title: Two year randomized controlled trial of etidronate in rheumatoid arthritis: changes in serum aminoterminal telopeptides correlate with radiographic progression of disease.
abstract: OBJECTIVE
  To investigate the effect of intermittent cyclical etidronate treatment on radiographic progression, bone collagen markers, and clinical disease activity in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  Forty patients with RA of less than 5 years' duration were randomized to receive intermittent cyclical etidronate therapy in conjunction with antirheumatic therapy or antirheumatic therapy alone (without etidronate) in a 2 year open-label protocol. Radiographs of hands and feet and serum samples for determination of aminoterminal propeptide (PINP), crosslinked C-telopeptide (ICTP), and aminoterminal telopeptides (NTx) of type I collagen were obtained at baseline and at 24 months.
  
  
  RESULTS
  There was significant and similar worsening of the radiologic scores in both treatment groups. Both PINP, a marker of bone formation, and ICTP, an indicator of collagen degradation, declined in the etidronate group compared to the control group (p = 0.001 and p = 0.042, respectively). The groups did not differ for the change in serum NTx, a specific systemic marker of osteoclastic bone resorption. However, the change in serum NTx correlated significantly with the increase in erosion score in the total study population and in the control group (r = 0.41, p = 0.01 and r = 0.48, p = 0.034, respectively).
  
  
  CONCLUSIONS
  Etidronate therapy did not prevent radiologic progression in patients with RA, but the decline in serum PINP and ICTP concentrations suggests a favorable effect on general bone metabolism. Correlation between the change in serum NTx and worsening of the erosion score provides biochemical evidence that osteoclast is the principal cell type responsible for focal bone resorption in RA.
authors.affiliation: Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland. heikki.valleala@hus.fi
authors.forename: Heikki
authors.initials: H
authors.lastname: Valleala
authors.forename: Leena
authors.initials: L
authors.lastname: Laasonen
authors.forename: Marja-Kaisa
authors.initials: MK
authors.lastname: Koivula
authors.forename: Jami
authors.initials: J
authors.lastname: Mandelin
authors.forename: Claes
authors.initials: C
authors.lastname: Friman
authors.forename: Juha
authors.initials: J
authors.lastname: Risteli
authors.forename: Yrjö T
authors.initials: YT
authors.lastname: Konttinen
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D015415:Biomarkers; D003094:Collagen / Q000097:blood*; D024042:Collagen Type I; D018450:Disease Progression; D004359:Drug Therapy, Combination; D012968:Etidronic Acid / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood*; D011347:Procollagen / Q000097:blood; D011859:Radiography
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D003094:Collagen; D012968:Etidronic Acid