The three-year efficacy of iguratimod in clinical daily practice in patients with rheumatoid arthritis.

Objectives: To assess the middle-term outcome of iguratimod (IGU) in rheumatoid arthritis (RA) patients. Methods: Sixty-nine RA patients (14 males and 55 females, mean age of 64.0 years) receiving IGU-containing therapies were enrolled. We divided these patients into three groups based on the treatment at the baseline: an IGU group, a methotrexate (MTX) plus IGU group, and a biologics plus IGU group. The baseline characteristics and clinical course were evaluated over three years. Predictive factors associated with the achievement of low disease activity (LDA) were statistically analyzed. Results: The survival rate of IGU therapy at 3 years was 40.6%. The disease activity was significantly decreased in the IGU group and MTX plus IGU group compared with the baseline. Furthermore, 38 patients (55.1%) were in remission or had LDA at 3 years. The patient gender, use of prednisolone (PSL) and DAS28-CRP at baseline were the factors associated with the achievement of remission or LDA at three years. Conclusion: IGU was effective without MTX or bDMARDs as well as in combination with MTX. A female gender, no use of PSL and a low DAS28-CRP at the initiation of IGU were associated with clinical remission or LDA achievement at three years.

Short-term daily teriparatide in patients with rheumatoid arthritis.

OBJECTIVE: The aim of this study was to compare the efficacy of six-month teriparatide treatment followed by six-month bisphosphonate therapy with 12-month bisphosphonate monotherapy in Japanese rheumatoid arthritis (RA) patients who had not been previously treated for osteoporosis. METHODS: A total of 34 RA patients with osteoporosis were enrolled. Thirteen patients received six-month teriparatide prior to six-month minodronate therapy (PTH group), and 21 patients received 12-month minodronate therapy (BP group). Bone mineral density (BMD), and bone turnover markers were measured prior to and 6 and 12 months after the initiation of treatment. RESULTS: Bone mineral density of the spine was significantly increased after 12 months of treatment in both groups. In the PTH group, the mean percent change of BMD of the spine was significantly higher at 12 months after the initiation of treatment, as compared to the BP group (PTH group: 9.9 ± 1.5%, BP group: 5.5 ± 0.7%). Femoral neck BMD was significantly increased only in the PTH group after 12 months. CONCLUSION: Therapy involving six-month teriparatide followed by six-month minodronate therapy increased spine BMD to a greater degree than 12-month minodronate monotherapy. The strategy of short-term administration of teriparatide for RA patients with osteoporosis might be useful when additional bisphosphonate therapy is considered.

Bony ankylosis of the facet joint of the cervical spine in rheumatoid arthritis: Its characteristics and relationship to the clinical findings.

OBJECTIVES: The purpose of this study was to clarify the characteristics of bony ankylosis of the facet joint of the cervical spine in rheumatoid arthritis (RA) patients who required cervical spine surgery, and its relationship to the clinical findings. METHODS: Eighty consecutive RA patients with cervical spine disorder who received initial surgery were reviewed. The occurrence of bony ankylosis of the facet joint of the cervical spine was investigated using computed tomography (CT) before surgery. We also evaluated the severity of neurological symptoms and the plain wrist radiographs taken before surgery; furthermore, we evaluated each patient's medical history for total knee arthroplasty (TKA) or hip arthroplasty (THA). RESULTS: The preoperative CT imaging demonstrated bony ankylosis of the facet joint of the cervical spine in 45 facet levels of 19 cases (BA + group). In all patients, responsible instability or stenosis was demonstrated just caudal or on the cranial side of those bony ankylosis. Before surgery, the BA + group included significantly more patients showing severe cervical myelopathy (p < 0.05), and significantly more cases showing progressed ankylosis in the wrist joint bilaterally (p < 0.01). There were also significantly more patients who received two or more TKA or THA before the cervical spine surgery in the BA + group (p < 0.01). CONCLUSIONS: Bony ankylosis of the facet joint of the cervical spine may be a risk factor of instability or stenosis at the adjacent disc level and severe cervical myelopathy. Furthermore, its ankylosis was demonstrated in RA patients with severe destroyed joints.

Predictive factors associated with the progression of large-joint destruction in patients with rheumatoid arthritis after biologic therapy: A post-hoc analysis using FDG-PET/CT and the ARASHI (assessment of rheumatoid arthritis by scoring of large-joint destruction and healing in radiographic imaging) scoring method.

OBJECTIVE: To investigate the associations between large-joint damage and findings on fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) using the "assessment of rheumatoid arthritis by scoring of large-joint destruction and healing in radiographic imaging (ARASHI)" scoring system. METHODS: A total of 270 large joints (shoulders, elbows, hips, knees, and ankles) in 27 rheumatoid arthritis patients were assessed. FDG-PET/CT was performed at the initiation of biologics. Radiographs at baseline and at 3 years were evaluated using the ARASHI score. RESULTS: Radiographic progression of damage was detected in 35 by Larsen grade vs. 87 by the ARASHI score. The maximum standardized uptake value (SUVmax) at baseline, Steinbrocker stage at baseline, concomitant prednisolone use, and disease activity score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) at 6 months were significantly higher in the radiographic progression group. An SUVmax higher than 1.65 at baseline was a significant predictive factor for progressive damage at 3 years. CONCLUSIONS: The ARASHI score may allow more detailed evaluation of large joints than the Larsen method. Joint destruction is likely to have progressed at 3 years in large joints, which had a higher SUVmax at the initiation of biologics.

Predictive factors related to shoulder joint destruction in rheumatoid arthritis patients treated with biologics: A prospective study.

OBJECTIVE: The aim of this study was to assess the risk factors for shoulder joint destruction in rheumatoid arthritis (RA) patients treated with biologics. METHODS: Thirty shoulders of 29 patients with RA were assessed using 18F-fluorodeoxyglucose positron emission tomography (PET) and magnetic resonance imaging (MRI) before starting biologics and 6 months later. The mean age (range) was 54 (18-72) years, and the mean disease duration was 7 (0.8-30) years. The radiographic findings were assessed at baseline and 3 years later. The inflammation markers and RA disease activity were also assessed. These parameters were compared between the progression of joint destruction group and the no progression group. RESULTS: The SUVmax on PET, the rate of synovitis, and the rate of rotator cuff tear on MRI before biologic treatment were significantly higher in the progression of joint destruction group. SUVmax and synovitis on MRI after 6 months were also significantly higher in the progression of joint destruction group. On logistic regression analysis, the SUV at baseline of the shoulder joint was the main risk factor for joint destruction. CONCLUSION: The detection of synovitis by imaging was more important than disease activity and inflammation markers for assessing the progression of shoulder joint destruction.

[18F]fluorodeoxyglucose uptake as a predictor of large joint destruction in patients with rheumatoid arthritis.

The present retrospective study investigated the relationship between [(18)F]fluorodeoxyglucose-positron emission tomography (FDG-PET) findings and subsequent progression of joint destruction on plain X-ray. Nineteen rheumatoid arthritis (RA) patients (59 joints) who underwent FDG-PET and whose joints could be evaluated on plain X-ray 5 years later were included in this retrospective investigation. The relationship between the standardized uptake value (SUV) on FDG-PET and Larsen grade progression on plain X-ray was investigated for each joint. Factors related to progression of joint destruction were also investigated. Joints with advanced joint destruction (Larsen grades IV and V) on X-ray imaging at the time of FDG-PET were excluded. On initial plain X-ray images taken at the time of FDG-PET, a significant correlation was observed between the initial SUV of each joint and the progression of joint destruction 5 years later (R = 0.47, P < 0.01). Significant correlations between the SUV and progression of joint destruction were observed in both load-bearing (R = 0.52, P < 0.01) and non-load-bearing joints (R = 0.52, P < 0.01). On logistic regression analysis, higher SUV and lower prednisolone dose were associated with greater risk of progressive joint destruction (P < 0.05). On receiver operating characteristics curve analysis, the optimum threshold for identifying preceding joint destruction was an SUVmean of 1.33. In RA joints, FDG uptake was seen mostly by inflammatory cells; therefore, FDG uptake reflected joint inflammation. Additionally, the activity seen on FDG-PET might be associated with future radiographic changes in RA patients.

Comparison of golimumab 100-mg monotherapy to golimumab 50 mg plus methotrexate in patients with rheumatoid arthritis: Results from a multicenter, cohort study.

OBJECTIVE: The aim of this study was to compare the efficacy and safety of golimumab (GLM) 50 mg + methotrexate (MTX) combination therapy and GLM 100 mg monotherapy in patients with rheumatoid arthritis (RA). METHODS: The subjects were 115 RA patients (92 females and 23 males; median (range) age, 64 (17-87) years; median (range) disease duration, 8 (0.6-48) years) started on GLM. Eighty-three patients received GLM 50 mg/4 weeks + MTX (C group; median (range) MTX dosage 8 (2-16) mg/week), and 32 patients received GLM 100 mg/4 weeks (M group). Serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), matrix metalloproteinase-3, disease activity score (DAS) 28-ESR, DAS28-CRP, simplified disease activity index, and clinical disease activity index were evaluated 4, 12, and 24 weeks after starting GLM. RESULTS: There were no significant differences in disease activity, adverse events, and drug continuation rates at 24 weeks between the groups. The DAS28-ESR remission rate was 34% in the C group and 26% in the M group. CONCLUSIONS: GLM 100 mg monotherapy improved disease activity as well as GLM 50 mg + MTX combination therapy. GLM 100 mg monotherapy appears to have a sufficient therapeutic effect in RA patients who cannot take MTX.

Efficacy at 52 weeks of daily clinical use of iguratimod in patients with rheumatoid arthritis.

OBJECTIVE: In recent years, the use of one or more conventional synthetic disease-modifying antirheumatic drugs has been recommended for the treatment of rheumatoid arthritis (RA). We performed a 52-week study on the efficacy and safety of iguratimod (IGU) against patients with RA in daily clinical use. METHODS: Forty-one patients were enrolled in this study, and the clinical course of RA was regularly evaluated during the 52 weeks of treatment. RESULTS: The survival rate at week 52 was 53.7%. The disease activity score (DAS) 28-erythrocyte sedimentation rate, DAS28-C-reactive protein, simplified disease activity index, and clinical disease activity index were all significantly decreased at week 52. The matrix metalloproteinase-3 level was significantly decreased at week 52 by combination therapy of IGU and methotrexate. There were one case of the onset of interstitial pneumonia (IP), one exacerbation of IP, and one case of the onset of Pneumocystis jiroveci pneumonia. CONCLUSIONS: IGU is effective for RA patients when used for daily clinical treatment for 52 weeks.

Efficacy of the clinical use of iguratimod therapy in patients with rheumatoid arthritis.

OBJECTIVE: Iguratimod (IGU) is a new synthetic disease-modifying antirheumatic drug intended to treat patients with rheumatoid arthritis (RA). We conducted a 24-week study on the efficacy of IGU in RA patients with daily clinical use. METHODS: Forty-one patients were enrolled in this study, and the improvement in RA was evaluated every 4 weeks during the 24 weeks. RESULTS: The patient's global assessment of the disease activity with a scale (Pt VAS) was significantly decreased beginning at week 4. The disease activity score (DAS) 28-erythrocyte sedimentation rate, DAS28-C-reactive protein (CRP), simplified disease activity index and clinical disease activity index all significantly decreased at week 24. The matrix metalloproteinase-3 level was significantly decreased by the combination treatment with methotrexate at week 24. According to a logistic regression analysis, the factor which was most associated with the achievement of low disease activity (DAS28-CRP < 2.7) at week 24 was the DAS28-CRP at week 0. CONCLUSIONS: IGU had significant clinical effects on the RA patients within 24 weeks. IGU might therefore represent a new practical choice to treat RA patients.

Evaluation of tocilizumab therapy in patients with rheumatoid arthritis based on FDG-PET/CT.

BACKGROUND: Positron emission tomography (PET) with 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) can detect the presence of synovitis in rheumatoid arthritis (RA) patients. The aim of this study was to investigate whether the findings of FDG-PET matched the conventional assessments of the disease activity score (DAS) 28, DAS28-CRP, simplified disease activity index (SDAI) and clinical disease activity index (CDAI) in RA patients receiving tocilizumab (TCZ) therapy. METHODS: Seventeen RA patients treated with TCZ were assessed. FDG-PET was performed at baseline and three and six months after the initiation of TCZ therapy. The maximum SUV (SUVmax) of the bilateral shoulder, elbow, wrist, hip, knee and ankle joints were added together (total SUV) and were used to assess the degree of FDG uptake as a representative parameter. The correlations between the ΔSUV and the difference in the clinical parameters at baseline and at each observation period, and the differences in each clinical parameters, were assessed. RESULTS: The ΔSUV, the differences in the total SUV at baseline and at three/six months after starting treatment positively correlated with the ΔDAS28 (r = 0.615 p = 0.009/ r = 0.775 p < 0.001), ΔDAS28-CRP (r = 0.696, p = 0.002/ r = 0.828, p < 0.001), ΔSDAI (r = 0.652, p = 0.005/ r = 0.686, p = 0.002) and ΔCDAI (r = 0.662, p = 0.004/ r = 0.711, p = 0.001) for each period. The total SUV was significantly decreased at three and six months after the initiation of TCZ (p < 0.05). CONCLUSIONS: A reduction in the FDG uptake was observed at three and six months after the initiation of TCZ therapy. The disease activity estimated on FDG-PET/CT matched the conventional parameters following the TCZ therapy in RA patients.

Efficacy of switching from originator etanercept to biosimilar YLB113 in real-world patients with rheumatoid arthritis: A retrospective 12 months follow-up study.

Purpose: To investigate the disease activity in real-world patients with rheumatoid arthritis (RA) who switched from originator etanercept (ETN) to biosimilar YLB113. Methods: Forty one RA patients who switched from ETN to YLB113 were divided into 2 groups based on the Disease Activity Score based on the 28-joint count (DAS28) 12 months after switching (R group: DAS28 < 2.6, N group: DAS28 ≥ 2.6), and the baseline characteristics were statistically examined. A receiver operating characteristics (ROC) analysis was performed to estimate the cut-off value of DAS28 at baseline to achieve remission 12 months after switching. Results: There was no significant difference in the DAS28 at baseline and 12 months after switching (p = .83). Sixteen out of the 20 patients in remission at baseline achieved remission after switching. A univariate analysis revealed the rheumatoid factor (p = .04) and DAS28 (p < .001) at baseline were significantly lower in the R group than in the N group. Furthermore, logistic regression analysis revealed DAS28 was an independent factor (p = .004) for achieving remission 12 months after switching. An ROC curve analysis showed the optimal cut-off value for DAS28 at baseline to achieve remission at 12 months after switching was 2.5. Conclusions: RA patients who achieved remission using originator ETN, were able to maintain remission even if they switched to YLB113.

The assessment of biologic treatment in patients with rheumatoid arthritis using FDG-PET/CT.

OBJECTIVES: To evaluate whether there is a correlation between the differences in joint uptake of 2-[18F]-fluoro-2-deoxy-d-glucose ((18)F-FDG) and the improvement of clinical findings in RA patients undergoing anti-TNF therapies. METHODS: Twenty-two patients who received anti-TNF therapies, including infliximab for 16 patients and etanercept for 6 patients, were assessed. PET with (18)F-FDG studies and clinical assessments were performed at baseline and 6 months after the initiation of therapy. The maximal standardized uptake value (SUV(max)) was used as a representative value for the assessment of the FDG uptake in the bilateral shoulder, elbow, wrist, hip, knee and ankle joints. Spearman's rank correlation test was applied to assess the correlation between the SUV and the clinical parameters. RESULTS: The ΔSUV (12 joints), the difference in the SUV(max) of the affected 12 joints before and after treatment, was positively correlated with the ΔDAS28 (r = 0.609, P = 0.003), ΔDAS28-CRP (r = 0.656, P = 0.001) and Δtender joint count (TJC) (r = 0.609, P = 0.003). There were also significantly positive correlations between ΔSUV (8 joints); the difference in the SUV(max) of the bilateral shoulder, elbow, wrist and knee joints before and after treatment and the ΔDAS28 (r = 0.642, P = 0.001), ΔDAS28-CRP (r = 0.712, P < 0.001) and ΔTJC (r = 0.608, P = 0.003), respectively. CONCLUSION: The FDG uptake observed in the inflamed RA joints may reflect disease activity. The FDG-PET response was correlated with the clinical response to the biologic treatment of RA.

Anti-drug antibodies and rheumatoid factor level in patients with rheumatoid arthritis using the infliximab biosimilar CT-P13.

BACKGROUND: This study evaluated the existence of anti-drug antibodies (ADAs) before and 52 weeks after switching from intravenous infliximab (IFX) to intravenous CT-P13 in patients with rheumatoid arthritis (RA). METHODS: We performed a prospective observational study. Twenty-eight patients (7 males and 21 females) received intravenous CT-P13 after intravenous IFX, and the clinical data were collected from medical records. Rheumatoid factor (RF) and anti-CCP antibody were examined at baseline. At baseline and 52 weeks after the start of CT-P13 treatment, the Disease Activity Score based on the 28-joint count and the levels of C-reactive protein, matrix metalloproteinase-3, and ADA, as well as the erythrocyte sedimentation rate were evaluated. ADAs were measured using an enzyme-linked immunosorbent assay kit. RESULTS: Seven (25%) and 6 (21.4%) cases were positive for ADAs at baseline and 52 weeks after, respectively. One case became newly positive for ADAs at week 52. Two of the ADA-positive cases became ADA-negative 52 weeks after. The ADA-positive group showed significantly higher RF values at baseline than the ADA-negative group (p = 0.03). No difference was observed between the ADA-positive group and the ADA-negative group regarding other clinical parameters. CONCLUSIONS: The positive rate of ADAs did not increase after switching from intravenous IFX to intravenous CT-P13. Among the patients with ADAs, a high level of RF was observed at baseline.

Do biologic therapies reduce aortic inflammation in rheumatoid arthritis patients?

OBJECTIVES: Rheumatoid arthritis (RA) patients have an increased risk of cardiovascular disease (CVD). In the present study, we evaluated the inflammatory activity of the ascending aorta in RA patients who received biological treatment. METHODS: We assessed the aortic wall inflammation of RA patients using 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography before and after 6 months of biologic therapies. We also compared the inflammatory activity at the aortic wall in RA patients with remission or low disease activity (RLDA) and those with moderate or high disease activity (MHDA). The aortic uptake was measured by the standardized uptake value (SUV) and the target-to-background ratio (TBR). RESULTS: A total of 64 patients were included in the analysis (mean age, 58.4 ± 13.8 years old; female, 77%). The Disease Activity Score for 28 joints (DAS28) erythrocyte sedimentation rate (ESR) had significantly decreased after 6 months: from 5.0 ± 1.2 to 3.3 ± 1.2 (p < 0.001). The FDG uptake in the ascending aorta changed from baseline to 6 months, showing a maximum SUV (SUVmax) of 1.83 ± 0.34 to 1.90 ± 0.34 (p = 0.059) and TBR of 1.71 ± 0.23 to 1.75 ± 0.24 (p = 0.222). The SUVmax and TBR after 6 months were significantly higher in the RLDA group than in the MHDA group (2.05 ± 0.32 vs. 1.79 ± 0.33 (p = 0.002) and 1.89 ± 0.33 vs. 1.65 ± 0.20 (p = 0.001), respectively). The percentage of monocytes also significantly increased from baseline to 6 months: from 5.9 ± 1.6 to 6.9 ± 2.6 (p = 0.032). CONCLUSION: The inflammation activity at the ascending aorta in RA patients did not change significantly after 6 months of biological treatment. RA patients with a low disease activity or in clinical remission after 6 months of biological treatment still had an increased inflammatory activity at the aortic wall.

Does periodontitis affect the treatment response of biologics in the treatment of rheumatoid arthritis?

BACKGROUND: Rheumatoid arthritis (RA) and periodontitis (PD) have been suggested to share many clinical and pathological features. However, few reports have investigated the relationship between the degree of PD and the treatment response to RA. This study aimed to examine the relationship between the extent of PD and the treatment response to biologics in RA patients using FDG-PET/CT. METHODS: Sixty RA patients (male, n = 14; female, n = 46; average age, 58.3 years) treated with biologic agents were included in this study. FDG-PET/CT was performed at baseline and 6 months after the initiation of biological therapy. The maximum standardized uptake value (SUVmax) was used as a representative value for the assessment of the FDG uptake in periodontal tissue and joints including the bilateral shoulders, elbows, wrists, hip, knees, and ankle joints. The Disease Activity Score (DAS) 28-CRP and the following clinical parameters were assessed: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide antibody (ACPA), rheumatoid factor (RF), and matrix metalloproteinase 3 (MMP-3). The relationship between the treatment response of RA and the baseline SUVmax of the periodontal tissue was evaluated. RESULTS: The baseline periodontal SUVmax was related to patient age (r = 0.302, p = 0.009) and the ACPA level (r = 0.265, p = 0.025). The DAS28-CRP, CRP, ESR, MMP-3, and joint SUVmax values were significantly decreased after 6 months of biological therapy. However, the mean periodontal SUVmax, ACPA, and RF showed no significant changes after treatment. There was a significantly negative correlation between the baseline periodontal SUVmax and the treatment response of DAS28-CRP (r = - 0.369, p = 0.004). CONCLUSION: There was a negative correlation between the extent of PD at baseline and the treatment response of RA patients who received biological therapy. The evaluation of the periodontal condition is considered to be an essential part for the management of RA.

Demographic and clinical characteristics of spinal calcinosis in systemic sclerosis: Possible association with peripheral angiopathy.

The objective was to evaluate the demographic and clinical characteristics of systemic sclerosis (SSc) patients with spinal calcinosis. Paraspinal and intraspinal calcinosis was assessed blindly by orthopedic surgeons specializing in spinal diseases using chest high-resolution computed tomography (CT) that was performed for the screening and prospecting of interstitial lung disease in 159 Japanese SSc patients. Among these patients, we identified 27 (17%) with spinal calcinosis, and the most common site was cervical level at 77.8% (21/27). The frequency of spinal calcinosis in the late stage was higher than in the early stage (44.4% vs 29.6%). Multiple calcinosis was identified in 18.5% (5/27). The frequency of paraspinal calcinosis only was 59.3%, intraspinal calcinosis only 18.5%, and both intraspinal and paraspinal calcinosis 22.2%. Among SSc patients, 4.4% (7/159) had CT-based evidence of spinal cord compression. Among cases with spinal cord compression, only one had neurological symptoms, and surgical removal improved the symptoms. The other six SSc patients with spinal calcinosis (3.8% of 159) had no symptoms. Male sex (29.6%) and severe peripheral vasculopathy such as digital ulcers (55.6%) and acro-osteolysis (33.3%) were significantly more frequent in the SSc patients with spinal calcinosis than in the SSc patients without spinal calcinosis (10.6%, 32.6% and 14.4%, respectively). Our results suggest that severe peripheral vasculopathy may be associated with the development of spinal calcinosis. Because SSc patients are prone to spinal calcinosis, when SSc patients claim symptoms such as pain, numbness and movement disorder of the extremities, spinal calcinosis is a complication that should be taken into consideration.

Adult hypophosphatasia with compound heterozygous p.Phe327Leu missense and c.1559delT frameshift mutations in tissue-nonspecific alkaline phosphatase gene: a case report.

BACKGROUND: Hypophosphatasia is an inherited bone disease characterized by low alkaline phosphatase activity encoded by ALPL. Clinically, hypophosphatasia can be categorized as perinatal, infantile, childhood, and adult forms, as well as odonto-hypophosphatasia, according to the age at first sign or dental manifestations. Adult hypophosphatasia typically presents in middle-aged patients who appear to be in good health in early adulthood and manifests as painful feet caused by recurrent, slow-healing stress fractures of the lower limb. Because the symptoms of adult hypophosphatasia vary and are common, many patients with hypophosphatasia might be not diagnosed accurately and thus may receive inappropriate treatment. CASE PRESENTATION: We report a case of a 35-year-old Japanese woman with low serum alkaline phosphatase detected at a routine medical checkup. She had mild muscle/bone pain but no history of rickets, fractures, or dental problems. Measurement of bone mineral density of the lumbar spine and the femoral neck revealed osteopenia below the expected range for age in a young adult. Abdominal ultrasonography revealed numerous microcalcifications in both kidneys. Analysis of amino acids in urine revealed that phosphoethanolamine was elevated. Low serum alkaline phosphatase activity, elevation of phosphoethanolamine, and low bone mineral density supported the diagnosis of hypophosphatasia. ALPL mutation analysis revealed two mutations: p.Phe327Leu and c.1559delT. These genetic abnormalities were previously reported in perinatal, infantile, and childhood but not adult hypophosphatasia. On the basis of the clinical presentation, laboratory and imaging findings, and genetic analyses, the patient was definitively diagnosed with adult hypophosphatasia. To the best of our knowledge, this is the first case report of adult hypophosphatasia with the compound heterozygous mutations p.Phe327Leu and c.1559delT. CONCLUSIONS: Although the risk of bone fracture was high in this case, treatment approaches differ between osteoporosis and hypophosphatasia. Because adult hypophosphatasia diagnosis is often difficult because of their varied symptoms, hypophosphatasia should be considered in the differential diagnosis of low serum alkaline phosphatase. Early diagnosis is important so that appropriate treatment can be initiated.

Effects of denosumab on bone mineral density and bone turnover markers in rheumatoid arthritis patients switching from bisphosphonates.

BACKGROUND: To compare the efficacy of 12-month denosumab treatment on bone mineral density (BMD) and bone turnover markers (BTMs) between treatment-naïve osteoporosis patients with rheumatoid arthritis (RA) and those with previous bisphosphonate (BP) therapy. METHODS: A total of 36 RA patients with osteoporosis completed 12-month follow-up. Twenty-five patients were osteoporotic treatment-naïve (naïve group), and 11 patients were previously treated with BPs (switch group) (average 7.9 years). BMD and BTMs were measured before and 6 and 12 months after treatment. RESULTS: BTM levels were higher in the naïve group at baseline. However, the same level of suppression was achieved at 6 months in both groups. Spine BMD increased significantly in both groups. There was no significant difference in the mean percent changes of BMD of the spine (naïve group: 6.8 ± 0.8, switch group: 5.1 ± 1.5), femoral neck (2.9 ± 1.4, 2.9 ± 1.3), and total hip (1.7 ± 0.9, 1.4 ± 1.1) between these two groups at 12 months. CONCLUSIONS: The effects of denosumab on BMD and BTMs of the switch group after long-term BP treatment are comparable to those of the naïve group in RA patients. Thus, switching BPs to denosumab is one of the useful options to treat osteoporosis with RA.

Shoulder tenderness was associated with the inflammatory changes on magnetic resonance imaging in patients with rheumatoid arthritis.

The aim of this study was to assess the association between the shoulder tenderness and the inflammatory changes on magnetic resonance imaging (MRI) in the rheumatoid shoulder. Forty-one shoulders of 41 patients with rheumatoid arthritis (RA) were examined. We evaluated synovitis, erosion and bone marrow edema, by counting the numbers of each positive site, and rotator cuff tears on shoulder MRI. The association between the shoulder tenderness and the MRI findings were statistically analyzed. Twenty-three of 41 patients had tenderness in the shoulder joints. There were 20 shoulders (48.8%) with rotator cuff tear, and no significant difference was observed in the prevalence of rotator cuff tear between the tenderness group and non-tenderness group (p = 0.080). There were no significant differences in the demographic data between these two groups. In MRI findings, we found significant difference for the synovitis (p = 0.001) and bone marrow edema (p = 0.021). Synovitis was strongly associated with the shoulder tenderness (OR: 3.996, 95% CI: 1.651-9.671). Synovitis was the factor most associated with shoulder tenderness.