Pediatric Rheumatology Online Journal → June 2003 → Miscellaneous Topics→ Abstract #75
                                                                August 2003 → Bone → Abstract #75

OSTEOPENIA IN JUVENILE CHRONIC ARTHRITIS: ALTERED REGULATION OF OSTEOCLASTOGENESIS

J. M. Burnham,¹ R. Q. Cron,¹ T. H. Finkel,¹ M. Leonard.¹

¹Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA

INTRODUCTION: Juvenile Chronic Arthritis (JCA) results in a multifactorial disorder of bone metabolism during growth. Proinflammatory cytokines, glucocorticoids, malnutrition, poor growth, and inactivity may impair bone accretion. Altered osteoprotegerin (OPG) and receptor activator of nuclear factor ΚB ligand (RANKL) may contribute to abnormal osteoclastogenesis in JCA.
OBJECTIVE: To perform a longitudinal study of bone mineralization in children with JCA to determine the impact on cortical bone dimensions and trabecular density; to identify risk factors for bone deficits; and to determine if TNF-a inhibitors decrease RANKL, increase OPG, and improve bone mineralization.
METHODS: A baseline assessment will evaluate bone mass with DEXA and quantitative CT, in addition to growth, serum TNF-a, IL-1, IL-6, OPG, RANKL, and disease characteristics in 100 children with JCA and 200 healthy controls. Bone mass will be evaluated over 12 months to assess the impact of inflammatory cytokines, OPG, RANKL, and pharmacologic therapies on bone mineralization.
PRELIMINARY DATA: A pilot study of ELISA measures of IL-6, OPG, and RANKL was performed in 7 subjects with active JCA and 13 healthy controls, ages 5 to 15 yr. In this small sample, there were no significant differences in Mean ± SD serum levels of OPG (3.1 ± 1.7 vs. 2.6 ± 0.7 pmol/l) or RANKL (0.7 ±0.3 vs. 1.0 ± 0.7 pmol/l) levels in JCA compared to healthy controls. Serum IL-6 levels were 10 pg/ml in all controls and 5 JCA subjects; however, IL-6 levels were markedly elevated in 2 JCA subjects. Systemic JRA-346 pg/ml; Psoriatic Arthritis-330 pg/ml. Synovial fluid was available in 3 of the JCA subjects, all with serum IL-6 10 pg/ml. Synovial levels of OPG and RANKL were comparable with serum levels; however, synovial IL-6 levels were increased, ranging from 164-407 pg/ml.
CONCLUSIONS: This longitudinal study will identify determinants of impaired bone accretion in children with JCA, and help to guide future interventions to maximize bone mineral accretion in this high-risk population.