Effect of TNF-alpha inhibitor treatment on bone mineral density in patients with ankylosing spondylitis: a systematic review and meta-analysis

Semin Arthritis Rheum. 2014 Oct;44(2):155-61. doi: 10.1016/j.semarthrit.2014.05.008. Epub 2014 May 9.


Objectives: Ankylosing spondylitis (AS) is a chronic inflammatory disease associated with an increased risk of osteoporosis and fractures. TNF inhibitors have been used to treat AS, but their effect on bone is unclear. Thus, we conducted a meta-analysis to study the effect of TNF inhibitors on spine and hip BMD in patients with AS.

Methods: Two authors independently searched MEDLINE and PubMed for longitudinal studies that had assessed the effect of TNF inhibitors on BMD in patients with AS. Studies with a minimum follow-up period of 1 year were included.

Results: Seven longitudinal studies and one randomized control trial were included, with a total of 568 AS patients (mean age range of 36-48 years and disease duration of 9-17 years). Lumbar spine BMD increased by 5.1% (95% CI: 4.0-6.1%, p = 0.00000) after 1 year of treatment with TNF inhibitors and by 8.6% (95% CI: 6.8-10.3%, p < 0.00001) after 2 years. Significant improvements in total hip BMD were also noted after 1 [1.8% (1.0-2.5%)] and 2 years [2.5% (1.9-3.0%)]. Compared to baseline, femoral neck BMD remained stable after 1 year [0.7% (-0.8% to 2.2%), p = 0.34]. No significant heterogeneity was noted amongst the included studies.

Conclusions: TNF inhibitors can increase lumbar spine and total hip BMD and maintain femoral neck BMD for up to 2 years in patients with AS. More research is needed to assess the effect of TNF inhibitors on bone quality and fracture risk.

Keywords: Anti-tumor necrosis factor-alpha; BMD; TNF inhibitors; ankylosing spondylitis; bone mineral density; osteoporosis; spondyloarthropathy.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Aged
  • Antirheumatic Agents / pharmacology*
  • Antirheumatic Agents / therapeutic use*
  • Bone Density / drug effects*
  • Bone Density / physiology
  • Femur Neck / physiopathology
  • Fractures, Bone / epidemiology
  • Fractures, Bone / physiopathology
  • Hip Joint / physiopathology
  • Humans
  • Lumbar Vertebrae / physiopathology
  • Middle Aged
  • Risk Factors
  • Spondylitis, Ankylosing / drug therapy*
  • Spondylitis, Ankylosing / physiopathology
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Antirheumatic Agents
  • Tumor Necrosis Factor-alpha