title: Effect of Osteoprotegerin and Dickkopf-Related Protein 1 on Radiological Progression in Tightly Controlled Rheumatoid Arthritis.
abstract: OBJECTIVE
  To analyze the association between circulating osteoprotegerin (OPG) and Dickkopf-related protein 1 (DKK-1) and radiological progression in patients with tightly controlled rheumatoid arthritis (RA).
  
  
  METHODS
  Serum levels of OPG and DKK-1 were measured in 97 RA patients who were treated according to a treat-to-target strategy (T2T) aimed at remission (DAS28<2.6). Radiologic joint damage progression was assessed by changes in the total Sharp-van der Heijde score (SHS) on serial radiographs of the hands and feet. The independent association between these biomarker levels and the structural damage endpoint was examined using regression analysis.
  
  
  RESULTS
  The mean age of the 97 RA patients (68 women) at the time of the study was 54 ± 14 years, and the median disease duration was 1.6 ± 1.5 years. Most patients were seropositive for either RF or ACPA, and the large majority (76%) were in remission or had low disease activity. After a median follow-up time of 3.3 ± 1.5 years (range, 1-7.5 yrs.), the mean total SHS annual progression was 0.88 ± 2.20 units. Fifty-two percent of the patients had no progression (defined as a total SHS of zero). The mean serum OPG level did not change significantly over the study period (from 3.9 ± 1.8 to 4.07 ± 2.23 pmol/L), whereas the mean serum DKK-1 level decreased, although not significantly (from 29.9 ± 10.9 to 23.6 ± 18.8 pmol/L). In the multivariate analysis, the predictive factors increasing the likelihood of total SHS progression were age (OR per year = 1.10; p = 0.003) and a high mean C-reactive protein level over the study period (OR = 1.29; p = 0.005). Circulating OPG showed a protective effect reducing the likelihood of joint space narrowing by 60% (95% CI: 0.38-0.94) and the total SHS progression by 48% (95% CI: 0.28-0.83). The DKK-1 levels were not associated with radiological progression.
  
  
  CONCLUSIONS
  In patients with tightly controlled RA, serum OPG was inversely associated with progression of joint destruction. This biomarker may be useful in combination with other risk factors to improve prediction in patients in clinical remission or low disease activity state.
authors.affiliation: Department of Rheumatology. Hospital Universitari de Bellvitge. Barcelona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Gómez-Vaquero
authors.affiliation: Department of Rheumatology. Hospital Universitari de Bellvitge. Barcelona, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Martín
authors.affiliation: Instituto de Salud Músculoesquelética. Madrid, Spain.
authors.forename: Estibaliz
authors.initials: E
authors.lastname: Loza
authors.affiliation: Instituto de Salud Músculoesquelética. Madrid, Spain.
authors.forename: Loreto
authors.initials: L
authors.lastname: Carmona
authors.affiliation: Department of Rheumatology. Hospital Universitario La Fe. Valencia. Spain.
authors.forename: José
authors.initials: J
authors.lastname: Ivorra
authors.affiliation: Department of Radiology. Hospital Universitari de Bellvitge. Barcelona, Spain.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Narváez
authors.affiliation: Department of Radiology. Hospital Universitari de Bellvitge. Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Hernández-Gañán
authors.affiliation: Department of Clinical Laboratory. Hospital Universitari de Bellvitge. Barcelona, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Alía
authors.affiliation: Department of Rheumatology. Hospital Universitari de Bellvitge. Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Narváez
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000000981:diagnostic imaging* / Q000628:therapy*; D015415:Biomarkers / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D007596:Joints / Q000000981:diagnostic imaging* / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood*; D011446:Prospective Studies
chemical_list: D015415:Biomarkers; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D053244:Osteoprotegerin; C506030:TNFRSF11B protein, human