Therapeutic glucocorticoids prevent bone loss but drive muscle wasting when administered in chronic polyarthritis

Research output: Contribution to journalArticle

Authors

  • Chloe Fenton
  • Justine Webster
  • Claire Martin
  • Syeda Fareed
  • C Wehmeyer
  • H Mackie
  • Alex Seabright
  • Jonathan Lewis
  • C S Goodyear
  • M. S. Cooper
  • R Langen
  • Rowan Hardy

External organisations

  • University of Glasgow
  • Maastricht University
  • University of Sydney

Abstract

Background
Patients with rheumatoid arthritis (RA) experience extra-articular manifestations including osteoporosis and muscle wasting, which closely associate with severity of disease. Whilst therapeutic glucocorticoids (GCs) reduce inflammation in RA, their actions on muscle and bone metabolism in the context of chronic inflammation remain unclear. We utilised the TNF-tg model of chronic polyarthritis to ascertain the impact of therapeutic GCs on bone and muscle homeostasis in the context of systemic inflammation.

Methods
TNF-tg and wild-type (WT) animals received either vehicle or the GC corticosterone (100 μg/ml) in drinking water at onset of arthritis. Arthritis severity and clinical parameters were measured, serum collected for ELISA and muscle and bone biopsies collected for μCT, histology and mRNA analysis. In vivo findings were examined in primary cultures of osteoblasts, osteoclasts and myotubes.

Results
TNF-tg mice receiving GCs showed protection from inflammatory bone loss, characterised by a reduction in serum markers of bone resorption, osteoclast numbers and osteoclast activity. In contrast, muscle wasting was markedly increased in WT and TNF-tg animals receiving GCs, independently of inflammation. This was characterised by a reduction in muscle weight and fibre size, and an induction in anti-anabolic and catabolic signalling.

Conclusions
This study demonstrates that when given in early onset chronic polyarthritis, oral GCs partially protect against inflammatory bone loss, but induce marked muscle wasting. These results suggest that in patients with inflammatory arthritis receiving GCs, the development of interventions to manage deleterious side effects in muscle should be prioritised.

Details

Original languageEnglish
Article number182
JournalArthritis Research & Therapy
Volume21
Issue number1
Publication statusPublished - 1 Aug 2019

Keywords

  • polyarthritis, glucocorticoids, muscle wasting, osteoporosis