title: Biomarkers of bone metabolism in ankylosing spondylitis in relation to osteoproliferation and osteoporosis.
abstract: OBJECTIVE
  To identify biomarkers for bone metabolism in patients with ankylosing spondylitis (AS) and to determine the relationship between these biomarkers and disease activity, back mobility, osteoproliferation, and bone mineral density (BMD).
  
  
  METHODS
  Serum levels of Wingless protein (Wnt-3a), Dickkopf-1 (DKK-1), sclerostin, soluble receptor activator of nuclear factor-κB ligand (sRANKL), and osteoprotegerin were assessed using ELISA. Ankylosing Spondylitis Disease Activity Score-C reactive protein, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis patient global score, and C-reactive protein (CRP) were used as disease activity measures, and Bath Ankylosing Spondylitis Metrology Index (BASMI) as a measure of spinal mobility. Lateral spine radiographs were scored for chronic AS-related changes (mSASSS). BMD was measured with dual-energy x-ray absorptiometry.
  
  
  RESULTS
  Two hundred four patients with AS (NY criteria; 57% men), with a mean age of 50 ± 13 years and disease duration 15 ± 11 years, and 80 age and sex-matched controls were included. The patients with AS had significantly higher serum levels of Wnt-3a (p < 0.001) and lower levels of sclerostin (p = 0.014) and sRANKL (p = 0.047) compared with the controls. High CRP was associated with low sclerostin (r(S) = -0.21, p = 0.003) and DKK-1 (r(S) = -0.14, p = 0.045). In multiple linear regression analyses, increasing BASMI and mSASSS were independently associated with older age, male sex, high CRP, and elevated serum levels of Wnt-3a. In addition, mSASSS remained associated with a high number of smoking pack-years after adjusting for age. Low BMD of femoral neck was associated with high mSASSS after adjusting for age.
  
  
  CONCLUSIONS
  Serum levels of Wnt-3a are elevated in AS and associated with increased BASMI and mSASSS, independent of age, indicating that Wnt-3a could be a biomarker for the osteoproliferative process.
authors.affiliation: From the Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Sweden.E. Klingberg, MD, PhD; M. Nurkkala, PhD; H. Carlsten, MD, PhD, Professor; H. Forsblad-d'Elia, MD, PhD, Associate professor, Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at the University of Gothenburg. Eva.Klingberg@vgregion.se.
authors.forename: Eva
authors.initials: E
authors.lastname: Klingberg
authors.affiliation: From the Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Sweden.E. Klingberg, MD, PhD; M. Nurkkala, PhD; H. Carlsten, MD, PhD, Professor; H. Forsblad-d'Elia, MD, PhD, Associate professor, Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at the University of Gothenburg.
authors.forename: Merja
authors.initials: M
authors.lastname: Nurkkala
authors.affiliation: From the Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Sweden.E. Klingberg, MD, PhD; M. Nurkkala, PhD; H. Carlsten, MD, PhD, Professor; H. Forsblad-d'Elia, MD, PhD, Associate professor, Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at the University of Gothenburg.
authors.forename: Hans
authors.initials: H
authors.lastname: Carlsten
authors.affiliation: From the Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Sweden.E. Klingberg, MD, PhD; M. Nurkkala, PhD; H. Carlsten, MD, PhD, Professor; H. Forsblad-d'Elia, MD, PhD, Associate professor, Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at the University of Gothenburg.
authors.forename: Helena
authors.initials: H
authors.lastname: Forsblad-d'Elia
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000097:blood; D001842:Bone and Bones / Q000378:metabolism*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D053244:Osteoprotegerin / Q000097:blood; D053245:RANK Ligand / Q000097:blood; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000097:blood* / Q000150:complications; D060509:Wnt3A Protein / Q000097:blood; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; D053244:Osteoprotegerin; D053245:RANK Ligand; C422903:SOST protein, human; D060509:Wnt3A Protein
keywords: ANKYLOSING SPONDYLITIS; BIOMARKERS; DICKKOPF-1; OSTEOPOROSIS; SCLEROSTIN; WNT