Osteoprotegerin (OPG)/RANK-L system in juvenile idiopathic arthritis: is there a potential modulating role for OPG/RANK-L in bone injury?
OBJECTIVE
To evaluate serum levels of osteoprotegerin (OPG) and receptor activator of nuclear factor kB-ligand (RANK-L) in patients with juvenile idiopathic arthritis (JIA); to correlate these values with disease activity variables, radiological bone damage, and bone mass; and to correlate OPG gene polymorphisms with bone mass.


METHODS
Eighty-four patients (66 girls and 18 boys) with JIA and 40 sex and age-matched controls were enrolled. Serum OPG and RANK-L were measured using an enzyme-linked immunosorbent assay. OPG genotyping was performed by polymerase chain reaction.


RESULTS
Patients with JIA had significantly higher levels of serum OPG than controls (p = 0.001) and lower levels of RANK-L in comparison with controls (p = 0.0003). The OPG/RANK-L ratio in patients was higher than in controls (p = 0.004). No significant correlations were found between disease duration, erythrocyte sedimentation rate, and C-reactive protein values with either OPG or RANK-L serum levels. A significant difference in serum OPG levels (but not in RANK-L) was found between patients with and without erosions (p = 0.008). No correlation was found between OPG and RANK-L levels and bone mass (DXA Z scores). A higher prevalence of OPG CC genotype was found in both patients (65.4%) and controls (82.5%) (p = 0.006). Subjects with CC genotype had a higher lumbar spine bone mineral density (LS-BMD).


CONCLUSIONS
We evaluated for the first time levels of OPG and RANK-L in children with JIA. The higher OPG/RANK-L ratio in JIA might be the result of a compensatory production of OPG. The presence of the T allele of the OPG gene appears to be associated with low BMD.
Masi
Laura
L
Department of Internal Medicine, University of Florence, Florence, Italy.
Simonini
Gabriele
G
Piscitelli
Elisabetta
E
Del Monte
Francesca
F
Giani
Teresa
T
Cimaz
Rolando
R
Vierucci
Silvia
S
Brandi
Maria Luisa
ML
Falcini
Fernanda
F
D001171:Arthritis, Juvenile / Q000097:blood* / Q000235:genetics / Q000473:pathology; D001799:Blood Sedimentation; D015519:Bone Density; D001862:Bone Resorption / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000032:analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006023:Glycoproteins / Q000097:blood* / Q000235:genetics; D006801:Humans; D007596:Joints / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D053244:Osteoprotegerin; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood* / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*; D013582:Synovial Fluid / Q000378:metabolism; D013997:Time Factors
D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D004247:DNA