Organophotocatalytic access to C-glycosides: multicomponent coupling reactions using glycosyl bromides.

Photochemical multi-component coupling reactions initiated by the activation of glycosyl bromides in the presence of 1,4-bis(diphenylamino)benzene (BDB) as an organic photocatalyst were developed. C-glycosides accompanied by olefin (di)functionalization were obtained. This method allows us to access various C-glycosides with alkene, carbonyl, alcohol, ether, and amide functionalities.

Prognostic nutritional index as an indicator for the development of bone fragility fracture in patients with rheumatoid arthritis.

OBJECTIVES: The validity of prognostic nutritional index (PNI) as an index of incident bone fragility fracture (inc-BFF) in rheumatoid arthritis (RA) patients was investigated. METHODS: RA patients whom continuously followed up for >3 years were picked up. Patients were classified in accordance with inc-BFF positivity (BFF+ and BFF-). Their clinical background including PNI was statistically examined for inc-BFF. The background factors were compared between the two groups. Patients were narrowed into subgroups according to the factor that showed a significant difference between the two groups, and they were statistically examined according to the PNI for the inc-BFF. The two groups were narrowed with propensity score matching and compared to the PNI. RESULTS: A total of 278 patients with 44 BFF+ and 234 BFF- were recruited. In the background factors, the presence of prevalent BFF and the simplified disease activity index remission rate had a significantly higher risk ratio. In a subgroup who comorbid lifestyle-related diseases, PNI had a significantly higher risk ratio for the inc-BFF. After the propensity score matching, the PNI showed no significant difference between the two groups. CONCLUSIONS: PNI is available when patients with RA comorbid lifestyle-related diseases. PNI is not an independent key for the inc-BFF in RA patients.

The impact of time length to Boolean remission for tight disease activity control after acquisition in rheumatoid arthritis patients.

Clinical importance of time length from initiation under treat-to-target (T2T) strategy to acquisition of clinical remission (TL) in treating patients with rheumatoid arthritis (RA) on disease activity control, daily activities, and quality of life maintenance was investigated. In patients who achieved Boolean remission once or more, relationship between TL and patients' background data at initiation, and relationship between TL and mean simplified disease activity score (SDAI), Health Assessment Questionnaire Disability Index (HAQ-DI) score, pain score with visual analog scale (PS-VAS), Sharp/van der Heijde Score (SHS) and quality of life score (QOLS) at the first remission and thereafter were evaluated statistically. Patients were divided into two groups whether TL was within 6 months or longer (G ≤ 6 and G > 6). Change of the parameters and Boolean remission rate (BRR) after the first remission between the two groups were compared statistically. In 465 patients, TL correlated significantly with the SDAI score, the HAQ score, PS-VAS, SHS, and the QOLS after the remission. The SDAI score and the BRR after the remission were significantly better in the G ≤ 6 than in the G > 6. TL is an important key to guarantee good and stable clinical course in treating under T2T.

Clinical significance of serum cystatin C-to-creatinine ratio as a surrogate marker for incident osteoporotic fracture predictions.

Background: Detection of appropriate indicators is valuable for preventing incidental osteoporotic fractures. We statistically evaluated the significance of serum cystatin C-to-creatinine ratio (CysC/Cr) as a surrogate marker for incident major osteoporotic fractures (MOF) prediction. Methods: Eligible patients with simultaneous measurement of CysC/Cr and bone mineral density in the lumbar spine and proximal femur were selected, and their fracture histories until 5 years after baseline were observed in the retrospective area cohort data. Patients who were followed up until termination or the first osteoporotic fracture were included, and loss of follow-up or death was excluded. Candidate risk factors for osteoporotic fractures were tested for risk ratios using a cox regression analysis. Receiver operating characteristic tests were performed on factors with significantly higher risk ratios and evaluated with Kaplan-Meier survival analysis to determine the hazard ratios of the factors. Results: A total of 175 patients of whom 28 had incident MOF, 38 men, and 137 women, were enrolled. The mean age was 70.2 years. A significantly higher risk ratio was shown in the presence of prevalent MOF, hyper fall-ability, lifestyle-related diseases, chronic kidney diseases ≥ Grade3a, and higher CysC/Cr. All parameters had cutoff indices and showed significantly higher hazard ratios. Conclusions: These results suggested that CysC/Cr may be a predictive marker of incident osteoporotic fractures. It might work as a screening tool for MOF risk.

Associations between clinical metrics of joint deformity, disease duration, disease activity, functional capacity, quality of life, pain, and fatigue in patients with rheumatoid arthritis.

OBJECTIVES: Aim of this study is to clarify associations between metrics of patient's clinical status statistically using retrospective cohort data. METHODS: Patients with RA who were followed up more than 3 years were recruited. Their EuroQol-5th dimension (EQ5D) as an index of quality of life (QOL), Health Assessment Questionnaire Disability Index (HAQ) as an index of functional capacity (FC), simplified disease activity index (SDAI), pain score using visual analog scale (PS-VAS), and fatigue score using visual analog scale (FS-VAS) were monitored every three months. Sharp/van der Heijde score (SHS) was calculated annually. Associations between average values of these factors at beginning of follow-up (baseline) and change from baseline to final year in follow-up (change), and patient's sex, age, and disease duration (DD) were evaluated statistically. RESULTS: A total of 447 patients were analyzed. EQ5D score correlated significantly with HAQ score both at baseline and change of that, and FS-VAS. HAQ score correlated significantly with EQ5D and HAQ score at baseline. SDAI score correlated significantly with SHS and FS-VAS at baseline. SHS correlated significantly with the SHS at baseline. PS-VAS correlated significantly with the PS-VAS, EQ5D at baseline, change of theEQ5D and HAQ scores. FS-VAS correlated significantly with change of the EQ5D score and FS-VAS at baseline. CONCLUSIONS: These results suggested that these clinical metrics are influenced by each variable at baseline. QOL and fatigue are correlated each other, as well as QOL and FC, whereas disease activity correlated with joint deformity level and fatigue. Key Points • It is questionable whether improvement of disease activity leads to improvements in functional capacity and QOL in treating rheumatoid arthritis. • We evaluated the association among metrics of clinical outcomes, such as EQ5D, HAQ, SDAI, SHS, pain score, and fatigue score using retrospective cohort data. • Results suggested that metrics are influenced by each items at baseline, and QOL and fatigue are correlated each other, as well as QOL and functional capacity.

Pain score as a predictor of subsequent fragility fracture in postmenopausal patients with rheumatoid arthritis: A retrospective case-control study.

Objectives: Bone fragility fracture (BFF) is a serious incident in treating rheumatoid arthritis (RA). We hypothesized that pain degree during treatment RA correlated with incident BFF and validated how pain affects incident BFF (inc-BFF). Methods: Postmenopausal RA patients treated for at least 3 years were recruited. The primary endpoint was the development of inc-BFF. Follow-up began with the first bone mineral density measurement (baseline) and continued until the development of the first BFF or termination of the study. Clinical indicators at baseline, including pain score using a visual analog scale (PS-VAS), were analyzed statistically using Cox regression analysis, receiver operation characteristics (ROC), Kaplan-Meier survival curve analysis (K-M), and chi-square test. Results: A total of 239 patients were recruited. Using a multivariate Cox regression analysis, the baseline's PS-VAS and prevalent BFF (pr-BFF) demonstrated significantly higher risk ratios. For ROC, pr-BFF and PS-VAS had significant cutoff index (COI) (positive, 21.0) and an area under-curve of 0.692 (P < 0.001) and 0.616 (P < 0.01), respectively. PS-VAS > COI had a 2.24-fold higher hazard ratio than PS-VAS ≤ COI using K-M. When these 2 conditions were combined, patients with pr-BFF-positive and PS-VAS-positive had a sensitivity of 42.3% and a specificity of 88.8% for the inc-BFF. PS-VAS > COI had no statistical significance in the subgroup without pr-BFF, whereas the existence of pr-BFF had a significantly higher risk ratio in the PS-VAS ≤ COI. Conclusions: The PS-VAS during RA treatment is a good indicator for predicting the inc-BFF in postmenopausal RA patients with pr-BFF.

Clinical Advantage of Attaining Index-Based Remission Prior to Composite Remission in Treating Rheumatoid Arthritis / Ventaja clínica de lograr la remisión basada en índices antes que la remisión compuesta en el tratamiento de la artritis reumatoide

Background and objectives: The clinical advantage of targeting index-based remission prior to Boolean remission was evaluated retrospectively. Materials and methods: A total of 578 patients with rheumatoid arthritis (RA), who were treated for more than three years, were recruited. Patients who were treated to targeted index-based remission and composite measure remission criteria such as Boolean remission from the first consultation were divided according to the turn of attaining Boolean remission and index-based remission: G-IBR, a group that matched index-based remission at the same time Boolean remission is attained or earlier; G-BR_IF, a group that attained Boolean remission followed by index-based remission or failed; G-IR_BF, a group that could not attain Boolean remission despite attaining index-based remission; G-BothF, a group that failed to attain either Boolean remission or index-based remission. Background factors were statistically compared among groups. The Boolean remission rate in patients who attained index-based remission (BRR) and the rate of failure to attain index-based remission in patients who failed to attain Boolean remission (BFR) were statistically evaluated. Results: Groups comprising 225, 231, and 482 in G-IBR; 160, 154, and 8 in G-BR_IF; 18, 18, and 75 in G-IR_BF; and 175, 175, and 13 in G-BothF when indexing the clinical disease activity index (CDAI), simplified disease activity index (SDAI), and 28-joints disease activity score with C-reactive protein (DAS28-CRP), respectively. Disease activity indices’ scores after Boolean remission were demonstrated to be significantly higher in the G-BR_IF group than in the G-IBR group. BRR was 92.6%, 92.8%, and 86.5%, while BFR was 71.3%, 71.3%, and 13.8% when indexing CDAI, SDAI, and DAS28-CRP, respectively. Conclusions: Targeting CDAI and SDAI remission prior to Boolean remission contributes to a stable clinical course.(AU)

Antecedentes y objetivos: Se evaluó prospectivamente la ventaja clínica de centrarse en la remisión basada en índices de manera previa a la remisión booleana. Materiales y métodos: Se seleccionó a un total de 578 pacientes con artritis reumatoide que habían sido tratados durante más de 3 años. Se dividió en grupos a los pacientes según los criterios de remisión: remisión basada en índices o remisión de medidas compuestas, tales como remisión booleana desde la primera consulta, de acuerdo con el plazo de logro: G-IBR, un grupo que equiparó la remisión basada en índices al mismo tiempo que logró la remisión booleana o antes; G-BR_IF, un grupo que logró la remisión booleana seguida de remisión basada en índices o que fracasó; G-IR_BF, un grupo que no logró la remisión booleana a pesar de lograr la remisión basada en índices; G-BothF, un grupo que no logró la remisión booleana ni la remisión basada en índices. Se compararon entre los grupos los factores antecedentes. Se evaluaron estadísticamente la tasa de remisión booleana en los pacientes que lograron la remisión basada en índices (BRR) y la tasa de fracaso en el logro de la remisión booleana (BFR). Resultados: Los grupos estuvieron formados por 225, 231 y 482 en G-IBR; 160, 154 y 8 en G-BR_IF; 18, 18 y 75 en G-IR_BF y 175, 175 y 13 en G-BothF al indexar el índice de actividad de la enfermedad clínica (CDAI), el índice simplificado de actividad de la enfermedad (SDAI) y el índice DAS-28 con proteína C reactiva (DAS28-CRP), respectivamente. Las puntuaciones de los índices de actividad de la enfermedad tras la remisión booleana fueron significativamente más altas en el grupo G-BR_IF que en el grupo G-IBR. BRR fue del 92,6; 92,8 y 86,5%, mientras que BFR fue del 71,3; 71,3 y 13,8% al indexar CDAI, SDAI y DAS28-CRP, respectivamente. Conclusiones: Centrarse en las remisiones CDAI y SDAI de forma previa a la remisión booleana contribuye a un curso clínico estable.(AU)

Clinical Advantage of Attaining Index-Based Remission Prior to Composite Remission in Treating Rheumatoid Arthritis.

BACKGROUND AND OBJECTIVES: The clinical advantage of targeting index-based remission prior to Boolean remission was evaluated retrospectively. MATERIALS AND METHODS: A total of 578 patients with rheumatoid arthritis (RA), who were treated for more than three years, were recruited. Patients who were treated to targeted index-based remission and composite measure remission criteria such as Boolean remission from the first consultation were divided according to the turn of attaining Boolean remission and index-based remission: G-IBR, a group that matched index-based remission at the same time Boolean remission is attained or earlier; G-BR_IF, a group that attained Boolean remission followed by index-based remission or failed; G-IR_BF, a group that could not attain Boolean remission despite attaining index-based remission; G-BothF, a group that failed to attain either Boolean remission or index-based remission. Background factors were statistically compared among groups. The Boolean remission rate in patients who attained index-based remission (BRR) and the rate of failure to attain index-based remission in patients who failed to attain Boolean remission (BFR) were statistically evaluated. RESULTS: Groups comprising 225, 231, and 482 in G-IBR; 160, 154, and 8 in G-BR_IF; 18, 18, and 75 in G-IR_BF; and 175, 175, and 13 in G-BothF when indexing the clinical disease activity index (CDAI), simplified disease activity index (SDAI), and 28-joints disease activity score with C-reactive protein (DAS28-CRP), respectively. Disease activity indices' scores after Boolean remission were demonstrated to be significantly higher in the G-BR_IF group than in the G-IBR group. BRR was 92.6%, 92.8%, and 86.5%, while BFR was 71.3%, 71.3%, and 13.8% when indexing CDAI, SDAI, and DAS28-CRP, respectively. CONCLUSIONS: Targeting CDAI and SDAI remission prior to Boolean remission contributes to a stable clinical course.

Association of serum creatinine-to-cystatin C ratio with skeletal muscle mass and strength in nonalcoholic fatty liver disease in the Iwaki Health Promotion Project.

We evaluated the feasibility of using serum creatinine-to-cystatin C ratio in the assessments of muscle mass and strength in nonalcoholic fatty liver disease. In a community-based cross-sectional study, skeletal muscle mass and handgrip strength were assessed in 641 Japanese adults. Low skeletal muscle mass index and low handgrip strength were defined as indicated in the sarcopenia diagnostic criteria of the Japan Society of Hepatology. Nonalcoholic fatty liver disease was defined as fatty liver on ultrasonography in the absence of other causes of steatosis. The creatinine-to-cystatin C ratio was useful for identifying the participants with low skeletal muscle mass index, with an area under the receiver-operating characteristic curve of 0.84 [95% confidence interval (CI), 0.77-0.91] in men and 0.72 in women (95% CI, 0.65-0.78), and those with low handgrip strength, with an area under the receiver-operating characteristic curve of 0.96 (95% CI, 0.93-0.99) in men and 0.79 (95% CI, 0.66-0.92) in women. Moreover, the creatinine-to-cystatin C ratio correlated with skeletal muscle mass index (r = 0.511, p<0.001) and handgrip strength (r = 0.657, p<0.001), whereas it did not correlate with exacerbation of hepatic steatosis. In this study, creatinine-to-cystatin C ratio correlated with muscle mass and strength in nonalcoholic fatty liver disease regardless of hepatic steatosis.

Clinical characteristics and variants that predict prognosis of difficult-to-treat rheumatoid arthritis.

Factors influencing prognosis after administration of the last biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) to patients with difficult-to-treat rheumatoid arthritis (D2T_RA) were evaluated in a clinical setting. RA patients who met the EULAR definition of D2T_RA were recruited. These patients were grouped according to success/failure. Success was defined as sustained within light disease activity or discontinued after clinical remission, and all of the following were met, including glucocorticoid (GCS) < 7.5 mg/day, no rapid radiographic progression, and improved quality of life from the beginning of the b/tsDMARD (baseline). Failure was defined as any other condition from success. The primary endpoint of the study was success or failure at 12 months after baseline. Factors influencing success/failure were statistically evaluated. A total of 71 D2T_RA patients were selected, 22 were in the success group and 49 in the failure group. For patients taking GCS and methotrexate (MTX) ≤ 8.6 mg/week, only one was included in the success group and the other 24 were included in the failure group (p < 0.001). Of the 18 patients without GCS and with MTX ≥ 8.7 mg, 12 patients whose 28-joint disease activity score ≤ 1.90 at 3 months or ≤ 2.54 at 6 months were in the success group (p < 0.01). D2T_RA patients with GCS or MTX ≤ 8.6 mg at baseline are considered to be at high risk of repeat D2T_RA. Patients with no GCS and MTX ≥ 8.7 mg are more likely to withdraw from D2T_RA if their disease activity is tightly controlled.

Validity and risk of adopting PGA ≤ 2 as a remission criteria of Boolean in clinical practice in patient with rheumatoid arthritis.

Validity and risk of setting patient's global assessment (PGA) ≤ 2 as a Boolean remission criteria substituting PGA ≤ 1 in treating rheumatoid arthritis (RA) was investigated. Patients were recruited from an area cohort, of whom attained Boolean remission (Boolean-1) or near remission with PGA ≤ 2 and the rest components were ≤ 1 (Boolean-2). Simplified disease activity index (SDAI) score was compared according to the criteria variations. A total of 517 patients were studied. Mean SDAI score of patients with Boolean-1 was significantly lower than that of patients with Boolean-2 at acquisition. The trend was evident in the patients who attained Boolean-1 remission. Mean SDAI score at acquisition, 6 months after, and 1 year after of patients who attained Boolean-2 first and then Boolean-1, was significantly inferior to that of patients who attained the remissions at the same time. The mean SDAI score at month 6 in the Boolean-2 was not SDAI remission at all. We concluded that setting PGA ≤ 2 as a remission criteria may not have statistical difference in disease activity from PGA ≤ 1, however, there was an determinant risk to misread that includes patient who losses clinical remission after acquisition.

Usefulness of cortical thickness ratio of the third metacarpal bone for prediction of major osteoporotic fractures.

OBJECTIVE: Patients with rheumatoid arthritis (RA) are at high risk for osteoporotic fractures. We developed an index called the third metacarpal cortical thickness ratio (CTR), which reflects bone mineral density (BMD) in RA patients. A longitudinal study was conducted to verify the usefulness of CTR during the follow-up period. METHODS: Patients with RA who underwent dual energy X-ray absorptiometry (DXA) and hand X-ray simultaneously were monitored for disease activity and activities of daily living at 3-month intervals, and BMD and CTR were measured at 1-year intervals. Mean CTR during follow-up was tested for correlation with mean BMD at both the lumbar spine (LS) and femoral neck (FN) during follow-up. Correlations were examined, including other variants potentially correlated with BMD. The risk ratio of accidental major osteoporotic fractures (MOF) in the variance including CTR and BMD was evaluated. RESULTS: A total of 300 patients, 40 men and 260 women, were enrolled. Mean follow-up length was 49.6 months. CTR was significantly associated with BMD in FN using a multivariate model of linear regression analysis (p < 0.0001), whereas CTR was significantly associated with BMD in LS using only a univariate model (p < 0.01). The only variant with a significantly higher risk ratio for incident MOF was the presence of prevalent MOF. CTR and BMD did not show a significantly higher risk ratio using Cox regression analysis. CONCLUSION: CTR correlated significantly with BMD even during follow-up, especially in FN. However, CTR and BMD were not risk factors for major MOF.

Musculoskeletal ambulation disability symptom complex as a risk factor of incident bone fragility fracture.

OBJECTIVES: Influence of presenting musculoskeletal ambulation disability symptom complex (MADS) on occurrence of bone fragility fracture (BFF) is investigated with retrospective cohort study. METHODS: A total of 931 subjects joined in the study. Subjects were selected as bone fragility risk positive in the fracture assessment tool questionnaire. Their assumed risk factors were harvested from the medical records and X-ray pictures. They were followed up at least 8 years consecutively, and occurrence of incident BFF was set as primary endpoint. Each assumed risk factor including MADS was evaluated using Cox regression analysis. Subjects were divided into 2 groups according to presence of MADS (G-MADS and G-noMADS). Adjusted hazard ratios between the 2 groups was evaluated using Cox regression analysis. The statistical procedures were performed before and after propensity score matching (PSM) procedures in order to make parallel with assumed risk factors. RESULTS: Statistically significant risk factors within 5% were prevalent vertebral body fracture, disuse, MADS, cognitive disorder, hypertension, contracture, Parkinsonism, being female sex, hyperlipidemia, insomnia, T-score in the femoral neck ≤ -2.3, chronic kidney disease ≥ stage 2, chronic obstructive pulmonary diseases, glucocorticoid steroid administrated, and osteoarthritis in order of the adjusted hazard ratios (from highest to lowest). Adjusted hazard ratios between G-MADS and G-noMADS were 2.70 and 1.83 for before and after PSM, respectively. CONCLUSIONS: MADS demonstrated as a significant risk factor of BFF occurrence. In treating osteoporosis, fall risk should be aware of as well as bone fragility risk.

Regulation of inorganic polyphosphate is required for proper vacuolar proteolysis in fission yeast.

Regulation of cellular proliferation and quiescence is a central issue in biology that has been studied using model unicellular eukaryotes, such as the fission yeast Schizosaccharomyces pombe. We previously reported that the ubiquitin/proteasome pathway and autophagy are essential to maintain quiescence induced by nitrogen deprivation in S. pombe; however, specific ubiquitin ligases that maintain quiescence are not fully understood. Here we investigated the SPX-RING-type ubiquitin ligase Pqr1, identified as required for quiescence in a genetic screen. Pqr1 is found to be crucial for vacuolar proteolysis, the final step of autophagy, through proper regulation of phosphate and its polymer polyphosphate. Pqr1 restricts phosphate uptake into the cell through ubiquitination and subsequent degradation of phosphate transporters on plasma membranes. We hypothesized that Pqr1 may act as the central regulator for phosphate control in S. pombe, through the function of the SPX domain involved in phosphate sensing. Deletion of pqr1+ resulted in hyperaccumulation of intracellular phosphate and polyphosphate and in improper autophagy-dependent proteolysis under conditions of nitrogen starvation. Polyphosphate hyperaccumulation in pqr1+-deficient cells was mediated by the polyphosphate synthase VTC complex in vacuoles. Simultaneous deletion of VTC complex subunits rescued Pqr1 mutant phenotypes, including defects in proteolysis and loss of viability during quiescence. We conclude that excess polyphosphate may interfere with proteolysis in vacuoles by mechanisms that as yet remain unknown. The present results demonstrate a connection between polyphosphate metabolism and vacuolar functions for proper autophagy-dependent proteolysis, and we propose that polyphosphate homeostasis contributes to maintenance of cellular viability during quiescence.

Association between serum ß-carotene-to-retinol ratio and severity of hepatic steatosis in non-alcoholic fatty liver disease in Japan: A cross-sectional study.

OBJECTIVES: Retinol and ß-carotene have been reported to be involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, clinical studies are limited. The aim of this study was to investigate the relationship between serum the ratio of ß-carotene to retinol (SC/SR) and hepatic steatosis in NAFLD diagnosed by ultrasonography. METHODS: The participants were 606 Japanese adults who were enrolled in a health survey. Clinical profile, dietary nutrition intake, blood biochemistry, serum retinol, and carotenoids were analyzed. NAFLD was defined as fatty liver on ultrasonography in the absence of other causes of steatosis. RESULTS: Women had higher daily intake of α- and ß-carotene, although there were no differences in daily retinol and carotenoid intake between participants with or without NAFLD in both men and women. Women had a higher SC/SR ratio than men regardless of the presence or absence of NAFLD, and the SC/SR ratio in women decreased with exacerbation of hepatic steatosis, whereas the SC/SR ratio in men did not change despite exacerbation of hepatic steatosis. After adjusting for confounding factors, the likelihood of NAFLD among participants in the highest quartile of SC/SR ratio decreased by two-thirds compared with participants in the lowest quartile (adjusted odds ratio, 0.64; 95% confidence interval, 0.21-1.92; P = 0.041). The SC/SR ratio was positively correlated with serum high-density lipoprotein cholesterol level, and negatively correlated with serum triacylglycerol level. CONCLUSIONS: The SC/SR ratio was lower in NAFLD with sex differences, and was associated with the severity of hepatic steatosis and lipid profile. Future studies are needed to expand on these findings.

Rheumatoid arthritis in tight disease control is no longer risk of bone mineral density loss.

OBJECTIVES: Rheumatoid arthritis (RA) is an independent risk factor of osteoporosis. However, if disease activity is successfully controlled using the treat-to-target (T2T) strategy, the risk of bone mineral density (BMD) loss can be diminished. We evaluated if RA is a risk factor even when the T2T is applied in clinical cases. METHODS: From September 2017 to August 2019, 741 patients were examined using dual-energy X-ray absorptiometry; of these, 279 were diagnosed with RA who attained clinical remission within 6 months (RA-rem) and 53 could not attain clinical remission (RA-nonrem), while 409 were not diagnosed with RA (non-RA). The following characteristics between RA-rem and non-RA were matched using the propensity score matching (PSM) technique: age, sex, past bone fragility fracture experience, osteoporosis drug intervention ratio, glucocorticoid administration ratio, mean dose, Barthel Index score, body mass index, serum-creatinine-to-cystatin C ratio, and the number of comorbidities. The BMDs and changes of the lumbar spine, femoral neck, total hip, and greater trochanter were statistically compared between the RA-rem and the non-RA after PSM, and between RA-nonrem and RA-rem after PSM using the Mann-Whitney U test. RESULTS: In total, 107 patients of RA-rem and 108 of non-RA were recruited. BMDs and changes of every part demonstrated no significant differences between the 2 groups. BMDs in every part of RA-rem after PSM were significantly greater than those in every part of RA-nonrem, while no significant difference in change during follow-up. CONCLUSIONS: If disease activity is controlled in clinical remission, RA will not contribute to BMD reduction.

Changed Amino Acids in NAFLD and Liver Fibrosis: A Large Cross-Sectional Study without Influence of Insulin Resistance.

Altered amino acid levels have been found in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). However, it is not clear whether this alteration is due to altered hepatic metabolism or insulin resistance. The aim of this study was to clarify the association among amino acid levels, fatty liver, and liver fibrosis while eliminating the influence of insulin resistance. NAFLD and liver fibrosis were diagnosed using transient elastography and subjects were divided into three groups: normal, NAFLD, and liver fibrosis. To exclude the influence of insulin resistance, the subjects were matched using the homeostasis model assessment of insulin resistance (HOMA-IR). The amino acid serum levels were compared among the groups. Of 731 enrolled subjects, 251 and 33 were diagnosed with NAFLD and liver fibrosis. Although significant differences were observed among the groups in the serum levels of most amino acids, all but those of glutamate and glycine disappeared after matching for HOMA-IR. The multivariate logistic regression revealed that glutamate, glycine, and HOMA-IR were independent risk factors for liver fibrosis. The altered serum levels of most amino acids were associated with insulin resistance, while the increase in glutamate and the decrease in glycine levels were strongly associated not only with insulin resistance, but also with altered liver metabolism in patients with liver fibrosis.

Association of Bone Metabolism with Fatty Liver Disease in the Elderly in Japan: A Community-based Study.

Objective With the aging of society, both osteoporosis and fatty liver disease (FLD) are becoming important issues. However, the relationship between osteoporosis and FLD remains controversial. We investigated the association between bone metabolism and FLD in a Japanese community in a cross-sectional study. Methods A total of 1,020 participants were enrolled in a health survey. FLD was diagnosed by ultrasonography. Bone metabolism was evaluated based on bone mineral density (BMD), which was assessed using dual-energy X-ray absorptiometry, and with the bone formation index (total type I procollagen N-terminal propeptide/bone-alkaline phosphatase ratio; P1NP/BAP ratio) and the bone resorption index (crosslinked N-telopeptide of type I collagen/tartrate-resistant acid phosphatase-5b ratio; NTx/TRACP-5b ratio) calculated from serum bone turnover markers. Results The BMD (percentage of the young adult mean) was the same level in both male and female participants with and without FLD. Both men and women showed an age-dependent decrease in their bone formation index and bone resorption index values. Men of ≥70 years of age and women of 60-69 years of age with FLD had significantly lower bone formation index values and higher bone resorption index values. However, similar findings were not seen in women of ≥70 years of age. Conclusion Although the BMD levels were the same, regardless of the presence or absence of FLD, elderly participants with FLD showed decreased bone formation and increased bone resorption, with sex differences. Because our results suggest that FLD in elderly individuals is detrimental for bone metabolism, and that it leads to bone loss and osteoporosis, further studies using a cohort population are warranted.