Low-dose prednisolone in early rheumatoid arthritis inhibits collagen type I degradation by matrix metalloproteinases as assessed by serum 1CTP--a possible mechanism for specific inhibition of radiological destruction

BARFOT Study Group, Sofia Ajeganova

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

OBJECTIVE: To study the effects of low-dose prednisolone on the osteoclast-regulating proteins osteoprotegerin (OPG) and RANK ligand (RANKL) and on markers of bone resorption, 1CTP generated by MMPs and CTX-1 generated by cathepsin K, in patients with early RA in relation to inflammation and joint destruction.

METHODS: In 225 patients, who at the start of the first DMARD had been randomized to 7.5 mg prednisolone daily for 2 years, the P-group, or no prednisolone, the NoP-group, OPG and RANKL were analysed at 0-24 months and 1CTP and CTX-1 at 0-12 months. Radiographs of hands and feet were assessed at 0, 1 and 2 years using the modified Sharp-van der Heijde score and radiological progression defined as increase in total Sharp score above 5.8. Data were analysed with a mixed linear model and by the GENMOD procedure.

RESULTS: In the P-group, RANKL and the ratio OPG/RANKL were stable between baseline and 24 months, whereas in the NoP-group, RANKL increased and the ratio OPG/RANKL decreased. CTX-1 decreased significantly more in the P-group. 1CTP decreased over time in both groups, but more in the P-group, P < 0.001, a difference also present in the subgroups of patients in remission. The decrease in 1CTP was associated with less radiological progression after 2 years and displayed a significant interaction with treatment.

CONCLUSION: Low-dose prednisolone may inhibit progression of joint destruction by interfering with MMP activity, seen as a marked decrease in 1CTP, as well as by impairing osteoclast activation, shown by a stable OPG/RANKL ratio.

Original languageEnglish
Pages (from-to)733-742
Number of pages10
JournalRheumatology (Oxford, England)
Volume52
Issue number4
DOIs
Publication statusPublished - Apr 2013

Keywords

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Arthritis, Rheumatoid/diagnostic imaging
  • Bone Resorption
  • Collagen Type I/antagonists & inhibitors
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Glucocorticoids/administration & dosage
  • Humans
  • Male
  • Matrix Metalloproteinases/metabolism
  • Middle Aged
  • Osteoclasts/drug effects
  • Osteoprotegerin/metabolism
  • Peptides/blood
  • Prednisolone/administration & dosage
  • Prospective Studies
  • RANK Ligand/metabolism
  • Radiography
  • Remission Induction
  • Young Adult

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