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
2013 (English)In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 52, no 4, 733-742 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2013. Vol. 52, no 4, 733-742 p.
rheumatoid arthritis, prednisolone, joint destruction, OPG, RANKL, 1CTP, CTX-1
Dentistry Rheumatology and Autoimmunity
IdentifiersURN: urn:nbn:se:umu:diva-82922DOI: 10.1093/rheumatology/kes369ISI: 000316698400023PubMedID: 23275387OAI: oai:DiVA.org:umu-82922DiVA: diva2:663932