Cytokine-Induced and Stretch-Induced Sphingosine 1-Phosphate Production by Enthesis Cells Could Favor Abnormal Ossification in Spondyloarthritis.

Spondyloarthritis (SpA) is a common rheumatic disease characterized by enthesis inflammation (enthesitis) and ectopic ossification (enthesophytes). The current pathogenesis model suggests that inflammation and mechanical stress are both strongly involved in SpA pathophysiology. We have previously observed that the levels of sphingosine 1-phosphate (S1P), a bone anabolic molecule, were particularly high in SpA patients' serum compared to healthy donors. Therefore, we wondered how this deregulation was related to SpA molecular mechanisms. Mouse primary osteoblasts, chondrocytes, and tenocytes were used as cell culture models. The sphingosine kinase 1 (Sphk1) gene expression and S1P secretion were significantly enhanced by cyclic stretch in osteoblasts and chondrocytes. Further, TNF-α and IL-17, cytokines implicated in enthesitis, increased Sphk1 mRNA in chondrocytes in an additive manner when combined to stretch. The immunochemistry on mouse ankles showed that sphingosine kinase 1 (SK1) was localized in some chondrocytes; the addition of a pro-inflammatory cocktail augmented Sphk1 expression in cultured ankles. Subsequently, fingolimod was used to block S1P metabolism in cell cultures. It inhibited S1P receptors (S1PRs) signaling and SK1 and SK2 activity in both osteoblasts and chondrocytes. Fingolimod also reduced S1PR-induced activation by SpA patients' synovial fluid (SF), demonstrating that the stimulation of chondrocytes by SFs from SpA patients involves S1P. In addition, when the osteogenic culture medium was supplemented with fingolimod, alkaline phosphatase activity, matrix mineralization, and bone formation markers were significantly reduced in osteoblasts and hypertrophic chondrocytes. Osteogenic differentiation was accompanied by an increase in S1prs mRNA, especially S1P1/3 , but their contribution to S1P-impact on mineralization seemed limited. Our results suggest that S1P might be overproduced in SpA enthesis in response to cytokines and mechanical stress, most likely by chondrocytes. Moreover, S1P could locally favor the abnormal ossification of the enthesis; therefore, blocking the S1P metabolic pathway could be a potential therapeutic approach for the treatment of SpA. © 2019 American Society for Bone and Mineral Research.

Vitamin D, disease activity and comorbidities in early spondyloarthritis.

OBJECTIVES: To assess the vitamin D status in patients presenting inflammatory back pain suggestive of axial spondyloarthritis and to assess the relationship between vitamin D status and disease activity/severity; comorbidities at baseline and during the first two years of follow-up. METHODS: DESIR is a prospective, multicentre, observational study. Vitamin D deficiency was defined as <50 nmol/L and severe deficiency less than 25 nmol/L. Clinical variables were collected at each six month interval visits during the two-year follow-up. RESULTS: A total of 700 patients were analysed. The mean vitamin D was 54.2±28.7 nmol/L. Severe deficiency were observed in 11.7% versus 5% in the DESIR cohort versus the French population respectively. In the DESIR cohort, after adjusting for season and ethnicity, vitamin D deficiency remained significantly associated with presence of radiological sacroiliitis, higher ASDAS score and elevated BASDAI. Such association was also found between vitamin D deficiency and the mean value of disease activity/severity parameters during the two-year follow-up. Otherwise, vitamin D deficiency was significantly associated with the presence of baseline abdominal obesity (OR=1.65 [1.05-2.61], p=0.03), low HDL (OR=1.71 [1.14-2.55], p=0.01) and presence of metabolic syndrome (OR=2.20 [1.04-4.64], p=0.03) at baseline. CONCLUSIONS: We found a higher percentage of patients with severe vitamin D deficiency in early axial spondyloarthritis. Vitamin D deficiency was associated with higher disease activity and severity and presence of metabolic syndrome. Further longitudinal studies are required to evaluate the interest of vitamin D supplementation on the long-term outcome of the disease.

Impaired quality of life in adults with X-linked hypophosphatemia and skeletal symptoms.

OBJECTIVE: Adults with X-linked hypophosphatemia (XLH) may suffer from skeletal symptoms leading to functional disability. No data on their quality of life (QoL) have been reported so far. Our objectives were to evaluate the QoL and its determinants in XLH adults. PATIENTS AND METHODS: We conducted a prospective study in XLH adults, who consulted for musculoskeletal symptoms between 2013 and 2014. We assessed their QoL using HAQ, RAPID3 and SF36, and analysed the variables associated with low QoL. We compared their QoL to that of patients affected with axial spondyloarthritis (ax-SpA) (paired on age and gender), a rheumatologic disorder with a known low QoL. RESULTS: Fifty-two XLH adults (37 women (71.1%); mean age 41.8±13.3 years) were included; 44 (84.6%) patients had an altered QoL. Increased age and presence of structural lesions were significantly associated with worse QoL (HAQ, RAPID3) (P<0.05). Presence of enthesopathies was significantly associated with worse RAPID3 (OR=4.45 (1.09-18.29), P=0.038). Treatment with phosphate supplements and vitamin D in XLH adults were significantly associated with a better SF36-mental component score (OR=0.14 (0.03-0.57), P=0.007 and OR=0.26 (0.07-0.98), P=0.047 respectively). QoL was significantly worse in XLH than in ax-SpA adults (VAS pain, SF36-PCS, RAPID3) (P<0.05). CONCLUSION: Our study showed i) QoL of XLH adults is altered and significantly worse than that of ax-SpA patients (VAS pain, SF36-PCS and RAPID3), ii) structural lesions and especially enthesopathies are associated with a worse QoL and iii) treatment using phosphate supplements and/or vitamin D is associated with a better mental health score.

Artritis psoriásica axial / Axial psoriatic arthritis

La afección espinal en la artritis psoriásica (APs) es un tema controvertido, a pesar de que no existen dudas desde el punto de vista clínico de la afectación espinal en la APs, actualmente no hay un consenso que permita definir la APs axial. En este trabajo se analizan los datos más recientes acerca de la clasificación, aspectos clínicos, de evaluación y terapia en la afección axial de la APs (AU)

Spinal involvement in PsA is a controversial issue. Currently, in spite of clinical recognition of axial involvement in axial PsA, there is a lack of consensus that impedes elaborating a definition for axial Psa. Recent advances in classification, clinical features, outcome measures and therapeutics are reviewed in this paper (AU)