The paradoxical effects of TNF inhibitors on bone mineral density and radiographic progression in patients with ankylosing spondylitis

Rheumatology (Oxford). 2013 Apr;52(4):718-26. doi: 10.1093/rheumatology/kes364. Epub 2012 Dec 28.


Objectives: To determine the longitudinal effects of TNF inhibitors on BMD and radiographic progression in patients with AS and to assess independent factors associated with increased BMD in the lumbar spine.

Methods: Sixty-three patients with AS were included. Twenty-six patients were treated with TNF inhibitors and 37 were not. BMD in the lumbar spine and right femur was measured by DXA at baseline and 1 and 2 years later. Lumbar spine radiography was performed at baseline and after 2 years. Radiographic progression was scored using the Stoke AS Spinal Score (SASSS) and the modified SASSS. Univariate and multivariate linear regression analyses were performed to identify factors independently associated with spinal BMD increase.

Results: BMD in the lumbar spine and total proximal femur of patients receiving TNF inhibitors increased consistently over 2 years compared with that in patients not receiving TNF inhibitors (P < 0.01 and P = 0.02), and treated patients showed increased SASSS scores (P = 0.05); however, syndesmophyte development was no different between the two groups. There was a significant difference in the change of SASSS in patients treated with both TNF inhibitors and bisphosphonates compared with those treated with TNF inhibitors alone (P < 0.01). TNF inhibitor therapy and the increase in SASSS were independently associated with increased lumbar spine BMD (P = 0.009 and P < 0.001).

Conclusion: TNF inhibitors appear to be associated with increased SASSS scores and improvements in BMD. Further prospective studies with larger subject numbers are needed to validate this paradoxical role of TNF inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab
  • Adult
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antirheumatic Agents / therapeutic use*
  • Bone Density / drug effects*
  • Cohort Studies
  • Diphosphonates / therapeutic use
  • Disease Progression
  • Drug Therapy, Combination
  • Etanercept
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoglobulin G / therapeutic use
  • Infliximab
  • Longitudinal Studies
  • Lumbar Vertebrae / diagnostic imaging
  • Male
  • Middle Aged
  • Radiography
  • Receptors, Tumor Necrosis Factor / therapeutic use
  • Spondylitis, Ankylosing / diagnostic imaging*
  • Spondylitis, Ankylosing / drug therapy*
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Young Adult


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Diphosphonates
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Adalimumab
  • Etanercept