Clinical efficacy of alternative TNF inhibitor and secukinumab between primary non-responder and secondary non-responder of prior TNF inhibitor in ankylosing spondylitis.

OBJECTIVES: To compare the drug retention times and clinical efficacy of alternative tumour necrosis factor inhibitors (TNFi) and secukinumab in primary and secondary non-responders with ankylosing spondylitis (AS). METHODS: AS patients treated with biologics and enrolled in the Korean College of Rheumatology Biologics registry were examined. Patients who did not respond to previous TNFi treatment were defined as primary and secondary non-responders. Data regarding drug discontinuation and clinical efficacy were collected after 1 year. Kaplan-Meier and Cox regression analyses were performed to compare drug survival and associated factors. Logistic regression analyses were conducted to compare the clinical efficacy secukinumab with that of alternative TNFi. RESULTS: In total, 124 patients (83 receiving alternative TNFi and 41 receiving secukinumab) had biologic changes due to clinical inefficacy. Drug retention rates in the alternative TNFi and secukinumab groups were similar (P = 0.096). However, subgroup analyses including only secondary non-responders revealed that secukinumab users showed a higher hazard ratio (HR) for drug discontinuation (HR = 3.77, P = 0.045). In addition, secukinumab was negatively associated with achieving BASDAI50 or a major improvement in the ASDAS. CONCLUSION: Alternative TNFi showed better drug retention and clinical efficacy in AS patients experiencing previous TNFi failure, in secondary non-responders. Therefore, alternative TNFi may be a more suitable treatment for secondary non-responders.

Biologic retention rate and efficacy in patients with cluster-based phenotypes of ankylosing spondylitis: data from a Korean national biologics registry.

OBJECTIVES: Patients with ankylosing spondylitis (AS) have a heterogenic disease course and treatment response. Cluster-based phenotypes are useful for predicting AS disease course. Here, we compared drug retention and clinical efficacy of biologic disease-modifying anti-rheumatic drugs (bDMARDs) in AS patients with cluster A and cluster B phenotypes. METHODS: AS patients enrolled in the Korean College of Rheumatology BIOlogics registry were divided into cluster A (axial symptoms predominant) and cluster B (both axial and peripheral symptoms). Retention of bDMARDs was measured using Kaplan-Meier curve and Cox regression analyses. Clinical efficacy (BASDAI50, ASAS20, ASAS40, ASDAS inactive state, and clinically important improvement/major improvement of ASDAS) at 1-year follow-up was measured by logistic regression analysis. Also, propensity score (PS)-matched analyses were conducted. RESULTS: 1600 AS patients (1468 for cluster A, 132 for cluster B) were included. Kaplan-Meier curve analysis revealed that the drug retention rate was lower in cluster B patients (p=0.03). PS-matched analyses showed that the hazard ratio (HR) for drug discontinuation was signi cantly higher in cluster B patients (HR=1.568; 95% con dence interval =1.055-2.329). The odds ratio for BASDAI50 at 1-year was comparable between cluster A and cluster B patients in PS-matched and multivariate logistic regression analyses. A similar result was obtained in other clinical efficacy assessments. CONCLUSIONS: The drug retention rate was lower in cluster B patients than in cluster A patients; clinical efficacy was comparable between the two groups at 1-year follow-up. These results may help predict drug retention and clinical efficacy in AS patients.

Retention rate and effectiveness of secukinumab vs TNF inhibitor in ankylosing spondylitis patients with prior TNF inhibitor exposure.

OBJECTIVES: The choice of second-line biologics for AS patients previously treated with a TNF inhibitor (TNFi) remains unclear. Here, we compared drug retention and clinical efficacy between AS patients who switched biologics to secukinumab and those who switched to a different TNFi. METHODS: AS patients enrolled in the Korean College of Rheumatology BIOlogics registry were included, and patients with non-radiographic axial spondyloarthritis were excluded. Patients with previous TNFi exposure were divided into the secukinumab group and the TNFi switching group. Drug retention and clinical efficacy [BASDAI50, Assessment of Spondylo-Arthritis International Society (ASAS)20, ASAS40, AS disease activity score (ASDAS) <2.1, ASDAS clinically important improvement and ASDAS major improvement] were assessed at the 1 year follow-up. Propensity score (PS)-matched and covariate-adjusted logistic regression analyses were performed. RESULTS: Two hundred and forty-six had available 1 year follow-up data. Secukinumab as third- or later-line biologic was more frequent than alternative TNFi (54% vs 14%). PS-matched and multiple covariate-adjusted analyses showed that the odds ratio (OR) for drug discontinuation was comparable between the secukinumab and TNFi switching groups [OR 1.136 (95% CI 0.843, 1.531) and 1.000 (95% CI 0.433-2.308), respectively]. The proportion of patients who achieved BASDAI50 was also comparable between the two groups [OR 0.833 (95% CI 0.481, 1.441) in PS-matched analysis]. Other clinical efficacy parameters were also comparable. In the subgroup analysis of AS patients with previous TNFi discontinuation due to ineffectiveness, all clinical efficacy parameters were comparable between the two groups. CONCLUSION: In AS patients with previous exposure to a TNFi, switching biologics to secukinumab and switching to an alternative TNFi resulted in comparable drug retention and clinical efficacy.

Trabecular bone scores in young HIV-infected men: a matched case-control study.

BACKGROUND: Screening for osteoporosis with dual-energy X-ray absorptiometry (DXA) is recommended for male HIV-infected patients only above the age of 50. Recently, trabecular bone score (TBS) has been introduced as a novel tool to assess bone microarchitecture using DXA of the lumbar spine. Few studies have reported TBS values in HIV-infected individuals younger than 50 years of age. This study compared TBS values in young males infected with HIV and matched controls, and investigated the associations between TBS and demographic parameters, clinical parameters, and bone mineral density (BMD) scores. METHODS: A cross-sectional study of BMD and TBS in HIV-infected men (n = 80) aged between 18 and 50 years and age- and sex-matched controls (n = 80) was conducted. RESULTS: The proportion of patients with low BMD (Z-score ≤ - 2) was significantly greater among HIV-infected patients than among matched controls (21.3% [17/80] vs. 8.8% [7/80], p = 0.027). Mean TBS values were significantly lower in HIV-infected patients than in controls (1.41 ± 0.07 vs. 1.45 ± 0.07, p = 0.008). In both groups, TBS values were positively correlated with BMD at the lumbar spine, femoral neck, and total hip (p < 0.001); however, TBS was not correlated with body mass index. In the HIV group, TBS was negatively correlated with the duration of tenofovir disoproxil fumarate(TDF) exposure (p = 0.04). CONCLUSION: Young men infected with HIV had abnormal bone trabecular microarchitecture, as assessed by both TBS and BMD. TBS values were correlated with both BMD and the duration of TDF exposure.

Factors associated with low trabecular bone scores in patients with end-stage kidney disease.

The trabecular bone score (TBS) is a textural index that indirectly assesses bone trabecular microarchitecture using lumbar spine images obtained by dual-energy X-ray absorptiometry (DXA). This study compared the TBS of patients with end-stage kidney disease (ESKD) with that of matched controls to identify risk factors associated with a low TBS. TBS and bone mineral density (BMD) were assessed in ESKD patients (n = 76) and age- and sex-matched control subjects (n = 76) using DXA. The TBS of both groups was then compared, and risk factors associated with a low TBS (defined as ≤ 1.31) were evaluated. The mean TBS in the ESKD group was significantly lower than that in the control group (1.34 ± 0.15 vs. 1.43 ± 0.08, respectively; p < 0.001). More subjects in the ESKD group had a low TBS [34.2% (ESRD) vs. 5.3% (controls); p < 0.001]. The TBS was negatively correlated with age, alkaline phosphatase and C-reactive protein levels, and dialysis vintage, and positively correlated with BMD at the lumbar spine, femoral neck, and hip. Multivariate analysis identified lower estimated glomerular filtration rate and increased C-reactive protein levels as being significantly associated with a low TBS. In conclusion, ESKD patients had abnormal bone microarchitecture (as assessed by the TBS). The TBS was positively correlated with BMD. Renal function and inflammatory marker levels were independently associated with a low TBS. Thus, TBS may be a useful clinical tool for assessing cancellous bone connectivity in ESKD patients.

Inflammation on spinal magnetic resonance imaging is associated with poor bone quality in patients with ankylosing spondylitis.

Objective: To determine the association between inflammatory lesions on spinal magnetic resonance imaging (MRI) and trabecular bone score (TBS) in patients with ankylosing spondylitis (AS). Methods: Ninety-seven patients with AS underwent spine MRI and dual energy X-ray absorptiometry of the lumbar spine to measure TBS and bone mineral density (BMD). Bone marrow edema (BME) on MRI was considered an inflammatory lesion. The presence, depth (>1 cm), and intensity of BME on MRI were scored for the 1st-4th lumbar spine segments. Inflammatory markers and spinal structural damage scores at the time of MRI examination were recorded. The association between inflammatory activity score on MRI and TBS was evaluated. Results: Among the 97 patients, 52 had BME on spinal MRI (L1-L4). The mean TBS values were 1.38 ± 0.11 and 1.43 ± 0.11 for patients with and without BME, respectively (p = .022). Total inflammatory activity scores on spinal MRI correlated negatively with TBS, but not with BMD. Patients with a TBS value representing a high fracture risk had more deep BME (>1 cm) (p = .048) on MRI. After adjustment for age, symptom duration, and lumbar spinal structural damage, the TBS decreased as inflammation severity on MRI increased (p = .026). Discussion: In AS patients, inflammation on spinal MRI was negatively correlated with TBS. The severity of local bone inflammation in the spine was associated with poor bone quality. These findings suggest that the control of active bone inflammation may be effective for preventing osteoporosis in AS patients.

Trabecular bone score as an assessment tool to identify the risk of osteoporosis in axial spondyloarthritis: a case-control study.

OBJECTIVES: To compare the trabecular bone score (TBS) between patients with axial spondyloarthritis (axSpA) and matched normal controls and identify risk factors associated with a low TBS. METHODS: TBS and BMD were assessed in the two groups (axSpA and control) using DXA. Osteoporosis risk factors and inflammatory markers were also assessed. Disease activity and radiographic progression in the sacroiliac joint and spine were evaluated in the axSpA group. Multivariate linear regression analysis was performed to identify risk factors associated with TBS. RESULTS: In the axSpA group, 248 subjects were enrolled; an equal number of age- and sex-matched subjects comprised the control group. The mean TBS was 1.43 (0.08) and 1.38 (0.12) in the control and axSpA groups, respectively (P < 0.001); BMD at the lumbar spine did not differ between the two groups. The TBS was negatively correlated with ESR and CRP levels in the axSpA group only (P < 0.001 and P = 0.007, respectively). Syndesmophytes in the axSpA group was associated with lower TBS (P < 0.001) but higher lumbar BMD (P = 0.021) vs controls. In the multivariate analyses, ESR, CRP and spinal radiographic progression were significantly associated with TBS. CONCLUSION: TBS assessments revealed poor bone quality in patients with axSpA compared with the matched controls. In axSpA, systemic inflammatory markers were negatively correlated with TBS and spinal radiographic progression and inflammatory markers were independently correlated with low TBS. TBS may, therefore, be a useful clinical tool to identify the risk of osteoporosis in patients with axSpA.

Associations between trabecular bone score and vertebral fractures in patients with axial spondyloarthritis.

OBJECTIVES: To compare trabecular bone scores (TBS) between axial SpA (axSpA) patients with and without vertebral fractures and investigate associations between TBS and vertebral fractures. METHODS: Two hundred and fifty-five patients fulfilling the imaging arm of the Assessment of SpondyloArthritis International Society axSpA criteria were enrolled. TBS and BMD were assessed using dual-energy X-ray absorptiometry. Vertebral fracture of the thoracic and lumbar spine was defined according to the Genant criteria. Osteoporosis risk factors, inflammatory markers, DAS and spinal structural damage were also assessed. Univariate logistic regression analysis was performed to identify factors associated with vertebral fractures. RESULTS: There were 31 vertebral fractures in 28/255 axSpA patients (11%). The mean (s.d.) TBS was 1.39 (0.11) and 1.30 (0.13) in patients without and with vertebral fractures, respectively (P < 0.001). BMD in the femoral neck was lower in patients with vertebral fractures (P = 0.027), but BMDs in the lumbar spine and total hip were not. Univariate logistic regression analyses identified old age (⩾50 years), TNF inhibitor treatment, the presence of syndesmophytes and a low TBS (<1.23) as associated with prevalent vertebral fractures [odds ratio (95% CI): 6.9 (2.0, 24.4), 2.4 (1.0, 5.5), 5.5 (2.2, 13.5) and 5.3 (2.0, 14.1), respectively]. TBS has a better discriminatory value than BMD at the total hip for prediction of vertebral fractures in axSpA patients (P = 0.034). CONCLUSION: Similar to individuals with primary osteoporosis, axSpA patients with vertebral fractures have a lower TBS. This suggests that TBS has the potential to predict future vertebral fractures in patients with axSpA.

Low Skeletal Muscle Mass is Associated with the Risk of Low Bone Mineral Density in Urban Dwelling Premenopausal Women.

To evaluate the relationship between skeletal muscle mass and bone mineral density (BMD) and to determine the association between low skeletal muscle mass and low BMD in urban dwelling young adults. This study was based on data from the 2008-2011 Korea National Health and Nutrition Examination Surveys. The subjects were 1702 20-49-year-old men and 2192 premenopausal women (age 20-55 years). BMD at the lumbar spine, femoral neck, and total hip and the appendicular skeletal muscle mass (ASM) were measured by dual-energy X-ray absorptiometry. Skeletal muscle mass index (SMI) was defined as weight-adjusted ASM. Mildly and severely low muscle skeletal mass were defined as SMI that was 1-2 and >2 standard deviations below the sex-specific mean ASM of young adults, respectively. Low BMD was defined as T score of less than -1.0 at the lumbar spine, femoral neck, and/or total hip. After adjusting for confounders, skeletal muscle mass was positively associated with BMD at the lumbar spine, femoral neck, and total hip in both men and women. Mildly and severely low skeletal muscle mass increased the risk of low BMD in premenopausal women [OR (95% CI) = 1.4 (1.1-1.9) and 2.4 (1.2-4.6), respectively] but not men. In women, low skeletal muscle mass independently was associated with the risk of low BMD at the femoral neck and total hip but not the lumbar spine. Skeletal muscle mass was independently associated with BMD in urban dwelling young men and women, but low skeletal muscle mass was associated with the risk of low BMD in premenopausal women only.

Positive correlation between inflammation on sacroiliac joint MRI and serum C-terminal telopeptide of type-I collagen in ankylosing spondylitis but not in non-radiographic axial spondyloarthritis.

OBJECTIVES: To identify the clinical disease activity scores and laboratory markers that best reflect magnetic resonance imaging (MRI)-determined sacroiliac joint (SIJ) inflammation in ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA). METHODS: This cross-sectional study included all consecutive patients who presented with axial spondyloarthritis in 2013-2015. All underwent SIJ MRI. The bone marrow oedema in the inflammatory lesions on MRI was scored using the SPondyloArthritis Research Consortium of Canada (SPARCC) method. Bone-specific alkaline phosphatase (BALP), serum C-terminal telopeptide of type-I collagen (sCTX-I), and inflammatory markers were measured. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) were assessed. The correlations between the MRI-determined SIJ inflammation scores and disease activity scores and laboratory variables were evaluated. RESULTS: Of the 81 patients with axSpA, 45 had AS and 36 had nr-axSpA. The AS and nr-axSpA groups did not differ in terms of disease activity scores, physical functional index, or MRI-determined SIJ inflammation. Erythrocyte sedimentation rate, C-reactive protein, and ASDAS correlated with MRI inflammatory scores in nr-axSpA but not in AS. sCTX-I correlated with MRI-determined SIJ inflammatory scores in AS only. BASDAI and BALP levels did not associate with MRI inflammatory scores in either group. Multivariate analysis showed that sCTX-I associated independently with MRI inflammatory score in AS (ß=17.047, p=0.038). CONCLUSIONS: Inflammatory markers and ASDAS correlated with active sacroiliitis on MRI in nr-axSpA only. In AS, only sCTX-I correlated with active inflammation on SIJ MRI. sCTX-I may be useful as a marker of objective inflammation in AS.

Gender-Specific Associations between Low Skeletal Muscle Mass and Albuminuria in the Middle-Aged and Elderly Population.

Objective This study assessed gender-specific associations between low muscle mass (LMM) and albuminuria. Methods Data from the Korea National Health and Nutrition Examination Survey 2011 were employed. The study consisted of 1,087 subjects (≥50 years old). Skeletal muscle index (SMI) was defined as the weight-adjusted appendicular skeletal muscle mass. Mild LMM and severe LMM were defined as SMI that were 1-2 and >2 standard deviations below the sex-specific mean appendicular skeletal muscle mass of young adults, respectively. Increased albuminuria was defined as albumin-to-creatinine ratio ≥30mg/g Results Men with mild and severe LMM were significantly more likely to have increased albuminuria (15.2% and 45.45%, respectively) than men with normal SMI (9.86%, P<0.0001), but not women. Severe LMM associated independently with increased albuminuria in men (OR=7.661, 95% CI=2.72-21.579) but not women. Severe LMM was an independent predictor of increased albuminuria in hypertensive males (OR=11.449, 95% CI=3.037-43.156), non-diabetic males (OR=8.782, 95% CI=3.046-25.322), and males without metabolic syndrome (MetS) (OR=8.183, 95% CI=1.539-43.156). This was not observed in males without hypertension, males with diabetes or MetS, and all female subgroups. Conclusion Severe LMM associated with increased albuminuria in men, especially those with hypertension and without diabetes or MetS.

Radiographic progression is associated with increased cardiovascular risk in patients with axial spondyloarthritis.

OBJECTIVES: To compare the cardiovascular disease (CVD) risk between axial spondyloarthritis (axSpA) patients and matched controls, and to identify factors associated with increased CVD risk in axSpA patients. METHODS: This cross-sectional study enrolled 185 axSpA patients who fulfilled the Assessment for Spondyloarthritis (ASAS) criteria and 925 age- and sex-matched controls. None of the subjects had a previous history of CVD or diabetes mellitus. Traditional CVD risk factors were assessed and the 10-year CVD risk was calculated using the Framingham risk score (FRS). Estimated 10-year CVD risk was compared between axSpA patients and matched controls. Disease activity and radiographic progression in the sacroiliac joint and spine of axSpA patients were evaluated at the time of CVD risk assessment. RESULTS: High-density lipoprotein (HDL) cholesterol levels were lower in axSpA patients than in the matched controls (p = 0.004); however, systolic blood pressure was higher (p < 0.001). The FRS was 5.0 ± 6.6% for controls and 6.3 ± 8.7% for axSpA patients (p = 0.046). Both the grade of sacroiliitis on X-ray and the number of syndesmophytes correlated with the FRS (p = 0.009 and p = 0.001, respectively), but disease activity variables did not. The FRS was significantly higher in axSpA patients with a greater number of syndesmophytes (p = 0.035). Multivariate analysis identified the number of syndesmophytes as being independently associated with the FRS (p < 0.001). CONCLUSIONS: The FRS was higher in axSpA patients than in a matched general population. Radiographic progression in the spine was associated with a high estimated 10-year CVD risk.

Human adipose-derived mesenchymal stem cells attenuate collagen antibody-induced autoimmune arthritis by inducing expression of FCGIIB receptors.

BACKGROUND: Adipose-derived stem cells (ASCs) are mesenchymal stem cells (MSCs) derived from adipose tissue. MSCs have multiple properties including anti-inflammatory and immunomodulatory effects in various disease models and human diseases. However, the mechanisms underlying this wide range of effects need to be explored. METHODS: Collagen antibody-induced arthritis (CAIA) is a unique model in which arthritis is rapidly and strongly induced. ASCs were intraperitoneally infused into CAIA mice before or after arthritis induction. The serum levels of various cytokines, adipokines, and chemokines were measured. The expression of FC gamma receptors (FCGRs) was investigated in peritoneal macrophages ex vivo. RAW264.7 cells and ASCs were co-cultured to elucidate the direct and indirect role of ASCs on FCGR expression. RESULTS: ASCs attenuated arthritis in CAIA mice. Serum levels of tumor necrosis factor α, interleukin (IL)-15, resistin, and leptin were reduced in ASC-treated CAIA mice, whereas serum levels of IL-6 and adiponectin were not affected. In peritoneal macrophages isolated from ASC-treated mice, expression of FCGRIIB, which is immunoinhibitory, was higher than that of FCGRI. Co-culture of ASCs with RAW264.7 cells modulated the expression of FCGRs. The expression patterns and timings of peak expression differed among FCGRs. Expression of FCGRIIB was higher and peaked earlier than that of FCGRI. FCGRIII expression was not affected by this co-culture. CONCLUSIONS: This is a study to show that ASCs have anti-arthritic effects in CAIA mice. Modulation of FCGRs by ASCs might be a therapeutic mechanism in this antibody-associated arthritis model.

Prevalence of systemic lupus erythematosus in South Korea: an administrative database study.

BACKGROUND: Systemic lupus erythematosus (SLE) is a rare autoimmune disease for which a population-based survey on the prevalence of the disease in South Korea has not yet been conducted. Our goal was to estimate the nationwide prevalence of SLE. METHODS: The International Classification of Diseases, Tenth Revision (ICD-10) code for SLE diagnosis-M32-was tentatively given when patients were suspected to have SLE before 2009. As such, the positive predictive value (PPV) of the M32 code shown in medical bills reflecting true SLE was uncertain. We attempted to estimate the prevalence of SLE in South Korea using national administrative database data from 2004-2006. We approximated the actual number of SLE patients by analyzing a list of SLE-coded patients provided by the National Health Insurance (NHI) and Health Insurance Review and Assessment Service. Prevalence was estimated by multiplying the PPV of the M32 diagnostic code by the number of patients receiving the code. The PPV was determined by three methods: direct investigation of the medical records of patients randomly selected from the SLE-coded patients list; assessment of all SLE patients treated at 56 selected hospitals in South Korea; and extrapolation from sub-groups at a single institute to the sub-groups of the national NHI data. RESULTS: The estimated number of national SLE cases was between 9000 and 11,000, depending on the method of ascertainment, corresponding to a prevalence of 18.8-21.7 per 100,000 people. CONCLUSIONS: This is the first report of a nationwide prevalence survey of SLE in South Korea. National databases may serve as a resource for epidemiologic studies of rare autoimmune diseases like SLE.

The paradoxical effects of TNF inhibitors on bone mineral density and radiographic progression in patients with ankylosing spondylitis.

OBJECTIVES: To determine the longitudinal effects of TNF inhibitors on BMD and radiographic progression in patients with AS and to assess independent factors associated with increased BMD in the lumbar spine. METHODS: Sixty-three patients with AS were included. Twenty-six patients were treated with TNF inhibitors and 37 were not. BMD in the lumbar spine and right femur was measured by DXA at baseline and 1 and 2 years later. Lumbar spine radiography was performed at baseline and after 2 years. Radiographic progression was scored using the Stoke AS Spinal Score (SASSS) and the modified SASSS. Univariate and multivariate linear regression analyses were performed to identify factors independently associated with spinal BMD increase. RESULTS: BMD in the lumbar spine and total proximal femur of patients receiving TNF inhibitors increased consistently over 2 years compared with that in patients not receiving TNF inhibitors (P < 0.01 and P = 0.02), and treated patients showed increased SASSS scores (P = 0.05); however, syndesmophyte development was no different between the two groups. There was a significant difference in the change of SASSS in patients treated with both TNF inhibitors and bisphosphonates compared with those treated with TNF inhibitors alone (P < 0.01). TNF inhibitor therapy and the increase in SASSS were independently associated with increased lumbar spine BMD (P = 0.009 and P < 0.001). CONCLUSION: TNF inhibitors appear to be associated with increased SASSS scores and improvements in BMD. Further prospective studies with larger subject numbers are needed to validate this paradoxical role of TNF inhibitors.

Tacrolimus treatment increases bone formation in patients with rheumatoid arthritis.

Tacrolimus is a calcineurin inhibitor, and it is used for the treatment of rheumatoid arthritis (RA). It works by inhibiting nuclear factor of activated T cells and inducting immunosuppression. This study aims to evaluate the influence of tacrolimus on the bone metabolism of patients with RA. Twenty-eight RA patients in three centers received tacrolimus 3 mg once daily for 24 weeks. Blood samples for evaluating bone metabolism and cytokines were collected at Weeks 0 and 24. We measured the serum C-telopeptide of type I collagen (sCTx-I), osteocalcin and inflammatory cytokines. We analyzed the data using the Kruskal-Wallis test and Spearman's correlation. IL-2 and IL-6 were significantly decreased after the administration of tacrolimus (p = 0.027 and p = 0.024). There was no significant difference in the serum level of sCTx-I before and after treatment. The level of serum osteocalcin at Week 24 was significantly increased compared to the level at Week 0 (p = 0.002). The increase of osteocalcin was correlated with the reductions of IL-2 and IFN-γ (r = 0.405, p = 0.033 and r = 0.380, p = 0.046, respectively). Tacrolimus treatment increased bone formation markers in RA patients. This suggests that tacrolimus may play a role to inhibit bone erosion by increasing bone formation as well as improving the clinical symptoms of RA.

The effects of antihypertensive drugs on bone mineral density in ovariectomized mice.

The effects of several antihypertensive drugs on bone mineral density (BMD) and micro-architectural changes in ovariectomized (OVX) mice were investigated. Eight-week-old female C57/BL6 mice were used for this study. Three days after ovariectomy, mice were treated intraperitoneally with nifedipine (15 mg/kg), telmisartan (5 mg/kg), enalapril (20 mg/kg), propranolol (1 mg/kg) or hydrochlorothiazide (12.5 mg/kg) for 35 consecutive days. Uterine atrophy of all mice was confirmed to evaluate estrogen deficiency state. BMD and micro-architectural analyses were performed on tibial proximal ends by micro-computed tomography (micro-CT). When OVX mice with uterine atrophy were compared with mice without atrophy, BMD decreased (P < 0.001). There were significant differences in BMD loss between different antihypertensive drugs (P = 0.005). Enalapril and propranolol increased BMD loss in mice with atrophied uteri compared with control mice. By contrast, thiazide increased BMD in mice with uterine atrophy compared with vehicle-treated mice (P = 0.048). Thiazide (P = 0.032) and telmisartan (P = 0.051) reduced bone loss and bone fraction in mice with uterine atrophy compared with the control. Thiazide affects BMD in OVX mice positively. The reduction in bone loss by thiazide and telmisartan suggest that these drugs may benefit menopausal women with hypertension and osteoporosis.

Costovertebral joint involvement in patients with axial spondyloarthritis.

OBJECTIVES: To evaluate costovertebral joint involvement in patients with axial spondyloarthritis (axSpA) and to assess its association with disease features. METHODS: We included 150 patients from the Incheon Saint Mary's axSpA observational cohort who underwent whole spine low-dose computed tomography (ldCT). Costovertebral joint abnormalities were scored by two readers on a scale of 0-48 based on the presence or absence of erosion, syndesmophyte, and ankylosis. The interobserver reliability of costovertebral joint abnormalities was assessed using intraclass correlation coefficients (ICCs). Associations between costovertebral joint abnormality scores and clinical variables were evaluated using a generalized linear model. RESULTS: Two independent readers found costovertebral joint abnormalities in 74 (49%) patients and 108 (72%) patients. The ICCs of scores for erosion, syndesmophyte, ankylosis, and total abnormality were 0.85, 0.77, 0.93, and 0.95, respectively. For both readers, total abnormality score was correlated with age, symptom duration, Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath AS functional index (BASFI), CT syndesmophyte score (CTSS), and number of bridging spines. Multivariate analyses showed age, ASDAS, CTSS to be independently associated with total abnormality scores in both readers. The frequency of ankylosed costovertebral joint was 10.2% (reader 1) and 17.0% (reader 2) in patients without radiographic syndesmophytes (n=62), and 10.3% (reader 1) and 17.2% (reader 2) in patients without radiographic sacroiliitis (n=29). CONCLUSIONS: Costovertebral joint involvement was common in patients with axSpA, even in the absence of radiographic damage. LdCT is recommended for evaluating structural damage in patients with clinically suspected costovertebral joint involvement.

Prevalence and Associated Factors of Facet Joint Ankylosis in Patients With Axial Spondyloarthritis.

OBJECTIVE: To investigate the prevalence of facet joint ankylosis in the whole spine in axial spondyloarthritis (axSpA) using low-dose computed tomography (LDCT), and to identify factors associated with facet joint ankylosis. METHODS: Whole spine LDCT images from 161 patients with axSpA were examined, and the presence of facet joint ankylosis was assessed (right and left, C2-S1) by 2 readers. Facet joint ankylosis was scored from 0 to 46. Structural damage of vertebral body was assessed using CT Syndesmophyte Score (CTSS). Factors associated with ankylosed facet joint scores for the whole spine were identified using a generalized linear model with a negative binomial distribution. RESULTS: Seventy-nine patients (49%) and 70 patients (43%; reader 1 and reader 2, respectively) had ≥ 1 ankylosed facet joint. Facet joint ankylosis was most common in the thoracic spine. The mean score of facet joint ankylosis for the whole spine was 6.6 (SD 11.2) in reader 1 and 4.2 (SD 8.4) in reader 2. Whole spine facet joint ankylosis score positively correlated with Ankylosing Spondylitis Disease Activity Score (ASDAS) and CTSS. In multivariable analysis, the ankylosed facet joint score was associated with ASDAS, sacroiliitis, CTSS, and a history of uveitis in both readers. Uveitis history, ASDAS, and CTSS were associated with whole spine facet joint ankylosis score in subgroup analysis of only radiographic axSpA. CONCLUSION: The prevalence of ankylosed facet joints is high in axSpA, especially in the thoracic segment. The whole spine ankylosed facet joint score is significantly associated with a history of uveitis, ASDAS, sacroiliitis, and syndesmophyte score.