Osteoprotegerin in juvenile rheumatoid arthritis: cross talk between the immune and the skeletal systems

Abstract

Background: Previous studies have linked the decreased local production of osteoprotegerin (OPG), an osteoclastogenesis blocking agent, in the inflamed joints of rheumatoid arthritis patients to the development of bone erosion. Objective: We sought to assess OPG expression in juvenile rheumatoid arthritis (JRA) and to determine its relation to clinical and laboratory markers of disease activity, and radiologic evidence of bone resorption, as well as its relation to the type of onset, duration of illness and different therapeutic modalities. Methods: The study included 40 children and adolescents with JRA, as well as, 20 clinically healthy age- and sex- matched subjects for comparison. The patients underwent clinical evaluation for disease activity by the summed joint index and investigations including assessment of ESR, CRP, antinuclear antibodies and rheumatoid factor. were Serum levels of osteoprotegerin were assayed by ELISA in the patient and control groups. Joints were evaluated radiologically using the modified Larsen index (LI). Results: The serum levels of OPG in the patients [ median (interquartile range): 0.474 (0.4) ng/ml] were comparable to those of the control group [0.495 (0.41) ng/ml] (p=0.29). However, patients with pauciarticular onset JRA had significantly lower OPG levels [0.3 (0.23) ng/ml] than the control group (p= 0.007). The OPG levels were below the 5^th percentile of the control value in 60% of pauciarticular and 16.7% of polyarticular JRA cases. Patients with polyarticular JRA had significantly higher values of ESR, activity score and Larsen indices as well as serum OPG levels (p= 0.001, 0.001, 0.002 and 0.02, respectively). OPG levels did not correlate to the ESR or the activity score index values. On the other hand, the duration of illness showed a tendency to be negatively correlated to serum OPG (r= -0.309, p=0.05). LI correlated positively to the activity score index and to the ESR in the JRA patients, whether compiled in one group or classified into subgroups according to disease onset. However, OPG was not significantly correlated to the LI (r= 0.023). The different modalities of therapy did not seem to influence the serum levels of OPG (χ² = 4.21). Conclusion: Serum OPG expression was low in JRA, especially in the pauciarticular variety. OPG levels were higher in polyarticular JRA, but this does not necessarily have a protective effect since the proinflammatory process is known to promote also the expression of RANKL, an osteoclastogenesis enhancer. While clinical and biochemical parameters of activity, and LI did not correlate to OPG, the latter seemed to be adversely affected by increased disease duration.

Keywords: Osteoprotegerin, JRA, osteoclastogenesis, RANKL, bone resorption

Egypt J Pediatr Allergy Immunol 2004; 2(1): 38-45