Osteoprotegerin (OPG)/RANK-L System in Juvenile Idiopathic Arthritis: Is There a Potential Modulating Role for OPG/RANK-L in Bone Injury?

LAURA MASI, GABRIELE SIMONINI, ELISABETTA PISCITELLI, FRANCESCA DEL MONTE, TERESA GIANI, ROLANDO CIMAZ, SILVIA VIERUCCI, MARIA LUISA BRANDI, and FERNANDA FALCINI

ABSTRACT.

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).

Conclusion. 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. (J Rheumatol 2004;31:986-91)

Key Indexing Terms:

OSTEOPROTEGERIN
RANK-LIGAND
JUVENILE IDIOPATHIC ARTHRITIS
BONE AND CARTILAGE DAMAGE

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From the Departments of Internal Medicine, Pediatric Rheumatology, and Orthodontics, University of Florence, Florence, and the Istituti Clinici di Perfezionamento, Milano, Italy.

L. Masi, MD; E. Piscitelli, Biologist; F. Del Monte, Biologist; M.L. Bianchi, Chief, Department of Internal Medicine; G. Simonini, MD, Fellow in Pediatric Rheumatology; T. Giani, MD, Fellow in Pediatric Rheumatology; F. Falcini, Associate Professor of Pediatrics, Department of Pediatrics, Rheumatology Unit; S. Vierucci, DDS, PhD, Department of Orthodontics, University of Florence; R. Cimaz, MD, Assistant Professor, Pediatrics, Istituti Clinici di Perfezionamento.

Address reprint requests to Dr. F. Falcini, Department of Paediatrics, Rheumatology Unit, Via Pico della Mirandola 24, 50132 Firenze, Italy. E-mail: falcini@unifi.it

Submitted June 16, 2003; revision accepted December 12, 2003.

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