title: Evaluation of bone mineral density, bone metabolism, osteoprotegerin and receptor activator of the NFkappaB ligand serum levels during treatment with infliximab in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  To examine whether treatment with anti-tumour necrosis factor (TNF) alpha 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 NFkappaB ligand (RANKL) and osteoprotegerin (OPG), during anti-TNF treatment.
  
  
  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, beta-isomerised carboxy terminal telopeptide of type 1 collagen (beta-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 beta-CTx and RANKL were both considerably decreased compared with baseline at all time points. The decrease in beta-CTx was associated with the decrease in Disease Activity Score of 28 joints and C reactive protein during the 0-14 weeks interval.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Rheumatology, VU University Medical Centre, Amsterdam, The Netherlands. m.vis@vumc.nl
authors.forename: M
authors.initials: M
authors.lastname: Vis
authors.forename: E A
authors.initials: EA
authors.lastname: Havaardsholm
authors.forename: G
authors.initials: G
authors.lastname: Haugeberg
authors.forename: T
authors.initials: T
authors.lastname: Uhlig
authors.forename: A E
authors.initials: AE
authors.lastname: Voskuyl
authors.forename: R J
authors.initials: RJ
authors.lastname: van de Stadt
authors.forename: B A C
authors.initials: BA
authors.lastname: Dijkmans
authors.forename: A D
authors.initials: AD
authors.lastname: Woolf
authors.forename: T K
authors.initials: TK
authors.lastname: Kvien
authors.forename: W F
authors.initials: WF
authors.lastname: Lems
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000378:metabolism*; D002352:Carrier Proteins / Q000097:blood; D005260:Female; D006023:Glycoproteins / Q000097:blood; D050276:Hand Bones / Q000503:physiopathology; D006621:Hip Joint / Q000503:physiopathology; D006801:Humans; D000069285:Infliximab; D008024:Ligands; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D010024:Osteoporosis / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D012720:Severity of Illness Index; D013131:Spine / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D015415:Biomarkers; D002352:Carrier Proteins; D006023:Glycoproteins; D008024:Ligands; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab