title: A 1-year prospective study of the effect of infliximab on bone metabolism in inflammatory bowel disease patients.
abstract: OBJECTIVE
  Infliximab (IFX) treatment has shown potentially beneficial effects on bone metabolism in inflammatory bowel disease (IBD) patients. We aimed to prospectively evaluate the impact of IFX treatment on bone metabolism in antitumour necrosis factor (TNF)-α-naive IBD patients using established bone metabolism markers and an in-vitro osteoblast model.
  
  
  METHODS
  A total of 37 anti-TNFα-naive IBD patients and 20 healthy controls were included. All measurements were performed at baseline and repeated in IBD patients following IFX therapy. Bone mineral density was measured by dual-energy X-ray absorptiometry. Parathyroid hormone, vitamin D, osteoprotegerin, soluble receptor activator of nuclear factor B ligand and proinflammatory and anti-inflammatory cytokines were measured. Bone formation was measured using osteocalcin (OC) and procollagen type 1N propeptide, and bone resorption was measured using serum type 1 collage c-telopeptide. The effect of control and IBD patient sera on human osteoblast viability and differentiation was analysed.
  
  
  RESULTS
  OC level was higher in controls than IBD patients (P=0.018). After IFX, OC and procollagen type 1N propeptide increased significantly (P=0.002 and 0.011) and (P<0.001 and P=0.016) at weeks 6 and 30 after treatment, respectively. There was a nonsignificant decrease in serum type 1 collage c-telopeptide. After IFX therapy, proinflammatory cytokines TNF-α, interleukin-6 and interleukin-13 decreased significantly (P=0.016, week 54; P=0.005, week 6 and P=0.025, week 6), respectively. Sera from IBD patients before IFX showed increased osteoblast viability compared with the controls (P=0.003 to P<0.005), but induced reduced osteoblast differentiation. After IFX, viability reduced to control levels, but osteoblast differentiation increased (P=0.041).
  
  
  CONCLUSIONS
  IFX treatment induced beneficial effects on bone metabolism. Osteoblast culture results suggest that IBD patients may have increased osteoblast viability, but reduced differentiation, which has implications for bone strength.
authors: aDeparment of Gastroenterology, Adelaide & Meath Hospital, Tallaght, Dublin 24 Departments of bBiochemistry cGerontology, St James's Hospital, Dublin 8 dDepartment of Anatomy, Divison of Biology, Royal College of Surgeons in Ireland, Dublin 2, Republic of Ireland.
authors: Sundaram G
authors: SG
authors: Veerappan
authors: Martin
authors: M
authors: Healy
authors: Bernard
authors: B
authors: Walsh
authors: Colm A
authors: CA
authors: O'Morain
authors: Jacqueline S
authors: JS
authors: Daly
authors: Barbara M
authors: BM
authors: Ryan
mesh_terms: D015502:Absorptiometry, Photon; D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D016723:Bone Remodeling / Q000187:drug effects; D001842:Bone and Bones / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D005260:Female; D005765:Gastrointestinal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D000069285:Infliximab / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects; D011446:Prospective Studies; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines; D005765:Gastrointestinal Agents; D002097:C-Reactive Protein; D000069285:Infliximab