Proteomics analyses of human plasma reveal triosephosphate isomerase as a potential blood marker of methotrexate resistance in rheumatoid arthritis.

OBJECTIVES: To assess differentially expressed blood proteins between patients with active rheumatoid arthritis (RA) and patients in remission after methotrexate (MTX) treatment, with the aim of identifying a biomarker of methotrexate resistance (MTXR). METHODS: Two populations of RA patients treated with a stable dose of subcutaneous MTX for at least 3 months were constituted according to the DAS28: remission (DAS28 < 2.6; n = 24) and active disease (DAS28 > 3.2; n = 32). The two groups of RA patients were homogeneous regarding their epidemiological characteristics, except for the duration of treatment which was longer in the remission group. After collection of a blood sample, plasma protein digestion was performed, followed by untargeted proteomics analysis. Then, a targeted analysis was performed to confirm the results of the untargeted approach. RESULTS: Untargeted proteomics analysis revealed 8 plasma proteins differentially expressed between the two groups of patients. Among them, triosephosphate isomerase (TPI-1) and glucose-6-phosphate isomerase (GPI), which are main actors of glycolysis, were found down-regulated in the active group. This result was confirmed for TPI-1 in the targeted proteomics analysis. CONCLUSIONS: A first step was achieved in the search for biomarker of MTXR with identification of two actors of glycolysis (TPI-1 and GPI). The next step will be to confirm these results in a larger cohort, including samples from treatment-naive patients, to assess the predictive potential of these protein markers.

Evaluation of bone quality with trabecular bone score in active spondyloarthritis.

OBJECTIVE: Many patients with spondyloarthritis (SpA) are at risk of fracture due to bone fragility, whereas their bone mineral density (BMD) is not significantly diminished. Other tools, such as trabecular bone score (TBS), evaluating other characteristics of bone tissue are therefore necessary in order to evaluate bone changes in these patients. Therefore we evaluated TBS as a bone quality marker, in a cohort of patients with SpA and investigated which clinical and biological factors were correlated with TBS values. METHODS: Patients fulfilling ASAS criteria of SpA with a BMD assessment and visiting our department for initiation or switch of a biologic treatment were selected. The clinical and biological data were collected at the time of BMD measurement. RESULTS: Ninety-five patients were included in the study, with a mean age of 40.2 and a mean disease duration of 8.2 years. Lumbar BMD T-score was <-1 and <-2.5 in 17% and 3% of patients, respectively. On average, TBS value was 1.34±0.12. Lumbar BMD was positively correlated with TBS (r=0.61), while disease duration, disease activity score and serum PTH levels were negatively correlated with TBS (r=-0.24, r=-0.33, and r=-0.27, respectively). These correlations persisted in a multivariate analysis. Furthermore, more than half of the patients with a BMD level above -2.5 T-score had a low TBS value. CONCLUSION: Our results show that TBS provides information additional to BMD on the bone status of patients with SpA. They suggest that TBS may help in identifying those patients at risk of fracture.

Remaining local subclinical joint inflammation is associated with deteriorated metacarpeal head bone microarchitecture in rheumatoid arthritis patients low disease activity.

OBJECTIVES: Bone alterations at the subchondral level during rheumatoid arthritis (RA) remain under investigation. It remains unknown whether subchondral bone damage might still occur in RA patients in clinical remission, which could then infer suggesting that even minor subclinical inflammatory changes in the joint can induce local bone loss. METHODS: Thirty-two RA patients treated with biological disease-modifying anti-rheumatic drugs (bDMARDs) with low disease activity since at least 6 months and having erosion on the second or third metacarpeal head were enrolled in this pilot cross-sectional study. They were divided in two groups according to local inflammation assessed by Doppler-ultrasound exam surrounding the site of erosion. Cortical and trabecular parameters of the metacarpeal head were then assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) and compared in both groups. RESULTS: Twenty and twelve RA patients were enrolled in the "Doppler positive erosion" (DE+) group and Doppler negative erosion (DE-) group, respectively. No difference was observed in their clinical or biological RA characteristics. Both cortical density and thickness were similar among groups. Within the trabecular network, while no difference in bone volume was observed, trabecular density as well as trabecular number were decreased (P<0.001 and P<0.05 respectively), whereas trabecular separation and distribution of trabecular separation were increased in DE+ compared to DE- (P<0.05). CONCLUSION: In RA patients in low disease activity under bDMARDs, persistence of local inflammation was associated with alteration of the trabecular compartment. Trabecular density was the most strongly altered parameter and could be a candidate to assess drug effect on periarticular bone damage.

Rheumatoid arthritis treated with tocilizumab in two patients with complicated chronic liver disease with portal hypertension.

Erosive, active rheumatoid arthritis inpatients with portal hypertension combining esophageal varices and ascites complicating chronic liver disease poses serious management problems. Current literature does not provide any valid therapeutic management. We report the case of a woman and a man aged 52 and 66 years respectively having this combination of pathologies. Infusions of 4mg/kg of tocilizumab as monotherapy have produced a weaning from corticosteroids, both clinical and structural remission, with particular liver safety satisfactory at 10 and 18 months.

High prevalence of dementia in women with osteoporosis.

INTRODUCTION: Alzheimer's disease or other Dementias (ADD) and postmenopausal osteoporosis are two major public health problems with a huge impact on mortality. Here, we examined the prevalence of ADD in postmenopausal women with osteoporosis, monitored within a dedicated fracture liaison service. METHODS: We conducted a cross-sectional observational study in a population of 2041 women, visiting the university hospital of Saint-Etienne for a peripheral fragility fracture. We assessed the prevalence of ADD among these patients and compared to French population. We also compared the characteristics of women with ADD and without ADD. RESULTS: ADD prevalence was on average 13.5% in the population of interest with a mean age of 85years. As women with ADD were older than women without ADD, the prevalence of the disease significantly increased with age as 0%, 1.8%, 13% and 29.7% in<55, 55-74, 75-79 and 85-89years old groups, respectively. Proximal femoral fracture was the most frequent fracture (77%) followed by wrist fracture (13%), and then proximal humerus fracture (10%). ADD prevalence observed in our study was 3 to 4 times the ADD prevalence in France. Despite the overall increase of the ADD prevalence with age, it was still 2.2 and 1.9 times that of the French female population in the 80-84 and 85-89 age groups respectively. CONCLUSION: ADD prevalence was higher in postmenopausal women with severe osteoporosis, especially those with femoral fractures. Thus, our results incite to a more efficient care of this population with a high risk of fracture and mortality.

Functional hypoparathyroidism in postmenopausal women with fragility fracture.

INTRODUCTION: Secondary hyperparathyroidism sometimes is lacking despite authentic vitamin D insufficiency (VDI) and the concept of functional hypoparathyroidism with a protective role on bone status has been proposed. Therefore, we tested the hypothesis that its prevalence was very low in a population of women with a peripheral fragility fracture. METHODS: We conducted our study in postmenopausal women, admitted for such a fracture in our Fracture Liaison Service. All had bone mineral density (BMD), biochemical assessment and a medical visit. RESULTS: Two hundred and thirty seven women (72.9±11.6-year-old) were included and 90.4% had VDI (25[OH]D≤30 ng/mL). Yet, 87.9% of the latter had normal PTH levels less or equal to 64 ng/L. In this population with VDI (n=214), we found no PTH plateau level related to 25(OH)D. Since a recent study reported an increase in the risk of fracture only when 25(OH)D was below 15 ng/mL, we then used this value as a new threshold. We observed a significant difference in hip BMD between patients with 25(OH)D either less or equal to or greater than 15 ng/mL. However, 81.2% of the formers were still with normal PTH with no difference in BMD whether PTH level was above or within normal range. CONCLUSION: In a population of postmenopausal women with a fragility fracture, we found that 25(OH)D less or equal to 15 ng/mL was associated with significantly lower hip BMD. Even using this low threshold, we found a high prevalence of functional hypoparathyroidism and it was not associated with any difference in hip or spine BMD. Overall, our results do not support the hypothesis of a protective effect of this biological profile.