Adalimumab Therapy Has a Beneficial Effect on Bone Metabolism in Patients with Crohn's Disease

Dig Dis Sci. 2015 Jul;60(7):2119-29. doi: 10.1007/s10620-015-3606-z. Epub 2015 Mar 3.

Abstract

Background: Infliximab has been shown to have beneficial effects on bone metabolism in patients with Crohn's disease (CD) although as yet the exact mechanisms have not been fully elucidated.

Aim: To evaluate the impact of adalimumab therapy on bone metabolism using a combined in vivo and in vitro model.

Methods: Parathyroid hormone, vitamin D, bone formation markers, bone resorption marker, pro-inflammatory cytokines, anti-inflammatory cytokines, osteoprotegerin, and sRANKL were measured in control patients and pre- and post-treatment with adalimumab in CD patients. The effect of control patients' and pre- and post-treatment CD patients' sera on human osteoblasts (hFOB 1.19) in vitro cell viability and differentiation was also analyzed.

Results: There was a significant increase in bone formation markers osteocalcin (P < 0.05) and procollagen type 1 N-terminal propeptide (P < 0.01) at 1 and 3 months post-treatment. Moreover, there was a sustained but not significant fall in serum CTx, a bone resorption marker. No significant change was seen over time with other parameters measured. Serum from CD patients pre-treated with adalimumab showed increased osteoblast viability compared with that of post-treated patients at 6 months (P = 0.002) and controls. However, post-adalimumab treatment sera at 6 months appeared to increase osteoblast differentiation (P = 0.001), which is likely to be important in new bone formation.

Conclusions: This first study evaluating the role of adalimumab as a possible bone protector in Crohn's disease patients has shown that similar to infliximab, adalimumab has complex and potentially beneficial effects on bone metabolism.

Publication types

  • Clinical Trial

MeSH terms

  • Adalimumab
  • Adolescent
  • Adult
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use*
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Biomarkers
  • Bone Density / drug effects*
  • Case-Control Studies
  • Cell Line
  • Crohn Disease / drug therapy*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Osteoblasts / drug effects
  • Young Adult

Substances

  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • Adalimumab