title: The effect of tocilizumab on bone mineral density, serum levels of Dickkopf-1 and bone remodeling markers in patients with rheumatoid arthritis.
abstract: Previous studies showed that the control of inflammation by biological therapies has a positive effect on bone in inflammatory diseases. The objective of this study was to assess the effects on bone mineral density (BMD) and bone remodeling of an anti-IL-6 monoclonal antibody (tocilizumab (TCZ)) in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  One hundred and three patients (75% women, 52±12years) with active RA were treated with TCZ 8mg/kg + methotrexate (MTX) every 4 weeks during 48 weeks. Hip and lumbar spine BMDs were measured at baseline and after 48 weeks by dual energy X-ray absorptiometry (DXA). Pro-collagen serum type I N-terminal propeptide (PINP), serum C-terminal cross-linked telopeptide of type I collagen (CTX-I), and serum levels of total Dickkopf-1 (Dkk-1) and sclerostin were assessed at baseline, 12 and 48 weeks.
  
  
  RESULTS
  BMD was available for 76 patients at baseline and at the end of the study. There was no change in lumbar spine and hip BMD over 48 weeks. Serum PINP increased from baseline by 22% (P≤0.001) and 19% (P≤0.001) at week 12 and week 48, whereas serum CTX-I remained stable. Serum DKK-1 significantly decreased from baseline by -31% (P≤0.001) and -25% (P=0.025) at week 12 and 48. Similar results were observed in the patients receiving low doses of oral corticosteroids.
  
  
  CONCLUSIONS
  In this 1-year prospective open study, patients with active RA receiving TCZ and MTX had no change in BMD, a decrease in serum DKK-1 and an increase in bone formation marker.
authors.affiliation: Paris Descartes University, Department of Rheumatology, Cochin Hospital, Epidemiology and Biostatistics Unit, Sorbonne Paris Cité Research Center, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France. Electronic address: karine.briot@cch.aphp.fr.
authors.forename: Karine
authors.initials: K
authors.lastname: Briot
authors.affiliation: Roche, 92650 Boulogne, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Rouanet
authors.affiliation: Pellegrin Hospital, 33000 Bordeaux, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Schaeverbeke
authors.affiliation: Groupe hospitalier Pitié-Salpêtrière, 75013 Paris, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Etchepare
authors.affiliation: CHU Hôpital Sud, 38000 Grenoble, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Gaudin
authors.affiliation: Hôpital Sud, 35200 Rennes, France.
authors.forename: Aleth
authors.initials: A
authors.lastname: Perdriger
authors.affiliation: Unité d'épidémiologie des maladies émergentes, Institut Pasteur, 75015 Paris, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Vray
authors.affiliation: Roche, 92650 Boulogne, France.
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Steinberg
authors.affiliation: Paris Descartes University, Department of Rheumatology, Cochin Hospital, Epidemiology and Biostatistics Unit, Sorbonne Paris Cité Research Center, 27, rue du Faubourg-Saint-Jacques, 75014 Paris, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Roux
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001688:Biological Products / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects*; D024042:Collagen Type I / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D000093242:Interleukin-6 Inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D061067:Antibodies, Monoclonal, Humanized; D001688:Biological Products; D015415:Biomarkers; D024042:Collagen Type I; D005938:Glucocorticoids; D036341:Intercellular Signaling Peptides and Proteins; D008727:Methotrexate; D000093242:Interleukin-6 Inhibitors; C501126:DKK1 protein, human; C502936:tocilizumab
keywords: Bone mineral density; Bone remodeling; DKK-1; Rheumatoid arthritis