title: Dickkopf-1 level is lower in patients with ankylosing spondylitis than in healthy people and is not influenced by anti-tumor necrosis factor therapy.
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.
authors.affiliation: Rheumatism Center, Inha University Hospital, 3rd street Sinheung-dong, Jung-gu, Incheon 400-711, Republic of Korea.
authors.forename: Seong-Ryul
authors.initials: SR
authors.lastname: Kwon
authors.forename: Mie-Jin
authors.initials: MJ
authors.lastname: Lim
authors.forename: Chang-Hee
authors.initials: CH
authors.lastname: Suh
authors.forename: Shin-Goo
authors.initials: SG
authors.lastname: Park
authors.forename: Yeon-Sik
authors.initials: YS
authors.lastname: Hong
authors.forename: Bo-Young
authors.initials: BY
authors.lastname: Yoon
authors.forename: Hyoun-Ah
authors.initials: HA
authors.lastname: Kim
authors.forename: Hyo-Jin
authors.initials: HJ
authors.lastname: Choi
authors.forename: Won
authors.initials: W
authors.lastname: Park
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D024042:Collagen Type I / Q000097:blood; D015536:Down-Regulation; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007155:Immunologic Factors / Q000627:therapeutic use*; D000069285:Infliximab; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010012:Osteogenesis / Q000187:drug effects; D053244:Osteoprotegerin / Q000097:blood; D010455:Peptides / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D056910:Republic of Korea; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D024042:Collagen Type I; C501126:DKK1 protein, human; D007074:Immunoglobulin G; D007155:Immunologic Factors; D036341:Intercellular Signaling Peptides and Proteins; D053244:Osteoprotegerin; D010455:Peptides; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human; D014409:Tumor Necrosis Factor-alpha; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept