Session Type: Abstract Submissions (ACR)
Background/Purpose: Ankylosing Spondylitis (AS) is an inflammatory arthritis characterized by erosions and new bone formation. These processes appear to be related by the fine balance of mediators involved in osteoclast activation, such as LIGHT (TNFSF14) protein and cathepsin K, and inhibition of osteoblast influenced by DKK-1 and sclerostin, although data available is still controversial. The aim of this study was to investigate in AS the main mediators involved in bone methabolism, and their relation to disease activity and anti-TNF-α treatment.
Methods: 63 patients with AS have been consecutively recruited as well as 19 healthy controls (HC). 15 patients underwent anti-TNF-α treament (Adalimumab), and were evaluated at baseline (w0) and 12 weeks after treatment (w12). Serum levels of DKK-1, Sclerostin, Cathepsin K and LIGHT were measured by ELISA assay (Biomedica, R&D System) and correlated with clinical scores (BASMI, BASFI e BASDAI) and inflammatory markers (ESR and CRP). Data were expressed as mean +/-SD. Differences among groups and statistical correlation have been analyzed according to data distribution by means of paired t-test, unpaired t-test with Welch’s correction and Spearman’s test.
Results: Mediators of osteoclast activation were increased in AS patients compared to HC: LIGHT (115.1 pg/mL±74.8 vs 75.8 pg/mL ± 49.2; p= 0.009), cathepsin-k (21 pmol/L ± 35.9 vs 9.6 pmol/L ± 5.8; p= 0.03), as well as mediators involved in osteoblast function: DKK-1 (36.4 pmol/L ± 18.8 vs 23.5 pmol/L; ± 17.6; p=0.009), sclerostin (36.4 pmol/L ± 21.8 vs 25.1 pmol/L ± 9.1; p=0.001). The increase of these mediators resulted unrelated to disease activity, as evidenced by the lack of correlation of DKK-1, sclerostin, LIGHT and cathepsin-K with clinical scores; only LIGHT showed to correlate with ESR (p=0,01; r=0,4). It is also noteworthy the little modulation induced on these mediators by TNF-α antagonists, regardless the good clinical response according to EULAR criteria: DKK-1, LIGHT and cathepsin-k, w0 vs w12 p= ns, while increased sclerostin levels were observed at w12 compared with baseline (p=0.03).
Conclusion: AS patients showed an increased bone metabolism, characterised by an increase of both mediators responsible of osteoclast activation and erosions, and mediators of osteoblast activation and new bone formation. This increased bone turn-over appear not linked to the inflammatory process and to disease activity, as perceived by the patient. Furthermore it appear to be independent to TNF-α related mechanisms, as recently suggested by radiological progression in patients with disease in clinical remission following anti-TNF-α treatment.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/light-tnfsf14-cathepsin-k-dkk-1-and-sclerostin-in-ankylosing-spondylitis-osteoclastosteoblast-imbalance-unrelated-to-disease-activity-and-effect-of-anti-tnf%ce%b1-treatment-on-the-wnt/