title: Long-term effects of infliximab on bone and cartilage turnover markers in patients with rheumatoid arthritis.
abstract: BACKGROUND
  Rheumatoid arthritis (RA) is associated with systemic bone loss, subchondral bone erosion and cartilage degradation under the control of pro-inflammatory cytokines, including tumour necrosis factor alpha (TNFalpha). Therefore, we tested the hypothesis that administration of infliximab, an anti-TNFalpha drug in the treatment of RA, would modulate systemic and local bone resorption and reduce cartilage degradation.
  
  
  METHODS
  We performed a prospective study of a multicentric cohort of 48 women, mean (SD) age 54.2 (12.1) years old, with severe RA for 11.4 (7.8) years, who started infliximab after failure of other disease-modifying antirheumatic drugs. At baseline and 6, 22 and 54 weeks after initiating Infliximab therapy we measured the following biochemical markers: pro-collagen serum type I N-terminal propeptide (PINP), a marker of bone formation; serum C-terminal cross-linked telopeptide of type I collagen (CTX-I), a marker of cathepsin K-mediated bone collagen degradation believed to reflect systemic bone resorption; serum C-terminal cross-linked telopeptide of type I collagen (ICTP), an index of matrix metalloprotease (MMP) mediated type I collagen degradation reflecting preferential joint metabolism; and urinary CTX-II a biochemical markers of cartilage degradation. Total hip and lumbar spine bone mineral density (BMD) was assessed at baseline, and after 6 and 12 months by dual-energy x-ray absorptiometry (DXA). No patient received bisphosphonates while 77% were under oral glucocorticoids.
  
  
  RESULTS
  BMD remained stable over 1 year. Serum CTX-I levels rapidly decreased by 19% and 28% at week 6 and week 22, respectively (analysis of variance (ANOVA) p = 0.032) values returning to pre-treatment level at week 54. By contrast, ICTP levels progressively declined with a maximal 25% decrease at week 54 (ANOVA p = 0.028). By contrast, PINP levels remained stable over time, which led to a 30 to 40% improvement in bone remodelling balance, as assessed by the ratios PINP/CTX and PINP/ICTP (p<0.05). There was no significant change of urinary CTX-II in the whole population, but a slight decrease (ANOVA p = 0.041) in those with pre-treatment levels above the upper limit of normal range.
  
  
  CONCLUSIONS
  In summary, the improvement in the formation/resorption marker ratio suggests beneficial systemic and local bone effects of infliximab in patients with RA.
authors.affiliation: INSERM U890, Rheumatology Department, University Hospital of St-Etienne, France.
authors.forename: F
authors.initials: F
authors.lastname: Chopin
authors.forename: P
authors.initials: P
authors.lastname: Garnero
authors.forename: A
authors.initials: A
authors.lastname: le Henanff
authors.forename: F
authors.initials: F
authors.lastname: Debiais
authors.forename: A
authors.initials: A
authors.lastname: Daragon
authors.forename: C
authors.initials: C
authors.lastname: Roux
authors.forename: J
authors.initials: J
authors.lastname: Sany
authors.forename: D
authors.initials: D
authors.lastname: Wendling
authors.forename: C
authors.initials: C
authors.lastname: Zarnitsky
authors.forename: P
authors.initials: P
authors.lastname: Ravaud
authors.forename: T
authors.initials: T
authors.lastname: Thomas
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects*; D001862:Bone Resorption / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D002358:Cartilage, Articular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D006621:Hip Joint / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D000069285:Infliximab; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000503:physiopathology; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab