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Evaluation of bone mineral density, bone metabolism, osteoprotegerin and receptor activator of the NFκB ligand serum levels during treatment with infliximab in patients with rheumatoid arthritis
  1. M Vis1,
  2. E A Havaardsholm3,
  3. G Haugeberg3,
  4. T Uhlig3,
  5. A E Voskuyl1,
  6. R J van de Stadt4,
  7. B A C Dijkmans1,2,4,
  8. A D Woolf5,
  9. T K Kvien3,
  10. W F Lems1,2,4
  1. 1VU University Medical Centre, Amsterdam, The Netherlands
  2. 2Slotervaart Hospital, Amsterdam
  3. 3Diakonhjemmet Hospital, Oslo, Norway
  4. 4Jan van Breemen Institute, Amsterdam
  5. 5Royal Cornwall Hospital, Truro, UK
  1. Correspondence to:
    M Vis
    Department of Rheumatology, 4A 42, VU University Medical Centre, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands;m.vis{at}


Objectives: To examine whether treatment with anti-tumour necrosis factor (TNF) α prevents loss of bone mineral density (BMD) at the spine and hip (generalised) and in the hands (local) of patients with rheumatoid arthritis, and to study the changes in markers of bone metabolism, including receptor activator of the NFκB ligand (RANKL) and osteoprotegerin (OPG), during anti-TNF treatment.

Patients and methods: 102 patients with active rheumatoid arthritis, who were treated with infliximab during 1 year, were included in this open cohort study. The BMD of the spine and hip (dual x ray absorptiometry) and hands dual x ray radiogrammetry was measured before the start of treatment and after 1 year. Changes in osteocalcin formation, β-isomerised carboxy terminal telopeptide of type 1 collagen (β-CTx, resorption), RANKL and OPG were determined at 0, 14, 30 and 46 weeks.

Results: The BMD of the spine and hip was unchanged during treatment with infliximab, whereas BMD of the hand decreased significantly by 0.8% (p<0.01). The BMD of the hip in patients with a good European League Against Rheumatism response showed a favourable change compared with patients not achieving such a response. Serum β-CTx and RANKL were both considerably decreased compared with baseline at all time points. The decrease in β-CTx was associated with the decrease in Disease Activity Score of 28 joints and C reactive protein during the 0–14 weeks interval.

Conclusion: In patients with rheumatoid arthritis treated with infliximab, spine and hip bone loss is arrested, whereas metacarpal cortical hand bone loss is not stopped. The outcome of the study also supports a relationship between clinical response, in terms of reduced inflammatory activity, and changes in bone loss of the spine, hip and hands.

  • BMD, bone mineral density
  • β-CTx, β-isomerised carboxy terminal telopeptide of type 1 collagen
  • DAS-28, Disease Activity Score of 28 joints
  • DEXA, dual x ray absorptiometry
  • DMARD, disease-modifying antirheumatic drug
  • DXR, digital x ray radiogrammetry
  • EULAR, European League Against Rheumatism
  • IL1, interleukin 1
  • JBI, Jan van Breemen Institute
  • OPG, osteoprotegerin
  • RANKL, receptor activator of the NFκB ligand
  • TNF, tumour necrosis factor
  • VUMC, VU University Medical Centre

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