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Long-Term Bone Health in Glucocorticoid-Treated Children with Rheumatic Diseases

  • PEDIATRIC RHEUMATOLOGY (TJA LEHMAN, SECTION EDITOR)
  • Published:
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Abstract

Glucocorticoids (GC) are a standard treatment for pediatric rheumatic disease. Recent literature highlights skeletal vulnerability in children with rheumatic illness, including vertebral and peripheral fractures and reductions in bone mineral density in longitudinal follow-up. Annual vertebral fracture incidence of 4–6 % in those recently diagnosed and prevalence of 7–28 % in those several years post diagnosis have been reported. The fractures are often asymptomatic, often thoracic in location, and usually of mild, anterior wedge morphology. Diseases with more systemic involvement and severe inflammation (SLE, JDM) seem to be at higher risk. Neither BMD nor GC dose are ideal predictors for risk of fractures. These children also seem to have an increased incidence of long-bone fractures, particularly in the forearm and wrist; in the scant literature, long-bone fractures are not predictive of vertebral fractures. Bone mass accrual is typically suboptimum across time, although the use of potent steroid-sparing anti-inflammatory agents may counteract the effects of GC and active disease. Vitamin D insufficiency warrants ongoing monitoring. Additional targeted studies are justified to increase understanding of bone health risks in this population.

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Abbreviations

aBMD:

Areal bone mineral density

BMAD:

Apparent bone mineral density

BMD:

Bone mineral density

BMI:

Body mass index

D:

Day

DMARDs:

Disease-modifying antirheumatic drugs

DXA:

Dual-energy X-ray absorptiometry

GC:

Glucocorticoids

JIA:

Juvenile idiopathic arthritis

JDM:

Juvenile dermatomyositis

kg:

Kilogram

L:

Lumbar

MCTD:

Mixed connective tissue disease

SLE:

Systemic lupus erythematosus

T:

Thoracic

VF:

Vertebral fractures

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Cassidy J, Petty R, Laxer R, et al. Textbook of Pediatric Rheumatology. 6th ed. Saunders; 2011.

  2. Beukelman T, Patkar NM, Saag KG, et al. 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features. Arthritis Care Res. 2011;63(4):465–82. doi:10.1002/acr.20460.

    Article  Google Scholar 

  3. Mukhtyar C, Guillevin L, Cid MC, et al. EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis. 2009;68(3):310–7. doi:10.1136/ard.2008.088096.

    Article  PubMed  CAS  Google Scholar 

  4. Mukhtyar C, Guillevin L, Cid MC, et al. EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis. 2009;68(3):318–23. doi:10.1136/ard.2008.088351.

    Article  PubMed  CAS  Google Scholar 

  5. Hahn BH, McMahon MA, Wilkinson A, et al. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res. 2012;64(6):797–808. doi:10.1002/acr.21664.

    Article  Google Scholar 

  6. Thornton J, Ashcroft D, O'Neill T, et al. A systematic review of the effectiveness of strategies for reducing fracture risk in children with juvenile idiopathic arthritis with additional data on long-term risk of fracture and cost of disease management. Health Technology Assessment (Winchester, England). 2008;12(3):iii–ix, xi–xiv, 1–208.

  7. Varonos S, Ansell BM, Reeve J. Vertebral collapse in juvenile chronic arthritis: its relationship with glucocorticoid therapy. Calcif Tissue Int. 1987;41(2):75–8.

    Article  PubMed  CAS  Google Scholar 

  8. Burnham JM, Shults J, Weinstein R, et al. 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):1074–9. doi:10.1136/ard.2005.048835.

    Article  PubMed  CAS  Google Scholar 

  9. Lien G, Flato B, Haugen M, et al. 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):2214–23. doi:10.1002/art.11097.

    Article  PubMed  Google Scholar 

  10. Canalis E. Effects of tumor necrosis factor on bone formation in vitro. Endocrinology. 1987;121(5):1596–604.

    Article  PubMed  CAS  Google Scholar 

  11. Alsufyani KA, Ortiz-Alvarez O, Cabral DA, et al. Bone mineral density in children and adolescents with systemic lupus erythematosus, juvenile dermatomyositis, and systemic vasculitis: relationship to disease duration, cumulative corticosteroid dose, calcium intake, and exercise. J Rheumatol. 2005;32(4):729–33.

    PubMed  CAS  Google Scholar 

  12. • Stagi S, Masi L, Capannini S, et al. Cross-sectional and longitudinal evaluation of bone mass in children and young adults with juvenile idiopathic arthritis: the role of bone mass determinants in a large cohort of patients. J Rheumatol. 2010;37(9):1935–43. doi:10.3899/jrheum.091241. This retrospective and longitudinal case-control study provides new insight into bone mass and its determinants in children with JIA. In general, children followed over nearly three years did not attain healthy norms for bone mass despite the use of more effective medications.

    Article  PubMed  Google Scholar 

  13. Liu WG, He SC, Deng G, et al. Risk factors for new vertebral fractures after percutaneous vertebroplasty in patients with osteoporosis: a prospective study. J Vasc Int Radiol: JVIR. 2012;23(9):1143–9. doi:10.1016/j.jvir.2012.06.019.

    Article  Google Scholar 

  14. Nakamura T, Sugimoto T, Nakano T, et al. Randomized Teriparatide [Human Parathyroid Hormone (PTH) 1–34] Once-Weekly Efficacy Research (TOWER) Trial for Examining the Reduction in New Vertebral Fractures in Subjects with Primary Osteoporosis and High Fracture Risk. J Clin Endocrinol Metab. 2012;97(9):3097–106. doi:10.1210/jc.2011-3479.

    Article  PubMed  CAS  Google Scholar 

  15. Rho YJ, Choe WJ, Chun YI. Risk factors predicting the new symptomatic vertebral compression fractures after percutaneous vertebroplasty or kyphoplasty. Eur Spine J. 2012;21(5):905–11. doi:10.1007/s00586-011-2099-5.

    Article  PubMed  Google Scholar 

  16. Nakhla M, Scuccimarri R, Duffy KN, et al. Prevalence of vertebral fractures in children with chronic rheumatic diseases at risk for osteopenia. J Pediatr. 2009;154(3):438–43. doi:10.1016/j.jpeds.2008.09.023.

    Article  PubMed  Google Scholar 

  17. • Markula-Patjas KP, Valta HL, Kerttula LI, et al. Prevalence of vertebral compression fractures and associated factors in children and adolescents with severe juvenile idiopathic arthritis. J Rheumatol. 2012;39(2):365–73. doi:10.3899/jrheum.110305. Fifty children with severe, treatment-resistant JIA were assessed by use of BMD and spine radiographs. Twenty-two had vertebral fractures; these were associated with high disease activity and high recent cumulative glucocorticoid dose. Thirty percent had at least one peripheral fragility fracture.

    Article  PubMed  CAS  Google Scholar 

  18. Genant HK, Wu CY, van Kuijk C, et al. Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res. 1993;8(9):1137–48. doi:10.1002/jbmr.5650080915.

    Article  PubMed  CAS  Google Scholar 

  19. Makitie O, Doria AS, Henriques F, Cole WG, Compeyrot S, Silverman E, et al. Radiographic vertebral morphology: a diagnostic tool in pediatric osteoporosis. J Pediatr. 2005;146(3):395–401. doi:10.1016/j.jpeds.2004.10.052.

    Article  PubMed  Google Scholar 

  20. Regio P, Bonfa E, Takayama L, et al. The influence of lean mass in trabecular and cortical bone in juvenile onset systemic lupus erythematosus. Lupus. 2008;17(9):787–92. doi:10.1177/0961203308089446.

    Article  PubMed  Google Scholar 

  21. Reyes ML, Hernandez MI, King A, et al. Corticosteroid-induced osteoporosis in children: outcome after two-year follow-up, risk factors, densitometric predictive cut-off values for vertebral fractures. Clin Exp Rheumatol. 2007;25(2):329–35.

    PubMed  CAS  Google Scholar 

  22. Valta H, Lahdenne P, Jalanko H, et al. Bone health and growth in glucocorticoid-treated patients with juvenile idiopathic arthritis. J Rheumatol. 2007;34(4):831–6.

    PubMed  Google Scholar 

  23. Huber AM, Gaboury I, Cabral DA, et al. Prevalent vertebral fractures among children initiating glucocorticoid therapy for the treatment of rheumatic disorders. Arthritis Care Res. 2010;62(4):516–26. doi:10.1002/acr.20171.

    Article  CAS  Google Scholar 

  24. • Toiviainen-Salo S, Markula-Patjas K, Kerttula L, et al. The thoracic and lumbar spine in severe juvenile idiopathic arthritis: magnetic resonance imaging analysis in 50 children. J Pediatr. 2012;160(1):140–6. doi:10.1016/j.jpeds.2011.06.030. The same cohort of children described in Ref. [17] underwent spine MRI. The prevalence of vertebral fractures was 28 % and most were thoracic in location. Disc degeneration and prolapses were noted in about 50 % and 25 %, respectively.

    Article  PubMed  Google Scholar 

  25. • Lim LS, Benseler SM, Tyrrell PN, et al. Predicting longitudinal trajectory of bone mineral density in paediatric systemic lupus erythematosus patients. Ann Rheum Dis. 2012. doi:10.1136/annrheumdis-2011-200805. Nearly 70 children with SLE were followed with annual bone health assessments. There was a decrement in their BMD, a 4 % incidence in vertebral fractures and an improvement in vitamin D status post monitoring of 25(OH)D concentrations.

  26. Kjaer P, Leboeuf-Yde C, Sorensen JS, et al. An epidemiologic study of MRI and low back pain in 13-year-old children. Spine. 2005;30(7):798–806.

    Article  PubMed  Google Scholar 

  27. Tertti MO, Salminen JJ, Paajanen HE, et al. Low-back pain and disk degeneration in children: a case–control MR imaging study. Radiology. 1991;180(2):503–7.

    PubMed  CAS  Google Scholar 

  28. Salminen JJ, Erkintalo MO, Pentti J, et al. Recurrent low back pain and early disc degeneration in the young. Spine. 1999;24(13):1316–21.

    Article  PubMed  CAS  Google Scholar 

  29. • Rodd C, Lang B, Ramsay T, et al. Incident vertebral fractures among children with rheumatic disorders 12 months after glucocorticoid initiation: a national observational study. Arthritis Care Res. 2012;64(1):122–31. doi:10.1002/acr.20589. The manuscript summarises the incidence of vertebral fractures in a large, well characterized prospective study, approximately 12 months post-initiation of glucocorticoids. The incidence was low, those children with prevalent fractures described at recruitment did not sustain additional fractures. Cumulative glucocorticoid dose was associated with fractures; no BMD threshold was observed. The fractures were largely thoracic in location and of anterior wedge morphology.

    Article  Google Scholar 

  30. Fields AJ, Keaveny TM. Trabecular architecture and vertebral fragility in osteoporosis. Curr Osteoporos Rep. 2012;10(2):132–40. doi:10.1007/s11914-012-0097-0.

    Article  PubMed  Google Scholar 

  31. Wetzsteon RJ, Shults J, Zemel BS, et al. Divergent effects of glucocorticoids on cortical and trabecular compartment BMD in childhood nephrotic syndrome. J Bone Miner Res. 2009;24(3):503–13. doi:10.1359/jbmr.081101.

    Article  PubMed  CAS  Google Scholar 

  32. Simonini G, Giani T, Stagi S, et al. Bone status over 1 yr of etanercept treatment in juvenile idiopathic arthritis. Rheumatology (Oxford). 2005;44(6):777–80. doi:10.1093/rheumatology/keh592.

    Article  CAS  Google Scholar 

  33. Siminoski K, Lee KC, Jen H, et al. Anatomical distribution of vertebral fractures: comparison of pediatric and adult spines. Osteoporos Int. 2012;23(7):1999–2008. doi:10.1007/s00198-011-1837-1.

    Article  PubMed  CAS  Google Scholar 

  34. Lien G, Selvaag AM, Flato B, et al. A two-year prospective controlled study of bone mass and bone turnover in children with early juvenile idiopathic arthritis. Arthritis Rheum. 2005;52(3):833–40. doi:10.1002/art.20963.

    Article  PubMed  Google Scholar 

  35. Kroger H, Kotaniemi A, Vainio P, et al. Bone densitometry of the spine and femur in children by dual-energy x-ray absorptiometry. Bone Miner. 1992;17(1):75–85.

    Article  PubMed  CAS  Google Scholar 

  36. Lin WC, Cheng TT, Lee YC, et al. New vertebral osteoporotic compression fractures after percutaneous vertebroplasty: retrospective analysis of risk factors. J Vasc Int Radiol: JVIR. 2008;19(2 Pt 1):225–31. doi:10.1016/j.jvir.2007.09.008.

    Article  Google Scholar 

  37. Pelajo CF, Lopez-Benitez JM, Miller LC. 25-hydroxyvitamin D levels and vitamin D deficiency in children with rheumatologic disorders and controls. J Rheumatol. 2011;38(9):2000–4. doi:10.3899/jrheum.110123.

    Article  PubMed  CAS  Google Scholar 

  38. Wright TB, Shults J, Leonard MB, et al. Hypovitaminosis D is associated with greater body mass index and disease activity in pediatric systemic lupus erythematosus. J Pediatr. 2009;155(2):260–5. doi:10.1016/j.jpeds.2009.02.033.

    Article  PubMed  CAS  Google Scholar 

  39. Lovell DJ, Glass D, Ranz J, et al. A randomized controlled trial of calcium supplementation to increase bone mineral density in children with juvenile rheumatoid arthritis. Arthritis Rheum. 2006;54(7):2235–42. doi:10.1002/art.21956.

    Article  PubMed  CAS  Google Scholar 

  40. Ross AC, Taylor CL, Yaktine AL, et al. Dietary Reference Intakes for Calcium and Vitamin D. Institute of Medicine. The National Academies Press. 2011.

  41. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911–30. doi:10.1210/jc.2011-0385.

    Article  PubMed  CAS  Google Scholar 

  42. Roux C, Fechtenbaum J, Kolta S, et al. Mild prevalent and incident vertebral fractures are risk factors for new fractures. Osteoporos Int. 2007;18(12):1617–24. doi:10.1007/s00198-007-0413-1.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

Dr Rodd’s work was funded in part by grant support from the Canadian Institute for Health Research, the Dairy Farmers of Canada, the Canadian Foundation for Dietetic Research, and Montreal Children’s Hospital-Research Institute.

Disclosure

Dr Lang has received grant support from Novartis Canada. Dr Rodd has received grant support from Novartis Canada. Dr Rousseau-Nepton reported no potential conflicts of interest relevant to this article.

Author information

Authors and Affiliations

  1. Pediatric Endocrinology, Department of Pediatrics, Montreal Children’s Hospital, Montreal, Quebec, H3H 1P3, Canada

    Isabelle Rousseau-Nepton & Celia Rodd

  2. Division of Rheumatology, Department of Pediatrics, IWK Health Center, Dalhousie University, Halifax, Nova Scotia, B3K6R8, Canada

    Bianca Lang

Authors
  1. Isabelle Rousseau-Nepton
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  2. Bianca Lang
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  3. Celia Rodd
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Correspondence to Celia Rodd.

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This article is part of the Topical Collection on Pediatric Rheumatology

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Rousseau-Nepton, I., Lang, B. & Rodd, C. Long-Term Bone Health in Glucocorticoid-Treated Children with Rheumatic Diseases. Curr Rheumatol Rep 15, 315 (2013). https://doi.org/10.1007/s11926-012-0315-x

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