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.

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.

Risk factor analysis of fragility fractures in rheumatoid arthritis: A 3-year longitudinal, real-world, observational, cohort study.

OBJECTIVES: To explore the risk factors for fragility fractures in rheumatoid arthritis (RA) patients using a 3-year longitudinal, observational cohort study. METHODS: This RA registry study included consecutive RA patients in the outpatient clinic of Chang Gung Memorial Hospital since September 1, 2014. The demographics, clinical characteristics, lifestyle, evidence of previous fracture, risk factors according to the Fracture Risk Assessment Tool (FRAX®), and the FRAX score of each participant were recorded. The participants were categorized into the new incident fracture (group A) and no incident fracture (group B) groups based on evidence or absence of new incident fractures and propensity score matching (age and gender, 1:2). RESULTS: Overall, 477 participants completed the 3-year observation period. After matching, 103 and 206 participants were allocated to groups A and B, respectively. The non-adjusted model revealed, presented as hazard ratio (HR) (95% confidence interval [CI]), that the presence of co-morbidity (1.80 [1.17-2.78], p = 0.008), Health Assessment Questionnaire Disability Index (1.35 [1.07-1.69], p = 0.010), lower baseline hip bone mineral density (0.11 [0.02-0.48], p = 0.004), longer disease duration (1.02 [1.00-1.04], p = 0.026), higher FRAX score of major fracture (1.03 [1.02-1.04], p<0.001) or hip fracture (1.03 [1.02-1.04], p<0.001), and previous fracture history (2.65 [1.79-3.94], p<0.001) were associated with new incident fracture. After adjustment, it was disclosed that a previous fracture is an independent risk factor for fragility fractures in RA patients (2.17 [1.20-3.90], p = 0.010). CONCLUSIONS: In addition to aging and disease-related factors, previous fracture history is the most important risk factor for fragility fractures in RA patients.

Different Effects of Biologics on Systemic Bone Loss Protection in Rheumatoid Arthritis: An Interim Analysis of a Three-Year Longitudinal Cohort Study.

Objective: To compare changes in bone mineral density (BMD) in rheumatoid arthritis (RA) patients receiving three-year conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD), tumor necrosis factor-α inhibitors (TNFi), and abatacept. Methods: Patients with RA were recruited from September 2014 to February 2021. Dual-energy X-ray absorptiometry was used to measure BMD at the femoral neck (FN), total hip (TH), and lumbar spine (L1-4) at enrollment and three years later. Changes in the BMD of each regimen group were analyzed. Multiple ordinary least squares regression was used with the dependent variables to develop a model to predict the change in BMD. Results: A total of 752 participants were enrolled and 485 completed the three-year follow-up period. Of these, 375 (Group I), 84 (Group II), and 26 (Group III) participants received csDMARDs, TNFi, and abatacept therapy, respectively. Considering both type of therapy and completion of the follow-up period, participants were divided into groups A (csDMARDs, n = 104), B (TNFi, n = 52), and C (abatacept, n = 26). Compared to baseline, BMD decreased significantly at FN (p = 0.003) and L1-4 (p = 0.002) in Group A and at L1-4 (p = 0.005) in Group B, but remained stable at all sites in Group C. In terms of regression-adjusted percent change in BMD, there was a significant difference seen at all measured sites between group C compared to both groups A and B (+0.8%, -2.7%, -1.8% at FN; +0.5%, -1.1%, -1.0% at TH; +0.8%, -2.0%, -3.5% at L1-4, respectively; all p < 0.05). Anti-osteoporosis therapy had a BMD-preserving effect in RA. Conclusion: Compared with csDMARDs and TNFi, abatacept may have a better BMD-preserving effect in RA. Anti-osteoporosis therapy can prevent systemic bone loss irrespective of RA therapy.

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.

Time-averaged disease activity of rheumatoid arthritis associated with long-term bone mineral density changes.

BACKGROUND: Rheumatoid arthritis (RA) is associated with poor bone mineral density (BMD). We designed the current study owing to the lack of long-term prospective studies regarding whether a high disease activity leads to increased bone loss. METHODS: We have continually enrolled patients with RA. According to the average disease activity score in 28 joints based on the erythrocyte sedimentation rate (DAS28-ESR) during follow-up, the patients were classified into remission, low disease activity, and moderate or high disease activity groups. Patients were examined with dual-energy X-ray absorptiometry at baseline and after 3 years of follow-up. BMD changes were compared among the groups. RESULTS: We have studied 477 patients. Overall BMD was significantly reduced from baseline to the 3-year follow-up (p < 0.05). After stratifying according to the time-averaged DAS28-ESR levels and use of anti-osteoporosis treatment (AOT), the BMD values of the femur and spine significantly increased in patients in the remission group with AOT. The BMD changes of different DAS28-ESR patients were further compared using the generalized estimation equation model. For the patients on AOT, the negative change in femoral BMD values of the moderate or high activity group was significant when compared with the remission group with positive BMD changes (regression coefficient, -0.038; 95% confidence interval, -0.055 to -0.021). CONCLUSION: For RA patients, if remission is achieved, AOT can better improve BMD, especially in the femur. In addition, moderate or high disease activity will lead to significant bone loss; therefore, disease activity must be actively controlled.

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 role of bone mineral density in therapeutic decision-making using the Fracture Risk Assessment Tool (FRAX): a sub-study of the Taiwan OsteoPorosis Survey (TOPS).

Fracture Risk Assessment Tool (FRAX)-based intervention threshold (IT) is widely applied for treatment decision-making; however, an IT based on FRAX without the measurement of bone mass density (BMD) has not been validated. The study demonstrated that estimates of fracture risk by FRAX without BMD were higher than those by FRAX with BMD in women with old age. INTRODUCTION: BMD is an integral component for bone strength assessment, but age-specific impacts of BMD on fracture risk assessment and therapeutic decision-making remained unclear. We aimed to investigate whether using BMD measurement changed the interpretation of the FRAX-based fracture probability assessment and treatment decision. METHODOLOGY: The database was provided by the Taiwanese Osteoporosis Association (TOA) which conducted a nationwide survey of BMD. We calculated the 10-year major and hip fracture probabilities using the FRAX for each participant, either with (FRAX + BMD) or without BMD (FRAX - BMD). Age-specific individual intervention thresholds (IITs) were established using the FRAX-based fracture risk, equivalent to a woman with a prior fracture. Participants whose FRAX scores of major fracture were greater than or equal to their IITs were deemed suitable for therapeutic intervention. RESULTS: A total of 14,007 postmenopausal women were enrolled. Compared with FRAX + BMD, FRAX - BMD predicted lower FRAX scores in major and hip fractures in subjects aged 40-60 years; however, FRAX - BMD estimated higher risks for those aged 61-90 years. The therapeutic decision using FRAX - BMD was concordant to that using FRAX + BMD in 90.5% of the subjects, especially in the younger age group (40-70 years). FRAX - BMD identified more treatment candidates (7.7-16.4%) among those aged 71-90 years. CONCLUSIONS: The FRAX scores are influenced by age, irrespective of the consideration of BMD. FRAX - BMD is able to identify more subjects for therapeutic intervention in the elderly population. We should reconsider the role of BMD at different ages for therapeutic decision-making.

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.

High power Doppler ultrasound score is associated with the risk of triangular fibrocartilage complex (TFCC) tears in severe rheumatoid arthritis.

In the distal radioulnar joint, the triangular fibrocartilage complex (TFCC) is an important stabilizer and are frequently found in patients with rheumatoid arthritis (RA) with wrist pain. This study was designed to predict TFCC tears using high-resolution ultrasound in severe RA. We retrospectively reviewed patients with severe RA. MRI and ultrasound were performed at baseline and after 1 year of follow-up. TFCC tears were recorded. The predictive factors for TFCC tears were analyzed by logistic regression. During the 1-year follow-up period, 54 patients were enrolled (42 females and 12 males), of whom 21 (38.9%) developed TFCC tears. The body mass index was 22.81±2.59 kg/m2 in the TFCC tear group compared with 23.61±2.76 kg/m2 in the non-tear group (p=0.136). The mean age was 55.14±9.54 years in the TFCC tear group compared with 56.45±14.04 years in the non-tear group (p=0.596). The tear group had a higher Disease Activity Score in 28 joints (DAS28) (6.36±0.47 vs 5.58±0.65, p=0.011) and higher power Doppler (PD) ultrasound score at the dorsal radiocarpal joint (1.90±1.30 vs 1.33±0.99, p=0.011) than the non-tear group. We found that high DAS28 (OR 2.96, 95% CI 1.95 to 4.50; p=0.001) and higher baseline PD score (OR 1.51, 95% CI 1.07 to 2.14; p=0.019) were significantly associated with a higher risk of TFCC tears by logistic regression. So we conclude a higher wrist PD score in severe RA predicted future TFCC tears. Therefore, we suggest to use PD score in such patients to monitor the risk of future TFCC tears.

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.

The impact of low-dose glucocorticoids on disease activity, bone mineral density, fragility fractures, and 10-year probability of fractures in patients with rheumatoid arthritis.

This study aimed to investigate the effect of low-dose glucocorticoids (LDGs) on disease activity, bone density, and fractures in patients with rheumatoid arthritis (RA). This was an interim analysis of the RA Registry. Demographic data and clinical characteristics, including fracture risk assessment tool, were collected. 25(OH) Vitamin D, bone mineral density (BMD), and intact parathyroid hormone were measured at enrollment. The study group were those who took LDGs (2.5-7.5 mg/day prednisolone or equivalent dose), and the others were included as the control group. A total of 425 participants were enrolled, including 85 (20%) in the control group and 340 (80%) in the study group. The demographics and clinical characteristics were comparable between the two groups. Compared with the control group, the LDGs group had a significantly lower vertebral BMD (L 1-4) (g/cm2), (0.854 vs 0.896, p=0.046), significantly higher rate of previous fractures (103 (30.3%) vs 13 (15.3%), p=0.006), higher 10-year probability of major fractures (14 (15.5) vs 8 (8.6), p<0.0001), and higher 10-year probability of hip fractures (4.4 (8.4) vs 2 (3.9), p<0.0001). Disease activity appeared to be similar in the patients with RA regardless of whether or not they received LDG treatment. However, the patients with RA who received LDG treatment had a lower BMD at the spine (L1-4) and a higher rate of previous fractures that was associated with a significantly higher 10-year probability of fractures than those who did not receive LDG treatment.

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.

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.

Beyond bone mineral density, FRAX-based tailor-made intervention thresholds for therapeutic decision in subjects on glucocorticoid: A nationwide osteoporosis survey.

Glucocorticoid-induced osteoporosis (GIOP) is the most common cause of secondary osteoporosis and confers a substantial risk for future fractures. Several recent guidelines for GIOP management have recommended the use of intervention thresholds to direct pharmacological therapy in those at high risk of fracture. The aim of this study was to analyze the characteristics of subjects on a glucocorticoid (GC) and to implement the Fracture Risk Assessment Tool (FRAX)-based intervention threshold for therapeutic decision-making.This was a cohort substudy of a nationwide osteoporosis screening program conducted in Taiwan from 2008 to 2011. All participants were requested to complete a questionnaire including FRAX elements, and antiosteoporosis medication (AOM) history was assessed before bone mineral density (BMD) measurement. GC users were recruited as the study group. Controls comprised randomly selected age- and sex-matched non-GC users. Individual intervention threshold (IIT) was set at individual-specific FRAX probability of a major osteoporotic fracture, relative to subjects with prior fractures. The characteristics and calculated IIT of all participants were analyzed.A total of 8704 participants were enrolled, including GC users (n = 807) and controls (n = 7897). There was no significant difference in BMD between GC users and controls. Clinical fracture risks, including previous fracture, parental hip fracture, rheumatoid arthritis, and secondary osteoporosis were higher in GC users than in controls. GC users had a higher 10-year probability of either major or hip fracture than controls. The proportion of GC users with a 10-year probability of major osteoporotic fracture above IIT was higher than in controls (75.0% vs 10.6%; P < 0.001). Only 20.3% of GC users and 30.5% of controls whose fracture risk was above IIT reported taking AOM.These findings suggest that more GC users should receive active intervention based on IIT, regardless of BMD. However, less than one-fourth of GC users whose fracture risk was above IIT received AOM, indicating that GIOP is markedly undertreated. We recommend commencing AOM for GIOP according to IIT, instead of BMD alone.

Predictor of Hand Radiological Progression in Patients With Rheumatoid Arthritis Receiving TNF Antagonist Therapy by Change in Grayscale Synovitis-A Preliminary Study.

OBJECTIVES: This prospective study aimed to compare synovial ultrasound scores to conventional measures (DAS28, CRP levels) in predicting radiographic progression in patients with rheumatoid arthritis under TNF antagonist therapy. METHODS: Patients with RA who received TNF antagonist therapy were enrolled, all of whom underwent clinical, laboratory, and ultrasonographic assessments with grayscale and power Doppler assessments of bilateral elbows (anterior and posterior recess), wrists (dorsal, palmar, and ulnar aspects), second and third MCP joints (dorsal and palmar recess), and PIP II and III (dorsal and palmar) at baseline and at 1, 3 months. Hand radiographic damage was evaluated using van der Heijde modified Total Sharp Score (TSS) at baseline and 12 months. RESULTS: Thirty-two patients (384 joints, 832 synovial sites) continued the same treatment regimen for 12 months and completed the study, 41.6% of whom showed radiographic progression during the study period. Baseline DAS28 (P = 0.123), CRP level (P = 0.177), grayscale synovitis (P = 0.092), and power Doppler synovitis (P = 0.120) could not predict radiological damage in the TNF antagonist therapy group. However, ΔTSS was significantly related to changes in grayscale synovitis between baseline and 1 month (P = 0.011), but not at 3 months (P = 0.591), and was not related to changes in the power Doppler score at 1 (P = 0.634) and 3 months (P = 0.298). CONCLUSIONS: Our data confirm that delayed improvement in grayscale synovitis between baseline and 1 month more accurately reflects 1-year radiological damage than conventional measures such as DAS28 score and CRP level. Therefore, we recommend serial ultrasound follow-up of patients with RA receiving TNF antagonist therapy.

Additive composite ABCG2, SLC2A9 and SLC22A12 scores of high-risk alleles with alcohol use modulate gout risk.

The aim of the present study was to evaluate the contribution of urate transporter genes and alcohol use to the risk of gout/tophi. Eight variants of ABCG2, SLC2A9, SLC22A12, SLC22A11 and SLC17A3 were genotyped in male individuals in a case-control study with 157 gout (33% tophi), 106 asymptomatic hyperuricaemia and 295 control subjects from Taiwan. The multilocus profiles of the genetic risk scores for urate gene variants were used to evaluate the risk of asymptomatic hyperuricaemia, gout and tophi. ABCG2 Q141K (T), SLC2A9 rs1014290 (A) and SLC22A12 rs475688 (C) under an additive model and alcohol use independently predicted the risk of gout (respective odds ratio for each factor=2.48, 2.03, 1.95 and 2.48). The additive composite Q141K, rs1014290 and rs475688 scores of high-risk alleles were associated with gout risk (P<0.0001). We observed the supramultiplicative interaction effect of genetic urate scores and alcohol use on gout and tophi risk (P for interaction=0.0452, 0.0033). The synergistic effect of genetic urate score 5-6 and alcohol use indicates that these combined factors correlate with gout and tophi occurrence.