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Current Osteoporosis Reports

, Volume 15, Issue 4, pp 271–282 | Cite as

Osteoporosis in Children with Chronic Illnesses: Diagnosis, Monitoring, and Treatment

  • Monica Grover
  • Laura K. BachrachEmail author
Pediatrics (L Ward and E Imel, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Pediatrics

Abstract

Purpose of Review

Osteoporosis is an under-recognized complication of chronic illness in childhood. This review will summarize recent literature addressing the risk factors, evaluation, and treatment for early bone fragility.

Recent Findings

Criteria for the diagnosis of pediatric osteoporosis include the presence of low trauma vertebral fractures alone or the combination of low bone mineral density and several long bone fractures. Monitoring for bone health may include screening for vertebral fractures that are common but often asymptomatic. Pharmacologic agents should be offered to those with fragility fractures especially when spontaneous recovery is unlikely. Controversies persist about the optimal bisphosphonate agent, dose, and duration. Newer osteoporosis drugs have not yet been adequately tested in pediatrics, though clinical trials are underway.

Summary

The prevalence of osteoporosis is increased in children with chronic illness. To reduce the frequency of fragility fractures requires increased attention to risk factors, early intervention, and additional research to optimize therapy and potentially prevent their occurrence.

Keywords

Pediatric osteoporosis Secondary osteoporosis Vertebral fractures Bisphosphonates Bone fragility 

Notes

Compliance with Ethical Standards

Conflict of Interest

Monica Grover and Laura Bachrach declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

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

  1. 1.
    Wang Q, Seeman E. Skeletal growth and peak bone strength. In: Rosen CJ, editor. Primer on the metabolic bone diseases and disorders of mineral metabolism. Eighth ed. Ames: John Wiley & Sons, Inc.; 2013. p. 127–34.CrossRefGoogle Scholar
  2. 2.
    Weaver CM, Gordon CM, Janz KF, Kalkwarf HJ, Lappe JM, Lewis R, et al. The National Osteoporosis Foundation’s position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations. Osteoporos Int. 2016;27(4):1281–386. doi: 10.1007/s00198-015-3440-3.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Rizzoli R, Bianchi ML, Garabédian M, McKay HA, Moreno LA. Maximizing bone mineral mass gain during growth for the prevention of fractures in the adolescents and the elderly. Bone. 2010;46(2):294–305. doi: 10.1016/j.bone.2009.10.005.CrossRefPubMedGoogle Scholar
  4. 4.
    Stagi S, Cavalli L, Seminara S, de Martino M, Brandi ML. The ever-expanding conundrum of primary osteoporosis: aetiopathogenesis, diagnosis, and treatment. Ital J Pediatr. 2014;40:55. doi: 10.1186/1824-7288-40-55.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Mäkitie O. Causes, mechanisms and management of paediatric osteoporosis. Nat Rev Rheumatol. 2013;9(8):465–75. doi: 10.1038/nrrheum.2013.45.CrossRefPubMedGoogle Scholar
  6. 6.
    •• Ward LM, Konji VN, Ma J. The management of osteoporosis in children. Osteoporos Int. 2016;27(7):2147–79. doi: 10.1007/s00198-016-3515-9. An extensive review of literature detailing risk factors, evaluation, and management of pediatric osteoporosis including pharmacologic trials to date.CrossRefPubMedGoogle Scholar
  7. 7.
    •• Bianchi ML, Leonard MB, Bechtold S, Högler W, Mughal MZ, Schönau E, et al. Bone health in children and adolescents with chronic diseases that may affect the skeleton: the 2013 ISCD pediatric Official Positions. J Clin Densitom. 2014;17(2):281–94. doi: 10.1016/j.jocd.2014.01.005. This position statement summarizes the guidelines for screening and monitoring of bone health in children and adolescents at risk for bone fragility due to chronic illnesses.CrossRefPubMedGoogle Scholar
  8. 8.
    Report of a WHO Study Group. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. World Health Organ Tech Rep Ser. 1994;843:1–129.Google Scholar
  9. 9.
    Ma J, Siminoski K, Alos N, Halton J, Ho J, Lentle B, et al. The choice of normative pediatric reference database changes spine bone mineral density Z-scores but not the relationship between bone mineral density and prevalent vertebral fractures. J Clin Endocrinol Metab. 2015;100(3):1018–27. doi: 10.1210/jc.2014-3096.CrossRefPubMedGoogle Scholar
  10. 10.
    Sbrocchi AM, Rauch F, Matzinger M, Feber J, Ward LM. Vertebral fractures despite normal spine bone mineral density in a boy with nephrotic syndrome. Pediatr Nephrol. 2011;26(1):139–42. doi: 10.1007/s00467-010-1652-5.CrossRefPubMedGoogle Scholar
  11. 11.
    • Bishop N, Arundel P, Clark E, Dimitri P, Farr J, Jones G, et al. Fracture prediction and the definition of osteoporosis in children and adolescents: the ISCD 2013 pediatric Official Positions. J Clin Densitom. 2014;17(2):275–80. doi: 10.1016/j.jocd.2014.01.004. This position statement reviews the updated definition of pediatric osteoporosis to include low trauma verterbral fracture irrespective of bone density and discusses limitations of DXA to predict fractures.CrossRefPubMedGoogle Scholar
  12. 12.
    Henderson RC, Berglund LM, May R, Zemel BS, Grossberg RI, Johnson J, et al. The relationship between fractures and DXA measures of BMD in the distal femur of children and adolescents with cerebral palsy or muscular dystrophy. J Bone Miner Res. 2010;25(3):520–6. doi: 10.1359/jbmr.091007.CrossRefPubMedGoogle Scholar
  13. 13.
    •• Cummings EA, Ma J, Fernandez CV, Halton J, Alos N, Miettunen PM, et al. Incident vertebral fractures in children with leukemia during the four years following diagnosis. J Clin Endocrinol Metab. 2015;100(9):3408–17. doi: 10.1210/JC.2015-2176. Prospective study determined that a third of children with ALL had vertebral fractures with the highest incidence in the first year since diagnosis. Nearly a third of VF were asymptomatic. Younger age, lower BMD Z-scores and higher glucocorticoid dose were determined to be predictors of bone fragility.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    •• LeBlanc CM, Ma J, Taljaard M, Roth J, Scuccimarri R, Miettunen P, et al. Incident vertebral fractures and risk factors in the first three years following glucocorticoid initiation among pediatric patients with rheumatic disorders. J Bone Miner Res. 2015;30(9):1667–75. doi: 10.1002/jbmr.2511. Longitudinal observational study in children with rheumatic disorders showed the incidence of vertebral fractures was around 12% with maximum occuring within the first year of diagnosis. Up to 50% were asymptomatic. Higher glucocorticoid dose, increased disease severity, lower BMD Z-scores and higher BMI Z-scores were predictors of bone fragility.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Jaremko JL, Siminoski K, Firth GB, Matzinger MA, Shenouda N, Konji VN, et al. Common normal variants of pediatric vertebral development that mimic fractures: a pictorial review from a national longitudinal bone health study. Pediatr Radiol. 2015;45(4):593–605. doi: 10.1007/s00247-014-3210-y.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Kerkeni S, Kolta S, Fechtenbaum J, Roux C. Spinal deformity index (SDI) is a good predictor of incident vertebral fractures. Osteoporos Int. 2009;20(9):1547–52. doi: 10.1007/s00198-008-0832-7.CrossRefPubMedGoogle Scholar
  17. 17.
    Genant HK, Wu CY, van Kuijk C, Nevitt MC. Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res. 1993;8(9):1137–48. doi: 10.1002/jbmr.5650080915.CrossRefGoogle Scholar
  18. 18.
    Kyriakou A, Shepherd S, Mason A, Ahmed SF. Prevalence of vertebral fractures in children with suspected osteoporosis. J Pediatr. 2016; doi: 10.1016/j.jpeds.2016.08.075.CrossRefGoogle Scholar
  19. 19.
    Mäyränpää MK, Helenius I, Valta H, Mäyränpää MI, Toiviainen-Salo S, Mäkitie O. Bone densitometry in the diagnosis of vertebral fractures in children: accuracy of vertebral fracture assessment. Bone. 2007;41(3):353–9. doi: 10.1016/j.bone.2007.05.012.CrossRefPubMedGoogle Scholar
  20. 20.
    Crabtree NJ, Högler W, Cooper MS, Shaw NJ. Diagnostic evaluation of bone densitometric size adjustment techniques in children with and without low trauma fractures. Osteoporos Int. 2013;24(7):2015–24. doi: 10.1007/s00198-012-2263-8.CrossRefPubMedGoogle Scholar
  21. 21.
    Zemel BS, Kalkwarf HJ, Gilsanz V, Lappe JM, Oberfield S, Shepherd JA, et al. Revised reference curves for bone mineral content and areal bone mineral density according to age and sex for black and non-black children: results of the bone mineral density in childhood study. J Clin Endocrinol Metab. 2011;96(10):3160–9. doi: 10.1210/jc.2011-1111.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Zemel BS, Leonard MB, Kelly A, Lappe JM, Gilsanz V, Oberfield S, et al. Height adjustment in assessing dual energy x-ray absorptiometry measurements of bone mass and density in children. J Clin Endocrinol Metab. 2010;95(3):1265–73. doi: 10.1172/jci20641.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Kalkwarf HJ, Abrams SA, DiMeglio LA, Koo WW, Specker BL, Weiler H, et al. Bone densitometry in infants and young children: the 2013 ISCD pediatric Official Positions. J Clin Densitom. 2014;17(2):243–57. doi: 10.1016/j.jocd.2014.01.002.CrossRefPubMedGoogle Scholar
  24. 24.
    Tian C, Wong BL, Hornung L, Khoury JC, Miller L, Bange J, et al. Bone health measures in glucocorticoid-treated ambulatory boys with Duchenne muscular dystrophy. Neuromuscul Disord. 2016;26(11):760–7. doi: 10.1016/j.nmd.2016.08.011.CrossRefPubMedGoogle Scholar
  25. 25.
    Halton J, Gaboury I, Grant R, Alos N, Cummings EA, Matzinger M, et al. Advanced vertebral fracture among newly diagnosed children with acute lymphoblastic leukemia: results of the Canadian steroid-associated osteoporosis in the pediatric population (STOPP) research program. J Bone Miner Res. 2009;24(7):1326–34. doi: 10.1359/jbmr.090202.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Zemel BS, Stallings VA, Leonard MB, Paulhamus DR, Kecskemethy HH, Harcke HT, et al. Revised pediatric reference data for the lateral distal femur measured by Hologic discovery/Delphi dual-energy X-ray absorptiometry. J Clin Densitom. 2009;12(2):207–18. doi: 10.1016/j.jocd.2009.01.005.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    • Crabtree NJ, Arabi A, Bachrach LK, Fewtrell M, El-Hajj Fuleihan G, Kecskemethy HH, et al. Dual-energy X-ray absorptiometry interpretation and reporting in children and adolescents: the revised 2013 ISCD pediatric Official Positions. J Clin Densitom. 2014;17(2):225–42. doi: 10.1016/j.jocd.2014.01.003. Guidelines defined whole body less head and AP spine as preferred sites for DXA. Appropriate reporting should include age, sex, ethnicity, and height adjusted Z-scores and avoid “osteopenia” or “osteoporosis” based on results.CrossRefPubMedGoogle Scholar
  28. 28.
    • Adams JE, Engelke K, Zemel BS, Ward KA, Densitometry ISoC. Quantitative computer tomography in children and adolescents: the 2013 ISCD pediatric Official Positions. J Clin Densitom. 2014;17(2):258–74. doi: 10.1016/j.jocd.2014.01.006. ISCD task force has reviewed the literature and summarized the clinical use of pQCT and HRpQCT in youth.CrossRefPubMedGoogle Scholar
  29. 29.
    Glorieux FH, Travers R, Taylor A, Bowen JR, Rauch F, Norman M, et al. Normative data for iliac bone histomorphometry in growing children. Bone. 2000;26(2):103–9.CrossRefGoogle Scholar
  30. 30.
    •• Misof BM, Roschger P, McMillan HJ, Ma J, Klaushofer K, Rauch F, et al. Histomorphometry and bone matrix mineralization before and after bisphosphonate treatment in boys with Duchenne muscular dystrophy: a paired Transiliac biopsy study. J Bone Miner Res. 2016;31(5):1060–9. doi: 10.1002/jbmr.2756. Histomorphometric study showing low bone turnover rate in patients with DMD was further reduced during bisphosphonate therapy.CrossRefPubMedGoogle Scholar
  31. 31.
    Huang Y, Eapen E, Steele S, Grey V. Establishment of reference intervals for bone markers in children and adolescents. Clin Biochem. 2011;44(10–11):771–8. doi: 10.1016/j.clinbiochem.2011.04.008.CrossRefPubMedGoogle Scholar
  32. 32.
    Tuchman S, Thayu M, Shults J, Zemel BS, Burnham JM, Leonard MB. Interpretation of biomarkers of bone metabolism in children: impact of growth velocity and body size in healthy children and chronic disease. J Pediatr. 2008;153(4):484–90. doi: 10.1016/j.jpeds.2008.04.028.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    McCloskey EV, Vasikaran S, Cooper C, Members FPDC. Official Positions for FRAX® clinical regarding biochemical markers from joint Official Positions development conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX®. J Clin Densitom. 2011;14(3):220–2. doi: 10.1016/j.jocd.2011.05.008.CrossRefPubMedGoogle Scholar
  34. 34.
    Weinstein RS, Jilka RL, Parfitt AM, Manolagas SC. Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J Clin Invest. 1998;102(2):274–82. doi: 10.1172/JCI2799.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    De Vries F, Bracke M, Leufkens HG, Lammers JW, Cooper C, Van Staa TP. Fracture risk with intermittent high-dose oral glucocorticoid therapy. Arthritis Rheum. 2007;56(1):208–14. doi: 10.1002/art.22294.CrossRefPubMedGoogle Scholar
  36. 36.
    van Staa TP, Leufkens HG, Cooper C. The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int. 2002;13(10):777–87. doi: 10.1007/s001980200108.CrossRefPubMedGoogle Scholar
  37. 37.
    van Staa TP, Cooper C, Leufkens HG, Bishop N. Children and the risk of fractures caused by oral corticosteroids. J Bone Miner Res. 2003;18(5):913–8. doi: 10.1359/jbmr.2003.18.5.913.CrossRefPubMedGoogle Scholar
  38. 38.
    Rodd C, Lang B, Ramsay T, Alos N, Huber AM, Cabral DA, 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.CrossRefGoogle Scholar
  39. 39.
    Leonard MB. Glucocorticoid-induced osteoporosis in children: impact of the underlying disease. Pediatrics. 2007;119(Suppl 2):S166–74. doi: 10.1542/peds.2006-2023J.CrossRefPubMedGoogle Scholar
  40. 40.
    Leonard MB, Feldman HI, Shults J, Zemel BS, Foster BJ, Stallings VA. Long-term, high-dose glucocorticoids and bone mineral content in childhood glucocorticoid-sensitive nephrotic syndrome. N Engl J Med. 2004;351(9):868–75. doi: 10.1056/NEJMoa040367.CrossRefPubMedGoogle Scholar
  41. 41.
    Dubner SE, Shults J, Baldassano RN, Zemel BS, Thayu M, Burnham JM, et al. Longitudinal assessment of bone density and structure in an incident cohort of children with Crohn’s disease. Gastroenterology. 2009;136(1):123–30. doi: 10.1053/j.gastro.2008.09.072.CrossRefPubMedGoogle Scholar
  42. 42.
    Burnham JM, Shults J, Dubner SE, Sembhi H, Zemel BS, Leonard MB. Bone density, structure, and strength in juvenile idiopathic arthritis: importance of disease severity and muscle deficits. Arthritis Rheum. 2008;58(8):2518–27. doi: 10.1002/art.23683.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Werkstetter KJ, Pozza SB, Filipiak-Pittroff B, Schatz SB, Prell C, Bufler P, et al. Long-term development of bone geometry and muscle in pediatric inflammatory bowel disease. Am J Gastroenterol. 2011;106(5):988–98. doi: 10.1038/ajg.2010.495.CrossRefPubMedGoogle Scholar
  44. 44.
    Laakso S, Valta H, Verkasalo M, Toiviainen-Salo S, Viljakainen H, Mäkitie O. Impaired bone health in inflammatory bowel disease: a case-control study in 80 pediatric patients. Calcif Tissue Int. 2012;91(2):121–30. doi: 10.1007/s00223-012-9617-2.CrossRefPubMedGoogle Scholar
  45. 45.
    Ward LM, Rauch F, Matzinger MA, Benchimol EI, Boland M, Mack DR. Iliac bone histomorphometry in children with newly diagnosed inflammatory bowel disease. Osteoporos Int. 2010;21(2):331–7. doi: 10.1007/s00198-009-0969-z.CrossRefPubMedGoogle Scholar
  46. 46.
    Huber AM, Gaboury I, Cabral DA, Lang B, Ni A, Stephure D, 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.CrossRefGoogle Scholar
  47. 47.
    Jayanthan A, Miettunen PM, Incoronato A, Ortiz-Neira CL, Lewis VA, Anderson R, et al. Childhood acute lymphoblastic leukemia (ALL) presenting with severe osteolysis: a model to study leukemia-bone interactions and potential targeted therapeutics. Pediatr Hematol Oncol. 2010;27(3):212–27. doi: 10.3109/08880011003663382.CrossRefPubMedGoogle Scholar
  48. 48.
    Alos N, Grant RM, Ramsay T, Halton J, Cummings EA, Miettunen PM, et al. High incidence of vertebral fractures in children with acute lymphoblastic leukemia 12 months after the initiation of therapy. J Clin Oncol. 2012;30(22):2760–7. doi: 10.1200/JCO.2011.40.4830.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Gurney JG, Kaste SC, Liu W, Srivastava DK, Chemaitilly W, Ness KK, et al. Bone mineral density among long-term survivors of childhood acute lymphoblastic leukemia: results from the St. Jude lifetime cohort study. Pediatr Blood Cancer. 2014;61(7):1270–6. doi: 10.1002/pbc.25010.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Mostoufi-Moab S, Brodsky J, Isaacoff EJ, Tsampalieros A, Ginsberg JP, Zemel B, et al. Longitudinal assessment of bone density and structure in childhood survivors of acute lymphoblastic leukemia without cranial radiation. J Clin Endocrinol Metab. 2012;97(10):3584–92. doi: 10.1210/jc.2012-2393.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Fazeli PK, Klibanski A. Bone metabolism in anorexia nervosa. Curr Osteoporos Rep. 2014;12(1):82–9. doi: 10.1007/s11914-013-0186-8.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Robinson L, Aldridge V, Clark EM, Misra M, Micali N. A systematic review and meta-analysis of the association between eating disorders and bone density. Osteoporos Int. 2016;27(6):1953–66. doi: 10.1007/s00198-015-3468-4.CrossRefPubMedGoogle Scholar
  53. 53.
    •• Faje AT, Karim L, Taylor A, Lee H, Miller KK, Mendes N, et al. Adolescent girls with anorexia nervosa have impaired cortical and trabecular microarchitecture and lower estimated bone strength at the distal radius. J Clin Endocrinol Metab. 2013;98(5):1923–9. doi: 10.1210/jc.2012-4153. Reduced radius bone strength in patients with anorexia nervosa was attributed to abnormal cortical and trabecular microarchitecture. aBMD at the radius by DXA was not different from controls.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Ecklund K, Vajapeyam S, Feldman HA, Buzney CD, Mulkern RV, Kleinman PK, et al. Bone marrow changes in adolescent girls with anorexia nervosa. J Bone Miner Res. 2010;25(2):298–304. doi: 10.1359/jbmr.090805.CrossRefPubMedGoogle Scholar
  55. 55.
    Fazeli PK, Bredella MA, Freedman L, Thomas BJ, Breggia A, Meenaghan E, et al. Marrow fat and preadipocyte factor-1 levels decrease with recovery in women with anorexia nervosa. J Bone Miner Res. 2012;27(9):1864–71. doi: 10.1002/jbmr.1640.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Faje AT, Fazeli PK, Miller KK, Katzman DK, Ebrahimi S, Lee H, et al. Fracture risk and areal bone mineral density in adolescent females with anorexia nervosa. Int J Eat Disord. 2014;47(5):458–66. doi: 10.1002/eat.22248.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Misra M, Katzman DK, Clarke H, Snelgrove D, Brigham K, Miller KK, et al. Hip structural analysis in adolescent boys with anorexia nervosa and controls. J Clin Endocrinol Metab. 2013;98(7):2952–8. doi: 10.1210/jc.2013-1457.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    DiVasta AD, Feldman HA, O’Donnell JM, Long J, Leonard MB, Gordon CM. Skeletal outcomes by peripheral quantitative computed tomography and dual-energy X-ray absorptiometry in adolescent girls with anorexia nervosa. Osteoporos Int. 2016; doi: 10.1007/s00198-016-3685-5.CrossRefGoogle Scholar
  59. 59.
    Bachmann KN, Schorr M, Bruno AG, Bredella MA, Lawson EA, Gill CM, et al. Vertebral volumetric bone density and strength are impaired in women with low-weight and atypical anorexia nervosa. J Clin Endocrinol Metab. 2017;102:57–68. doi: 10.1210/jc.2016-2099.
  60. 60.
    Lucas AR, Melton LJ, Crowson CS, O’Fallon WM. Long-term fracture risk among women with anorexia nervosa: a population-based cohort study. Mayo Clin Proc. 1999;74(10):972–7. doi: 10.4065/74.10.972.CrossRefPubMedGoogle Scholar
  61. 61.
    Högler W, Baumann U, Kelly D. Endocrine and bone metabolic complications in chronic liver disease and after liver transplantation in children. J Pediatr Gastroenterol Nutr. 2012;54(3):313–21. doi: 10.1097/MPG.0b013e31823e9412.CrossRefPubMedGoogle Scholar
  62. 62.
    Stein EM, Cohen A, Freeby M, Rogers H, Kokolus S, Scott V, et al. Severe vitamin D deficiency among heart and liver transplant recipients. Clin Transpl. 2009;23(6):861–5. doi: 10.1111/j.1399-0012.2009.00989.x.CrossRefGoogle Scholar
  63. 63.
    Cohen A, Sambrook P, Shane E. Management of bone loss after organ transplantation. J Bone Miner Res. 2004;19(12):1919–32. doi: 10.1359/JBMR.040912.CrossRefPubMedGoogle Scholar
  64. 64.
    Bechtold S, Putzker S, Birnbaum J, Schwarz HP, Netz H, Dalla PR. Impaired bone geometry after heart and heart-lung transplantation in childhood. Transplantation. 2010;90(9):1006–10. doi: 10.1097/TP.0b013e3181f6300b.CrossRefPubMedGoogle Scholar
  65. 65.
    Tamminen IS, Valta H, Jalanko H, Salminen S, Mäyränpää MK, Isaksson H, et al. Pediatric solid organ transplantation and osteoporosis: a descriptive study on bone histomorphometric findings. Pediatr Nephrol. 2014;29(8):1431–40. doi: 10.1007/s00467-014-2771-1.CrossRefPubMedGoogle Scholar
  66. 66.
    Helenius I, Remes V, Salminen S, Valta H, Mäkitie O, Holmberg C, et al. Incidence and predictors of fractures in children after solid organ transplantation: a 5-year prospective, population-based study. J Bone Miner Res. 2006;21(3):380–7. doi: 10.1359/JBMR.051107.CrossRefPubMedGoogle Scholar
  67. 67.
    Valta H, Jalanko H, Holmberg C, Helenius I, Mäkitie O. Impaired bone health in adolescents after liver transplantation. Am J Transplant. 2008;8(1):150–7. doi: 10.1111/j.1600-6143.2007.02015.x.CrossRefPubMedGoogle Scholar
  68. 68.
    Cohen A, Shane E. Osteoporosis after solid organ and bone marrow transplantation. Osteoporos Int. 2003;14(8):617–30. doi: 10.1007/s00198-003-1426-z.CrossRefPubMedGoogle Scholar
  69. 69.
    Buckner JL, Bowden SA, Mahan JD. Optimizing bone health in Duchenne muscular dystrophy. Int J Endocrinol. 2015;2015:928385. doi: 10.1155/2015/928385.CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    McDonald DG, Kinali M, Gallagher AC, Mercuri E, Muntoni F, Roper H, et al. Fracture prevalence in Duchenne muscular dystrophy. Dev Med Child Neurol. 2002;44(10):695–8.CrossRefGoogle Scholar
  71. 71.
    Mayo AL, Craven BC, McAdam LC, Biggar WD. Bone health in boys with Duchenne muscular dystrophy on long-term daily deflazacort therapy. Neuromuscul Disord. 2012;22(12):1040–5. doi: 10.1016/j.nmd.2012.06.354.CrossRefPubMedGoogle Scholar
  72. 72.
    King WM, Ruttencutter R, Nagaraja HN, Matkovic V, Landoll J, Hoyle C, et al. Orthopedic outcomes of long-term daily corticosteroid treatment in Duchenne muscular dystrophy. Neurology. 2007;68(19):1607–13. doi: 10.1212/01.wnl.0000260974.41514.83.CrossRefPubMedGoogle Scholar
  73. 73.
    •• Ma J, McMillan HJ, Karagüzel G, Goodin C, Wasson J, Matzinger MA, et al. The time to and determinants of first fractures in boys with Duchenne muscular dystrophy. Osteoporos Int. 2016; doi: 10.1007/s00198-016-3774-5. Routine lateral spine radiographs at the initiation of GC therapy detected asymptomatic VF. Vertebral body reshaping following VF was absent, and VF were frequent after the first long bone fracture.CrossRefGoogle Scholar
  74. 74.
    Binkley T, Johnson J, Vogel L, Kecskemethy H, Henderson R, Specker B. Bone measurements by peripheral quantitative computed tomography (pQCT) in children with cerebral palsy. J Pediatr. 2005;147(6):791–6. doi: 10.1016/j.jpeds.2005.07.014.CrossRefPubMedGoogle Scholar
  75. 75.
    • Modlesky CM, Whitney DG, Singh H, Barbe MF, Kirby JT, Miller F. Underdevelopment of trabecular bone microarchitecture in the distal femur of nonambulatory children with cerebral palsy becomes more pronounced with distance from the growth plate. Osteoporos Int. 2015;26(2):505–12. doi: 10.1007/s00198-014-2873-4. MRI showed underdeveloped trabecular bone microarchitecture in non ambulatory children with CP more pronounced with increased distance from the growth plate.CrossRefGoogle Scholar
  76. 76.
    Finbråten AK, Syversen U, Skranes J, Andersen GL, Stevenson RD, Vik T. Bone mineral density and vitamin D status in ambulatory and non-ambulatory children with cerebral palsy. Osteoporos Int. 2015;26(1):141–50. doi: 10.1007/s00198-014-2840-0.CrossRefPubMedGoogle Scholar
  77. 77.
    Mughal MZ. Fractures in children with cerebral palsy. Curr Osteoporos Rep. 2014;12(3):313–8. doi: 10.1007/s11914-014-0224-1.CrossRefPubMedGoogle Scholar
  78. 78.
    Wang MC, Crawford PB, Hudes M, Van Loan M, Siemering K, Bachrach LK. Diet in midpuberty and sedentary activity in prepuberty predict peak bone mass. Am J Clin Nutr. 2003;77(2):495–503.CrossRefGoogle Scholar
  79. 79.
    Remer T, Manz F, Alexy U, Schoenau E, Wudy SA, Shi L. Long-term high urinary potential renal acid load and low nitrogen excretion predict reduced diaphyseal bone mass and bone size in children. J Clin Endocrinol Metab. 2011;96(9):2861–8. doi: 10.1210/jc.2011-1005.CrossRefPubMedGoogle Scholar
  80. 80.
    Frost HM, Schönau E. The “muscle-bone unit” in children and adolescents: a 2000 overview. J Pediatr Endocrinol Metab. 2000;13(6):571–90.CrossRefGoogle Scholar
  81. 81.
    El Ghoch M, Gatti D, Calugi S, Viapiana O, Bazzani PV, Dalle Grave R. The Association between Weight Gain/Restoration and Bone Mineral Density in Adolescents with Anorexia Nervosa: A Systematic Review. Nutrients. 2016;8(12). doi: 10.3390/nu8120769.CrossRefGoogle Scholar
  82. 82.
    Matute-Llorente A, González-Agüero A, Gómez-Cabello A, Vicente-Rodríguez G, Casajús Mallén JA. Effect of whole-body vibration therapy on health-related physical fitness in children and adolescents with disabilities: a systematic review. J Adolesc Health. 2014;54(4):385–96. doi: 10.1016/j.jadohealth.2013.11.001.CrossRefPubMedGoogle Scholar
  83. 83.
    • Leonard MB, Shults J, Long J, Baldassano RN, Brown JK, Hommel K, et al. Effect of low-magnitude mechanical stimuli on bone density and structure in pediatric Crohn’s disease: a randomized placebo-controlled trial. J Bone Miner Res. 2016;31(6):1177–88. doi: 10.1002/jbmr.2799. Randomized placebo control trial of low magnitude mechanical stimulation as an anabolic therapy in patients with Crohn’s disease. No significant changes were noted in trabecular or cortical bone as compared to placebo using DXA and pQCT scans.CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    •• Griffin LM, Thayu M, Baldassano RN, DeBoer MD, Zemel BS, Denburg MR, et al. Improvements in bone density and structure during anti-TNF-α therapy in pediatric Crohn’s disease. J Clin Endocrinol Metab. 2015;100(7):2630–9. doi: 10.1210/jc.2014-4152. Anti-TNF- α Therapy in children with Crohn’s disease was associated with decreased disease activity and gains in vBMD and microarchitecture. The study highlights the importance of controlling inflammation to improve bone health.CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Billiau AD, Loop M, Le PQ, Berthet F, Philippet P, Kasran A, et al. Etanercept improves linear growth and bone mass acquisition in MTX-resistant polyarticular-course juvenile idiopathic arthritis. Rheumatology (Oxford). 2010;49(8):1550–8. doi: 10.1093/rheumatology/keq123.CrossRefGoogle Scholar
  86. 86.
    Grinspoon S, Thomas L, Miller K, Herzog D, Klibanski A. Effects of recombinant human IGF-I and oral contraceptive administration on bone density in anorexia nervosa. J Clin Endocrinol Metab. 2002;87(6):2883–91. doi: 10.1210/jcem.87.6.8574.CrossRefPubMedGoogle Scholar
  87. 87.
    Misra M, Katzman D, Miller KK, Mendes N, Snelgrove D, Russell M, et al. Physiologic estrogen replacement increases bone density in adolescent girls with anorexia nervosa. J Bone Miner Res. 2011;26(10):2430–8. doi: 10.1002/jbmr.447.CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Ward L, Tricco AC, Phuong P, Cranney A, Barrowman N, Gaboury I, et al. Bisphosphonate therapy for children and adolescents with secondary osteoporosis. Cochrane Database Syst Rev. 2007;4:CD005324. doi: 10.1002/14651858.CD005324.pub2.CrossRefGoogle Scholar
  89. 89.
    Rudge S, Hailwood S, Horne A, Lucas J, Wu F, Cundy T. Effects of once-weekly oral alendronate on bone in children on glucocorticoid treatment. Rheumatology (Oxford). 2005;44(6):813–8. doi: 10.1093/rheumatology/keh538.CrossRefGoogle Scholar
  90. 90.
    Sbrocchi AM, Forget S, Laforte D, Azouz EM, Rodd C. Zoledronic acid for the treatment of osteopenia in pediatric Crohn’s disease. Pediatr Int. 2010;52(5):754–61. doi: 10.1111/j.1442-200X.2010.03174.x.CrossRefPubMedGoogle Scholar
  91. 91.
    Sbrocchi AM, Rauch F, Jacob P, McCormick A, McMillan HJ, Matzinger MA, et al. The use of intravenous bisphosphonate therapy to treat vertebral fractures due to osteoporosis among boys with Duchenne muscular dystrophy. Osteoporos Int. 2012;23(11):2703–11. doi: 10.1007/s00198-012-1911-3.CrossRefPubMedGoogle Scholar
  92. 92.
    Houston C, Mathews K, Shibli-Rahhal A. Bone density and alendronate effects in Duchenne muscular dystrophy patients. Muscle Nerve. 2014;49(4):506–11. doi: 10.1002/mus.23948.CrossRefPubMedGoogle Scholar
  93. 93.
    Kim MJ, Kim SN, Lee IS, Chung S, Lee J, Yang Y, et al. Effects of bisphosphonates to treat osteoporosis in children with cerebral palsy: a meta-analysis. J Pediatr Endocrinol Metab. 2015;28(11–12):1343–50. doi: 10.1515/jpem-2014-0527.CrossRefPubMedGoogle Scholar
  94. 94.
    Ooi HL, Briody J, Biggin A, Cowell CT, Munns CF. Intravenous zoledronic acid given every 6 months in childhood osteoporosis. Horm Res Paediatr. 2013;80(3):179–84. doi: 10.1159/000354303.CrossRefPubMedGoogle Scholar
  95. 95.
    Brown JP, Morin S, Leslie W, Papaioannou A, Cheung AM, Davison KS, et al. Bisphosphonates for treatment of osteoporosis: expected benefits, potential harms, and drug holidays. Can Fam Physician. 2014;60(4):324–33.PubMedPubMedCentralGoogle Scholar
  96. 96.
    Biggin A, Zheng L, Briody JN, Coorey CP, Munns CF. The long-term effects of switching from active intravenous bisphosphonate treatment to low-dose maintenance therapy in children with osteogenesis imperfecta. Horm Res Paediatr. 2015;83(3):183–9. doi: 10.1159/000369582.CrossRefPubMedGoogle Scholar
  97. 97.
    Harcke HT, Stevenson KL, Kecskemethy HH, Bachrach SJ, Grissom LE. Fracture after bisphosphonate treatment in children with cerebral palsy: the role of stress risers. Pediatr Radiol. 2012;42(1):76–81. doi: 10.1007/s00247-011-2198-9.CrossRefPubMedGoogle Scholar
  98. 98.
    •• Vasanwala RF, Sanghrajka A, Bishop NJ, Högler W. Recurrent proximal femur fractures in a teenager with osteogenesis imperfecta on continuous bisphosphonate therapy: are we Overtreating? J Bone Miner Res. 2016;31(7):1449–54. doi: 10.1002/jbmr.2805. Case report of atypical femur fracture in a pediatric patient with OI treated with long term bisphosphonate therapy.CrossRefPubMedGoogle Scholar
  99. 99.
    Trejo P, Fassier F, Glorieux FH, Rauch F. Diaphyseal femur fractures in osteogenesis imperfecta: characteristics and relationship with bisphosphonate treatment. J Bone Miner Res. 2016; doi: 10.1002/jbmr.3071.CrossRefGoogle Scholar
  100. 100.
    •• Srinivasan R, Rawlings D, Wood CL, Cheetham T, Moreno AC, Mayhew A, et al. Prophylactic oral bisphosphonate therapy in duchenne muscular dystrophy. Muscle Nerve. 2016;54(1):79–85. doi: 10.1002/mus.24991. A primary prevention trial with bisphosphonate in patients with DMD treated with glucocorticoids showed maintenance of BMD and lower fracture rate in treated patients.CrossRefPubMedGoogle Scholar
  101. 101.
    Brown JP, Reid IR, Wagman RB, Kendler D, Miller PD, Jensen JE, et al. Effects of up to 5 years of denosumab treatment on bone histology and histomorphometry: the FREEDOM study extension. J Bone Miner Res. 2014;29(9):2051–6. doi: 10.1002/jbmr.2236.CrossRefPubMedGoogle Scholar
  102. 102.
    Hoyer-Kuhn H, Netzer C, Koerber F, Schoenau E, Semler O. Two years’ experience with denosumab for children with osteogenesis imperfecta type VI. Orphanet J Rare Dis. 2014;9:145. doi: 10.1186/s13023-014-0145-1.CrossRefPubMedPubMedCentralGoogle Scholar
  103. 103.
    Setsu N, Kobayashi E, Asano N, Yasui N, Kawamoto H, Kawai A, et al. Severe hypercalcemia following denosumab treatment in a juvenile patient. J Bone Miner Metab. 2016;34(1):118–22. doi: 10.1007/s00774-015-0677-z.CrossRefPubMedGoogle Scholar
  104. 104.
    Boyce AM, Chong WH, Yao J, Gafni RI, Kelly MH, Chamberlain CE, et al. Denosumab treatment for fibrous dysplasia. J Bone Miner Res. 2012;27(7):1462–70. doi: 10.1002/jbmr.1603.CrossRefPubMedPubMedCentralGoogle Scholar
  105. 105.
    Grasemann C, Schündeln MM, Hövel M, Schweiger B, Bergmann C, Herrmann R, et al. Effects of RANK-ligand antibody (denosumab) treatment on bone turnover markers in a girl with juvenile Paget’s disease. J Clin Endocrinol Metab. 2013;98(8):3121–6. doi: 10.1210/jc.2013-1143.CrossRefPubMedGoogle Scholar
  106. 106.
    Anastasilakis AD, Polyzos SA, Makras P, Aubry-Rozier B, Kaouri S, Lamy O. Clinical features of 24 patients with rebound-associated vertebral fractures after Denosumab discontinuation: systematic review and additional cases. J Bone Miner Res. 2017; doi: 10.1002/jbmr.3110.CrossRefGoogle Scholar
  107. 107.
    •• Feurer E, Chapurlat R. Emerging drugs for osteoporosis. Expert Opin Emerg Drugs. 2014;19(3):385–95. doi: 10.1517/14728214.2014.936377. Review article discusses recent advances with novel drug therapies including Cathepsin K inhibitos, Anti-sclerostin antibodies, and PTHrp 1-34.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Department of Pediatrics, Division of Endocrinology, School of MedicineStanford UniversityStanfordUSA

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