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Serum levels of inhibitors of wingless / beta-catenin in patients with ankylosing spondylitis and the relationship with anti-tumour necrosis factor alpha treatments

Year 2019, , 252 - 258, 01.09.2019
https://doi.org/10.21601/ortadogutipdergisi.448931

Abstract

Aim: The primary aim of the study was to compare the serum levels of Dickkopf-1 (DKK-1) and sclerostin in patients with ankylosing spondylitis (AS) and healthy controls. The secondary aim was to evaluate the effects of anti-tumor necrosis factor alpha (TNF-α) treatments on levels of DKK-1 and sclerostin. The last aim was to evaluate any relationship between DKK-1, sclerostin, and radiologic progression in AS.
Material and Method: We included 70 patients with AS (35 anti-TNF-α treated, 35 anti-TNF-α naïve) and 31 healthy controls in this study. Serum DKK-1, sclerostin, C reactive protein, and erythrocyte sedimentation rate (ESR) were assessed in patients and healthy controls. The Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Metrology Index (BASMI), and Bath Ankylosing Spondylitis Functional Index (BASFI) were calculated for the patients. Radiographs were scored according to the modified Stoke AS Spine Score (mSASSS) by an experienced radiologist who was blinded to the patients’ identity.
Results: Patients with AS who were treated with anti-TNF-α agent had higher scores of BASMI and mSASSS compared with the anti-TNF-α naïve patients. Serum levels of DKK-1 and sclerostin were significantly lower in patients with AS than in healthy controls. There was a negative correlation between DKK-1 levels with ASDAS and BASMI in patients with AS. There was no correlation between DKK-1 or sclerostin levels with mSASSS. There was a positive correlation between BASMI score with mSASSS in patients with AS.
Conclusion: DKK-1 levels in patients with AS were negatively correlated with BASMI, on the other hand, BASMI had a strong positive correlation with mSASSS. Therefore, these findings suggest that lower DKK-1 levels in patients with AS may play a role in new bone formation.

References

  • Schett G. Bone formation versus bone resorption in ankylosing spondylitis. Adv Exp Med Biol 2009; 649: 114–21.
  • Braun J, Baraliakos X. Imaging of axial spondyloarthritis including ankylosing spondylitis. Ann Rheum Dis 2011; 70: 97–103.
  • van der Heijde D, Landewe R, Baraliakos X, et al. Radiographic findings following two years of infliximab therapy in patients with ankylosing spondylitis. Arthritis Rheum 2008; 58: 3063–70.
  • van der Heijde D, Landewe R, Einstein S, et al. Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept. Arthritis Rheum 2008; 58: 1324–31.
  • Daoussis D, Andonopoulos AP. The emerging role of Dickkopf-1 in bone biology: is it the main switch controlling bone and joint remodeling? Semin Arthritis Rheum 2011; 41: 170-7.
  • Klavdianou K, Liossis SN, Sakkas L, Daoussis D. The role of Dickkopf-1 in joint remodeling and fibrosis: A link connecting spondyloarthropathies and scleroderma? Semin Arthritis Rheum 2017; 46: 430-8.
  • Haynes KR, Pettit AR, Duan R, Tseng HW, et al. Excessive bone formation in a mouse model of ankylosing spondylitis is associated with decreases in Wnt pathway inhibitors. Arthritis Res Ther 2012; 14: R253.
  • Diarra D, Stolina M, Polzer K, et al. Dickkopf-1 is a master regulator of joint remodeling. Nat Med 2007; 13: 156–63.
  • Senolt L, Hulejova H, Krystufkova O, et al. Low circulating Dickkopf-1 and its link with severity of spinal involvement in diffuse idiopathic skeletal hyperostosis. Ann Rheum Dis 2012; 71: 71–4.
  • Daoussis D, Liossis SNC, Solomou EE, et al. Evidence that Dkk-1 is dysfunctional in ankylosing spondylitis. Arthritis Rheum 2010; 62: 150–8.
  • Nocturne G, Pavy S, Boudaoud S, et al. Increase in Dickkopf-1 serum level in recent spondyloarthritis. Data from the DESIR cohort. PLoS One 2015; 10: e0134974.
  • Kwon SR, Lim MJ, Suh CH, et al. Dickkopf-1 level is lower in patients with ankylosing spondylitis than in healthy people and is not influenced by anti tumor necrosis factor therapy. Rheumatol Int 2012; 32: 2523-7.
  • Van Der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 1984; 27: 361–8.
  • Akkoc Y, Karatepe AG, Akar S, Kirazli Y, Akkoc N. A Turkish version of the Bath Ankylosing Spondylitis Disease Activity Index: reliability and validity. Rheumatology international 2005; 25: 280-4.
  • Pedersen SJ, Sørensen IJ, Hermann KG, et al. Responsiveness of the Ankylosing Spondylitis Disease Activity Score (ASDAS) and clinical and MRI measures of disease activity in a 1-year follow-up study of patients with axial spondyloarthritis treated with tumour necrosis factor alpha inhibitors. Ann Rheum Dis 2010; 69: 1065-71.
  • Calin A, Garrett S, Whitelock H, et al. A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index. J Rheumatol 1994; 21: 2281–5.
  • Calin A, Mackay K, Santos H, Brophy S. A new dimension to outcome: application of the Bath Ankylosing Spondylitis Radiology Index. J Rheumatol 1999; 26: 988–92.
  • Creemers MC, Franssen MJ, van’t Hof MA, Gribnau FW, van de Putte LB, van Riel PL. Assessment of outcome in ankylosing spondylitis: an extended radiographic scoring system. Ann Rheum Dis 2005; 64: 127–9.
  • Heiland GR, Appel H, Poddubnyy D, et al. High level of functional dickkopf-1 predicts protection from syndesmophyte formation in patients with ankylosing spondylitis. Ann Rheum Dis 2012; 71: 572-4.
  • Huang J, Song G, Yin Z, Fu Z, Ye Z. Alteration of Bone Turnover Markers in Canonical Wingless Pathway in Patients With Ankylosing Spondylitis. Arch Rheumatol 2016; 31: 221-8.
  • Taylan A, Sari I, Akinci B, et al. Biomarkers and cytokines of bone turnover: extensive evaluation in a cohort of patients with ankylosing spondylitis. BMC Musculoskelet Disord 2012; 13: 191.
  • Saad CG, Ribeiro AC, Moraes JC, et al. Low sclerostin levels: a predictive marker of persistent inflammation in ankylosing spondylitis during anti-tumor necrosis factor therapy? Arthritis Res Ther 2012; 14: R216.
  • Appel H, Ruiz-Heiland G, Listing J, et al. Altered skeletal expression of sclerostin and its link to radiographic progression in ankylosing spondylitis. Arthritis Rheum 2009; 60: 3257–62.
  • Ustun N, Tok F, Kalyoncu U, et al. Sclerostin and Dkk-1 in patients with ankylosing spondylitis. Acta Reumatol Port 2014: 39; 146-51.

Ankilozan spondilit hastalarında wingless / beta-katenin inhibitörlerinin serum düzeyi ve anti-tümör nekrozis faktör alfa tedavileri ile ilişkisi

Year 2019, , 252 - 258, 01.09.2019
https://doi.org/10.21601/ortadogutipdergisi.448931

Abstract

Amaç: Bu çalışmadaki öncelikli amacımız ankilozan spondilit (AS) hastalarında ve sağlıklı kontrollerde Dickkopf-1 (DKK-1) ve sklerostinin serum düzeylerini karşılaştırmaktı. İkincil amacımız anti-tümör nekrozis faktör alfa (anti-TNF-a) tedavilerinin DKK-1 ve sklerostinin serum düzeylerine olan etkisini değerlendirmekti. Son olarak AS hastalarında DKK-1, sklerostin düzeyleri ile radyolojik progresyon arasında ilişki olup olmadığını değerlendirmeyi amaçladık.
Gereç ve Yöntem: Çalışmamıza 70 AS (35 anti-TNF tedavi alan, 35 anti-TNF almayan) hastası ve 31 sağlıklı kontrol alındı. Hastalarda ve sağlıklı kontrollerde serum DKK-1, sklerostin, C-reaktif protein ve eritrosit sedimentasyon hızı ölçüldü. Ankilozan spondilit hastalık aktivite skoru (ASDAS), Bath ankilozan spondilit hastalık aktivite indeksi (BASDAİ), Bath ankilozan spondilit metroloji indeksi (BASMİ), Bath ankilozan spondilit fonksiyonel indeksi (BASFİ) hesaplandı. Radyografiler hasta bilgilerine körleştirilmiş deneyimli bir radyolog tarafından modifiye stoke ankilozan spondilit spinal skoru (mSASSS) yöntemine göre skorlandı.
Bulgular: Anti-TNF-a tedavi alan AS hastalarında BASMI ve mSASSS skorları anti-TNF-a tedavi almayan hastalara göre daha yüksekti. AS hastalarında serum DKK-1 ve sklerostin düzeyleri sağlıklı kontrollere göre daha düşüktü. AS hastalarında DKK-1 düzeyleri ile ASDAS ve BASMİ arasında ters yönlü bir korelasyon vardı. DKK-1 ve sklerostin düzeyleri ile mSASSS arasında korelasyon yoktu. AS hastalarında BASMİ skoru ile mSASSS arasında anlamlı korelasyon vardı.
Sonuç: AS hastalarındaki DKK-1 düzeyleri ile BASMİ arasında ters yönlü bir korelasyon vardı, diğer yandan BASMİ ve mSASSS skorları arasında güçlü bir korelasyon vardı. Bu nedenler, bu bulgular AS hastalarındaki düşük DKK-1 seviyelerinin yeni kemik oluşumunda rol oynayabileceğini düşündürmektedir.

References

  • Schett G. Bone formation versus bone resorption in ankylosing spondylitis. Adv Exp Med Biol 2009; 649: 114–21.
  • Braun J, Baraliakos X. Imaging of axial spondyloarthritis including ankylosing spondylitis. Ann Rheum Dis 2011; 70: 97–103.
  • van der Heijde D, Landewe R, Baraliakos X, et al. Radiographic findings following two years of infliximab therapy in patients with ankylosing spondylitis. Arthritis Rheum 2008; 58: 3063–70.
  • van der Heijde D, Landewe R, Einstein S, et al. Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept. Arthritis Rheum 2008; 58: 1324–31.
  • Daoussis D, Andonopoulos AP. The emerging role of Dickkopf-1 in bone biology: is it the main switch controlling bone and joint remodeling? Semin Arthritis Rheum 2011; 41: 170-7.
  • Klavdianou K, Liossis SN, Sakkas L, Daoussis D. The role of Dickkopf-1 in joint remodeling and fibrosis: A link connecting spondyloarthropathies and scleroderma? Semin Arthritis Rheum 2017; 46: 430-8.
  • Haynes KR, Pettit AR, Duan R, Tseng HW, et al. Excessive bone formation in a mouse model of ankylosing spondylitis is associated with decreases in Wnt pathway inhibitors. Arthritis Res Ther 2012; 14: R253.
  • Diarra D, Stolina M, Polzer K, et al. Dickkopf-1 is a master regulator of joint remodeling. Nat Med 2007; 13: 156–63.
  • Senolt L, Hulejova H, Krystufkova O, et al. Low circulating Dickkopf-1 and its link with severity of spinal involvement in diffuse idiopathic skeletal hyperostosis. Ann Rheum Dis 2012; 71: 71–4.
  • Daoussis D, Liossis SNC, Solomou EE, et al. Evidence that Dkk-1 is dysfunctional in ankylosing spondylitis. Arthritis Rheum 2010; 62: 150–8.
  • Nocturne G, Pavy S, Boudaoud S, et al. Increase in Dickkopf-1 serum level in recent spondyloarthritis. Data from the DESIR cohort. PLoS One 2015; 10: e0134974.
  • Kwon SR, Lim MJ, Suh CH, et al. Dickkopf-1 level is lower in patients with ankylosing spondylitis than in healthy people and is not influenced by anti tumor necrosis factor therapy. Rheumatol Int 2012; 32: 2523-7.
  • Van Der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 1984; 27: 361–8.
  • Akkoc Y, Karatepe AG, Akar S, Kirazli Y, Akkoc N. A Turkish version of the Bath Ankylosing Spondylitis Disease Activity Index: reliability and validity. Rheumatology international 2005; 25: 280-4.
  • Pedersen SJ, Sørensen IJ, Hermann KG, et al. Responsiveness of the Ankylosing Spondylitis Disease Activity Score (ASDAS) and clinical and MRI measures of disease activity in a 1-year follow-up study of patients with axial spondyloarthritis treated with tumour necrosis factor alpha inhibitors. Ann Rheum Dis 2010; 69: 1065-71.
  • Calin A, Garrett S, Whitelock H, et al. A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index. J Rheumatol 1994; 21: 2281–5.
  • Calin A, Mackay K, Santos H, Brophy S. A new dimension to outcome: application of the Bath Ankylosing Spondylitis Radiology Index. J Rheumatol 1999; 26: 988–92.
  • Creemers MC, Franssen MJ, van’t Hof MA, Gribnau FW, van de Putte LB, van Riel PL. Assessment of outcome in ankylosing spondylitis: an extended radiographic scoring system. Ann Rheum Dis 2005; 64: 127–9.
  • Heiland GR, Appel H, Poddubnyy D, et al. High level of functional dickkopf-1 predicts protection from syndesmophyte formation in patients with ankylosing spondylitis. Ann Rheum Dis 2012; 71: 572-4.
  • Huang J, Song G, Yin Z, Fu Z, Ye Z. Alteration of Bone Turnover Markers in Canonical Wingless Pathway in Patients With Ankylosing Spondylitis. Arch Rheumatol 2016; 31: 221-8.
  • Taylan A, Sari I, Akinci B, et al. Biomarkers and cytokines of bone turnover: extensive evaluation in a cohort of patients with ankylosing spondylitis. BMC Musculoskelet Disord 2012; 13: 191.
  • Saad CG, Ribeiro AC, Moraes JC, et al. Low sclerostin levels: a predictive marker of persistent inflammation in ankylosing spondylitis during anti-tumor necrosis factor therapy? Arthritis Res Ther 2012; 14: R216.
  • Appel H, Ruiz-Heiland G, Listing J, et al. Altered skeletal expression of sclerostin and its link to radiographic progression in ankylosing spondylitis. Arthritis Rheum 2009; 60: 3257–62.
  • Ustun N, Tok F, Kalyoncu U, et al. Sclerostin and Dkk-1 in patients with ankylosing spondylitis. Acta Reumatol Port 2014: 39; 146-51.
There are 24 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Original article
Authors

Ahmet Akyol 0000-0002-8953-5196

Burhan Fatih Koçyiğit 0000-0002-6065-8002

Osman Konukoğlu This is me 0000-0002-3353-0230

Ali Gür This is me 0000-0001-9680-6268

Özlem Altındağ 0000-0003-1119-2987

Ali Aydeniz This is me 0000-0001-5701-3951

Müzeyyen Günay Örkmez This is me 0000-0002-4752-6689

Mehmet Tarakçıoğlu This is me 0000-0002-2398-8264

Hasan Ulusal This is me 0000-0003-3890-2088

Savaş Gürsoy This is me 0000-0002-1673-9905

Publication Date September 1, 2019
Published in Issue Year 2019

Cite

Vancouver Akyol A, Koçyiğit BF, Konukoğlu O, Gür A, Altındağ Ö, Aydeniz A, Günay Örkmez M, Tarakçıoğlu M, Ulusal H, Gürsoy S. Serum levels of inhibitors of wingless / beta-catenin in patients with ankylosing spondylitis and the relationship with anti-tumour necrosis factor alpha treatments. otd. 2019;11(3):252-8.

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