Bone demineralization is improved by ivacaftor in patients with cystic fibrosis carrying the p.Gly551Asp mutation

J Cyst Fibros. 2016 Nov;15(6):e67-e69. doi: 10.1016/j.jcf.2016.09.003. Epub 2016 Oct 10.

Abstract

Low bone mineral density (BMD) is a common problem in adults with cystic fibrosis (CF), the etiology of which is multifactorial. In this study, we provide the first evidence that ivacaftor improves BMD in CF patients carrying the p.Gly551Asp mutation. Consistently, in vitro experiments with TNF-α-stimulated primary F508del-CFTR osteoblasts demonstrated that correction of p.Phe508del-CFTR markedly decreased RANKL protein production, a major factor of bone resorption. These clinical and fundamental observations suggest that rescue of mutated CFTR protein improves bone remodeling and support the link between CFTR and bone cell physiology. These findings represent a step forward in the development of potential new therapies for CF-related bone disease.

Keywords: Bone density; CFTR corrector; Cystic fibrosis; RANKL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aminophenols / administration & dosage*
  • Bone Demineralization, Pathologic* / etiology
  • Bone Demineralization, Pathologic* / metabolism
  • Bone Demineralization, Pathologic* / therapy
  • Bone Density / drug effects*
  • Bone Density / physiology
  • Cells, Cultured
  • Chloride Channel Agonists / administration & dosage
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis* / complications
  • Cystic Fibrosis* / drug therapy
  • Cystic Fibrosis* / genetics
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Quinolones / administration & dosage*
  • Statistics as Topic

Substances

  • Aminophenols
  • Chloride Channel Agonists
  • Quinolones
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • ivacaftor