Development and Comparison of Treatment Decision Tools for Glucocorticoid-Induced Osteoporosis.

Long-term Glucocorticoid (GC) use results in compromised bone strength and fractures, and several treatment recommendations have been developed to prevent fractures, but none have been validated in a real-world setting. This study aims to create a treatment decision tool and compares this tool to the treatment suggestions from the American College of Rheumatology (ACR), International Osteoporosis Foundation and European Calcified Tissue Society (IOF-ECTS), and GC-adjusted Fracture Risk Assessment Tool (GC-FRAX), above the intervention threshold. We utilized registry data gathered at Chang Gung Memorial Hospital at Kaohsiung, Taiwan, between September 2014 and April 2021. This research is a single-center, observational, and case-controlled study. We recruited participants using prednisone for at least 2.5 mg/day or the equivalent dose for over 3 months, excluding those younger than 40, those with malignancies, or those currently undergoing anti-osteoporosis therapy. The primary endpoint was new fragility fractures within 3 years, including morphometric vertebral fractures detected at baseline and with a follow-up thoracic-lumbar spine X-ray. Participants were randomly allocated into derivation and validation sets. We developed the Steroid-Associated Fracture Evaluation (SAFE) tool in the derivation cohort by assessing the weights of exploratory variables via logistic regression. Prediction performance was compared in the validation set by the receiver operating characteristic (ROC) curve, the area under the curve (AUC), and sensitivity and specificity. A total of 424 treatment-naïve subjects were enrolled, and 83 (19.6%) experienced new fractures within 3 years. The final formula of the SAFE tool includes osteoporosis (1 point), an accumulated GC dose ≥ 750 mg within 6 months (or equivalent prednisolone of ≥4.5 mg/day for 6 months) (1 point), a BMI ≥ 23.5 (1 point), previous fractures (1 point), and elderliness of ≥70 years (2 points). In the validation set, a treatment decision based on the SAFE ≥ 2 points demonstrated an AUC of 0.65, with a sensitivity/specificity/accuracy of 75.9/54.0/58.9, with an ACR of 0.56 (100.0/11.0/31.0), IOF-ECTS 0.61 (75.9/46.0/52.7), and GC-FRAX 0.62 (82.8/42.0/51.2). Among current GIOP recommendations, the SAFE score serves as an appropriate treatment decision tool with increased accuracy and specificity.

Factors associated with subclinical inflammation of wrist joints in rheumatoid arthritis patients with low or no disease activity- a RA ultrasound registry study.

BACKGROUND: To evaluate the factors to predict subclinical inflammation of wrist joints in patients with RA who are in clinical remission or low disease activity. METHODS: Gray scale and power Doppler ultrasound were performed on the dorsal radio-lunate of both wrists. The presence of synovitis, comorbidities, and use of disease modifying anti-rheumatic drugs were recorded. A Multivariable forward logistical regression model was used to identify factors associated with subclinical inflammation. RESULTS: There were 1248 patients (1010 females, 238 males; mean age: 60.0 ± 10.5 years ). 57.4% of patients in complete remission and low disease activity had sonographic inflammation. Multivariable forward logistic regression analysis indicated that male sex, smoking are positively associated with inflammation and that age, alcohol consumption, and use of methotrexate, glucocorticoid, or a biological therapy are negatively associated with inflammation. Use of biological agents decreased the risk of inflammation by 40.9%. CONCLUSIONS: There was evidence of subclinical inflammation in most patients who were in low or no disease activity, those with biological therapy had lower risk of subclinical inflammation.

Therapeutic effects of kefir peptides on adjuvant-induced arthritis in rats through anti-inflammation and downregulation of matrix metalloproteinases.

AIMS: Rheumatoid arthritis (RA) is a chronic autoimmune disease. Its pathological features are synovial inflammation, bone erosion, and joint structural damages. Our previous studies have shown that kefir peptides (KPs) can reduce cardiovascular disease, osteoporosis and renal inflammation. In this study, we further evaluate the efficacy of KPs on adjuvant-induced arthritis (AIA) in a rat model. MAIN METHODS: After the 14th day of adjuvant induction, rats were subsequently orally administered KPs (83 or 166 mg/day/kg) or tofacitinib (6.2 mg/day/kg) for 14 days. On the 28th day, the rats were anesthetized with isoflurane for ultrasonic, in vivo imaging system (IVIS), and radiographic imaging and then sacrificed for ankle tissues collection and analysis. In vitro, IL-1ß-treated human synovial cells (SW982) were subjected to anti-arthritis mechanism study in the presence of KPs. KEY FINDINGS: The results of ultrasonography, radiograph, histology, the expression of matrix metalloproteinases (MMPs), inflammatory cytokines and RANKL/OPG ratio demonstrated decreasing severity of synovitis and bone erosion in the ankle joints after KPs treatment. Activation of the NF-κB and MAPK pathways was significantly reduced in KPs treated AIA group. Furthermore, KPs attenuated IL-1ß-induced inflammatory cytokine production and the expression of MMPs in a human synovial cell line SW982. These results demonstrated that KPs alleviated adjuvant-induced arthritis in rats by inhibiting IL-1ß-related inflammation and MMPs production. SIGNIFICANCE: We concluded that KPs can exhibit anti-inflammatory effects by reducing the levels of macrophage-related inflammatory cytokines and MMPs, thus alleviating bone erosion in the ankle joint and constituting a potential therapeutic strategy for rheumatoid arthritis.

Hip BMD is associated with visceral fat change: a registry study of osteoporosis and sarcopenia.

Background: Osteoporosis increases the risk of fractures. Visceral fat is associated with cardiovascular disease (CVD). There is inadequate knowledge on the relationship between osteoporosis and visceral fat. The study aimed to evaluate the relationship between bone mineral density (BMD) and visceral fat mass in the elderly. Methods: This was a prospective cohort study. Subjects were enrolled from the Rheumatology Clinic. All subjects underwent baseline bone mineral density and body composition measurements using dual-energy X-ray absorptiometry. Results: A total of 321 patients including 288 females and 33 males were enrolled in this study. We followed up DEXA for 1 year for fat and muscle mass change and found that 162 (50.5%) had a decrease in fat mass, 129 (40.2%) had decreased visceral fat, and 138 (43%) had decreased muscle mass. Furthermore, we found that the baseline hip T score was correlated with visceral fat decrease. Using visceral fat decrease as the outcome, we found that hip T score could predict visceral fat loss: the higher the T score, the more visceral fat loss was found [p < 0.001, OR: 1.6, CI: (1.3-2.1)]. Conclusion: A high hip T score was associated with a future decrease in visceral fat, which may decrease the risk of atherosclerosis and CV risk. Therefore, evaluation of visceral fat may be useful for assessing CVD risk in patients with osteoporosis. Effective management of the risk of atherosclerosis and CVD is important in improving the life expectancy of these patients.

SOD3 and IL-18 Predict the First Kidney Disease-Related Hospitalization or Death during the One-Year Follow-Up Period in Patients with End-Stage Renal Disease.

End-stage renal disease (ESRD) patients experience oxidative stress due to excess exogenous or endogenous oxidants and insufficient antioxidants. Hence, oxidative stress and inflammation cause endothelial damage, contributing to vascular dysfunction and atherosclerosis. Therefore, ESRD patients suffer more cardiovascular and hospitalization events than healthy people. This study aims to test the correlations between ROS, SOD3, IL-2, IL-6, and IL-18 and the first kidney disease-related hospitalization or death events in ESRD patients undergoing regular hemodialysis. A total of 212 participants was enrolled, including 45 normal healthy adults and 167 ESRD patients on regular dialysis. Blood samples from all participants were collected for ROS, SOD3, IL-2, IL-6, and IL-18 measurement at the beginning of the study, and every kidney disease-related admission or death was recorded for the next year. Multivariate analysis was conducted by fitting a linear regression model, logistic regression model, and Cox proportional hazards model to estimate the adjusted effects of risk factors, prognostic factors, or predictors on continuous, binary, and survival outcome data. The results showed that plasma SOD3 and serum IL-18 were two strong predictors of the first kidney disease-related hospitalization or death. In the Cox proportional hazards models (run in R), higher IL-18 concentration (>69.054 pg/mL) was associated with a hazard ratio of 3.376 for the first kidney disease-related hospitalization or death (95% CI: 1.2644 to 9.012), while log(SOD3) < 4.723 and dialysis clearance (Kt/V; 1.11 < value < 1.869) had a hazard ratio = 0.2730 (95% CI: 0.1133 to 0.6576) for reducing future kidney disease-related hospitalization or death. Other markers, including body mass index (BMI), transferrin saturation, total iron binding capacity, and sodium and alkaline phosphate, were also found to be significant in our study. These results reveal the new predictors SOD3 and IL-18 for the medical care of end-stage renal disease patients.

The Impact of Seropositivity on Systemic Bone Loss in Rheumatoid Arthritis-A 3-Year Interim Analysis of a Longitudinal Observational Cohort Study.

Objective: To explore the impact of seropositivity on systemic bone loss in rheumatoid arthritis (RA). Methods: We conducted an interim analysis of the RA registry. Patients were examined with dual-energy X-ray absorptiometry at baseline and again 3 years later. Participants were grouped into seropositive (SPRA) and seronegative (SNRA) based on the presence or absence of rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide antibodies (ACPA). After matching (1:2) for age and sex, SNRA and SPRA patients were divided into groups A and B. Each matched group (A or B) was further subdivided according to the number of antibodies present (0, group I; 1, group II; 2, group III). Multiple ordinary least squares regression was used with the dependent variables to develop a model to predict bone mineral density (BMD) change. Results: A total of 477 participants who completed a 3-year observation period were included. After matching, 312 participants were enrolled (group A, 104; group B, 208). Three years later, group B had significant BMD reduction in the femoral neck (FN) (p < 0.001), total hip (TH) (p = 0.001), and first through fourth lumbar vertebrae (L1-4) (p = 0.006), while group A had bone loss only at FN (p = 0.002). Groups I, II, and III included 104, 52, and 156 participants, respectively. Compared to baseline, BMD decreased significantly at FN (p = 0.002) in group I, FN (p < 0.001) in group II, and FN (p < 0.001), TH (p = 0.002), and L1-4 (p = 0.016) in group III. In terms of regression-adjusted percent change in BMD, more significantly negative changes were found at all measured sites in group B (p < 0.001, all) and at TH and L1-4 within groups I-III (p for trend < 0.001 and < 0.001, respectively). Regardless of antibodies, anti-osteoporotic therapy can preserve bone density in RA patients. Conclusion: After 3 years, SPRA patients lost more bone density than SNRA patients. More attention should be paid to SPRA patients, especially those with double-positive antibodies, including a vigorous evaluation of BMD and fracture risk. Anti-osteoporotic therapy can prevent BMD loss irrespective of autoantibodies.

Establishment of a preliminary FRAX®-based intervention threshold for rheumatoid arthritis-associated fragility fracture: a 3-year longitudinal, observational, cohort study.

BACKGROUND: To establish a FRAX®-based prediction model for rheumatoid arthritis (RA)-associated fragility fracture. METHODS: This study is a longitudinal, real-world, registry cohort study. Patients with RA were registered to start in September 2014. The baseline demographics, bone mineral density (BMD), and risk factors of osteoporosis or fragility fracture were recorded. Subsequent fragility fractures during the 3-year observation period were also recorded. We developed a fixed intervention threshold (FITD) to identify fractures by choosing an optimal cut-off point on the receiver operating characteristic (ROC) curve and FRAX®. Several models for intervention thresholds (IT), including fixed intervention threshold (Taiwan) (FITT), age-specific individual intervention threshold (IIT), and hybrid intervention threshold (HIT), were compared to evaluate which IT model will have better discriminative power. RESULTS: As of December 2020, a total of 493 RA participants have completed the 3-year observation study. The mean age of the participants was 59.3 ± 8.7, and 116 (23.5%) new fragility fractures were observed during the study period. In terms of pairwise comparisons of area under the curve (n, 95% confidence interval) in the ROC curve, the FITD (0.669, 0.610-0.727, p < 0.001) with a value of 22% in major osteoporotic fracture and FITT (0.640, 0.582-0.699, p < 0.001) is significantly better than reference, but not for IIT (0.543, 0.485-0.601, p = 0.165) and HIT (0.543, 0.485-0.601, p = 0.165). CONCLUSION: An optimal FIT is established for intervention decisions in RA-associated fragility fractures. This model can offer an easy and simple guide to aid RA caregivers to provide interventions to prevent fragility fractures in patients with RA.

Effects of Mean Artery Pressure and Blood pH on Survival Rate of Patients with Acute Kidney Injury Combined with Acute Hypoxic Respiratory Failure: A Retrospective Study.

Background and Objectives: In the intensive care unit (ICU), renal failure and respiratory failure are two of the most common organ failures in patients with systemic inflammatory response syndrome (SIRS). These clinical symptoms usually result from sepsis, trauma, hypermetabolism or shock. If this syndrome is caused by septic shock, the Surviving Sepsis Campaign Bundle suggests that vasopressin be given to maintain mean arterial pressure (MAP) > 65 mmHg if the patient is hypotensive after fluid resuscitation. Nevertheless, it is important to note that some studies found an effect of various mean arterial pressures on organ function; for example, a MAP of less than 75 mmHg was associated with the risk of acute kidney injury (AKI). However, no published study has evaluated the risk factors of mortality in the subgroup of acute kidney injury with respiratory failure, and little is known of the impact of general risk factors that may increase the mortality rate. Materials and Methods: The objective of this study was to determine the risk factors that might directly affect survival in critically ill patients with multiple organ failure in this subgroup. We retrospectively constructed a cohort study of patients who were admitted to the ICUs, including medical, surgical, and neurological, over 24 months (2015.1 to 2016.12) at Chiayi Chang Gung Memorial Hospital. We only considered patients who met the criteria of acute renal injury according to the Acute Kidney Injury Network (AKIN) and were undergoing mechanical ventilator support due to acute respiratory failure at admission. Results: Data showed that the overall ICU and hospital mortality rate was 63.5%. The most common cause of ICU admission in this cohort study was cardiovascular disease (31.7%) followed by respiratory disease (28.6%). Most patients (73%) suffered sepsis during their ICU admission and the mean length of hospital stay was 24.32 ± 25.73 days. In general, the factors independently associated with in-hospital mortality were lactate > 51.8 mg/dL, MAP ≤ 77.16 mmHg, and pH ≤ 7.22. The risk of in-patient mortality was analyzed using a multivariable Cox regression survival model. Adjusting for other covariates, MAP ≤ 77.16 mmHg was associated with higher probability of in-hospital death [OR = 3.06 (1.374-6.853), p = 0.006]. The other independent outcome predictor of mortality was pH ≤ 7.22 [OR = 2.40 (1.122-5.147), p = 0.024]. Kaplan-Meier survival curves were calculated and the log rank statistic was highly significant. Conclusions: Acute kidney injury combined with respiratory failure is associated with high mortality. High mean arterial pressure and normal blood pH might improve these outcomes. Therefore, the acid-base status and MAP should be considered when attempting to predict outcome. Moreover, the blood pressure targets for acute kidney injury in critical care should not be similar to those recommended for the general population and might prevent mortality.

Epidemiology and mortality of connective tissue disease-associated pulmonary arterial hypertension: A national cohort study in taiwan.

OBJECTIVE: To estimate and compare the incidence and survival impact of pulmonary arterial hypertension (PAH) among patients with various connective tissue diseases (CTDs). METHODS: We used a national health insurance database in Taiwan and enrolled patients with incident systemic sclerosis (SSc), systemic lupus erythematosus (SLE), primary Sjögren's syndrome (pSS), polymyositis/dermatomyositis (PM/DM) and rheumatoid arthritis (RA) between 2002 and 2013. We calculated the cumulative incidence of PAH and the probability of survival after PAH diagnosis by the Kaplan-Meier method. RESULTS: Of 1653 SSc patients, 127 (7.68%) developed PAH. Of 11,735 SLE patients, 242 (2.06%) developed PAH. Of 17,316 pSS patients, 1811 PM/DM patients, and 32,296 RA patients, 38 (0.22%), 6 (0.33%) and 15 (0.04%) patients developed PAH, respectively. The most common CTD among all CTD-PAH patients was SLE (57%), followed by SSc (30%), pSS (9%), RA (3%) and PM/DM (1%). The 1-, 3- and 5-year survival rates for SSc-PAH were 88.3%, 72.1% and 61.9%, respectively. The 1-, 3- and 5-year survival rates for SLE-PAH were 87.6%, 75.8% and 69.4%, respectively. The 1-, 3- and 5-year survival rates for pSS-PAH were 90.8%, 86.8% and 80.6%, respectively. CONCLUSIONS: SLE was the most common underlying CTD, followed by SSc, in the total CTD-PAH population. However, the highest risk of developing PAH was observed in the SSc groups. PAH is a very rare complication in pSS, PM/DM and RA. Patients with SSc-PAH have the worst survival rate compared to those with SLE-PAH or pSS-PAH.

The impact of long-term biologics/target therapy on bone mineral density in rheumatoid arthritis: a propensity score-matched analysis.

OBJECTIVES: To investigate changes in BMD in RA patients receiving 3-year biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) or conventional synthetic DMARD (csDMARD). METHODS: Patients with RA were recruited from September 2014 until March 2019. Clinical characteristics, BMD and evidence of fragility fractures at enrolment were documented. Participants were treated according to the National Institute for Health and Care Excellence (NICE) guidelines over a 3-year observation period. Repeated BMD was measured at the end of the study period. Participants were grouped into those receiving b/tsDMARD or csDMARD and by propensity score matching (1:2). RESULTS: A total of 388 participants completed the 3-year follow-up. After propensity score matching, 92 and 184 participants were allocated to the b/tsDMARD (Group I) and csDMARD (Group II), respectively. After 3 years, BMD remained stable at the femoral neck (FN), hip (total) (TH) and lumbar vertebra (L1-4) (P =0.09, 0.15, 0.87) in Group I. However, BMD decreased significantly in Group II (P=0.045, <0.001, 0.004) at corresponding sites. Participants receiving combined b/tsDMARD and anti-osteoporosis therapy experienced a greater BMD preserving effect than other subgroups. CONCLUSION: Long-term b/tsDMARDs therapy had protective effects on bone loss for patients with RA. Patients receiving concomitant anti-osteoporosis therapy and b/tsDMARDs therapy experienced the greatest BMD preserving effect.

Novel algorithm generating strategy to identify high fracture risk population using a hybrid intervention threshold.

INTRODUCTION: The aim of this study was to develop an algorithm to identify high-risk populations of fragility fractures in Taiwan. MATERIALS AND METHODS: A total of 16,539 postmenopausal women and men (age ≥ 50 years) were identified from the Taiwan Osteoporosis Survey database. Using the Taiwan FRAX® tool, the 10-year probability of major osteoporotic fracture (MOF) and hip fracture (HF) and the individual intervention threshold (IIT) of each participant were calculated. Subjects with either a probability above the IIT or those with MOF ≥ 20% or HF ≥ 9% were included as group A. Subjects with a bone mineral density (BMD) T-score at femoral neck based on healthy subjects of ≤ - 2.5 were included in group B. We tested several cutoff points for MOF and HF so that the number of patients in group A and group B were similar. A novel country-specific hybrid intervention threshold along with an algorithm was generated to identify high fracture risk individuals. RESULTS: 3173 (19.2%) and 3129 (18.9%) participants were categorized to groups A and B, respectively. Participants in group B had a significantly lower BMD (p < 0.001), but clinical characteristics, especially the 10-year probability of MOF (p < 0.001) or HF (p < 0.001), were significantly worse in group A. We found the algorithm generated from the hybrid intervention threshold is practical. CONCLUSION: The strategy of generating an algorithm for fracture prevention by novel hybrid intervention threshold is more efficient as it identifies patients with a higher risk of fragility fracture and could be a template for other country-specific policies.

The effect of pilocarpine on dental caries in patients with primary Sjögren's syndrome: a database prospective cohort study.

BACKGROUND: Primary Sjögren's syndrome (pSS) is associated with dental caries. Pilocarpine, a salivary stimulant, can improve the amount and flow rate of saliva in patients with pSS. This study aimed to assess whether the risk of dental caries decreases with the use of pilocarpine in patients with pSS. METHODS: For this prospective cohort study, we identified pSS patients from the catastrophic illnesses registry of the National Health Insurance Research Database of Taiwan between 2009 and 2013. We divided participants into pilocarpine and non-user groups based on the pilocarpine prescriptions available during the first 3-month follow-up. The primary endpoint was dental caries. The secondary endpoints were periodontitis and oral candidiasis. We compared the risk of these oral manifestations using the Cox proportional hazard model. RESULTS: A total of 4973 patients with new-onset pSS were eligible for analysis. After propensity score matching, we included 1014 patients in the pilocarpine group and 2028 patients in the non-user group. During the mean follow-up of 2.6 years, the number of events was 487 in the pilocarpine group (48.0%) and 1047 in the non-user group (51.6%); however, the difference was not significant (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.82 to 1.06). Furthermore, there was no significant difference between groups regarding risk of periodontitis (HR 0.91, 95% CI 0.81 to 1.03) and oral candidiasis (HR 1.16, 95% CI 0.70 to 1.94). CONCLUSION: Pilocarpine may have no protective effect on dental caries, periodontitis, or oral candidiasis in patients with pSS.

Adherence to anti-osteoporosis medication associated with lower mortality following hip fracture in older adults: a nationwide propensity score-matched cohort study.

BACKGROUND: We investigated the association of anti-osteoporosis medication with mortality risk in older adults with hip fractures and evaluated the influence of medication adherence on mortality. METHODS: We conducted a population-based cohort study and identified a total of 13,123 patients aged 65 years or older with hip fracture from the Taiwan National Health Insurance Database during the period 2001-2010. Individuals with (n = 2092) and without (n = 2092) receiving anti-osteoporosis medication were matched using propensity score matching (1:1 ratio). The 1-, 3- and 5-year survival rates after the index fracture were compared between patients with and without treatment. In the treated group, survival rate was compared between those with good and non-adherence. Good adherence was defined as the medication possession ratio of ≥80% and non-adherence as a ratio < 80%. RESULTS: The 1-, 3- and 5-year mortality rates were significantly lower in the treated vs. the non-treated group (all p < 0.0001). In the treated group, the estimated 1-, 3- and 5-year survival rates were higher in those with good adherence than in those with non-adherence (all p < 0.0001). Regarding all-cause mortality, the adjusted hazard ratio in the treated vs. the non-treated group was 0.63 (95% confidence interval 0.58-0.68, p < 0.0001). The good adherence subgroup showed a significantly lower mortality risk than that in the non-adherence subgroup (hazard ratio 0.41, 95% confidence interval 0.32-0.51, p < 0.0001). CONCLUSIONS: The 1-, 3- and 5-year survival rates were significantly higher in patients receiving anti-osteoporosis medication than in the untreated group. All-cause mortality rates were lower in patients with good adherence to anti-osteoporosis medication.

Comparing the burdens of opportunistic infections among patients with systemic rheumatic diseases: a nationally representative cohort study.

OBJECTIVE: To estimate and compare the burdens of opportunistic infections and herpes zoster in real-world practice among patients with various systemic rheumatic diseases. METHODS: This 13-year cohort study used national health insurance data to compare the incidence rates (IRs) of nine opportunistic infections among patients with five rheumatic diseases. The analyses were stratified according to follow-up duration using Poisson regression, and Cox models were used to compare the risk of first opportunistic infection. RESULTS: During 2000-2013, we identified 76,966 patients who had polymyositis/dermatomyositis (PM/DM, 2270 cases), systemic lupus erythematosus (SLE, 15,961 cases), systemic sclerosis (SSc, 2071 cases), rheumatoid arthritis (RA, 38,355 cases), or primary Sjögren's syndrome (pSS, 18,309 cases). The IR of opportunistic infections was highest for PM/DM cases (61.3/1000 person-years, 95% confidence interval [CI] 56.6-66.2), followed by SLE cases (43.1/1000 person-years, 95% CI 41.7-44.5), SSc cases (31.6/1000 person-years, 95% CI 28.3-35.1), RA cases (25.0/1000 person-years, 95% CI 24.4-25.7), and pSS cases (24.1/1000 person-years, 95% CI 23.1-25.2). Multivariable Cox analysis revealed that, relative to SLE, PM/DM was associated with a significantly higher risk of opportunistic infections (hazard ratio 1.18, 95% CI 1.08-1.29). The risk of opportunistic infections was highest during the first year after the diagnosis of all five rheumatic diseases. CONCLUSIONS: The risk of opportunistic infection was highest for PM/DM, followed by SLE, SSc, RA, and pSS. Careful observation and preventive therapy for opportunistic infections may be warranted in selected PM/DM patients, especially during the first year after the diagnosis.

High prevalence and correlates of osteoporosis in men aged 50 years and over: A nationwide osteoporosis survey in Taiwan.

AIMS: Osteoporosis is one of the consequences of aging, and it remains underdiagnosed and undertreated; this study aimed to present the characteristics and prevalence of osteoporosis in elderly men by conducting a nationwide survey in Taiwan. METHODS: The participants were enrolled between 2008 and 2011, and bone mineral density (BMD) was measured via dual-energy X-ray absorptiometry for the hip (total), lumbar spine (L1-4), and femoral neck (FN). Patients with rheumatoid arthritis, female patients, and those using steroids were excluded. Osteoporosis was defined as a T-score at the FN of ≤-2.5. RESULTS: This study included 3734 men of mean age 70.0 ± 9.3 years, accounting for the prevalence of osteoporosis at 9.7%. Participants with osteoporosis had a significantly older age, lower body weight, shorter height and more previous fractures than those without osteoporosis. The mean BMD at FN was 0.534 ± 0.056 and 0.791 ± 0.115 (g/cm2 ) in participants with and without osteoporosis, respectively (P < 0.001). The FN and hip (total) BMD showed a significant negative correlation with age (r = -0.234, P < 0.001) and (r = -0.003, P < 0.001), respectively, but not at L1-4 (r = 0.00, P = 0.540). A history of fracture is the most important risk factor associated with male osteoporosis (odds ratio, 2.50; 95% CI, 1.49-4.21; P = 0.006). CONCLUSIONS: The associated factors for male osteoporosis are aging, lower body weight, and a history of fracture; the BMDs at FN and hip (total), but not L1-4, are inversely correlated with age. We recommend that BMD at the proximal femur be the preferred site to evaluate osteoporosis for elderly male subjects.

Ultrasound is more reliable than inflammatory parameters to evaluate disease activity in patients with RA receiving tocilizumab therapy.

The target of treatment for rheumatoid arthritis (RA) is to keep low disease activity or remission. Tocilizumab can fully inhibit interleukin-6 and C reactive protein (CRP) production. The goal of the study is to search whether tocilizumab treatment compared with adalimumab treatment had the similar effect on sonography and inflammatory parameters in patients with RA. We compared ultrasound scores and inflammatory parameters between patients with RA receiving tocilizumab therapy and those receiving adalimumab therapy. Power Doppler (PD) ultrasound and grayscale synovial hypertrophy on bilateral radiocarpal joints were performed. Inflammatory mediators and ultrasound scores were compared by independent t-test between the adalimumab and tocilizumab groups. 65 patients with RA (32 tocilizumab and 33 adalimumab) were included. Between the two groups, there were no significant differences in age, gender, rheumatoid factors and anticyclic citrullinated peptide antibody. Following biological therapy, the ultrasound score was 2.33 in the tocilizumab group and 2.08 in the adalimumab group (p=0.570), while the erythrocyte sedimentation rate, CRP and Disease Activity Score in 28 joints (DAS28) were lower in the tocilizumab group. So ultrasound scores between the two groups were not significantly different, but the laboratory parameters and DAS28 were lower in the tocilizumab group than in the adalimumab group. Hence, to assess disease activity cannot be based only on clinical evaluations, so we suggest PD ultrasound to be used for all patients on tocilizumab therapy and reflect the true disease activity in these patients.

Anti-CCP-positive patients with RA have a higher 10-year probability of fracture evaluated by FRAX®: a registry study of RA with osteoporosis/fracture.

BACKGROUND: Positive anticyclic citrullinated peptide (anti-CCP+) is associated with bone loss in patients with rheumatoid arthritis (RA). However, whether overall positivity or specific levels of anti-CCP are associated with prevalent fracture or a 10-year probability of fracture remains unclear. METHODS: This interim analysis of an RA registry was conducted at Chang Gung Memorial Hospital in Kaohsiung (CGMHK) for RA-related osteoporosis/fracture. Consecutive patients with RA who had visited the rheumatology clinic at CGMHK since September 1, 2014, and fulfilled the classification criteria of RA were enrolled. The demographics, disease duration, Disease activity in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR), lifestyle, evidence of previous fracture, risk factors of fracture in the Fracture Risk Assessment Tool (FRAX®), and FRAX® score of each participant were collected. Anti-CCP, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and bone mineral density (BMD) were measured at enrollment. The patients were grouped by positivity or quartiles of anti-CCP level (I-IV). RESULTS: Five hundred twenty-one patients with RA were enrolled through May 31, 2016. In total, 359 (68.9%) patients were anti-CCP+. Compared with anti-CCP- patients, anti-CCP+ patients had a significantly higher DAS28-ESR (p = 0.0001) and 10-year probability of major (15.0 [18.9] vs. 12.0 [15.3], p = 0.0461) or hip (5.0 [9.2] vs. 3.6 [8.2], p = 0.0118) fracture, but a significantly lower BMD of the FN (p = 0.0196). The rates of osteoporosis and previous fracture were comparable. There were 130, 127, 132, and 132 patients in groups I-IV, respectively. The DAS28-ESR was significantly different (p = 0.0001) among the groups and correlated to anti-CCP levels. The BMD and 10-year probability of major (p = 0.0067) and hip (p = 0.0013) fracture among the groups were also different. CONCLUSIONS: Anti-CCP+ RA patients had a higher 10-year probability of major or hip fracture, independent of anti-CCP levels, and a lower BMD of the FN than anti-CCP- patients.

Biological tapering and sonographic flare in rheumatoid arthritis.

This study aimed to evaluate the risk of ultrasound-detected synovitis after antitumor necrosis factor (TNF) tapering in patients with rheumatoid arthritis. We recruited patients with rheumatoid arthritis who accepted TNF tapering. Gray-scale synovitis and power Doppler score in bilateral wrists at the dorsal radiolunate joint were evaluated. We defined a sum of bilateral wrist scores of ≥2 as sonographic inflammation. Logistical regression analysis was used to adjust for confounding factors. One hundred and twenty-two patients who received a tapered dose of anti-TNF were enrolled, of whom 96 (78%) had ultrasound-detected synovitis and 26 had no inflammation. There were no significant differences in age, gender, body mass index, antinuclear antibodies, rheumatoid factor or anticitrullinated protein antibodies between the inflammation and non-inflammation groups. Moderate tapering of anti-TNF (tapering 50%) was more common in the patients with ultrasound-detected synovitis than mild tapering (tapering 25%) (68.8% vs 38.5%, p=0.005). After adjusting for age, body mass index, gender and a 28-joint Disease Activity Score, the moderate tapering group still had a higher risk of ultrasound-detected synovitis (OR 5.786, 95% CI 1.986 to 16.852; p=0.001); that is, the moderate tapering group had a 5.786 times higher risk of developing sonographic inflammation than the mild tapering group. The dose of biological tapering was the major determinant of ultrasound synovitis. Patients with moderate tapering had a higher risk of synovitis than those with mild tapering. We recommend not tapering by more than 25% to reduce subclinical inflammation and future joint damage.

Anti-TNF-Alpha-Adalimumab Therapy Had Time Lag of Improvement in Synovial Hypertrophy Compared to Rapid Response in Power Doppler Synovial Vascularity.

OBJECTIVES: The quantification of synovitis is of great significance for follow-up in patients with rheumatoid arthritis (RA). This study aimed to validate the use of power Doppler ultrasonography (PDUS) for evaluating synovial vascularity and synovial hypertrophy for synovitis in patients with rheumatoid arthritis treated with adalimumab. MATERIALS AND METHODS: The synovial disease activity and vascularity of RA on both wrists (radio-carpal joint) were assessed using GS and PDUS to derive the composite US scores based on abnormal counts and severity. The relationship between each measure was determined. RESULTS: The 71 patients who received adalimumab therapy had significantly decreased DAS28, ESR, and CRP. After one month, PD score decreased and then remained low for 12 months. Synovial hypertrophy did not change until 3-6 months after, when it started to improve (p = 0.017). By multivariate analysis, sex, age, BMI, and DAS28 did not lead to any difference between synovial hypertrophy and PDUS changes (p = 0.498). DISCUSSION: Composite US markers of synovial hypertrophy correlate significantly to the DAS28 score and ESR/CRP in adult RA. The time needed for synovial hypertrophy to decrease may be up to 3-6 months after adalimumab therapy. Switching to biological therapy before 3-6 months is inappropriate and ineffective.

Delayed anti-TNF therapy increases the risk of total knee replacement in patients with severe rheumatoid arthritis.

BACKGROUND: This study evaluated the effect of early anti-tumor necrosis factor (TNF) therapy in patients with severe rheumatoid arthritis (RA) on the subsequent risk of total knee replacement (TKR) surgery. METHODS: This retrospective observational study included a hospital-based cohort of 200 patients diagnosed with severe RA who received treatment with anti-TNF therapy between 2003 and 2014. Clinical parameters including age, sex, body mass index, and the time from the diagnosis of RA to the initiation of anti-TNF therapy were analyzed. RESULTS: Of the 200 enrolled patients, 84 underwent an early intervention (≤3 years from the diagnosis of RA to the initiation of anti-TNF therapy), and 116 underwent a late intervention(>3 years from the diagnosis of RA to the initiation of anti-TNF therapy). Five (6.0%) patients in the early intervention group underwent TKR compared to 31 (26.7%) in the late intervention group (p = 0.023). After adjusting for confounding factors, the late intervention group still had a significantly higher risk of TKR (p = 0.004; odds ratio, 5.572; 95% confidence interval, 1.933-16.062). Those receiving treatment including methotrexate had a lower risk of TKR (p = 0.004; odds ratio, 0.287; 95% confidence interval, 0.122-0.672). CONCLUSIONS: Delayed initiation of anti-TNF therapy in the treatment of severe RA was associated with an increased risk of TKR surgery. Adding methotrexate treatment decreased the risk of future TKR.