Age-dependent inhibition of ectopic calcification: a possible role for fetuin-A and osteopontin in patients with juvenile dermatomyositis with calcinosis

• Published in: Rheumatology (Oxford, England) England), 2008-07, Vol.47 (7), p.1031-1037
• Main Authors: Marhaug, G., Shah, V., Shroff, R., Varsani, H., Wedderburn, L. R., Pilkington, C. A., Brogan, P. A.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age Factors; Age of Onset; Aging - blood; alpha-2-HS-Glycoprotein; Biological and medical sciences; Blood Proteins - analysis; Blood Proteins - physiology; Calcinosis; Calcinosis - blood; Calcinosis - etiology; Case-Control Studies; Child; Child, Preschool; Dermatomyositis - blood; Dermatomyositis - complications; Dermatomyositis - drug therapy; Diseases of the osteoarticular system; Fetuin-A; Humans; Juvenile dermatomyositis; Medical sciences; Metabolic diseases; Metals (hemochromatosis...); Osteopontin; Osteopontin - blood; Osteopontin - physiology; Other metabolic disorders; Risk Factors; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/ken136

Objectives. To assess if age and/or age-dependent variations in the levels of two major calcification regulatory proteins, fetuin-A and osteopontin, could be associated with an increased risk of calcinosis in children with juvenile dermatomyositis (JDM). Methods. The frequency of calcinosis was derived from a national UK database of 212 cases of JDM. Serum fetuin-A and plasma osteopontin levels were determined using ELISA in 15 JDM patients with calcinosis and 15 JDM patients without calcinosis. Healthy controls were 19 age-matched children, 24 adolescents and 13 adults. Sixteen patients with juvenile idiopathic arthritis (JIA) were additional paediatric disease controls. Results. Of the 212 JDM cases 10% had calcinosis. Calcinosis patients had younger age of disease onset than those without calcinosis (mean age of 5.3 yrs vs 7.1 yrs, respectively, P = 0.016). No significant difference in fetuin-A or osteopontin could be detected between the two JDM groups. Fetuin-A levels in all groups of children and the adolescent group were much lower than described previously in adults, and there was a significant positive correlation between age and fetuin-A level, and also between osteopontin levels in plasma and serum fetuin-A. Conclusions. Children who develop JDM at an younger age may have increased risk of developing calcinosis. Physiologically low levels of fetuin-A in young children combined with an additional negative acute-phase effect on fetuin-A due to chronic inflammation could explain in part the propensity to develop ectopic calcification observed in JDM patients, and why calcinosis is less frequent in adults with dermatomyositis.