Clinical Rheumatology

, Volume 36, Issue 10, pp 2377–2381 | Cite as

In psoriatic arthritis Dkk-1 and PTH are lower than in rheumatoid arthritis and healthy controls

  • Angelo FassioEmail author
  • Luca Idolazzi
  • Ombretta Viapiana
  • Camilla Benini
  • Elisabetta Vantaggiato
  • Francesco Bertoldo
  • Maurizio Rossini
  • Davide Gatti
Brief Report


Psoriatic Arthritis (PsA) is characterized by bone erosive damage often associated with exuberant bone formation especially in enthesial sites. Dkk-1 and sclerostin are the main inhibitors of the WNT/β-catenin signaling pathway and play a key role in the regulation of both bone formation and resorption. We performed this study in order to compare the serum levels of the WNT-pathway regulators along with bone turnover markers (BTM) and parathyroid hormone (PTH) between three different groups: one group of female patients affected by PsA, one group of female patients affected by rheumatoid arthritis (RA), and healthy female controls (HC). This is a cross-sectional study including 33 patients with PsA classified with the CASPAR criteria, 35 HC, and 28 patients with RA classified with the ACR/EULAR 2010 criteria. Intact N-propeptide of type I collagen (PINP), C-terminal telopeptide of type I collagen (CTX-I), Dickkopf-related-protein 1 (Dkk-1), sclerostin, PTH, and 25OH-vitamin D serum levels were dosed. The PsA group showed significantly lower Dkk-1 levels when compared to the HC and RA groups. Dkk-1 in the RA group was significantly higher than HC. A similar trend was documented for PTH. In the PsA group, CTX-I was found to be lower than in both the RA and HC groups. This study demonstrated for the first time that Dkk-1 levels in PsA are lower than HC, in contrast with RA, in which they are increased. These results might contribute to explain the different bone involvement of the two different diseases.


Bone turnover markers Dkk-1 Psoriatic arthritis Rheumatoid arthritis Sclerostin WNT 



The authors would like to thank Dr. Caterina Fraccarollo for the ELISA assays, Dr. Fabio Poli for the technical assistance, and the LURM (Laboratorio Universitario di Ricerca Medica) Research Center, University of Verona, where the biochemical analyses were performed.

Compliance with ethical standards

Ethical approval: all procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent: informed consent was obtained from all individual participants included in the study.

Disclosure statement

Angelo Fassio, Luca Idolazzi, Ombretta Viapiana, Camilla Benini, Elisabetta Vantaggiato, Francesco Bertoldo, Maurizio Rossini and Davide Gatti have no conflict of interest to declare.


  1. 1.
    Miao C, Yang Y, He X et al (2013) Wnt signaling pathway in rheumatoid arthritis, with special emphasis on the different roles in synovial inflammation and bone remodeling. Cell Signal 25:2069–2078. doi: 10.1016/j.cellsig.2013.04.002 CrossRefPubMedGoogle Scholar
  2. 2.
    Sen M (2005) Wnt signalling in rheumatoid arthritis. Rheumatol Oxf Engl 44:708–713. doi: 10.1093/rheumatology/keh553 CrossRefGoogle Scholar
  3. 3.
    Xie W, Zhou L, Li S et al (2016) Wnt/β-catenin signaling plays a key role in the development of spondyloarthritis. Ann N Y Acad Sci 1364:25–31. doi: 10.1111/nyas.12968 CrossRefPubMedGoogle Scholar
  4. 4.
    Rossini M, Gatti D, Adami S (2013) Involvement of WNT/β-catenin signaling in the treatment of osteoporosis. Calcif Tissue Int 93:121–132. doi: 10.1007/s00223-013-9749-z CrossRefPubMedGoogle Scholar
  5. 5.
    Glass DA, Bialek P, Ahn JD et al (2005) Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell 8:751–764. doi: 10.1016/j.devcel.2005.02.017 CrossRefPubMedGoogle Scholar
  6. 6.
    Spencer GJ, Utting JC, Etheridge SL et al (2006) Wnt signalling in osteoblasts regulates expression of the receptor activator of NFkappaB ligand and inhibits osteoclastogenesis in vitro. J Cell Sci 119:1283–1296. doi: 10.1242/jcs.02883 CrossRefPubMedGoogle Scholar
  7. 7.
    Rossini M, Viapiana O, Adami S et al (2015) In patients with rheumatoid arthritis, Dickkopf-1 serum levels are correlated with parathyroid hormone, bone erosions and bone mineral density. Clin Exp Rheumatol 33:77–83PubMedGoogle Scholar
  8. 8.
    Daoussis D, Andonopoulos AP (2011) The emerging role of Dickkopf-1 in bone biology: is it the main switch controlling bone and joint remodeling? Semin Arthritis Rheum 41:170–177. doi: 10.1016/j.semarthrit.2011.01.006 CrossRefPubMedGoogle Scholar
  9. 9.
    Carette S, Graham D, Little H et al (1983) The natural disease course of ankylosing spondylitis. Arthritis Rheum 26:186–190CrossRefPubMedGoogle Scholar
  10. 10.
    Rossini M, Viapiana O, Idolazzi L et al (2015) Higher level of Dickkopf-1 is associated with low bone mineral density and higher prevalence of vertebral fractures in patients with ankylosing spondylitis. Calcif Tissue Int. doi: 10.1007/s00223-015-0093-3
  11. 11.
    Appel H, Ruiz-Heiland G, Listing J et al (2009) Altered skeletal expression of sclerostin and its link to radiographic progression in ankylosing spondylitis. Arthritis Rheum 60:3257–3262. doi: 10.1002/art.24888 CrossRefPubMedGoogle Scholar
  12. 12.
    Daoussis D, Liossis S-NC, Solomou EE et al (2010) Evidence that Dkk-1 is dysfunctional in ankylosing spondylitis. Arthritis Rheum 62:150–158. doi: 10.1002/art.27231 CrossRefPubMedGoogle Scholar
  13. 13.
    Gatti D, Viapiana O, Idolazzi L et al (2011) The waning of teriparatide effect on bone formation markers in postmenopausal osteoporosis is associated with increasing serum levels of DKK1. J Clin Endocrinol Metab 96:1555–1559. doi: 10.1210/jc.2010-2552 CrossRefPubMedGoogle Scholar
  14. 14.
    Viapiana O, Fracassi E, Troplini S et al (2013) Sclerostin and DKK1 in primary hyperparathyroidism. Calcif Tissue Int 92:324–329. doi: 10.1007/s00223-012-9665-7 CrossRefPubMedGoogle Scholar
  15. 15.
    Boehncke W-H, Menter A (2013) Burden of disease: psoriasis and psoriatic arthritis. Am J Clin Dermatol 14:377–388. doi: 10.1007/s40257-013-0032-x CrossRefPubMedGoogle Scholar
  16. 16.
    Gladman DD, Antoni C, Mease P, et al (2005) Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis 64 Suppl 2:ii14-17. doi:  10.1136/ard.2004.032482
  17. 17.
    Heiland GR, Appel H, Poddubnyy D et al (2012) High level of functional dickkopf-1 predicts protection from syndesmophyte formation in patients with ankylosing spondylitis. Ann Rheum Dis 71:572–574. doi: 10.1136/annrheumdis-2011-200216 CrossRefPubMedGoogle Scholar
  18. 18.
    Taylor W, Gladman D, Helliwell P et al (2006) Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum 54:2665–2673. doi: 10.1002/art.21972 CrossRefPubMedGoogle Scholar
  19. 19.
    Aletaha D, Neogi T, Silman AJ et al (2010) 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 62:2569–2581. doi: 10.1002/art.27584 CrossRefPubMedGoogle Scholar
  20. 20.
    Schoels MM, Aletaha D, Alasti F, Smolen JS (2016) Disease activity in psoriatic arthritis (PsA): defining remission and treatment success using the DAPSA score. Ann Rheum Dis 75:811–818. doi: 10.1136/annrheumdis-2015-207507 CrossRefPubMedGoogle Scholar
  21. 21.
    Wells G, Boers M, Tugwell P, MDA Working Group (2006) Low disease activity state in rheumatoid arthritis: concepts and derivation of minimal disease activity. Clin Exp Rheumatol 24:S-52-59.Google Scholar
  22. 22.
    Dalbeth N, Pool B, Smith T et al (2010) Circulating mediators of bone remodeling in psoriatic arthritis: implications for disordered osteoclastogenesis and bone erosion. Arthritis Res Ther 12:R164. doi: 10.1186/ar3123 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Petho Z, Kulcsar-Jakab E, Kalina E et al (2015) Vitamin D status in men with psoriatic arthritis: a case-control study. Osteoporos Int J Establ Result Coop Eur Found Osteoporos Natl Osteoporos Found USA 26:1965–1970. doi: 10.1007/s00198-015-3069-2 CrossRefGoogle Scholar
  24. 24.
    Diarra D, Stolina M, Polzer K et al (2007) Dickkopf-1 is a master regulator of joint remodeling. Nat Med 13:156–163. doi: 10.1038/nm1538 CrossRefPubMedGoogle Scholar
  25. 25.
    Krönke G, Uderhardt S, Kim K-A et al (2010) R-spondin 1 protects against inflammatory bone damage during murine arthritis by modulating the Wnt pathway. Arthritis Rheum 62:2303–2312. doi: 10.1002/art.27496 CrossRefPubMedGoogle Scholar
  26. 26.
    Zou Y-C, Yang X-W, Yuan S-G et al (2016) Downregulation of dickkopf-1 enhances the proliferation and osteogenic potential of fibroblasts isolated from ankylosing spondylitis patients via the Wnt/β-catenin signaling pathway in vitro. Connect Tissue Res:1–12. doi: 10.3109/03008207.2015.1127916
  27. 27.
    Chen B, Cheng G, Wang H, Feng Y (2016) Increased risk of vertebral fracture in patients with rheumatoid arthritis. Medicine (Baltimore). doi: 10.1097/MD.0000000000005262
  28. 28.
    Chandran S, Aldei A, Johnson SR et al (2016) Prevalence and risk factors of low bone mineral density in psoriatic arthritis: a systematic review. Semin Arthritis Rheum 46:174–182. doi: 10.1016/j.semarthrit.2016.05.005 CrossRefPubMedGoogle Scholar
  29. 29.
    Ogdie A, Harter L, Shin D et al (2017) The risk of fracture among patients with psoriatic arthritis and psoriasis: a population-based study. Ann Rheum Dis 76:882–885. doi: 10.1136/annrheumdis-2016-210441 CrossRefPubMedGoogle Scholar
  30. 30.
    Zhou F, Meng S, Song H, Claret FX (2013) Dickkopf-1 is a key regulator of myeloma bone disease: opportunities and challenges for therapeutic intervention. Blood Rev 27:261–267. doi: 10.1016/j.blre.2013.08.002 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Fatima S, Lee NP, Luk JM (2011) Dickkopfs and Wnt/β-catenin signalling in liver cancer. World J Clin Oncol 2:311–325. doi: 10.5306/wjco.v2.i8.311 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Rachner TD, Thiele S, Göbel A et al (2014) High serum levels of Dickkopf-1 are associated with a poor prognosis in prostate cancer patients. BMC Cancer 14:649. doi: 10.1186/1471-2407-14-649 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Van Hees S, Michielsen P, Vanwolleghem T (2016) Circulating predictive and diagnostic biomarkers for hepatitis B virus-associated hepatocellular carcinoma. World J Gastroenterol 22:8271–8282. doi: 10.3748/wjg.v22.i37.8271 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2017

Authors and Affiliations

  1. 1.Unit of RheumatologyUniversity of Verona, Ospedale Civile MaggioreVeronaItaly
  2. 2.Department of Internal MedicineUniversity of VeronaVeronaItaly

Personalised recommendations