title: 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.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Inga-Lill
authors.initials: IL
authors.lastname: Engvall
authors.forename: Björn
authors.initials: B
authors.lastname: Svensson
authors.forename: Annelies
authors.initials: A
authors.lastname: Boonen
authors.forename: Désirée
authors.initials: D
authors.lastname: van der Heijde
authors.forename: Ulf H
authors.initials: UH
authors.lastname: Lerner
authors.forename: Ingiäld
authors.initials: I
authors.lastname: Hafström
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D001862:Bone Resorption; D024042:Collagen Type I / Q000037:antagonists & inhibitors* / Q000097:blood / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D053244:Osteoprotegerin / Q000378:metabolism; D010455:Peptides / Q000097:blood*; D011239:Prednisolone / Q000008:administration & dosage*; D011446:Prospective Studies; D053245:RANK Ligand / Q000378:metabolism; D011859:Radiography; D012074:Remission Induction; D055815:Young Adult
chemical_list: D024042:Collagen Type I; D005938:Glucocorticoids; D053244:Osteoprotegerin; D010455:Peptides; D053245:RANK Ligand; C052929:collagen type I trimeric cross-linked peptide; D011239:Prednisolone; D020782:Matrix Metalloproteinases