Comparison of clinical and radiographic results of mobile-bearing total ankle arthroplasty between osteoarthritis and rheumatoid arthritis.

OBJECTIVES: Clinical results of mobile-bearing total ankle arthroplasty (TAA) for rheumatoid arthritis (RA) have been reported, but no studies have compared osteoarthritis (OA) and RA. Clinical and radiographic outcomes after at least 3 years were compared between OA and RA. METHODS: Eleven ankles with OA and 22 ankles with RA were followed after mobile-bearing TAA (FINE total ankle system). Clinical outcomes were assessed by the American Orthopaedic Foot and Ankle Society (AOFAS) score. Radiographic outcomes were evaluated by the angular position of the implant, radiolucent lines, migration, and subsidence. Operative and postoperative complications were assessed. RESULTS: There were no significant differences in clinical outcomes, radiographic outcomes, or complications, except the final follow-up AOFAS total score (OA: 89.4 vs RA: 78.2; p = .044) and pain score (OA: 37.3 vs RA: 30.5; p = .041) at a mean follow-up of 83.4 months. Delayed wound healing occurred in 9.1% in RA and none in OA. Radiolucent lines were observed in 45% of both groups, and implant removal was performed in 9.1% and 18.2% of OA and RA, respectively; there were no significant differences. CONCLUSIONS: The final follow-up AOFAS total score and pain score were significantly higher in OA after the FINE total ankle system. There was a discrepancy between radiographic abnormalities and implant removal in both OA and RA.

The bioimpedance phase angle may be associated with frailty in rheumatoid arthritis patients: Results from a prospective, cohort study.

OBJECTIVES: This study investigated whether the phase angle (PhA) on bioelectrical impedance analysis is related to frailty in rheumatoid arthritis (RA) patients. METHODS: Data from a prospective cohort study of RA patients were analysed. The PhA was assessed by the bioelectrical impedance analysis method, and frailty was assessed by the Kihon Check List (KCL) annually. The cut-off value of the PhA for frailty was calculated by receiver-operating characteristic analysis. The relationships between the PhA and frailty were evaluated by logistic regression analysis. The relationships between the change in PhA and frailty status and the KCL score were evaluated by analysis of covariance and multiple regression analysis. RESULTS: A total of 170 patients (81.2% female, 66.2 ± 13.1 years) were included in the analysis. A PhA of less than the cut-off for frailty was significantly associated with frailty (odds ratio: 4.75, 95% confidence interval: 1.86, 12.17). The change in the PhA was significantly associated with the change in the KCL score (ß = -0.15). In robust patients, there was a significant difference in the rate of change of the PhA between the group that became pre-frail in the next year and the group that remained robust. CONCLUSIONS: The PhA may be associated with frailty in RA patients.

Incidence of new carotid plaques in rheumatoid arthritis patients: 6-Year prospective results of the TOMORROW study.

OBJECTIVES: The purpose of this study was to evaluate the new incidence of carotid plaques in rheumatoid arthritis (RA) patients over a 6-year prospective follow-up and to assess the risk factors. METHODS: This is a 10-year prospective cohort study that included 208 RA patients and 205 age- and gender-matched controls. Ultrasound assessment of the bilateral carotid arteries was performed in 2011 and 2017. RESULTS: There were no differences in the incidence of new carotid atherosclerotic plaques over 6 years between the two groups (35.5% vs. 37.0%, respectively; p = .936). The mean Disease Activity Score 28-C-reactive protein over 6 years in RA patients was 2.73 ± 0.95. Multiple logistic regression analysis showed that RA was not a risk factor for new carotid atherosclerotic plaques (odds ratios, 0.708; 95% confidence interval, 0.348-1.440; p = .340). An average glucocorticoid dose of >1.8 mg/day over 6 years was a risk factor for new carotid atherosclerotic plaques (odds ratios, 8.54; 95% confidence interval, 1.641-44.455; p = .011). CONCLUSIONS: Incidence of new carotid atherosclerotic plaques was similar between well-controlled disease activity RA patients and control subjects. A mean glucocorticoid dose of >1.8 mg/day over 6 years was a risk factor for new carotid atherosclerotic plaques.

Neck pain and related factors in patients with rheumatoid arthritis.

OBJECTIVES: In rheumatoid arthritis, neck pain can be caused by inflammatory reactions or cervical lesions, but the prevalence and associated factors have not been well studied. This study aimed to investigate the prevalence of neck pain in patients with rheumatoid arthritis and elucidate the related factors. METHODS: This study included 146 patients with rheumatoid arthritis. Neck pain, quality of life, and levels of anxiety and depression were evaluated using a questionnaire. Cervical lesions and spinal alignment were evaluated using plain radiograph and magnetic resonance imaging. Factors associated with neck pain were analysed using a logistic regression model. RESULTS: Fifty-six per cent of the patients had neck pain, and the quality of life scores were significantly worse in these patients. Multivariate analysis revealed age, C7 sagittal vertical axis, upper cervical lesion, and endplate erosion as factors associated with neck pain in patients with rheumatoid arthritis. CONCLUSIONS: More than half the patients with rheumatoid arthritis suffer from neck pain, and neck pain affects the quality of life and activities of daily living. Neck pain was associated with upper cervical lesion and endplate erosion suggesting the importance of radiological examination in patients with rheumatoid arthritis and neck pain.

Risk factors for poor response to denosumab treatment in Japanese postmenopausal women with osteoporosis.

INTRODUCTION: Denosumab has been reported to increase bone mineral density (BMD) and suppress fractures, but poor responders are not uncommon. This study aimed to identify risk factors for poor response to denosumab treatment. This is the first study to explore risk factors for poor response to denosumab. MATERIALS AND METHODS: This retrospective observational study investigated 227 Japanese postmenopausal women who received denosumab with monitoring of BMD by dual-energy X-ray absorptiometry at 6-month intervals. Risk factors were identified using Cox's proportional hazard modeling. Poor responders were defined as not exceeding the least significant change of BMD from baseline for 3 years. RESULTS: Mean relative change from baseline for 3 years in lumbar spine (LS)-BMD, femoral neck (FN)-BMD, and total hip (TH)-BMD were 12.6%, 6.8%, and 6.1%, respectively. Numbers of poor responders were 10 in LS-BMD, 47 in FN-BMD, 38 in TH-BMD. Risk factors for poor response were concomitant glucocorticoid use for LS-BMD, low body mass index or initiation at higher BMD for FN-BMD, and pretreatment with bisphosphonates or initiation at higher BMD for TH-BMD. CONCLUSION: Risk factors for insufficient denosumab effect differed between BMD measurement sites. These results should be taken into consideration when selecting denosumab in clinical practice.

Incidence of and risk factors for spondylolisthesis, scoliosis, and vertebral fracture in rheumatoid arthritis.

INTRODUCTION: Although lumbar lesions such as spondylolisthesis, scoliosis, and vertebral fracture are not specific to rheumatoid arthritis (RA), the prevalence is high in RA patients. However, no longitudinal study has evaluated lumbar lesions in RA. This study aimed to investigate the incidence of and risk factors for lumbar lesions in RA by a prospective longitudinal cohort study. MATERIALS AND METHODS: The study cohort comprised 110 patients with RA from the 'analysis of factors for RA spinal disorders (AFFORD)' study who completed the secondary survey at a single orthopaedic outpatient RA clinic. Radiological examination included standing radiographs and magnetic resonance imaging (MRI) of the lumbar spine. New development of spondylolisthesis, scoliosis, and vertebral fracture were assessed between baseline and secondary survey. RESULTS: The incidences of spondylolisthesis, scoliosis, and vertebral fracture were 42%, 16%, and 12%, respectively, during a mean follow-up of 7 years. The independent risk factor for de novo scoliosis was poor control of RA (adjusted odds ratio [aOR] 4.81, p = 0.011), while the independent risk factors for new vertebral fracture was use of glucocorticoid at secondary survey (aOR 14.87, p = 0.012). Patients with de novo scoliosis exhibited more severe low back pain and lower quality of life than those without. CONCLUSION: The incidence of scoliosis was related in patients with poor control of RA, while new vertebral fracture was more common in patients with use of glucocorticoid. Control of disease activity might be important in preventing radiological lumbar disorders in RA.

Risk factors for low back pain increase in rheumatoid arthritis: Analysis of a 7-year follow-up study.

OBJECTIVE: Several studies have demonstrated that low back pain (LBP) is related to disease activity in patients with rheumatoid arthritis (RA). However, there is no longitudinal research. This study aimed to determine the impacts and risk factors for LBP increase in RA in a longitudinal cohort study. METHODS: The study evaluated 113 patients with RA who completed the secondary survey. LBP increase was defined as ≥1 standard deviation of mean change in visual analogue scale (VAS) between the baseline and secondary surveys. The impacts of LBP increase on quality of life (QOL) and psychological status were evaluated. Risk factors were assessed among patient demographic characteristics and radiological changes. RESULTS: Mean change in VAS for LBP was -0.8 ± 30.4 mm during a mean 7-year follow-up. LBP increase was defined as ≥30-mm increase in VAS for LBP. Patients with LBP increase had significantly lower QOL and worse mental status than patients without it. Poor control of RA was identified as an independent risk factor for LBP increase (odds ratio, 9.82, p = .001). CONCLUSION: Patients with poor control of RA were likely to experience LBP increase in the long term. Control of RA disease activity is important for control of LBP, QOL, and mental status.

A case of successful radiofrequency catheter ablation for atrial tachycardia originating from the inferior vena cava using high-resolution mapping.

A 60-year-old man presented with sustained supraventricular tachycardia. Atrial tachycardia (AT), with the earliest atrial activation (EAA) occurring at the ostium of the coronary sinus, was reproducibly induced. Three-dimensional electroanatomical mapping (3DEAM) using a 3.5-mm distal electrode tip linear catheter (Thermocool) and radiofrequency energy (RF) was performed at the fractionated atrial electrogram site. It preceded at 30 ms to the EAA but did not terminate AT. Further 3DEAM using a multielectrode mapping catheter (Pentaray) demonstrated a centrifugal propagation pattern at the boundary zone between the right atrium and inferior vena cava. RF application here terminated AT, which then became non-inducible.

Ultrasound assessment, unlike clinical assessment, reflects enthesitis in patients with psoriatic arthritis.

OBJECTIVES: Enthesitis is a major musculoskeletal manifestation of psoriatic arthritis (PsA). It is conventionally assessed clinically, by the presence of tenderness, despite its low reliability. However, ultrasound (US) provides a sensitive and feasible method for evaluating enthesitis. We investigated enthesitis as assessed clinically and by US in patients with PsA. METHODS: Forty-seven patients with PsA underwent US examination of the bilateral humeral medial epicondyles and insertions of the triceps, distal quadriceps, proximal/distal patellae, Achilles tendons, and plantar fascia. These 14 entheses were also clinically evaluated by tenderness. The correspondence between US and clinical enthesitis was evaluated, as well as their associations with inflammatory markers (C-reactive protein [CRP], matrix metalloproteinase-3 [MMP-3]), disease activity indices (Disease Activity in Psoriatic Arthritis [DAPSA], Disease Activity Score 28 joints [DAS28-CRP], Psoriatic Arthritis Screening and Evaluation [PASE], Psoriasis Area Severity Index [PASI]), radiographic damage (modified Total Sharp Score [mTSS]), and functional status (health assessment questionnaire [HAQ]), and axial involvement. RESULTS: Among 47 patients with PsA, 37 and 23 had US and clinical enthesitis, respectively. US and clinical enthesitis had very low concordance (kappa coefficient 0.04), with no correlation between enthesitis counts (r=0.15, p=0.30). The US enthesitis count correlated only with the MMP-3 level (r=0.41, p=0.007), whereas the clinical enthesitis count correlated with the DAPSA, DAS28-CRP, HAQ, and PASE (r=0.50, p<0.001; r=0.44, p=0.002; r=0.41, p=0.008; r=0.54, p<0.001, respectively). CONCLUSIONS: US and clinical enthesitis are completely different entities. US enthesitis, but not clinical enthesitis, reflects inflammatory conditions.

Comparison of median nerve stiffness with and without rheumatoid arthritis by ultrasound real-time tissue elastography: A propensity score matching study.

Objectives: This study aimed to compare median nerve stiffness measured by ultrasound real-time tissue elastography in patients with and without rheumatoid arthritis (RA and non-RA groups, respectively).Methods: Altogether, 402 hands of 201 RA group and 222 hands of 111 non-RA group were included in the study. Ultrasonography was performed to evaluate the circumference, cross-sectional area (CSA) and strain ratio as an elasticity of the median nerve at the inlet level of the carpal tunnel and the proximal portion of the carpal tunnel inlet. Using propensity score matching, the difference between RA and non-RA group were analyzed.Results: After propensity score matching, 135 hands in 104 RA group and 70 non-RA group were finally analyzed. There were no significant differences in the circumference and CSA of the median nerve between the two groups. The strain ratio of the median nerve was significantly higher in RA group than in non-RA group only at the inlet of the carpal tunnel level.Conclusions: The nerve stiffness in patients with RA measured by ultrasound real-time tissue elastography was higher than without RA. Inflammatory condition of the flexor tendon and wrist joint in patients with RA may generate fibrotic changes in the median nerve.Trial registration: University Hospital Medical Information Network Clinical Trials Registry: UMIN000015314.

Soybean isoflavone can protect against osteoarthritis in ovariectomized rats.

Osteoarthritis (OA) is a chronic and incurable disease and a leading cause of significant pain and disability that is closely associated with aging and obesity. An appropriate long-term therapy regimen is presently unknown. An estrogen deficiency after menopause increases the incidence and severity of OA in women. Soybean isoflavone have weak estrogenic effects in several organs and have been considered as a potentially safe natural selective estrogen receptor modulator. The present study aimed to determine the effects of isoflavone on cartilage degradation in ovariectomized rats. Six-month-old female Sprague-Dawley (SD) rats (n = 40) were randomly assigned to sham operation (n = 10), ovariectomy (OVX) (n = 15) or OVX + isoflavone (OVXI) (n = 15) groups. The OVXI group was fed with soybean isoflavone (51.0 mg/kg/day) for nine weeks, then knee joints were excised. Cartilage degradation was evaluated by toluidine blue staining joint specimens, and by comparing values for serum C-telopeptides of Type II collagen (CTX-II) and cartilage oligomeric matrix protein (COMP) between baseline and the end of the study. Cartilage damage scored by Toluidine blue staining was significantly lower in the OXVI, than the OVX group (P < 0.016). The CTX-II values before the surgical procedure and the end of experiment, did not significantly differ among the groups. Values for COMP in all samples were below detection limits in all samples. Soy bean isoflavone limited the degeneration of cartilage induced by OVX in rats.

Abatacept might increase bone mineral density at femoral neck for patients with rheumatoid arthritis in clinical practice: AIRTIGHT study.

We investigated the influence of abatacept (ABT) on bone mineral density (BMD) and bone metabolic markers (BMMs) in patients with rheumatoid arthritis (RA) compared to other biologic disease-modifying anti-rheumatic drugs (bDMARDs). This prospective, comparative, non-randomized study (the AIRTIGHT study; UMIN000005570) investigated the effects of ABT and other bDMARDs on bone metabolism. A total of 165 RA patients were divided into ABT (n = 50) and non-ABT (n = 115). We evaluated percentage changes in BMD (%ΔBMD) at the lumbar spine and femoral neck using dual-energy X-ray absorptiometry. Urinary levels of cross-linked N-telopeptide of type I collagen (uNTx) and bone-specific alkaline phosphatase (BAP) were used as markers of bone resorption and formation, respectively. No significant differences in 1-year completion rates were seen between ABT (64%) and non-ABT (72%; p = 0.387). The %ΔBMD at the femoral neck was significantly higher in the ABT group (0.97%) than in the non-ABT group (- 2.19%; p = 0.026). Whereas, no significant difference in %ΔBMD at the lumbar spine was observed between groups (ABT, - 0.40%; Non-ABT, - 1.67%; p = 0.524). No significant differences were observed in changes to uNTx or BAP. ABT treatment was significantly associated with increased BMD at the femoral neck (odds ratio (OR) 8.84; 95% CI 1.08-72.4; p = 0.04), and baseline lumbar osteoarthritis was significantly associated with BMD at the lumbar spine (OR 2.97; 95% CI 1.23-7.13; p = 0.02). The efficacy of ABT for increasing BMD at the femoral neck was superior to that of other bDMARDs. ABT may offer good efficacy for improving BMD at the femoral neck in patients with RA.

Use of bisphosphonate might be important to improve bone mineral density in patients with rheumatoid arthritis even under tight control: the TOMORROW study.

Although patients with rheumatoid arthritis (RA) are prone to osteoporosis, tight control of disease activity might have a positive effect on bone metabolism. We aimed to determine whether bisphosphonate use is still important to improve bone mineral density (BMD) in RA patients whose disease activity was tightly controlled and the dose of glucocorticoid was reduced. This study was a sub-analysis of the 10-year prospective cohort TOtal Management Of Risk factors in Rheumatoid arthritis patients to lOWer morbidity and mortality: the TOMORROW which started from 2010. We compared BMD between 192 patients with RA and age- and sex-matched volunteers between 2010 and 2013 using dual-energy X-ray absorptiometry (DXA) in whole body mode. We then determined ratios of changes in BMD (%ΔBMD) to assess factors influencing increases in BMD among the patients using multivariate logistic regression analysis. The BMD was significantly lower in the patients than in the controls at all sites surveyed during 2010 and 2013. The %ΔBMD of the total spine was significantly higher among the patients treated with, than without bisphosphonate (6.2 vs. 1.8%, P = 0.0001). Multivariate logistic regression analysis revealed that use of bisphosphonate was a significant factor contributing to BMD increase (odds ratio 2.13; 95% confidence interval, 1.03-4.38, P = 0.041). Meanwhile, use of biologic agents, reducing glucocorticoid dose, and control of disease activity were not significant factors for gain of BMD. The BMD was lower among patients with RA than non-RA controls. Use of bisphosphonate significantly increased the BMD of the spine in patients over a period of 3 years and was important for maintaining the BMD among patients with RA under the control of inflammation and disease activity.

Incidence rate of falls and its risk factors in patients with rheumatoid arthritis compared to controls: Four years of the TOMORROW study.

OBJECTIVE: Patients with rheumatoid arthritis (RA) have been recognized to experience falls frequently due to functional disabilities. The aim of this study was to prospectively investigate factors influencing falls in patients with RA compared to controls. METHODS: We compared the frequency of falls in 208 RA patients and 205 age- and sex-matched volunteers for four years and analyzed risk factors for falls in RA patients using multivariate regression analysis. RESULTS: No significant difference in the incidence rate of falls (/person-year) between patients with RA (median [interquartile range]: 0 [0, 0.5]) and controls (0 [0, 0.5]) was evident during four years. Logistic regression analysis identified age, sex, body mass index, history of falls, and lower limb implant at baseline as significant risk factors for falls. The highest quartile of anti-CCP antibody level (>300.6 U/ml) was the strongest predictor for multiple falls (odds ratio, 2.97; 95% confidence interval, 1.12-7.91, p = 0.029) among RA patients. CONCLUSION: During four years we could not observe the higher incidence rate of falls in RA patients compared to controls in our cohort. Subjects with a higher titer of anti-CCP antibody might be at higher risk of frequent falls among RA patients.

Loss of lean body mass affects low bone mineral density in patients with rheumatoid arthritis - results from the TOMORROW study.

OBJECTIVES: Osteoporosis is one of the complications for patients with rheumatoid arthritis (RA). Rheumatoid cachexia, the loss of lean body mass, is another. However, the relationship between decreased lean body mass and reduced bone mineral density (BMD) in patients with RA has not been well studied. METHODS: This study included 413 participants, comprising 208 patients with RA and 205 age- and sex-matched healthy volunteers. Clinical data, BMD, bone metabolic markers (BMM) and body composition, such as lean body mass and percent fat, were collected. Risk factors for osteoporosis in patients with RA including the relationship BMD and body composition were analyzed. RESULTS: Patients with RA showed low BMD and high BMM compared with controls. Moreover, lean body mass was lower and percent fat was higher in patients with RA. Lean body mass correlated positively and percent fat negatively with BMD. Lean body mass was a positive and disease duration was a negative independent factor for BMD in multivariate statistical analysis. CONCLUSION: BMD and lean body mass were significantly lower in patients with RA compared to healthy controls. Lean body mass correlated positively with BMD and decreased lean body mass and disease duration affected low BMD in patients with RA. TRIAL REGISTRATION: [UMIN Clinical Trials Registry, http://www.umin.ac.jp/ctr/ , UMIN000003876].

High frequency of vertebral fracture and low bone quality in patients with rheumatoid arthritis-Results from TOMORROW study.

OBJECTIVES: Osteoporosis is one of the complications in patients with rheumatoid arthritis (RA). In this study, we researched the morbidity of existing vertebral fractures and the risk factors for vertebral fractures in patients with RA. METHODS: This study included 413 participants, 208 patients with RA, and 205 age- and sex-matched controls without RA. Clinical data, radiographic assessment of vertebral fracture from T4 to L4 in thoracic and lumber spine, bone mineral density (BMD), and bone metabolic markers (BMM) were analyzed. RESULTS: Vertebral fractures were observed more frequently, severe and multiple in patients with RA. In the logistic regression analysis, age (adjusted odds ratios (OR): 1.07, 95% confidence interval (CI): 1.04-1.09) and RA (adjusted OR: 1.72, 95% CI: 1.04-2.83) were risk factors for existing vertebral fracture. Moreover, two bone matrix-related markers, undercarboxylated osteocalcin (ucOC) (adjusted OR: 1.68, 95% CI: 1.02-2.78), and urinary pentocidine (adjusted OR: 2.51, 95% CI: 1.48-4.24) were associated with existing vertebral fracture. CONCLUSIONS: High frequent, multiple, and severe vertebral fractures were found in patients with RA compared to the controls. Low bone quality might be the cause of the frequent prevalence of vertebral fracture in patients with RA.

Levels of interleukin-1 beta can predict response to tocilizumab therapy in rheumatoid arthritis: the PETITE (predictors of effectiveness of tocilizumab therapy) study.

Predicting the responses of patients with rheumatoid arthritis (RA) to tocilizumab is difficult, because inflammatory markers such as C-reactive protein rapidly normalize regardless of clinical efficacy. We aimed to identify factors that could predict response to tocilizumab. Sixty-five patients completed 52 weeks of tocilizumab therapy. Serum fibrinogen, D-dimer and interleukin (IL)-1ß levels were measured at baseline and after 4 weeks of therapy. Clinical responses to tocilizumab were assessed using disease activity score 28-erythrocyte sedimentation rate and the clinical disease activity index at baseline and after 52 weeks of therapy (UMIN Clinical Trials Registry No. UMIN000002246). Mean age was 60.5 years (range 22-85 years). Mean disease duration was 11.2 years (range 0-45 years). All patients had moderate-to-severe disease activity and were resistant to disease-modifying anti-rheumatic drugs and/or other biologics. Baseline IL-1ß levels were significantly lower in responders than in non-responders (p = 0.045), but multiple logistic regression analysis found no significant difference (adjusted odds ratio 2.74; 95 % confidence interval 0.84-8.95; p = 0.096). Low D-dimer and IL-1ß levels at 4 weeks predicted greater decrease in disease activity after 52 weeks of treatment (p = 0.005 and p < 0.001, respectively). Effects of tocilizumab at 52 weeks could be predicted from D-dimer and IL-1ß levels after 4 weeks of tocilizumab treatment. These markers might be more useful than current inflammatory markers for early-stage prediction of response to tocilizumab in RA.