Skip to main content
Erschienen in: Rheumatology International 8/2012

01.08.2012 | Original Article

Dickkopf-1 level is lower in patients with ankylosing spondylitis than in healthy people and is not influenced by anti-tumor necrosis factor therapy

verfasst von: Seong-Ryul Kwon, Mie-Jin Lim, Chang-Hee Suh, Shin-Goo Park, Yeon-Sik Hong, Bo-Young Yoon, Hyoun-Ah Kim, Hyo-Jin Choi, Won Park

Erschienen in: Rheumatology International | Ausgabe 8/2012

Einloggen, um Zugang zu erhalten

Abstract

(1) To compare the serum levels of Dickkopf-1 (DKK-1) and bone biomarkers in patients with ankylosing spondylitis (AS) and healthy controls. (2) To examine the effects of anti-tumor necrosis factor-α (TNF-α) therapy for 3 months on bone biomarkers in patients with AS. We measured the levels of DKK-1, osteocalcin, osteoprotegerin, and C-terminal telopeptide of type I collagen (CTX-1) in patients with AS and in healthy controls at baseline and 3 months after initiating anti-TNF-α therapy in AS patients. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores were also measured before and after anti-TNF-α therapy in AS patients. Serum levels of DKK-1 were significantly lower in the AS patients than in the controls (P < 0.0001). Osteocalcin and osteoprotegerin levels were significantly higher in the AS patients than in the controls (P < 0.0001). Serum levels of DKK-1 were not changed after the 3-month anti-TNF-α therapy. Osteocalcin level increased (P < 0.0001), osteoprotegerin level and BASDAI scores decreased (P = 0.025 and P < 0.0001, respectively) significantly after the 3-months anti-TNF-α therapy. Serum DKK-1 level was lower in patients with AS than in healthy controls and did not change after 3 months of anti-TNF-α therapy in the AS patients despite the marked improvement in BASDAI scores. These findings suggest the low serum DKK-1 level is related to the pathogenesis of new bone formation in AS, which is resistant to TNF-α blocking therapy.
Literatur
1.
Zurück zum Zitat Braun J, Brandt J, Listing J et al (2003) Long-term efficacy and safety of infliximab in the treatment of ankylosing spondylitis: an open, observational, extension study of a three-month, randomized, placebo-controlled trial. Arthr Rheum 48:2224–2233CrossRef Braun J, Brandt J, Listing J et al (2003) Long-term efficacy and safety of infliximab in the treatment of ankylosing spondylitis: an open, observational, extension study of a three-month, randomized, placebo-controlled trial. Arthr Rheum 48:2224–2233CrossRef
2.
Zurück zum Zitat Davis JC, van der Heijde D et al (2005) Sustained durability and tolerability of etanercept in ankylosing spondylitis from 96 weeks. Ann Rheum Dis 64:1557–1562PubMedCrossRef Davis JC, van der Heijde D et al (2005) Sustained durability and tolerability of etanercept in ankylosing spondylitis from 96 weeks. Ann Rheum Dis 64:1557–1562PubMedCrossRef
3.
Zurück zum Zitat van der Heijde D, Kivitz A, Schiff MH, for the ATLAS Study Group et al (2006) Efficacy and safety of adalimumab in patients with ankylosing spondylitis: results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthr Rheum 54:2136–2146CrossRef van der Heijde D, Kivitz A, Schiff MH, for the ATLAS Study Group et al (2006) Efficacy and safety of adalimumab in patients with ankylosing spondylitis: results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthr Rheum 54:2136–2146CrossRef
4.
Zurück zum Zitat Davis JC, van der Heijde D, Dougados M, Woolley JM (2005) Reduction in health-related quality of life in patients with ankylosing spondylitis and improvements with etanercept therapy. Arthr Rheum 53:494–501CrossRef Davis JC, van der Heijde D, Dougados M, Woolley JM (2005) Reduction in health-related quality of life in patients with ankylosing spondylitis and improvements with etanercept therapy. Arthr Rheum 53:494–501CrossRef
5.
Zurück zum Zitat van der Heijde D, Landewé R, Einstein S et al (2008) Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept. Arthr Rheum 58:1324–1331CrossRef van der Heijde D, Landewé R, Einstein S et al (2008) Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept. Arthr Rheum 58:1324–1331CrossRef
6.
Zurück zum Zitat van der Heijde D, Landewé R, Baraliakos X et al (2008) Radiographic findings following two years of infliximab therapy in patients with ankylosing spondylitis. Arthr Rheum 58:3063–3070CrossRef van der Heijde D, Landewé R, Baraliakos X et al (2008) Radiographic findings following two years of infliximab therapy in patients with ankylosing spondylitis. Arthr Rheum 58:3063–3070CrossRef
7.
Zurück zum Zitat van der Heijde D (2007) Clinical features of ankylosing spondylitis. In: Klippel JH, Stone JH, Crofford LJ, White PH (eds) Primer on the rheumatic diseases, 13th edn. Springer, New York, pp 194–196 van der Heijde D (2007) Clinical features of ankylosing spondylitis. In: Klippel JH, Stone JH, Crofford LJ, White PH (eds) Primer on the rheumatic diseases, 13th edn. Springer, New York, pp 194–196
8.
Zurück zum Zitat Diarra D, Stolina M, Polzer K et al (2007) Dickkopf-1 is a master regulator of joint remodeling. Nat Med 13:156–163PubMedCrossRef Diarra D, Stolina M, Polzer K et al (2007) Dickkopf-1 is a master regulator of joint remodeling. Nat Med 13:156–163PubMedCrossRef
9.
Zurück zum Zitat Miller JR (2002) The Wnts. Genome Biol 3:3001.1–3001.15 Miller JR (2002) The Wnts. Genome Biol 3:3001.1–3001.15
10.
Zurück zum Zitat Mao B, Wu W, Davidson G et al (2002) Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin signalling. Nature 417:664–667PubMedCrossRef Mao B, Wu W, Davidson G et al (2002) Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin signalling. Nature 417:664–667PubMedCrossRef
11.
Zurück zum Zitat Holmen SL, Giambernardi TA, Zylstra CR et al (2004) Decreased BMD and limb deformities in mice carrying mutations in both Lrp5 and Lrp6. J Bone Miner Res 19:2033–2040PubMedCrossRef Holmen SL, Giambernardi TA, Zylstra CR et al (2004) Decreased BMD and limb deformities in mice carrying mutations in both Lrp5 and Lrp6. J Bone Miner Res 19:2033–2040PubMedCrossRef
12.
Zurück zum Zitat Glinka A, Wu W, Delius H, Monaqhan AP, Blumenstock C, Niehrs C (1998) Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction. Nature 391:357–362PubMedCrossRef Glinka A, Wu W, Delius H, Monaqhan AP, Blumenstock C, Niehrs C (1998) Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction. Nature 391:357–362PubMedCrossRef
13.
Zurück zum Zitat Bafico A, Liu G, Yaniv A, Gazit A, Aaronson SA (2001) Novel mechanism of Wnt signalling inhibition mediated by Dickkopf-1 interaction with LRP6. Nat Cell Biol 3:683–686PubMedCrossRef Bafico A, Liu G, Yaniv A, Gazit A, Aaronson SA (2001) Novel mechanism of Wnt signalling inhibition mediated by Dickkopf-1 interaction with LRP6. Nat Cell Biol 3:683–686PubMedCrossRef
14.
Zurück zum Zitat Morvan F, Boulukos K, Clément-Lacroix P et al (2006) Deletion of a single allele of the Dkk1 gene leads to an increase in bone formation and bone mass. J Bone Miner Res 21:934–945PubMedCrossRef Morvan F, Boulukos K, Clément-Lacroix P et al (2006) Deletion of a single allele of the Dkk1 gene leads to an increase in bone formation and bone mass. J Bone Miner Res 21:934–945PubMedCrossRef
15.
Zurück zum Zitat Tian E, Zhan F, Walker R et al (2003) The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med 349:2483–2494PubMedCrossRef Tian E, Zhan F, Walker R et al (2003) The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med 349:2483–2494PubMedCrossRef
16.
Zurück zum Zitat van der Linden S, Valkenburg HA, Cats A (1984) Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthr Rheum 27:361–368CrossRef van der Linden S, Valkenburg HA, Cats A (1984) Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthr Rheum 27:361–368CrossRef
17.
Zurück zum Zitat Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A (1994) A new approach to defining disease status in ankylosing spondylitis: the bath ankylosing spondylitis disease activity index. J Rheumatol 21:2286–2291PubMed Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A (1994) A new approach to defining disease status in ankylosing spondylitis: the bath ankylosing spondylitis disease activity index. J Rheumatol 21:2286–2291PubMed
18.
Zurück zum Zitat Glass DA II, Bialek P, Ahn JD et al (2005) Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell 8:751–764PubMedCrossRef Glass DA II, Bialek P, Ahn JD et al (2005) Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell 8:751–764PubMedCrossRef
19.
Zurück zum Zitat Uderhardt S, Diarra D, Katzenbeisser J et al (2009) Blockade of Dickkopf-1 induces fusion of sacroiliac joints. Ann Rheum Dis 69:592–597PubMedCrossRef Uderhardt S, Diarra D, Katzenbeisser J et al (2009) Blockade of Dickkopf-1 induces fusion of sacroiliac joints. Ann Rheum Dis 69:592–597PubMedCrossRef
20.
Zurück zum Zitat Allali F, Breban M, Porcher R, Maillefert JF, Dougados M, Roux C (2003) Increase in bone mineral density of patients with spondyloarthropathy treated with anti-tumor necrosis factor alpha. Ann Rheum Dis 62:347–349PubMedCrossRef Allali F, Breban M, Porcher R, Maillefert JF, Dougados M, Roux C (2003) Increase in bone mineral density of patients with spondyloarthropathy treated with anti-tumor necrosis factor alpha. Ann Rheum Dis 62:347–349PubMedCrossRef
21.
Zurück zum Zitat Briot K, Roux C, Gossec L et al (2008) Effects of etanercept on serum biochemical markers of cartilage metabolism in patients with spondyloarthropathy. J Rheumatol 35:310–314PubMed Briot K, Roux C, Gossec L et al (2008) Effects of etanercept on serum biochemical markers of cartilage metabolism in patients with spondyloarthropathy. J Rheumatol 35:310–314PubMed
22.
Zurück zum Zitat Visvanathan S, van der Heijde D, Deodhar A et al (2009) Effects of infliximab on markers of inflammation and bone turnover and associations with bone mineral density in patients with ankylosing spondylitis. Ann Rheum Dis 68:175–182PubMedCrossRef Visvanathan S, van der Heijde D, Deodhar A et al (2009) Effects of infliximab on markers of inflammation and bone turnover and associations with bone mineral density in patients with ankylosing spondylitis. Ann Rheum Dis 68:175–182PubMedCrossRef
23.
Zurück zum Zitat Schett G, Landewé R, van der Heijde D (2007) TNF blockers and structural remodeling in ankylosing spondylitis—what is reality and what is fiction? Ann Rheum Dis 66:709–711PubMedCrossRef Schett G, Landewé R, van der Heijde D (2007) TNF blockers and structural remodeling in ankylosing spondylitis—what is reality and what is fiction? Ann Rheum Dis 66:709–711PubMedCrossRef
24.
Zurück zum Zitat Hammer RE, Maika SD, Richardson JA, Tang JP, Taurog JD (1990) Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human beta 2 m: an animal model of HLA-B27-associated human disorders. Cell 63:1099–1112PubMedCrossRef Hammer RE, Maika SD, Richardson JA, Tang JP, Taurog JD (1990) Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human beta 2 m: an animal model of HLA-B27-associated human disorders. Cell 63:1099–1112PubMedCrossRef
25.
Zurück zum Zitat Glant TT, Mikecz K, Arzoumanian A, Poole AR (1987) Proteoglycan-induced arthritis in BALB/c mice. Clinical features and histopathology. Arthr Rheum 30:201–212CrossRef Glant TT, Mikecz K, Arzoumanian A, Poole AR (1987) Proteoglycan-induced arthritis in BALB/c mice. Clinical features and histopathology. Arthr Rheum 30:201–212CrossRef
Metadaten
Titel
Dickkopf-1 level is lower in patients with ankylosing spondylitis than in healthy people and is not influenced by anti-tumor necrosis factor therapy
verfasst von
Seong-Ryul Kwon
Mie-Jin Lim
Chang-Hee Suh
Shin-Goo Park
Yeon-Sik Hong
Bo-Young Yoon
Hyoun-Ah Kim
Hyo-Jin Choi
Won Park
Publikationsdatum
01.08.2012
Verlag
Springer-Verlag
Erschienen in
Rheumatology International / Ausgabe 8/2012
Print ISSN: 0172-8172
Elektronische ISSN: 1437-160X
DOI
https://doi.org/10.1007/s00296-011-1981-0

Weitere Artikel der Ausgabe 8/2012

Rheumatology International 8/2012 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.