title: Osteoprotegerin/RANKL system imbalance in active polyarticular-onset juvenile idiopathic arthritis: a bone damage biomarker?
abstract: OBJECTIVE
  To evaluate the importance of receptor activator of nuclear factor kappaB (RANK)/receptor activator of nuclear factor kappaB ligand (RANKL)/osteoprotegerin (OPG) modulation in active polyarticular juvenile idiopathic arthritis (pJIA) patients with and without bone erosions.
  
  
  METHODS
  Thirty female patients (mean age 11.07+/-3.77 years, range 4-17 years) with active pJIA and 30 healthy gender- and age-matched controls were consecutively selected for this study. All involved articulations were assessed by X-ray and examined for the presence of bone erosions. The serum levels of RANKL and OPG were measured using an enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  Patients with active pJIA had higher levels of serum RANKL than controls [2.90 (0.1-37.4) vs. 0.25 (0.1-5.7) pg/mL, p = 0.007] and a lower OPG/RANKL ratio [21.25 (1.8-897.6) vs. 347.5 (9-947.8), p = 0.005]. However, levels of OPG were comparable in both groups [55.24 (28.34-89.76) vs. 64.42 (30.68-111.28) pg/mL, p = 0.255]. Higher levels of serum RANKL and a lower OPG/RANKL ratio were also observed in active pJIA patients with bone erosions compared to controls [3.49 (0.1-37.4) vs. 0.25 (0.1-5.7) pg/mL, p = 0.0115 and 14.3 (1.8-897.6) vs. 347.5 (9-947.8), p = 0.016]. However, RANKL levels and OPG/RANKL ratio were similar in pJIA patients without bone erosion and controls [1.75 (0.1-10.9) vs. 0.25 (0.1-5.7) pg/mL, p = 0.055 and 29.2 (3.3-756.8) vs. 347.5 (9-947.8), p = 0.281].
  
  
  CONCLUSIONS
  These data suggest that active pJIA with bone erosions is associated with high serum levels of RANKL and a low OPG/RANKL ratio, indicating that these alterations may reflect bone damage in this disease.
authors.affiliation: Paediatric Rheumatology Division, Hospital Evangelico de Curitiba, Paraná, Brazil.
authors.forename: P
authors.initials: P
authors.lastname: Spelling
authors.forename: E
authors.initials: E
authors.lastname: Bonfá
authors.forename: V F
authors.initials: VF
authors.lastname: Caparbo
authors.forename: R M R
authors.initials: RM
authors.lastname: Pereira
mesh_terms: D000293:Adolescent; D001171:Arthritis, Juvenile / Q000097:blood* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D001842:Bone and Bones / Q000503:physiopathology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D053244:Osteoprotegerin / Q000097:blood*; D053245:RANK Ligand / Q000097:blood*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000097:blood*
chemical_list: D015415:Biomarkers; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human