title: Effects of tumor necrosis factor-α inhibitors on new bone formation in ankylosing spondylitis.
abstract: OBJECTIVE
  To better understand the effect of TNF-α inhibitors (TNFi) on new bone formation in ankylosing spondylitis (AS) patients.
  
  
  METHODS
  We systematically searched the articles in EMBASE and PubMed.
  
  
  RESULTS
  Fifteen articles were enrolled. In all the 9 TNFi-treated cohorts, the vertebral corners with inflammatory lesions at baseline were at higher risk to develop new syndesmophytes than those without inflammatory lesions, although a few syndesmophytes also developed at the vertebral corners without inflammatory lesions at baseline. The advanced inflammatory lesions including fat deposition on baseline MRI showed a higher risk for syndesmophyte formation than the acute inflammatory lesions. Because the number of analyzed vertebral corners were too small, it might not be true that new syndesmophytes developed more frequently at the corners with inflammatory lesions completely resolved than those with persistent inflammation after TNFi treatment. Four studies with 2-year follow-up revealed null effect of TNFi on radiographic progression compared with historical controls with lower disease activity, and 3 studies with ≥4-year follow-up proved inhibitory effect of TNFi on new bone formation in AS patients. Patients with a delay of >10 years in starting TNFi therapy were more likely to experience radiographic progression as compared to those who started earlier.
  
  
  CONCLUSIONS
  In TNFi treated AS patients, baseline inflammation is linked with syndesmophyte development. An earlier initiation of TNFi therapy may slow the radiographic progression in AS, and TNFi may lose its benefit of retarding new bone formation at advanced stage of AS especially after the focal fat infiltration or syndesmophyte formation.
authors.affiliation: Department of Rheumatology and Immunology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China.
authors.forename: Jing-Ru
authors.initials: JR
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology and Immunology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China.
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Liu
authors.affiliation: Department of Joint Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Xu
authors.affiliation: Department of Rheumatology and Immunology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433, China. Electronic address: dsm@medmail.com.cn.
authors.forename: Sheng-Ming
authors.initials: SM
authors.lastname: Dai
mesh_terms: D018501:Antirheumatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D010012:Osteogenesis / Q000187:drug effects*; D013167:Spondylitis, Ankylosing / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha
keywords: Ankylosing spondylitis; Inflammatory lesions; New bone formation; Tumor necrosis factor-α inhibitors