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 Aug;32(8):2523-7. doi: 10.1007/s00296-011-1981-0. Epub 2011 Jul 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab
  • Adult
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Biomarkers / blood
  • Case-Control Studies
  • Collagen Type I / blood
  • Down-Regulation
  • Etanercept
  • Female
  • Humans
  • Immunoglobulin G / therapeutic use
  • Immunologic Factors / therapeutic use*
  • Infliximab
  • Intercellular Signaling Peptides and Proteins / blood*
  • Male
  • Middle Aged
  • Osteocalcin / blood
  • Osteogenesis / drug effects
  • Osteoprotegerin / blood
  • Peptides / blood
  • Receptors, Tumor Necrosis Factor / therapeutic use
  • Republic of Korea
  • Severity of Illness Index
  • Spondylitis, Ankylosing / blood*
  • Spondylitis, Ankylosing / diagnosis
  • Spondylitis, Ankylosing / drug therapy*
  • Spondylitis, Ankylosing / immunology
  • Time Factors
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • Collagen Type I
  • DKK1 protein, human
  • Immunoglobulin G
  • Immunologic Factors
  • Intercellular Signaling Peptides and Proteins
  • Osteoprotegerin
  • Peptides
  • Receptors, Tumor Necrosis Factor
  • TNFRSF11B protein, human
  • Tumor Necrosis Factor-alpha
  • collagen type I trimeric cross-linked peptide
  • Osteocalcin
  • Infliximab
  • Adalimumab
  • Etanercept