Biomarkers and cytokines of bone turnover: extensive evaluation in a cohort of patients with ankylosing spondylitis

BMC Musculoskelet Disord. 2012 Oct 2:13:191. doi: 10.1186/1471-2474-13-191.


Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease of spine and sacroiliac joints; it is characterized by new bone formation, and the disease processes can be accompanied by osteoporosis. In the present study, we investigated changes in bone mineral density (BMD) and in the levels of various bone turnover-related biomarkers and cytokines in a cohort of AS patients, with regard to clinical parameters, disease activity, and treatment regimen.

Methods: 55 AS patients and 33 healthy controls included in the study. Spinal mobility was assessed by the Bath Ankylosing Spondylitis Metrology Index (BASMI), and radiologic changes were scored by the Bath Ankylosing Spondylitis Radiologic Index (BASRI). Patients were also evaluated with the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Bone mineral density (BMD) assessed by dual energy X-ray absorptiometry. Various biomarkers and cytokines of bone turnover including osteoprotegerin (OPG), serum band 5 tartrate-resistant acid phosphatase (TRAP-5), soluble receptor activator of nuclear factor kappa-B ligand (sRANKL), secreted frizzled-related protein 1 (sFRP-1), Dickkopf-related protein 1 (DKK-1), and sclerostin were studied.

Results: The levels of TRAP-5, NTX, sRANKL, sclerostin, sFRP-1, DKK-1, and IFNγ, were similar between the patients and controls (p > 0.05), while BMD of femoral neck, and OPG levels were significantly lower in AS patients (p < 0.05). In a subgroup analysis, patients with active disease had significantly higher concentrations of OPG compared with the inactive group. Rest of the biomarkers and cytokines of bone turnover were similar between the active and inactive disease groups. Subgroup analysis of patients receiving anti-TNFα agents and conventional therapy revealed that OPG concentrations were significantly lower in the patients receiving biological drugs, while BAP and DKK-1 were significantly higher in the patients treated with conventional agents.

Conclusions: In this cross-sectional study we showed that OPG levels were significantly lower in AS patients compared to healthy subjects. On the other hand, the levels of wingless (Wnt) signal pathway inhibitors seem not altered. Ectopic bone formation in AS may be related to dysfunction of these molecules at the cellular level.

MeSH terms

  • Absorptiometry, Photon
  • Acid Phosphatase / blood
  • Adaptor Proteins, Signal Transducing
  • Adult
  • Ataxia Telangiectasia Mutated Proteins
  • Biomarkers / blood
  • Biomechanical Phenomena
  • Bone Density
  • Bone Morphogenetic Proteins / blood
  • Bone Remodeling*
  • Case-Control Studies
  • Cell Cycle Proteins / blood
  • Cross-Sectional Studies
  • Cytokines / blood*
  • Female
  • Femur Neck / diagnostic imaging
  • Genetic Markers
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Intercellular Signaling Peptides and Proteins / blood
  • Isoenzymes / blood
  • Male
  • Middle Aged
  • Osteoprotegerin / blood
  • Protein Serine-Threonine Kinases / blood
  • RANK Ligand / blood
  • Severity of Illness Index
  • Spine / diagnostic imaging
  • Spine / drug effects
  • Spine / physiopathology*
  • Spondylitis, Ankylosing / blood
  • Spondylitis, Ankylosing / diagnosis
  • Spondylitis, Ankylosing / drug therapy
  • Spondylitis, Ankylosing / immunology
  • Spondylitis, Ankylosing / physiopathology*
  • Tartrate-Resistant Acid Phosphatase
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Young Adult


  • Adaptor Proteins, Signal Transducing
  • Biomarkers
  • Bone Morphogenetic Proteins
  • Cell Cycle Proteins
  • Cytokines
  • DKK1 protein, human
  • Genetic Markers
  • Immunosuppressive Agents
  • Intercellular Signaling Peptides and Proteins
  • Isoenzymes
  • Osteoprotegerin
  • RANK Ligand
  • SOST protein, human
  • TNFRSF11B protein, human
  • TNFSF11 protein, human
  • Tumor Necrosis Factor-alpha
  • ATR protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein Serine-Threonine Kinases
  • Acid Phosphatase
  • Tartrate-Resistant Acid Phosphatase