A 1-year prospective study of the effect of infliximab on bone metabolism in inflammatory bowel disease patients

Eur J Gastroenterol Hepatol. 2016 Nov;28(11):1335-44. doi: 10.1097/MEG.0000000000000719.

Abstract

Objectives: 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.

Materials and 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).

Conclusion: 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.

Publication types

  • Clinical Trial

MeSH terms

  • Absorptiometry, Photon
  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood
  • Bone Density / drug effects
  • Bone Diseases, Metabolic / drug therapy*
  • Bone Diseases, Metabolic / etiology
  • Bone Diseases, Metabolic / physiopathology
  • Bone Remodeling / drug effects
  • Bone and Bones / metabolism
  • C-Reactive Protein / metabolism
  • Case-Control Studies
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cytokines / blood
  • Female
  • Gastrointestinal Agents / pharmacology
  • Gastrointestinal Agents / therapeutic use*
  • Humans
  • Inflammatory Bowel Diseases / complications
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / physiopathology
  • Infliximab / pharmacology
  • Infliximab / therapeutic use*
  • Male
  • Middle Aged
  • Osteoblasts / drug effects
  • Osteoblasts / physiology
  • Osteogenesis / drug effects
  • Prospective Studies
  • Severity of Illness Index
  • Young Adult

Substances

  • Biomarkers
  • Cytokines
  • Gastrointestinal Agents
  • C-Reactive Protein
  • Infliximab