BACKGROUND: The study is aimed to evaluate body composition and bone status in adolescent and adult patients with active juvenile idiopathic arthritis (JIA) untreated with tumor necrosis factor alpha inhibitors. METHODS: Adult patients (12 male and 19 female) with active JIA and 84 healthy age- and gender- matched controls were enrolled into the study. Body composition (tissue mass in grams, lean mass, fat mass and bone mineral content as a fraction of tissue mass) and areal bone mineral density parameters (aBMD) at the lumbar spine, proximal femur, femoral neck, distal radius and total body were assessed using dual energy x-ray absorptiometry (DXA), and correlated with clinical characteristics of the disease and physical performance tests. Disease activity was assessed using high-sensitivity C-reactive protein (hsCRP) and disease activity score 28 (DAS 28). Differences between the groups were tested by t-test, and One-way ANOVA. Correlations were assessed using the Pearson correlation coefficients and multiple linear regression analysis. Significances were counted at the 0.05 level. RESULTS: In patients with clinically active JIA (DAS 28, 6.36 ± 0.64, hsCRP, 18.36 ± 16.95 mg/l), aBMD at all measured sites, bone mineral content (BMC) and lean mass were reduced, and fat mass was increased as compared with healthy controls. Significant negative correlations were observed between BMC and disease duration, use of glucocorticoids (GCs), and fat mass, respectively. A positive correlation was found between BMC and lean mass, and between the body fat fraction and the use of GCs. Using multiple linear regression analysis, lean mass was the only significant predictor of BMC of total body both in men and women, and of BMC of legs (only in men). Lean mass was also the only predicting factor of total proximal femur BMD and femoral neck BMD. No significant correlations have been determined among the body composition parameters and DAS 28 or hsCRP endpoints. CONCLUSIONS: In adult patients with long-term active JIA, lean mass was the main determining factor of total body and leg BMC, and total proximal femur and femoral neck aBMD.

Institute of Rheumatology Na Slupi 4 128 50 Prague Czech Republic

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Pepmueller PH, Cassidy JT, Allen SH, Hillman LS. Bone mineralization and bone mineral metabolism in children with juvenile rheumatoid arthritis. Arthritis Rheum. 1996;39(5):746–757. doi: 10.1002/art.1780390506. PubMed DOI

Lien G, Flato B, Haugen M, Vinje O, Sorskaar D, Dale K, Johnston V, Egeland T, Forre O. Frequency of osteopenia in adolescents with early-onset juvenile idiopathic arthritis: a long-term outcome study of one hundred five patients. Arthritis Rheum. 2003;48(8):2214–2223. doi: 10.1002/art.11097. PubMed DOI

Burnham JM, Shults J, Weinstein R, Lewis JD, Leonard MB. Childhood onset arthritis is associated with an increased risk of fracture: a population based study using the general practice research database. Ann Rheum Dis. 2006;65(8):1074–1079. doi: 10.1136/ard.2005.048835. PubMed DOI PMC

Brabnikova Maresova K. Secondary osteoporosis in patients with juvenile idiopathic arthritis. J Osteoporos. 2011;1:569417. doi: 10.4061/2011/569417. PubMed PMC

Goldring SR. Pathogenesis of bone and cartilage destruction in rheumatoid arthritis. Rheumatology (Oxford) 2003;42(Suppl 2):ii11–ii16. PubMed

Pereira RM, Falco V, Corrente JE, Chahade WH, Yoshinari NH. Abnormalities in the biochemical markers of bone turnover in children with juvenile chronic arthritis. Clin Exp Rheumatol. 1999;17(2):251–255. PubMed

Lien G, Selvaag AM, Flato B, Haugen M, Vinje O, Sorskaar D, Dale K, Egeland T, Forre O. A two-year prospective controlled study of bone mass and bone turnover in children with early juvenile idiopathic arthritis. Arthritis Rheum. 2005;52(3):833–840. doi: 10.1002/art.20963. PubMed DOI

Zak M, Hassager C, Lovell DJ, Nielsen S, Henderson CJ, Pedersen FK. Assessment of bone mineral density in adults with a history of juvenile chronic arthritis: a cross-sectional long-term followup study. Arthritis Rheum. 1999;42(4):790–798. doi: 10.1002/1529-0131(199904)42:4<790::AID-ANR24>3.0.CO;2-G. PubMed DOI

Wang SJ, Yang YH, Lin YT, Yang CM, Chiang BL. Attained adult height in juvenile rheumatoid arthritis with or without corticosteroid treatment. Clin Rheumatol. 2002;21(5):363–368. doi: 10.1007/s100670200098. PubMed DOI

Simonini G, Giani T, Stagi S, de Martino M, Falcini F. Bone status over 1 yr of etanercept treatment in juvenile idiopathic arthritis. Rheumatology (Oxford) 2005;44(6):777–780. doi: 10.1093/rheumatology/keh592. PubMed DOI

Schoenau E, Neu CM, Beck B, Manz F, Rauch F. Bone mineral content per muscle cross-sectional area as an index of the functional muscle-bone unit. J Bone Miner Res. 2002;17(6):1095–1101. doi: 10.1359/jbmr.2002.17.6.1095. PubMed DOI

Frost HM. From Wolff’s law to the Utah paradigm: insights about bone physiology and its clinical applications. Anat Rec. 2001;262(4):398–419. doi: 10.1002/ar.1049. PubMed DOI

Schoenau E, Frost HM. The “muscle-bone unit” in children and adolescents. Calcif Tissue Int. 2002;70(5):405–407. doi: 10.1007/s00223-001-0048-8. PubMed DOI

Pavelka K, Vencovsky J. Recommendations of the Czech Society for Rheumatology for the treatment of rheumatoid arthritis. Ces Revmatol. 2010;18(4):182–191.

Henderson CJ, Specker BL, Sierra RI, Campaigne BN, Lovell DJ. Total-body bone mineral content in non-corticosteroid-treated postpubertal females with juvenile rheumatoid arthritis: frequency of osteopenia and contributing factors. Arthritis Rheum. 2000;43(3):531–540. doi: 10.1002/1529-0131(200003)43:3<531::AID-ANR8>3.0.CO;2-X. PubMed DOI

Henderson CJ, Cawkwell GD, Specker BL, Sierra RI, Wilmott RW, Campaigne BN, Lovell DJ. Predictors of total body bone mineral density in non-corticosteroid-treated prepubertal children with juvenile rheumatoid arthritis. Arthritis Rheum. 1997;40(11):1967–1975. doi: 10.1002/art.1780401108. PubMed DOI

French AR, Mason T, Nelson AM, Crowson CS, O’Fallon WM, Khosla S, Gabriel SE. Osteopenia in adults with a history of juvenile rheumatoid arthritis. A population based study. J Rheumatol. 2002;29(5):1065–1070. PubMed

Mok CC, To CH, Ma KM. Changes in body composition after glucocorticoid therapy in patients with systemic lupus erythematosus. Lupus. 2008;17(11):1018–1022. doi: 10.1177/0961203308093552. PubMed DOI

Kaji H, Tobimatsu T, Naito J, Iu MF, Yamauchi M, Sugimoto T, Chihara K. Body composition and vertebral fracture risk in female patients treated with glucocorticoid. Osteoporos Int. 2006;17(4):627–633. doi: 10.1007/s00198-005-0026-5. PubMed DOI

Natsui K, Tanaka K, Suda M, Yasoda A, Sakuma Y, Ozasa A, Ozaki S, Nakao K. High-dose glucocorticoid treatment induces rapid loss of trabecular bone mineral density and lean body mass. Osteoporos Int. 2006;17(1):105–108. doi: 10.1007/s00198-005-1923-3. PubMed DOI

Azcue M, Rashid M, Griffiths A, Pencharz PB. Energy expenditure and body composition in children with Crohn’s disease: effect of enteral nutrition and treatment with prednisolone. Gut. 1997;41(2):203–208. doi: 10.1136/gut.41.2.203. PubMed DOI PMC

Formica CA, Cosman F, Nieves J, Herbert J, Lindsay R. Reduced bone mass and fat-free mass in women with multiple sclerosis: effects of ambulatory status and glucocorticoid Use. Calcif Tissue Int. 1997;61(2):129–133. doi: 10.1007/s002239900309. PubMed DOI

Haugen M, Lien G, Flato B, Kvammen J, Vinje O, Sorskaar D, Forre O. Young adults with juvenile arthritis in remission attain normal peak bone mass at the lumbar spine and forearm. Arthritis Rheum. 2000;43(7):1504–1510. doi: 10.1002/1529-0131(200007)43:7<1504::AID-ANR13>3.0.CO;2-0. PubMed DOI

Roth J, Palm C, Scheunemann I, Ranke MB, Schweizer R, Dannecker GE. Musculoskeletal abnormalities of the forearm in patients with juvenile idiopathic arthritis relate mainly to bone geometry. Arthritis Rheum. 2004;50(4):1277–1285. doi: 10.1002/art.20128. PubMed DOI

Felin EM, Prahalad S, Askew EW, Moyer-Mileur LJ. Musculoskeletal abnormalities of the tibia in juvenile rheumatoid arthritis. Arthritis Rheum. 2007;56(3):984–994. doi: 10.1002/art.22420. PubMed DOI

Vernikos J, Schneider VS. Space, gravity and the physiology of aging: parallel or convergent disciplines? A mini-review. Gerontology. 2010;56(2):157–166. doi: 10.1159/000252852. PubMed DOI

Gilsanz V, Wren TA, Sanchez M, Dorey F, Judex S, Rubin C. Low-level, high-frequency mechanical signals enhance musculoskeletal development of young women with low BMD. J Bone Miner Res. 2006;21(9):1464–1474. doi: 10.1359/jbmr.060612. PubMed DOI

Pedersen BK, Febbraio MA. Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol. 2012;8(8):457–465. doi: 10.1038/nrendo.2012.49. PubMed DOI

Fajardo RJ, Manoharan RK, Pearsall RS, Davies MV, Marvell T, Monnell TE, Ucran JA, Pearsall AE, Khanzode D, Kumar R, Underwood KW, Roberts B, Seehra J, Bouxsein ML. Treatment with a soluble receptor for activin improves bone mass and structure in the axial and appendicular skeleton of female cynomolgus macaques (Macaca fascicularis) Bone. 2010;46(1):64–71. doi: 10.1016/j.bone.2009.09.018. PubMed DOI

Lindehammar H, Lindvall B. Muscle involvement in juvenile idiopathic arthritis. Rheumatology (Oxford) 2004;43(12):1546–1554. doi: 10.1093/rheumatology/keh381. PubMed DOI

Lee SJ. Regulation of muscle mass by myostatin. Annu Rev Cell Dev Biol. 2004;20:61–86. doi: 10.1146/annurev.cellbio.20.012103.135836. PubMed DOI

Prieto-Alhambra D, Premaor MO, Fina Aviles F, Hermosilla E, Martinez-Laguna D, Carbonell-Abella C, Nogues X, Compston JE, Diez-Perez A. The association between fracture and obesity is site-dependent: a population-based study in postmenopausal women. J Bone Miner Res. 2012;27(2):294–300. doi: 10.1002/jbmr.1466. PubMed DOI

Hanaoka BY, Peterson CA, Horbinski C, Crofford LJ. Implications of glucocorticoid therapy in idiopathic inflammatory myopathies. Nat Rev Rheumatol. 2012;8(8):448–457. doi: 10.1038/nrrheum.2012.85. PubMed DOI

Schakman O, Dehoux M, Bouchuari S, Delaere S, Lause P, Decroly N, Shoelson SE, Thissen JP. Role of IGF-I and the TNFalpha/NF-kappaB pathway in the induction of muscle atrogenes by acute inflammation. Am J Physiol Endocrinol Metab. 2012;303(6):E729–E739. doi: 10.1152/ajpendo.00060.2012. PubMed DOI PMC

Schafer AL, Vittinghoff E, Lang TF, Sellmeyer DE, Harris TB, Kanaya AM, Strotmeyer ES, Cawthon PM, Cummings SR, Tylavsky FA, Scherzinger AL, Schwartz AV. Health, Aging, and Body Composition (Health ABC) Study. Fat infiltration of muscle, diabetes, and clinical fracture risk in older adults. J Clin Endocrinol Metab. 2010;95(11):E368–72. doi: 10.1210/jc.2010-0780. PubMed DOI PMC

Seeman E, Hopper JL, Young NR, Formica C, Goss P, Tsalamandris C. Do genetic factors explain associations between muscle strength, lean mass, and bone density? A twin study. Am J Physiol. 1996;270(2 Pt 1):E320–E327. PubMed

Lian JB, Stein GS, Canalis E, Gehron Robey P, Boskey AL. In: Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. Favus MJ, editor. Philadelphia: Lippincott, Williams and Wilkins; 1999. Bone Formation: Osteoblast Lineage Cells, Growth Factors, Matrix Proteins and the Mineralization Process. In: Favus MJ (ed) Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism; pp. 14–29.

Mundy GR, Chen D, Oyajobi BO. In: Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. Favus MJ, editor. Philadelphia: Lippincott, Williams and Wilkins; 2003. Bone Remodeling; pp. 46–58.