Growth in Juvenile Idiopathic Arthritis



Juvenile idiopathic arthritis (JIA) is the most common inflammatory disease of childhood characterized by chronic synovitis and associated with a number of extra-articular manifestations. The course of JIA is highly variable, ranging from a mild, self-limiting form to a very aggressive disease. Disease subtypes are significant predictors for persistent disease activity. Children with oligoarthritis have a better outcome than those with either systemic or polyarticular disease in relation to the main outcomes such as remission, functional limitation, and radiological damage. Disturbance of growth and bone metabolism is a serious complication of JIA. Growth disturbances vary from general growth retardation to local acceleration of growth in the affected joint. Short stature is an important complication in children with JIA. Patients with a history of systemic JIA treated with glucocorticoids for at least 2 years during childhood have a final height standard deviation score (SDS) under –2 SD and a final height below their target height. Decreased bone mineral density (BMD) and osteopenia with possible bone fractures are other complications of JIA. The precise etiology of growth retardation is unknown. Multiple factors such as decreased physical activity, nutritional insufficiency, increased proinflammatory cytokines, and medications may play a role in skeletal maturation. Several hormones are important for normal postnatal longitudinal bone growth, but it is generally accepted that growth hormone (GH) is the most important hormone in bone growth. Children with JIA and severe growth retardation may have normal pulsatile GH secretion and are reported to have reduced insulin-like growth factor-1 (IGF-1) levels and IGF-binding protein-3 (IGFBP-3). Growth retardation in these children may be due to direct effects of proinflammatory cytokines on the growth plate, or increased levels of inflammatory cytokines may inhibit the effects of GH on the growth plate. Inflammation and corticosteroid therapy are major determinants of linear growth impairment. Effective control of the inflammation with earlier use of disease-modifying anti-rheumatic drugs and modulators of cytokines improves growth velocity in patients with JIA. Treatment with GH earlier after the onset of the disease may prevent growth and metabolic complications induced by chronic inflammation and long-term steroid therapy. Care of children with JIA requires a multidisciplinary team consisting of a pediatric rheumatologist, a physiotherapist, a pediatric endocrinologist, a nutritionist, a psychotherapist, and a social worker.


Bone Mineral Density Juvenile Idiopathic Arthritis Standard Deviation Score Final Height Cartilage Oligomeric Matrix Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



American College of Rheumatology


Antinuclear antibody


Bone mineral content


Bone mineral density


Body mass index


Cartilage oligomeric matrix protein


C-reactive protein


Disease activity score


Dual-energy X-ray absorptiometry


European League Against Rheumatism


Growth hormone


Growth hormone receptors


Insulin-like growth factor-1


IGF-binding protein-3


International League Against Rheumatism


Interleukin 1β


Interleukin 6


Interleukin 17


Juvenile arthritis disease activity score


Juvenile idiopathic arthritis


Matrix metalloproteinase






Parathyroid hormone


Receptor activator of nuclear factor kappaB


Receptor activator of nuclear factor kappaB ligand


Rheumatoid factor


Recombinant human growth hormone


Simplified Disease Activity Index


Standard deviation score


Tissue inhibitor of metalloproteinase 1


Tumor necrosis factor α


  1. Adib N, Hyrich K, Thornton J, Lunt M, Davidson J, Gardner-Medwin J, Foster H, Baildam E, Wedderburn L, Thomson W. Association between duration of symptoms and severity of disease at first presentation to paediatric rheumatology: results from the childhood arthritis prospective study. Rheumatology (Oxford). 2008;47:991–5.CrossRefGoogle Scholar
  2. Agarwal S, Misra R, Aggarwal A. Interleukin 17 levels are increased in juvenile idiopathic arthritis synovial fluid and induce synovial fibroblasts to produce proinflammatory cytokines and matrix metalloproteinases. J Rheumatol. 2008;35:515–9.PubMedGoogle Scholar
  3. Allen RC, Jimenez M, Cowell CT. Insulin-like growth factor and growth hormone secretion in juvenile chronic arthritis. Ann Rheum Dis. 1991;50:602–6.PubMedCrossRefGoogle Scholar
  4. Bechtold S, Ripperger P, Häfner R, Said E, Schwarz HP. Growth hormone improves height in patients with juvenile idiopathic arthritis: 4-year data of a controlled study. J Pediatr. 2003;143:512–9.PubMedCrossRefGoogle Scholar
  5. Bechtold S, Ripperger P, Dalla Pozza R, Bonfig W, Häfner R, Michels H, Schwarz HP. Growth hormone increases final height in patients with juvenile idiopathic arthritis: data from a randomized controlled study. J Clin Endocrinol Metab. 2007;92:3013–8.PubMedCrossRefGoogle Scholar
  6. Bechtold S, Ripperger P, Mühlbayer D, Truckenbrodt H, Häfner R, Butenandt O, Schwarz HP. GH therapy in juvenile chronic arthritis: results of a two-year controlled study on growth and bone. J Clin Endocrinol Metab. 2001;86:5737–44.Google Scholar
  7. Bjornhart B, Juul A, Nielsen S, Zak M, Svenningsen P, Müller K. Cartilage oligomeric matrix protein in patients with juvenile idiopathic arthritis: relation to growth and disease activity. J Rheumatol. 2009;36:1749–54.PubMedCrossRefGoogle Scholar
  8. Caparbo VF, Prada F, Silva CA, Regio PL, Pereira RM. Serum from children with polyarticular juvenile idiopathic arthritis (pJIA) inhibits differentiation, mineralization and may increase apoptosis of human osteoblasts “in vitro”. Clin Rheumatol. 2009;28:71–7.PubMedCrossRefGoogle Scholar
  9. Carrasco R, Lovell DJ, Giannini EH, Henderson CJ, Huang B, Kramer S, Ranz J, Heubi J, Glass D. Biochemical markers of bone turnover associated with calcium supplementation in children with juvenile rheumatoid arthritis: results of a double-blind, placebo-controlled intervention trial. Arthritis Rheum. 2008;58:3932–40.PubMedCrossRefGoogle Scholar
  10. Cassidy JT, Petty RE. In: Cassidy JT, Petty RE, editors. Textbook of pediatric rheumatology, juvenile rheumatoid arthritis. 3rd ed. London: W.B. Saunders; 1995. pp. 133–223.Google Scholar
  11. Cleary AG, Lancaster GA, Annan F, Sills JA, Davidson JE. Nutritional impairment in juvenile idiopathic arthritis. Rheumatology (Oxford). 2004;43:1569–73.CrossRefGoogle Scholar
  12. Davies UM, Jones J, Reeve J, Camacho-Hubner C, Charlett A, Ansell BM, Preece M, Woo P. Juvenile rheumatoid arthritis. Effects of disease activity and recombinant human growth hormone on insulin-like growth factor 1, insulin-like growth factor binding proteins 1 and 3, and osteocalcin. Arthritis Rheum. 1997;40:332–40.PubMedCrossRefGoogle Scholar
  13. Davies UM, Rooney M, Preece MA, Ansell BM, Woo P. Treatment of growth retardation in juvenile chronic arthritis with recombinant human growth hormone. J Rheumatol. 1994;21:153–8.PubMedGoogle Scholar
  14. Erguven M, Sahin K, Yilmaz O, Halilpglu B. Evaluation of side effects of monotherapy and combined therapies on gastrointestinal system in patients with JIA. Calicut Med J. 2007;5:e2.Google Scholar
  15. Gannotti ME, Nahorniak M, Gorton GE 3rd, Sciascia K, Sueltenfuss M, Synder M, Zaniewski A. Can exercise influence low bone mineral density in children with juvenile rheumatoid arthritis? Pediatr Phys Ther. 2007;19:128–39.PubMedCrossRefGoogle Scholar
  16. Garcia-Consuegra Molina J, Merino Munoz R, Lama More R, Coya Viña J, Gracia Bouthelier R. Growth in children with juvenile idiopathic arthritis. An Pediatr (Barcelona). 2003;58:529–37.CrossRefGoogle Scholar
  17. Green H, Morikawa M, Nixon T. A dual effector theory of growth-hormone action. Differentiation. 1985;29:195–8.PubMedCrossRefGoogle Scholar
  18. Lien G, Selvaag AM, Flatø B, Haugen M, Vinje O, Sørskaar D, Dale K, Egeland T, Førre O. A two-year prospective controlled study of bone mass and bone turnover in children with early juvenile idiopathic arthritis. Arthritis Rheum. 2005;52:833–40.PubMedCrossRefGoogle Scholar
  19. MacRae VE, Farquharson C, Ahmed SF. The pathophysiology of the growth plate in juvenile idiopathic arthritis. Rheumatology. 2006;45:11–9.PubMedCrossRefGoogle Scholar
  20. MacRae VE, Wong SC, Smith W, Gracie A, McInnes I, Galea P, Gardner-Medwin J, Farquharson C, Ahmed SF. Cytokine profiling and in vitro studies of murine bone growth using biological fluids from children with juvenile idiopathic arthritis. Clin Endocrinol (Oxford). 2007;67:442–8.CrossRefGoogle Scholar
  21. Okumus O, Erguven M, Deveci M, Yilmaz O, Okumus M. Growth and bone mineralization in patients with juvenile idiopathic arthritis. Indian J Pediatr. 2008;75:239–43.PubMedCrossRefGoogle Scholar
  22. Rooney M, Davies UM, Reeve J, Preece M, Ansell BM, Woo PM. Bone mineral content and bone mineral metabolism: changes after growth hormone treatment in juvenile chronic arthritis. J Rheumatol. 2000;27:1073–81.PubMedGoogle Scholar
  23. Roth J, Bechtold S, Borte G, Dressler F, Girschick HJ, Borte M. Osteoporosis in juvenile idiopathic arthritis – a practical approach to diagnosis and therapy. Eur J Pediatr. 2007;166:775–84.PubMedCrossRefGoogle Scholar
  24. Sarma PK, Misra R, Aggarwal A. Elevated serum receptor activator of NFkappaB ligand (RANKL), osteoprotegerin (OPG), matrix metalloproteinase (MMP)3, and ProMMP1 in patients with juvenile idiopathic arthritis. Clin Rheumatol. 2008;27:289–94.PubMedCrossRefGoogle Scholar
  25. Simon D. Management of growth retardation in juvenile idiopathic arthritis. Horm Res. 2007;68:122–5.PubMedCrossRefGoogle Scholar
  26. Simon D, Lucidarme N, Prieur AM, Ruiz JC, Czernichow P. Effects on growth and body composition of growth hormone treatment in children with juvenile idiopathic arthritis requiring steroid therapy. J Rheumatol. 2003;30:2492–9.PubMedGoogle Scholar
  27. Simon D, Prieur AM, Quartier P, Charles Ruiz J, Czernichow P. Early recombinant human growth hormone treatment in glucocorticoid-treated children with juvenile idiopathic arthritis: a 3-year randomized study. J Clin Endocrinol Metab. 2007;92:2567–73.PubMedCrossRefGoogle Scholar
  28. Spelling P, Bonfá E, Caparbo VF, Pereira RM. Osteoprotegerin/RANKL system imbalance in active polyarticular-onset juvenile idiopathic arthritis: a bone damage biomarker? Scand J Rheumatol. 2008;37:439–44.PubMedCrossRefGoogle Scholar
  29. Takken T, Van Brussel M, Engelbert RH, Van Der Net J, Kuis W, Helders PJ. Exercise therapy in juvenile idiopathic arthritis: a Cochrane review. Eur J Phys Rehabil Med. 2008;44:287–97.PubMedGoogle Scholar
  30. Thornton J, Ashcroft DM, Mughal MZ, Elliott RA, O’Neill TW, Symmons D. Systematic review of effectiveness of bisphosphonates in treatment of low bone mineral density and fragility fractures in juvenile idiopathic arthritis. Arch Dis Child. 2006;91:753–61.PubMedCrossRefGoogle Scholar
  31. Veldhuis JD, Roemmich JN, Richmond EJ, Rogol AD, Lovejoy JC, Sheffield-Moore M, Mauras N, Bowers CY. Endocrine control of body composition in infancy, childhood, and puberty. Endocr Rev. 2005;26:114–46.PubMedCrossRefGoogle Scholar
  32. Wong SC, MacRae VE, Gracie JA, McInnes IB, Galea P, Gardner-Medwin J, Ahmed SF. Inflammatory cytokines in juvenile idiopathic arthritis: effects on physical growth and the insulin-like-growth factor axis. Growth Horm IGF Res. 2008;18:369–78.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Division of Pediatric ReumatologyGoztepe Educational & Research HospitalIstanbulTurkey
  2. 2.Department of PediatricsUmraniye Educational & Research HospitalIstanbulTurkey

Personalised recommendations