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Objective: Dicckopf-1 (Dkk-1) is a potent inhibitor of the Wnt canonical pathway. In rheumatoid arthritis (RA), Dkk-1 is upregulated by tumor necrosis factor-α (TNF). Certolizumab pegol (CMZ) is a biologic TNF-inhibitor (TNFi) effective in RA and slows radiographic progression. Data on the immediate effects (≤1-8 weeks) of TNFi on Wnt modulators are lacking. This study investigated the acute influence of TNFi treatment on Wnt modulators (Dkk-1 and sclerostin) and bone turnover markers (BTM), including intact N-terminal propeptide of collagen type I (PINP) and C-terminal telopeptide of type I collagen (CTX-I).

Methods: This longitudinal, uncontrolled study involved female RA patients with inadequate response to conventional methotrexate who underwent treatment with CMZ. ESR, Dkk-1, sclerostin, BTM, parathyroid hormone (PTH), and 25OH-vitamin D levels were evaluated at baseline, week 1, week 4, and week 8. Radiographs of the hands and feet were obtained at baseline and the total and erosion scores were assessed using the Simple Erosion Narrowing Score method (SENS).

Results: Seventeen patients were enrolled. Dkk-1 and CTX-I significantly decreased after one week of treatment with CMZ (-49.1 ± 17.1% and -25.0 ± 20.6%, respectively, p < 0.01), whereas PINP increased (+43.2 ± 31.5%, p < 0.01). These changes persisted at week 4 and 8.

Conclusions: Our study showed that TNF-alpha inhibition with CMZ promptly results in a rapid decline of serum Dkk-1 levels, alongside decreased bone resorption and increased bone formation.

Titel:	Inhibition of tumor necrosis factor-alpha (TNF-alpha) in patients with early rheumatoid arthritis results in acute changes of bone modulators.
Autor/in / Beteiligte Person:	Fassio, A ; Adami, G ; Gatti, D ; Orsolini, G ; Giollo, A ; Idolazzi, L ; Benini, C ; Vantaggiato, E ; Rossini, M ; Viapiana, O
Zeitschrift:	International immunopharmacology, Jg. 67 (2019-02-01), S. 487-489
Veröffentlichung:	Amsterdam ; New York : Elsevier Science, c2001-, 2019
Medientyp:	academicJournal
ISSN:	1878-1705 (electronic)
DOI:	10.1016/j.intimp.2018.12.050
Schlagwort:	Adaptor Proteins, Signal Transducing Aged Bone Morphogenetic Proteins genetics Bone Morphogenetic Proteins metabolism Gene Expression Regulation drug effects Genetic Markers genetics Humans Intercellular Signaling Peptides and Proteins genetics Middle Aged Antirheumatic Agents therapeutic use Arthritis, Rheumatoid drug therapy Certolizumab Pegol therapeutic use Intercellular Signaling Peptides and Proteins metabolism Tumor Necrosis Factor-alpha antagonists & inhibitors
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Int Immunopharmacol] 2019 Feb; Vol. 67, pp. 487-489. <i>Date of Electronic Publication: </i>2018 Dec 31. MeSH Terms: Antirheumatic Agents / therapeutic use ; Arthritis, Rheumatoid / drug therapy ; Certolizumab Pegol / therapeutic use ; Intercellular Signaling Peptides and Proteins / metabolism ; Tumor Necrosis Factor-alpha / *antagonists & inhibitors ; Adaptor Proteins, Signal Transducing ; Aged ; Bone Morphogenetic Proteins / genetics ; Bone Morphogenetic Proteins / metabolism ; Gene Expression Regulation / drug effects ; Genetic Markers / genetics ; Humans ; Intercellular Signaling Peptides and Proteins / genetics ; Middle Aged Contributed Indexing: Keywords: Anti-TNF; Bone turnover markers; Certolizumab pegol; DKK-1; Dicckopf-1; Erosions; Rheumatoid arthritis; Wnt Substance Nomenclature: 0 (Adaptor Proteins, Signal Transducing) ; 0 (Antirheumatic Agents) ; 0 (Bone Morphogenetic Proteins) ; 0 (DKK1 protein, human) ; 0 (Genetic Markers) ; 0 (Intercellular Signaling Peptides and Proteins) ; 0 (SOST protein, human) ; 0 (Tumor Necrosis Factor-alpha) ; UMD07X179E (Certolizumab Pegol) Entry Date(s): Date Created: 20190102 Date Completed: 20190509 Latest Revision: 20201209 Update Code: 20240513

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Inhibition of tumor necrosis factor-alpha (TNF-alpha) in patients with early rheumatoid arthritis results in acute changes of bone modulators.