quartiles, were evaluated. The effect of HLA-DRB1 alleles on the association was further investigated. RESULTS: CS at RA onset conferred the risks of high levels of both antibodies, especially RF (OR 2.06, p=7.4×10-14; ACPA, OR 1.29, p=0.012), suggesting that RF level is more sensitive to CS than ACPA level. The patients who had quitted CS before RA onset showed a trend of decreased risks of developing high levels of ACPA or RF, and the risks steadily decreased according to the cessation years. The association of CS with high ACPA level was observed only in subjects carrying SE alleles, while the association of high RF level was observed regardless of SE. CONCLUSIONS: CS confers the risks of high autoantibody levels in RA in different manners; CS interacts with SE alleles on ACPA level, while CS impacts on RF level despite SE allele. These data suggest novel distinct production mechanisms of RF and ACPA.

Clinical Characteristics of Patients with Spondyloarthritis in Japan in Comparison with Other Regions of the World.

OBJECTIVE: To delineate clinical characteristics of patients with spondyloarthritis (SpA) in Japan in comparison to other areas of the world. METHODS: Using the ASAS-COMOSPA (Assessment of Spondyloarthritis international Society-COMOrbidities in SPondyloArthritis) data, an international cross-sectional observational study of patients with SpA, we analyzed information on demographics, disease characteristics, comorbidities, and risk factors. Patients were classified by region: Japan, other Asian countries (China, Singapore, South Korea, Taiwan), and non-Asian countries (Europe, the Americas, Africa). Patient characteristics, including diagnosis and treatment, were compared. RESULTS: Among 3984 patients included in the study, 161 were from centers in Japan, 933 from other Asian countries, and 2890 from other regions. Of patients with SpA in Japan, 42 (26.1%) had peripheral SpA, substantially more than in other countries. This trend was explained by the predominance of psoriatic arthritis (PsA) among Japanese patients with SpA. In contrast to the relatively low number in Japan, 54% of patients from other Asian countries had pure axial SpA (axSpA) without peripheral features. HLA-B27 testing, considered an integral part of the classification of axSpA, was performed in only 63.6% of Japanese patients with axSpA. More than half of Japanese patients with axSpA were classified using imaging criteria. CONCLUSION: In our study, there was a more substantial number of peripheral SpA cases observed in Japan compared to other parts of Asia and other regions of the world. Aside from ethnic differences, increasing recognition of PsA in Japan, as well as a potential underdiagnosis of axSpA due to the insufficient use of HLA-B27 testing, may partly explain regional discrepancies.

Real-World Postmarketing Study of the Impact of Adalimumab Treatment on Work Productivity and Activity Impairment in Patients with Psoriatic Arthritis.

INTRODUCTION: This study investigated the effectiveness of adalimumab treatment in improving Work Productivity and Activity Impairment (WPAI) in patients with psoriatic arthritis (PsA) in real-world settings in Japan. METHODS: This 24-week, single-arm, postmarketing surveillance study (2014-2017), conducted at 75 centers in Japan, enrolled adalimumab-naïve patients (paid workers, including part-time) meeting ClASsification criteria for Psoriatic ARthritis (CASPAR). The primary endpoint was improvement in overall work impairment (OWI) scores from baseline to week 24. Secondary endpoints included changes in WPAI-PsA (OWI, absenteeism, presenteeism, and activity impairment), Psoriasis Area and Severity Index (PASI), psoriatic arthritis screening and evaluation (PASE) scores, Disease Activity Scores in 28 joints using C-reactive protein (DAS28[CRP]), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores, Health Assessment Questionnaire-Disability Index (HAQ-DI) scores, and PASI75/90 and American College of Rheumatology (ACR) 20/50/70 rates. RESULTS: In the effectiveness population (n = 106; 72.6% men; mean ± standard deviation [SD] age, 49.3 ± 10.7 years), OWI scores significantly improved (mean ± SD change, - 25.2 ± 35.3; p < 0.0001) from baseline to week 24. Other WPAI domain scores also improved significantly. Changes in OWI were significantly correlated (p < 0.0001) with PASE (r = 0.6284), DAS28(CRP) (r = 0.6059), BASDAI (r = 0.7281), and HAQ-DI (r = 0.6161) scores and were significantly influenced by previous nonsteroidal anti-inflammatory drug use (p = 0.0142), and baseline PASE (p = 0.0098), DAS28(CRP) (p = 0.0026), HAQ-DI (p = 0.0004), and BASDAI (p < 0.0001) scores. At the last evaluation, rate (95% confidence interval) of PASI 75 and 90 (n = 100) was 58.0% (47.7-67.8) and 39.0% (29.4-49.3), respectively, and that of ACR 20, 50, and 70 (n = 58) was 86.2% (74.6-93.9), 70.7% (57.3-81.9), and 53.4% (39.9-66.7), respectively. No new safety signals were observed in the safety population (n = 148). CONCLUSION: Adalimumab treatment improved WPAI in patients with PsA. Improvements in OWI and joint symptoms were significantly associated. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT02414633. FUNDING: AbbVie GK and Eisai Co., Ltd.

Incidence of comprehensive hospitalization due to infection, cardiovascular disease, fractures, and malignancies in patients with rheumatoid arthritis.

To comprehensively analyze the overall incidence of hospitalization for comorbidities in patients with rheumatoid arthritis (RA). We prospectively analyzed overall hospitalizations for comorbidities using the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort. The incidence of hospitalized comorbidity was calculated. Risk factors for the most frequent hospitalized comorbidities were determined by multivariate logistic regression analysis. Among 5519 RA patients contributing 5336.5 person-years of observation, 435 incidences of hospitalized comorbidity [8.15/100 person-years; 95% confidence interval (CI) 7.40-8.95] were confirmed. The most frequent cause of hospitalized comorbidity was infection (1.52/100 person-years), primarily respiratory system infection (0.77/100 person-years), followed by malignancy (1.03/100 person-years), extra-articular manifestations (0.78/100 person-years), bone fracture (0.77/100 person-years), and acute coronary syndrome (0.22/100 person-years). Death occurred in 0.34/100 person-years (95% CI 0.20-0.53), and in 94.4% of cases the cause of death was the same as that of admission. The risk factors for the most frequent cause of hospitalization, hospitalized infection, were age [odds ratio (OR) 1.03; 95% CI 1.00-1.05], serum albumin level (OR 0.30; 95% CI 0.13-0.69), and corticosteroid use (prednisone > 5 mg/day; OR 3.66; 95% CI 1.81-7.35), but not methotrexate or biological agent use. The present study determined the overall burden of hospitalized comorbidities in patients with RA. These comprehensive data on hospitalized comorbidities may provide a basis for future improvements in the treatment of RA.

Polygenic burdens on cell-specific pathways underlie the risk of rheumatoid arthritis.

Recent evidence suggests that a substantial portion of complex disease risk alleles modify gene expression in a cell-specific manner. To identify candidate causal genes and biological pathways of immune-related complex diseases, we conducted expression quantitative trait loci (eQTL) analysis on five subsets of immune cells (CD4+ T cells, CD8+ T cells, B cells, natural killer (NK) cells and monocytes) and unfractionated peripheral blood from 105 healthy Japanese volunteers. We developed a three-step analytical pipeline comprising (i) prediction of individual gene expression using our eQTL database and public epigenomic data, (ii) gene-level association analysis and (iii) prediction of cell-specific pathway activity by integrating the direction of eQTL effects. By applying this pipeline to rheumatoid arthritis data sets, we identified candidate causal genes and a cytokine pathway (upregulation of tumor necrosis factor (TNF) in CD4+ T cells). Our approach is an efficient way to characterize the polygenic contributions and potential biological mechanisms of complex diseases.

Characteristics and risk factors of lymphoproliferative disorders among patients with rheumatoid arthritis concurrently treated with methotrexate: a nested case-control study of the IORRA cohort.

The purpose of the study is to demonstrate the characteristics of lymphoproliferative disorders (LPDs) in patients with rheumatoid arthritis (RA) and risk factors for LPD among RA patients concurrently treated with methotrexate (MTX). Among patients who participated in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort study in October 2010, past existence of LPD from patient's report was confirmed through medical charts. Background factors, LPD pathological findings, and the clinical courses of LPD and RA after LPD were assessed. To analyze the risk of MTX-associated LPD among RA patients concurrently treated with MTX, a nested case-control study design was used to select control patients who had received MTX but did not develop LPD by matching calendar date, sex, and age (within 5 years) at a 1:10 ratio. Odds ratios (ORs) with 95% confidence intervals (95% CIs) for occurrence of LPD were analyzed by multivariate analysis. Forty-eight patients experienced LPD among 5757 patients, and 25 (52.1%) of those had lymphoma. LPD regressed in 60.4% of all LPD patients and 24.0% of lymphoma patients. In the 26 cases who developed LPD during MTX treatment, multivariate analysis revealed that 28-joint disease activity score (DAS28) (OR 1.57 [95% CI, 1.12-1.57]; p < 0.01) and lactate dehydrogenase (LDH) level (OR 1.01 [95% CI, 1.00-1.02]; p < 0.01), but not concomitant dose of MTX, were risk factors for LPD. Among RA patients concomitantly treated with MTX, high disease activity, but not MTX dose, was a risk factor for the occurrence of LPD.

Dental treatments, tooth extractions, and osteonecrosis of the jaw in Japanese patients with rheumatoid arthritis: results from the IORRA cohort study.

This study aimed to evaluate dental treatments, tooth extractions, and osteonecrosis of the jaw (ONJ) in Japanese patients with rheumatoid arthritis (RA). Patients with RA enrolled in our cohort completed self-administered questionnaires, which included questions regarding their dental treatments, tooth extractions by dentists during the past 6 months, and past history of ONJ. The history of ONJ was validated with the patients' medical records. Logistic regression was used to determine the association of variables with dental treatments and tooth extractions during the past 6 months. Among 5695 Japanese patients with RA who responded to the questionnaires (mean age, 61.0 years; 85.6 % female), 2323 patients (40.8 %) and 378 patients (6.6 %) reported having had dental treatments and tooth extractions performed by a dentist within the past 6 months, respectively. In multivariate models, advanced age was significantly (P < 0.0001) associated with both dental treatments and tooth extractions during the prior 6-month period, and ever smoking was significantly (P = 0.023) correlated with tooth extractions during that time. Among patients who reported a history of ONJ, we confirmed five cases of ONJ with patient medical records. The prevalence of ONJ was 0.094 % among all RA patients and 0.26 % among female RA patients ≥65 years of age (n = 1888). Our data suggest that more than a few Japanese patients with RA have dental complications that require care by dentists, and that Japanese rheumatologists and dentists should cooperate to improve dental health in patients with RA.

Pharmacoeconomic analysis of biological disease modifying antirheumatic drugs in patients with rheumatoid arthritis based on real-world data from the IORRA observational cohort study in Japan.

OBJECTIVES: To evaluate the cost-effectiveness of biological disease modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) in a real-world setting in Japan. METHODS: We used a state-transition model and parameters were determined from RA patients registered in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort study on 421 patients who had failed at least one DMARD and started either 1 of 4 bDMARDs (bDMARD group; adalimumab, etanercept, infliximab, and tocilizumab) or methotrexate (control group). bDMARD group was evaluated as two groups: sequence of any 1 of 4 bDMARDs with and without tocilizumab. The incremental cost-effectiveness ratios (ICERs) for bDMARD group were estimated using base-case analysis, probabilistic sensitivity analysis (PSA) and scenario sensitivity analyses. RESULTS: ICERs of bDMARD group with or without tocilizumab were $38,179 and $48,855, respectively. By PSA, these sequences had respective probabilities of 86.8% and 75.1% of falling below the assumed cost-effectiveness threshold of $50,000 in Japan. Scenario sensitivity analyses showed that the best population for initiating bDMARD was RA patients less than 50 years old with Japanese version of HAQ between 1.1 and 1.6 and using tocilizumab as the bDMARD. CONCLUSION: bDMARDs were cost-effective for RA patients based on a real-world setting in Japan.

Longer operative time is the risk for delayed wound healing after forefoot surgery in patients with rheumatoid arthritis.

OBJECTIVES: Forefoot deformities are common in patients with rheumatoid arthritis (RA) and often require operative treatment. There is a high rate of delayed wound healing after foot surgery, especially among patients with RA. The aim of this study was to identify risk factors of delayed wound healing in RA patients who had undergone forefoot surgery. METHODS: This study was a retrospective observational study designed to analyze the outcomes of all consecutive RA patients who had undergone toe arthroplasty from April 2010 through May 2014 at a single institute. Putative risk factors for delayed wound healing were assessed using univariate logistic regression analysis. Variables with α = 0.1 were then subjected to stepwise multivariate logistic regression analysis. RESULTS: A total of 192 RA patients (192 feet) were included in this study. Delayed wound healing was seen in 40 feet (40/192 [20.8%]). A stepwise multivariate logistic regression analysis revealed that longer operative time was the risk factor associated with delayed wound healing in RA patients undergoing forefoot surgery (p = 0.028, odds ratio = 1.19 [per 10 min], 95% confidence interval [CI]: 1.07-1.32). CONCLUSIONS: This finding emphasizes the importance of preventing operative complications during forefoot surgery.

Rheumatoid Factor Is Associated With the Distribution of Hand Joint Destruction in Rheumatoid Arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic disease leading to joint destruction. Although many studies have addressed factors potentially correlated with the speed of joint destruction, less attention has been paid to the distribution of joint destruction in patients with RA. In this study, destruction of the hand bones in patients with RA was classified into 2 anatomic subgroups, the fingers and the non-fingers, with the aim of analyzing which factors are associated with destruction of the finger joints. METHODS: A total of 1,215 Japanese patients with RA were recruited from 2 different populations. The degree of joint destruction was assessed using the total modified Sharp/van der Heijde score (SHS) of radiographic joint damage. The SHS score of joint damage in the finger joints was used as the dependent variable, and the SHS score in the non-finger joints was used as a covariate. Age, sex, disease duration, smoking, C-reactive protein level, treatment for RA, and positivity for and levels of anti-citrullinated protein antibodies and rheumatoid factor (RF) were evaluated as candidate correlates. Overall effect sizes were assessed in a meta-analysis. In addition, associations observed in the Japanese patients were compared to those in a cohort of 157 Dutch RA patients in the BeSt study (a randomized, controlled trial involving 4 different strictly specified treatment strategies for early RA). RESULTS: Not surprisingly, disease duration in Japanese patients with RA was associated with the finger SHS score (P ≤ 0.00037). Both positivity for and levels of RF showed significant associations with the finger SHS score after adjustment for covariates (P = 0.0022 and P = 8.1 × 10(-7) , respectively). These associations were also true in relation to the time-averaged finger SHS score. An association between RF positivity and the finger SHS score was also observed in Dutch patients with RA in the BeSt study (P = 0.049). CONCLUSION: Positivity for and levels of RF are associated with finger joint destruction independent of non-finger joint destruction and other covariates. Our findings suggest that there are different mechanisms of joint destruction operating in the finger joints of patients with RA.

Arterial Calcification Due to Deficiency of CD73 (ACDC) As One of Rheumatic Diseases Associated With Periarticular Calcification.

In 2011, St Hilaire et al (N Engl J Med. 2011;364:432-442) identified mutations in the ecto-5'-nucleotidase (NT5E) gene, which encodes CD73, in members of 3 families with symptomatic arterial and joint calcifications. The deficiency of CD73 involves the extracellular adenosine metabolism that influences inorganic pyrophosphate and phosphate metabolism and leads to tissue calcification. Herein, we report an additional case with arterial calcification due to deficiency of CD73. Genetic analyses revealed that the patient was a compound heterozygote of mutations in the NT5E gene. The present case had intermittent monoarthritis of the finger joints and early-onset osteoarthritis in the hands. Occlusion of calcified peripheral arteries is the most important outcome of the disease. However, the rheumatic manifestations may be important clues to the diagnosis. Rheumatologists should recognize deficiency of CD73 as a rheumatic disease.

Effect of Smoking on Remission Proportions Differs Between Male and Female Patients with Rheumatoid Arthritis: A Study Based on the IORRA Survey.

OBJECTIVE: To analyze sex difference in the effect of smoking on remission proportions in patients with rheumatoid arthritis (RA). METHODS: Subjects were Japanese patients with RA who participated in the IORRA survey conducted in April 2011 and reported smoking status. Clinical characteristics, treatment status, and the percentages achieving remission were compared between subjects stratified by sex and smoking status. To confirm the differential effects of sex and smoking status on remission, we used multivariate logistic regression models with the dependent variable as 28-joint Disease Activity Score (DAS28) remission. RESULTS: Among 810 men and 4206 women, 162 (20.0%) and 3173 (75.4%), respectively, were never smokers; 208 (25.7%) and 314 (7.5%), respectively, were current smokers. In men, never smokers tended to have higher remission proportions than past and current smokers. In contrast, smoking status seemed not to affect remission in women. Except for lower corticosteroid dose in male never smokers, no significant differences were observed in comparing treatment status. By multivariate analyses, male past and current smokers were negatively associated with DAS28-erythrocyte sedimentation rate remission compared to male never smokers [OR 0.66 and 0.61, 95% CI (0.44-0.98) and (0.39-0.96), respectively]. However, female past and current smokers were not associated with remission compared to female never smokers [OR 1.04 and 1.19, 95% CI (0.86-1.25) and (0.91-1.54), respectively]. CONCLUSION: We demonstrated that the effect of smoking on remission proportions differed between men and women. Our findings suggest that both sex and smoking status are important considerations when planning a treatment strategy for patients with RA.

A case of cryopyrin-associated periodic syndrome with kidney transplant failure.

The cryopyrin-associated periodic syndrome (CAPS) is an autosomal dominant autoinflammatory disease characterized by fever, skin rash, and joint involvement with acute inflammatory response. The genetic defect involves the NLRP3 gene that encodes cryopyrin and leads to an abnormal production of interleukin-1 (IL-1). Therefore, anti-IL-1 treatment represents an effective therapy. One of the most severe manifestations of the disease is secondary amyloidosis that causes renal failure. We present a patient with CAPS who underwent renal transplantation for renal insufficiency caused by amyloidosis. The function of the transplanted kidney deteriorated because of the late administration of IL-1 receptor antagonist, anakinra. This case may indicate the importance of early initiation of anti-IL-1 treatment in CAPS patients who have undergone kidney transplantation.

Long-term outcome of 114 adult JIA patients in a non-pediatric rheumatology institute in Japan.

OBJECTIVE: To evaluate the long-term outcome of patients with juvenile idiopathic arthritis (JIA) using data from a large cohort database, Institute of Rheumatology, Rheumatoid Arthritis, managed by the Tokyo Women's Medical University. METHODS: Of 182 patients identified from the database from 2000 to 2013, 114 were verified as having JIA. The transition of medical care and the contributions of biological DMARDs were evaluated. RESULTS: The mean age of the patients (93 females, 81.6%) at the latest examination was 36.6 ± 13.3 years. The mean age at disease onset and mean disease duration were 11.6 ± 3.4 and 25.0 ± 13.3 years, respectively. Of the 114 patients, 106 (93.0%) had poly- or oligoarthritis. Only one-fourth transferred from general pediatricians or pediatric rheumatologists. More patients with recent disease onset were treated with biological DMARDs (16.7% in the 1970s, vs. 80.0% in the 2000s). Disease activity assessed with DAS28 was significantly lower when disease onset was more recent (3.9 ± 1.3 for onset in the 1960s vs. 2.2 ± 1.1 for onset in the 2000s, p = 0.04). The percentage of patients requiring orthopedic surgery has decreased (53.8% before the 1970s vs. 10.0% in the 2000s). CONCLUSION: Patients with more recent disease onset showed an improved outcome. Establishing and sharing a transition program among pediatric and non-pediatric rheumatologists is desirable.

Construct validity, reliability, response rate, and association with disease activity of the quick disabilities of the arm, shoulder and hand questionnaire in the assessment of rheumatoid arthritis.

OBJECTIVE: First objective is to validate the Disabilities of the Arm, Shoulder and Hand (DASH) and Quick DASH (QuickDASH) questionnaire in rheumatoid arthritis (RA) patients with functional upper extremity impairment. Next is to clarify which clinical factor is associating with QuickDASH using a large cohort of RA. METHODS: The QuickDASH and DASH were applied to our 94 RA patients who underwent surgery for functional upper extremity impairment. Next, the QuickDASH was applied to our cohort of 5191 Japanese patients with RA. RESULTS: In the first cohort of 94 RA patients, both QuickDASH and DASH displayed excellent reliability and validity. The response rate of patients < 65 and ≥ 65 years of age showed significant difference in the DASH but not in the QuickDASH. In the second cohort with 5191 RA patients, QuickDASH showed a high response rate (93%) and good to moderate correlation with Japanese version of the Health Assessment Questionnaire (r = 0.88) and disease activity score of 28 (DAS28, r = 0.53). Change in QuickDASH score and DAS28-based European League Against Rheumatism response showed significant correlation. CONCLUSION: QuickDASH seems suitable for evaluating upper extremity impairment, disability index, and disease control in a large cohort of RA patients including elderly patients.

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.

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.

Effects of smoking and shared epitope on the production of anti-citrullinated peptide antibody in a Japanese adult population.

OBJECTIVE: Anti-citrullinated peptide antibody (ACPA) and rheumatoid factor (RF) are markers to rheumatoid arthritis (RA). Smoking and shared epitope (SE) in HLA-DRB1 are associated with the production of these autoantibodies in RA. Detailed distribution and characterization of ACPA and RF in the general population have remained unclear. We aimed to evaluate positivity of ACPA and RF in a general Japanese population and to detect correlates, including genetic components. METHODS: ACPA and RF were quantified in 9,804 Japanese volunteers ages 30-75 years. Logistic regression analyses were performed to evaluate the effects of candidates of correlates on the autoantibody positivity. A genome-wide association study (GWAS) was performed using 394,239 single nucleotide polymorphisms for 3,170 participants, and HLA-DRB1 alleles were imputed based on the GWAS data. RESULTS: A total of 1.7% and 6.4% of subjects were positive for ACPA and RF, respectively, and the 2 markers showed a significant correlation (P = 2.0 × 10(-23) ). Old age was associated with ACPA positivity (P = 0.00062). Sex, smoking, SE, and other candidates of correlates did not have significant effects. Interaction between smoking and SE positivity was not apparent, but smoking showed a significant association with high levels of ACPA (P = 0.0019). CONCLUSION: ACPA and RF could be detected in 1.7% and 6.4% of the Japanese adult population without RA, respectively. ACPA and RF were suggested to share mechanisms even in healthy populations. Old age was associated with increasing ACPA positivity. While positivity of ACPA and RF was not associated with SE and smoking, an association between high ACPA and smoking was observed.

Recent trends in orthopedic surgery aiming to improve quality of life for those with rheumatoid arthritis: data from a large observational cohort.

OBJECTIVE: To describe current trends in the numbers of rheumatoid arthritis (RA)-related surgeries. METHODS: The number of operations was determined for patients with RA in a large observational cohort [Institute of Rheumatology, Rheumatoid Arthritis (IORRA)] enrolled from 2001 to 2012. RESULTS: The total number of operations peaked in 2002 and gradually decreased thereafter, but began to increase again in 2008. The number of total knee replacements has decreased since 2003, while the number of wrist and foot arthroplasties and the number of artificial finger prosthesis surgeries have increased gradually. CONCLUSION: Our results suggest that the number of orthopedic surgeries may change in response to changes in the drug therapy for RA.