Osteoporosis International

, Volume 27, Issue 7, pp 2147–2179 | Cite as

The management of osteoporosis in children

  • L. M. WardEmail author
  • V. N. Konji
  • J. Ma


This article reviews the manifestations and risk factors associated with osteoporosis in childhood, the definition of osteoporosis and recommendations for monitoring and prevention. As well, this article discusses when a child should be considered a candidate for osteoporosis therapy, which agents should be prescribed, duration of therapy and side effects.


There has been significant progress in our understanding of risk factors and the natural history of osteoporosis in children over the past number of years. This knowledge has fostered the development of logical approaches to the diagnosis, monitoring, and optimal timing of osteoporosis intervention in this setting. Current management strategies are predicated upon monitoring at-risk children to identify and then treat earlier rather than later signs of osteoporosis in those with limited potential for spontaneous recovery. On the other hand, trials addressing the prevention of the first-ever fracture are still needed for children who have both a high likelihood of developing fractures and less potential for recovery. This review focuses on the evidence that shapes the current approach to diagnosis, monitoring, and treatment of osteoporosis in childhood, with emphasis on the key pediatric-specific biological principles that are pivotal to the overall approach and on the main questions with which clinicians struggle on a daily basis. The scope of this article is to review the manifestations of and risk factors for primary and secondary osteoporosis in children, to discuss the definition of pediatric osteoporosis, and to summarize recommendations for monitoring and prevention of bone fragility. As well, this article reviews when a child is a candidate for osteoporosis therapy, which agents and doses should be prescribed, the duration of therapy, how the response to therapy is adjudicated, and the short- and long-term side effects. With this information, the bone health clinician will be poised to diagnose osteoporosis in children and to identify when children need osteoporosis therapy and the clinical outcomes that gauge efficacy and safety of treatment.


Bisphosphonates Bone density Bone fragility Denosumab Diagnosis Monitoring Osteoporosis Treatment Vertebral fractures 



Acute lymphoblastic leukemia


Atypical femur fractures


Anorexia nervosa


Bone mineral density


Bone mineral apparent density


Bone turnover markers


Collagen type I cross-linked C-telopeptide


Duchenne muscular dystrophy


Dual energy X-ray absorptiometry




International Society for Clinical Densitometry




Lumbar spine


Collagen type I cross-linked N-telopeptides


Osteogenesis imperfecta


Osteonecrosis of the jaw


Procollagen type I N-terminal propeptide


Peripheral quantitative computed tomography


Parathyroid hormone


Standard deviation


Spinal deformity index


Vertebral fracture(s)


Vertebral fracture assessment (by DXA)



This work was supported by the following programs and organizations: (1) LMW: the Canadian Institutions for Health Research Operating Grants Program, the Canadian Institutes for Health Research New Investigator Program, The Canadian Child Health Clinician Scientist Program, the Children’s Hospital of Eastern Ontario (CHEO) Research Institute, The University of Ottawa Research Chair Program, and the CHEO Departments of Pediatrics and Surgery: (2) VK: The CHEO Department of Surgery; and (3) JM: The CHEO Research Institute.

Compliance with ethical standards

Conflicts of interest

LMW has been a consultant to Novartis Pharmaceuticals, Amgen, and Alexion Pharmaceuticals. VNK and JM have no conflicts of interest to disclose.


  1. 1.
    Bachrach LK (2014) Diagnosis and treatment of pediatric osteoporosis. Curr Opin Endocrinol Diabetes Obes 21:454–460PubMedCrossRefGoogle Scholar
  2. 2.
    Makitie O (2013) Causes, mechanisms and management of paediatric osteoporosis. Nat Rev Rheumatol 9:465–475PubMedCrossRefGoogle Scholar
  3. 3.
    Saraff V, Schneider J, Colleselli V, Ruepp M, Rauchenzauner M, Neururer S, Geiger R, Hogler W (2015) Sex-, age-, and height-specific reference curves for the 6-min walk test in healthy children and adolescents. Eur J Pediatr 174(6):837–840PubMedCrossRefGoogle Scholar
  4. 4.
    Bianchi ML, Leonard MB, Bechtold S, Hogler W, Mughal MZ, Schonau E, Sylvester FA, Vogiatzi M, van den Heuvel-Eibrink MM, Ward L (2014) Bone health in children and adolescents with chronic diseases that may affect the skeleton: the 2013 ISCD Pediatric Official Positions. J Clin Densitom 17:281–294PubMedCrossRefGoogle Scholar
  5. 5.
    Rauch F, Glorieux FH (2004) Osteogenesis imperfecta. Lancet 363:1377–1385PubMedCrossRefGoogle Scholar
  6. 6.
    Ben Amor IM, Roughley P, Glorieux FH, Rauch F (2013) Skeletal clinical characteristics of osteogenesis imperfecta caused by haploinsufficiency mutations in COL1A1. J Bone Miner Res 28:2001–2007PubMedCrossRefGoogle Scholar
  7. 7.
    Marini JC, Reich A, Smith SM (2014) Osteogenesis imperfecta due to mutations in non-collagenous genes: lessons in the biology of bone formation. Curr Opin Pediatr 26:500–507PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Rauch F, Lalic L, Roughley P, Glorieux FH (2010) Genotype-phenotype correlations in nonlethal osteogenesis imperfecta caused by mutations in the helical domain of collagen type I. Eur J Hum Genet 18:642–647PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Pui CH, Evans WE (2013) A 50-year journey to cure childhood acute lymphoblastic leukemia. Semin Hematol 50:185–196PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, Kaul A, Kinnett K, McDonald C, Pandya S, Poysky J, Shapiro F, Tomezsko J, Constantin C (2010) Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol 9:77–93PubMedCrossRefGoogle Scholar
  11. 11.
    Cummings EA, Ma J, Fernandez CV, Halton J, Alos N, Miettunen PM, Jaremko JL, Ho J, Shenouda N, Matzinger MA, Lentle B, Stephure D, Stein R, Sbrocchi AM, Rodd C, Lang B, Israels S, Grant RM, Couch R, Barr R, Hay J, Rauch F, Siminoski K, Ward LM (2015) Incident vertebral fractures in children with leukemia during the four years following diagnosis. J Clin Endocrinol Metab 100:3408–3417PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    LeBlanc CM, Ma J, Taljaard M, Roth J, Scuccimarri R, Miettunen P, Lang B, Huber AM, Houghton K, Jaremko JL, Ho J, Shenouda N, Matzinger MA, Lentle B, Stein R, Sbrocchi AM, Oen K, Rodd C, Jurencak R, Cummings EA, Couch R, Cabral DA, Atkinson S, Alos N, Rauch F, Siminoski K, Ward LM (2015) Incident vertebral fractures and risk factors in the first three years following glucocorticoid initiation among pediatric patients with rheumatic disorders. J Bone Miner Res 30:1667–1675PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    McMillan HJ, Campbell C, Mah JK (2010) Duchenne muscular dystrophy: Canadian paediatric neuromuscular physicians survey. Can J Neurol Sci 37:195–205PubMedCrossRefGoogle Scholar
  14. 14.
    Hyams JS (2014) Biologics in pediatric Crohn’s disease: is it time to move to an earlier therapeutic approach? Expert Rev Clin Immunol 10:1423–1426PubMedCrossRefGoogle Scholar
  15. 15.
    Thayu M, Leonard MB, Hyams JS, Crandall WV, Kugathasan S, Otley AR, Olson A, Johanns J, Marano CW, Heuschkel RB, Veereman-Wauters G, Griffiths AM, Baldassano RN (2008) Improvement in biomarkers of bone formation during infliximab therapy in pediatric Crohn’s disease: results of the REACH study. Clin Gastroenterol Hepatol 6:1378–1384PubMedCrossRefGoogle Scholar
  16. 16.
    Kessler EA, Becker ML (2014) Therapeutic advancements in juvenile idiopathic arthritis. Best Pract Res Clin Rheumatol 28:293–313PubMedCrossRefGoogle Scholar
  17. 17.
    Billiau AD, Loop M, Le PQ, Berthet F, Philippet P, Kasran A, Wouters CH (2010) Etanercept improves linear growth and bone mass acquisition in MTX-resistant polyarticular-course juvenile idiopathic arthritis. Rheumatology (Oxford) 49:1550–1558CrossRefGoogle Scholar
  18. 18.
    Simonini G, Giani T, Stagi S, de Martino M, Falcini F (2005) Bone status over 1 yr of etanercept treatment in juvenile idiopathic arthritis. Rheumatology (Oxford) 44:777–780CrossRefGoogle Scholar
  19. 19.
    Griffin LM, Thayu M, Baldassano RN, DeBoer MD, Zemel BS, Denburg MR, Denson LA, Shults J, Herskovitz R, Long J, Leonard MB (2015) Improvements in bone density and structure during anti-TNF-alpha therapy in pediatric Crohn’s disease. J Clin Endocrinol Metab 100:2630–2639PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Canalis E, Mazziotti G, Giustina A, Bilezikian JP (2007) Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporos Int 18:1319–1328PubMedCrossRefGoogle Scholar
  21. 21.
    King WM, Ruttencutter R, Nagaraja HN, Matkovic V, Landoll J, Hoyle C, Mendell JR, Kissel JT (2007) Orthopedic outcomes of long-term daily corticosteroid treatment in Duchenne muscular dystrophy. Neurology 68:1607–1613PubMedCrossRefGoogle Scholar
  22. 22.
    Halton J, Gaboury I, Grant R, Alos N, Cummings EA, Matzinger M, Shenouda N, Lentle B, Abish S, Atkinson S, Cairney E, Dix D, Israels S, Stephure D, Wilson B, Hay J, Moher D, Rauch F, Siminoski K, Ward LM, Canadian STOPP Consortium (2009) 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 24:1326–1334PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Feber J, Gaboury I, Ni A, Alos N, Arora S, Bell L, Blydt-Hansen T, Clarson C, Filler G, Hay J, Hebert D, Lentle B, Matzinger M, Midgley J, Moher D, Pinsk M, Rauch F, Rodd C, Shenouda N, Siminoski K, Ward LM (2012) Skeletal findings in children recently initiating glucocorticoids for the treatment of nephrotic syndrome. Osteoporos Int 23:751–760PubMedCrossRefGoogle Scholar
  24. 24.
    Huber AM, Gaboury I, Cabral DA, Lang B, Ni A, Stephure D, Taback S, Dent P, Ellsworth J, LeBlanc C, Saint-Cyr C, Scuccimarri R, Hay J, Lentle B, Matzinger M, Shenouda N, Moher D, Rauch F, Siminoski K, Ward LM (2010) Prevalent vertebral fractures among children initiating glucocorticoid therapy for the treatment of rheumatic disorders. Arthritis Care Res (Hoboken) 62:516–526CrossRefGoogle Scholar
  25. 25.
    Alos N, Grant RM, Ramsay T, Halton J, Cummings EA, Miettunen PM, Abish S, Atkinson S, Barr R, Cabral DA, Cairney E, Couch R, Dix DB, Fernandez CV, Hay J, Israels S, Laverdiere C, Lentle B, Lewis V, Matzinger M, Rodd C, Shenouda N, Stein R, Stephure D, Taback S, Wilson B, Williams K, Rauch F, Siminoski K, Ward LM (2012) High incidence of vertebral fractures in children with acute lymphoblastic leukemia 12 months after the initiation of therapy. J Clin Oncol 30:2760–2767PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Phan V, Blydt-Hansen T, Feber J, Alos N, Arora S, Atkinson S, Bell L, Clarson C, Couch R, Cummings EA, Filler G, Grant RM, Grimmer J, Hebert D, Lentle B, Ma J, Matzinger M, Midgley J, Pinsk M, Rodd C, Shenouda N, Stein R, Stephure D, Taback S, Williams K, Rauch F, Siminoski K, Ward LM (2014) Skeletal findings in the first 12 months following initiation of glucocorticoid therapy for pediatric nephrotic syndrome. Osteoporos Int 25:627–637PubMedCrossRefGoogle Scholar
  27. 27.
    Rodd C, Lang B, Ramsay T, Alos N, Huber AM, Cabral DA, Scuccimarri R, Miettunen PM, Roth J, Atkinson SA, Couch R, Cummings EA, Dent PB, Ellsworth J, Hay J, Houghton K, Jurencak R, Larche M, LeBlanc C, Oen K, Saint-Cyr C, Stein R, Stephure D, Taback S, Lentle B, Matzinger M, Shenouda N, Moher D, Rauch F, Siminoski K, Ward LM (2012) Incident vertebral fractures among children with rheumatic disorders 12 months after glucocorticoid initiation: a national observational study. Arthritis Care Res (Hoboken) 64:122–131CrossRefGoogle Scholar
  28. 28.
    Kilpinen-Loisa P, Paasio T, Soiva M, Ritanen UM, Lautala P, Palmu P, Pihko H, Makitie O (2010) Low bone mass in patients with motor disability: prevalence and risk factors in 59 Finnish children. Dev Med Child Neurol 52:276–282PubMedCrossRefGoogle Scholar
  29. 29.
    Bishop N, Arundel P, Clark E, Dimitri P, Farr J, Jones G, Makitie O, Munns CF, Shaw N (2014) Fracture prediction and the definition of osteoporosis in children and adolescents: the ISCD 2013 pediatric official positions. J Clin Densitom 17:275–280PubMedCrossRefGoogle Scholar
  30. 30.
    Hogler W, Wehl G, van Staa T, Meister B, Klein-Franke A, Kropshofer G (2007) Incidence of skeletal complications during treatment of childhood acute lymphoblastic leukemia: comparison of fracture risk with the General Practice Research Database. Pediatr Blood Cancer 48:21–27PubMedCrossRefGoogle Scholar
  31. 31.
    van Staa TP, Cooper C, Leufkens HG, Bishop N (2003) Children and the risk of fractures caused by oral corticosteroids. J Bone Miner Res 18:913–918PubMedCrossRefGoogle Scholar
  32. 32.
    Baty JM, Vogt EC (1935) Bone changes of leukemia in children. Am J Roentgenol 34:310–313Google Scholar
  33. 33.
    Helenius I, Remes V, Salminen S, Valta H, Makitie O, Holmberg C, Palmu P, Tervahartiala P, Sarna S, Helenius M, Peltonen J, Jalanko H (2006) Incidence and predictors of fractures in children after solid organ transplantation: a 5-year prospective, population-based study. J Bone Miner Res 21:380–387PubMedCrossRefGoogle Scholar
  34. 34.
    Valta H, Jalanko H, Holmberg C, Helenius I, Makitie O (2008) Impaired bone health in adolescents after liver transplantation. Am J Transplant 8:150–157PubMedGoogle Scholar
  35. 35.
    Valta H, Makitie O, Ronnholm K, Jalanko H (2009) Bone health in children and adolescents after renal transplantation. J Bone Miner Res 24:1699–1708PubMedCrossRefGoogle Scholar
  36. 36.
    Vautour LM, Melton LJ 3rd, Clarke BL, Achenbach SJ, Oberg AL, McCarthy JT (2004) Long-term fracture risk following renal transplantation: a population-based study. Osteoporos Int 15:160–167PubMedCrossRefGoogle Scholar
  37. 37.
    Henderson RC, Berglund LM, May R, Zemel BS, Grossberg RI, Johnson J, Plotkin H, Stevenson RD, Szalay E, Wong B, Kecskemethy HH, Harcke HT (2010) 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 25:520–526PubMedCrossRefGoogle Scholar
  38. 38.
    Nelson DA, Kleerekoper M, Peterson EL (1994) Reversal of vertebral deformities in osteoporosis: measurement error or “rebound”? J Bone Miner Res 9:977–982PubMedCrossRefGoogle Scholar
  39. 39.
    Sbrocchi AM, Rauch F, Jacob P, McCormick A, McMillan HJ, Matzinger MA, Ward LM (2012) The use of intravenous bisphosphonate therapy to treat vertebral fractures due to osteoporosis among boys with Duchenne muscular dystrophy. Osteoporos Int 23:2703–2711PubMedCrossRefGoogle Scholar
  40. 40.
    Mostoufi-Moab S, Brodsky J, Isaacoff EJ, Tsampalieros A, Ginsberg JP, Zemel B, Shults J, Leonard MB (2012) Longitudinal assessment of bone density and structure in childhood survivors of acute lymphoblastic leukemia without cranial radiation. J Clin Endocrinol Metab 97:3584–3592PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Marinovic D, Dorgeret S, Lescoeur B, Alberti C, Noel M, Czernichow P, Sebag G, Vilmer E, Leger J (2005) Improvement in bone mineral density and body composition in survivors of childhood acute lymphoblastic leukemia: a 1-year prospective study. Pediatrics 116:e102–e108PubMedCrossRefGoogle Scholar
  42. 42.
    Gurney JG, Kaste SC, Liu W, Srivastava DK, Chemaitilly W, Ness KK, Lanctot JQ, Ojha RP, Nottage KA, Wilson CL, Li Z, Robison LL, Hudson MM (2014) Bone mineral density among long-term survivors of childhood acute lymphoblastic leukemia: results from the St. Jude Lifetime Cohort Study. Pediatr Blood Cancer 61:1270–1276PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Makitie O, Heikkinen R, Toiviainen-Salo S, Henriksson M, Puukko-Viertomies LR, Jahnukainen K (2013) Long-term skeletal consequences of childhood acute lymphoblastic leukemia in adult males: a cohort study. Eur J Endocrinol 168:281–288PubMedCrossRefGoogle Scholar
  44. 44.
    Burger H, Van Daele PL, Grashuis K, Hofman A, Grobbee DE, Schutte HE, Birkenhager JC, Pols HA (1997) Vertebral deformities and functional impairment in men and women. J Bone Miner Res 12:152–157PubMedCrossRefGoogle Scholar
  45. 45.
    Nevitt MC, Ettinger B, Black DM, Stone K, Jamal SA, Ensrud K, Segal M, Genant HK, Cummings SR (1998) The association of radiographically detected vertebral fractures with back pain and function: a prospective study. Ann Intern Med 128:793–800PubMedCrossRefGoogle Scholar
  46. 46.
    Kerkeni S, Kolta S, Fechtenbaum J, Roux C (2009) Spinal deformity index (SDI) is a good predictor of incident vertebral fractures. Osteoporos Int 20:1547–1552PubMedCrossRefGoogle Scholar
  47. 47.
    Kocks J, Ward K, Mughal Z, Moncayo R, Adams J, Hogler W (2010) Z-score comparability of bone mineral density reference databases for children. J Clin Endocrinol Metab 95:4652–4659PubMedCrossRefGoogle Scholar
  48. 48.
    Leonard MB, Propert KJ, Zemel BS, Stallings VA, Feldman HI (1999) Discrepancies in pediatric bone mineral density reference data: potential for misdiagnosis of osteopenia. J Pediatr 135:182–188PubMedCrossRefGoogle Scholar
  49. 49.
    Ma J, Siminoski K, Alos N, Halton J, Ho J, Lentle B, Matzinger M, Shenouda N, Atkinson S, Barr R, Cabral DA, Couch R, Cummings EA, Fernandez CV, Grant RM, Rodd C, Sbrocchi AM, Scharke M, Rauch F, Ward LM (2015) 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 100:1018–1027PubMedCrossRefGoogle Scholar
  50. 50.
    Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137–1148PubMedCrossRefGoogle Scholar
  51. 51.
    Grigoryan M, Guermazi A, Roemer FW, Delmas PD, Genant HK (2003) Recognizing and reporting osteoporotic vertebral fractures. Eur Spine J 12(Suppl 2):S104–S112PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Eastell R, Cedel SL, Wahner HW, Riggs BL, Melton LJ 3rd (1991) Classification of vertebral fractures. J Bone Miner Res 6:207–215PubMedCrossRefGoogle Scholar
  53. 53.
    Palomo T, Fassier F, Ouellet J, Sato A, Montpetit K, Glorieux FH, Rauch F (2015) Intravenous bisphosphonate therapy of young children with osteogenesis imperfecta: skeletal findings during follow up throughout the growing years. J Bone Miner Res 30(12):2150–2157PubMedCrossRefGoogle Scholar
  54. 54.
    Genant HK, Jergas M, Palermo L, Nevitt M, Valentin RS, Black D, Cummings SR (1996) Comparison of semiquantitative visual and quantitative morphometric assessment of prevalent and incident vertebral fractures in osteoporosis. The Study of Osteoporotic Fractures Research Group. J Bone Miner Res 11:984–996PubMedCrossRefGoogle Scholar
  55. 55.
    Siminoski K, Lentle B, Matzinger MA, Shenouda N, Ward LM (2014) Observer agreement in pediatric semiquantitative vertebral fracture diagnosis. Pediatr Radiol 44:457–466PubMedCrossRefGoogle Scholar
  56. 56.
    Adachi JD, Olszynski WP, Hanley DA, Hodsman AB, Kendler DL, Siminoski KG, Brown J, Cowden EA, Goltzman D, Ioannidis G, Josse RG, Ste-Marie LG, Tenenhouse AM, Davison KS, Blocka KL, Pollock AP, Sibley J (2000) Management of corticosteroid-induced osteoporosis. Semin Arthritis Rheum 29:228–251PubMedCrossRefGoogle Scholar
  57. 57.
    Vallarta-Ast N, Krueger D, Wrase C, Agrawal S, Binkley N (2007) An evaluation of densitometric vertebral fracture assessment in men. Osteoporos Int 18:1405–1410PubMedCrossRefGoogle Scholar
  58. 58.
    Spiegel LR, Schneider R, Lang BA, Birdi N, Silverman ED, Laxer RM, Stephens D, Feldman BM (2000) Early predictors of poor functional outcome in systemic-onset juvenile rheumatoid arthritis: a multicenter cohort study. Arthritis Rheum 43:2402–2409PubMedCrossRefGoogle Scholar
  59. 59.
    Siminoski K, Lee KC, Jen H, Warshawski R, Matzinger MA, Shenouda N, Charron M, Coblentz C, Dubois J, Kloiber R, Nadel H, O’Brien K, Reed M, Sparrow K, Webber C, Lentle B, Ward LM (2012) Anatomical distribution of vertebral fractures: comparison of pediatric and adult spines. Osteoporos Int 23:1999–2008PubMedCrossRefGoogle Scholar
  60. 60.
    Buehring B, Krueger D, Checovich M, Gemar D, Vallarta-Ast N, Genant HK, Binkley N (2010) Vertebral fracture assessment: impact of instrument and reader. Osteoporos Int 21:487–494PubMedCrossRefGoogle Scholar
  61. 61.
    Mayranpaa MK, Helenius I, Valta H, Mayranpaa MI, Toiviainen-Salo S, Makitie O (2007) Bone densitometry in the diagnosis of vertebral fractures in children: accuracy of vertebral fracture assessment. Bone 41:353–359PubMedCrossRefGoogle Scholar
  62. 62.
    Glorieux FH, Travers R, Taylor A, Bowen JR, Rauch F, Norman M, Parfitt AM (2000) Normative data for iliac bone histomorphometry in growing children. Bone 26:103–109PubMedCrossRefGoogle Scholar
  63. 63.
    Bacchetta J, Wesseling-Perry K, Gilsanz V, Gales B, Pereira RC, Salusky IB (2013) Idiopathic juvenile osteoporosis: a cross-sectional single-centre experience with bone histomorphometry and quantitative computed tomography. Pediatr Rheumatol Online J 11:6PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Rauch F (2009) Bone biopsy: indications and methods. Endocr Dev 16:49–57PubMedCrossRefGoogle Scholar
  65. 65.
    Crabtree NJ, Arabi A, Bachrach LK, Fewtrell M, El-Hajj Fuleihan G, Kecskemethy HH, Jaworski M, Gordon CM (2014) Dual-energy X-ray absorptiometry interpretation and reporting in children and adolescents: the revised 2013 ISCD Pediatric Official Positions. J Clin Densitom 17:225–242PubMedCrossRefGoogle Scholar
  66. 66.
    Zemel BS, Stallings VA, Leonard MB, Paulhamus DR, Kecskemethy HH, Harcke HT, Henderson RC (2009) Revised pediatric reference data for the lateral distal femur measured by Hologic Discovery/Delphi dual-energy X-ray absorptiometry. J Clin Densitom 12:207–218PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Greulich WW, Pyle SI (1959) Radiographic atlas of skeletal development of the hand and wrist. Second edition. Stanford University Press, StanfordGoogle Scholar
  68. 68.
    Kroger H, Kotaniemi A, Vainio P, Alhava E (1992) Bone densitometry of the spine and femur in children by dual-energy X-ray absorptiometry. Bone Miner 17:75–85PubMedCrossRefGoogle Scholar
  69. 69.
    Zemel BS, Kalkwarf HJ, Gilsanz V, Lappe JM, Oberfield S, Shepherd JA, Frederick MM, Huang X, Lu M, Mahboubi S, Hangartner T, Winer KK (2011) 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 96:3160–3169PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Crabtree NJ, Hogler W, Cooper MS, Shaw NJ (2013) Diagnostic evaluation of bone densitometric size adjustment techniques in children with and without low trauma fractures. Osteoporos Int 24:2015–2024PubMedCrossRefGoogle Scholar
  71. 71.
    Binkley T, Johnson J, Vogel L, Kecskemethy H, Henderson R, Specker B (2005) Bone measurements by peripheral quantitative computed tomography (pQCT) in children with cerebral palsy. J Pediatr 147:791–796PubMedCrossRefGoogle Scholar
  72. 72.
    Hogler W, Shaw N (2010) Childhood growth hormone deficiency, bone density, structures and fractures: scrutinizing the evidence. Clin Endocrinol (Oxf) 72:281–289CrossRefGoogle Scholar
  73. 73.
    Vasikaran S, Cooper C, Eastell R, Griesmacher A, Morris HA, Trenti T, Kanis JA (2011) International Osteoporosis Foundation and International Federation of Clinical Chemistry and Laboratory Medicine position on bone marker standards in osteoporosis. Clin Chem Lab Med 49:1271–1274PubMedCrossRefGoogle Scholar
  74. 74.
    Rauchenzauner M, Schmid A, Heinz-Erian P, Kapelari K, Falkensammer G, Griesmacher A, Finkenstedt G, Hogler W (2007) Sex- and age-specific reference curves for serum markers of bone turnover in healthy children from 2 months to 18 years. J Clin Endocrinol Metab 92:443–449PubMedCrossRefGoogle Scholar
  75. 75.
    Bayer M (2014) Reference values of osteocalcin and procollagen type I N-propeptide plasma levels in a healthy Central European population aged 0–18 years. Osteoporos Int 25:729–736PubMedCrossRefGoogle Scholar
  76. 76.
    Morovat A, Catchpole A, Meurisse A, Carlisi A, Bekaert AC, Rousselle O, Paddon M, James T, Cavalier E (2013) IDS iSYS automated intact procollagen-1-N-terminus pro-peptide assay: method evaluation and reference intervals in adults and children. Clin Chem Lab Med 51:2009–2018PubMedCrossRefGoogle Scholar
  77. 77.
    Huang Y, Eapen E, Steele S, Grey V (2011) Establishment of reference intervals for bone markers in children and adolescents. Clin Biochem 44:771–778PubMedCrossRefGoogle Scholar
  78. 78.
    Biver E (2012) Use of bone turnover markers in clinical practice. Curr Opin Endocrinol Diabetes Obes 19:468–473PubMedCrossRefGoogle Scholar
  79. 79.
    McCloskey EV, Vasikaran S, Cooper C (2011) Official Positions for FRAX(R) clinical regarding biochemical markers from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX(R). J Clin Densitom 14:220–222PubMedCrossRefGoogle Scholar
  80. 80.
    Eastell R, Barton I, Hannon RA, Chines A, Garnero P, Delmas PD (2003) Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate. J Bone Miner Res 18:1051–1056PubMedCrossRefGoogle Scholar
  81. 81.
    Seibel MJ, Naganathan V, Barton I, Grauer A (2004) Relationship between pretreatment bone resorption and vertebral fracture incidence in postmenopausal osteoporotic women treated with risedronate. J Bone Miner Res 19:323–329PubMedCrossRefGoogle Scholar
  82. 82.
    Delmas PD, Licata AA, Reginster JY, Crans GG, Chen P, Misurski DA, Wagman RB, Mitlak BH (2006) Fracture risk reduction during treatment with teriparatide is independent of pretreatment bone turnover. Bone 39:237–243PubMedCrossRefGoogle Scholar
  83. 83.
    Eastell R, Hannon RA, Garnero P, Campbell MJ, Delmas PD (2007) Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate: review of statistical analysis. J Bone Miner Res 22:1656–1660PubMedCrossRefGoogle Scholar
  84. 84.
    Rauch F, Plotkin H, Travers R, Zeitlin L, Glorieux FH (2003) Osteogenesis imperfecta types I, III, and IV: effect of pamidronate therapy on bone and mineral metabolism. J Clin Endocrinol Metab 88:986–992PubMedCrossRefGoogle Scholar
  85. 85.
    Rauch F, Travers R, Plotkin H, Glorieux FH (2002) The effects of intravenous pamidronate on the bone tissue of children and adolescents with osteogenesis imperfecta. J Clin Invest 110:1293–1299PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Ward LM, Rauch F, Matzinger MA, Benchimol EI, Boland M, Mack DR (2010) Iliac bone histomorphometry in children with newly diagnosed inflammatory bowel disease. Osteoporos Int 21:331–337PubMedCrossRefGoogle Scholar
  87. 87.
    Hartikka H, Makitie O, Mannikko M, Doria AS, Daneman A, Cole WG, Ala-Kokko L, Sochett EB (2005) Heterozygous mutations in the LDL receptor-related protein 5 (LRP5) gene are associated with primary osteoporosis in children. J Bone Miner Res 20:783–789PubMedCrossRefGoogle Scholar
  88. 88.
    Fahiminiya S, Majewski J, Roughley P, Roschger P, Klaushofer K, Rauch F (2013) Whole-exome sequencing reveals a heterozygous LRP5 mutation in a 6-year-old boy with vertebral compression fractures and low trabecular bone density. Bone 57:41–46PubMedCrossRefGoogle Scholar
  89. 89.
    Whyte MP, Greenberg CR, Salman NJ, Bober MB, McAlister WH, Wenkert D, Van Sickle BJ, Simmons JH, Edgar TS, Bauer ML, Hamdan MA, Bishop N, Lutz RE, McGinn M, Craig S, Moore JN, Taylor JW, Cleveland RH, Cranley WR, Lim R, Thacher TD, Mayhew JE, Downs M, Millan JL, Skrinar AM, Crine P, Landy H (2012) Enzyme-replacement therapy in life-threatening hypophosphatasia. New Eng J Med 366:904–913PubMedCrossRefGoogle Scholar
  90. 90.
    Antoniazzi F, Zamboni G, Lauriola S, Donadi L, Adami S, Tato L (2006) Early bisphosphonate treatment in infants with severe osteogenesis imperfecta. J Pediatr 149:174–179PubMedCrossRefGoogle Scholar
  91. 91.
    Sakkers R, Kok D, Engelbert R, van Dongen A, Jansen M, Pruijs H, Verbout A, Schweitzer D, Uiterwaal C (2004) Skeletal effects and functional outcome with olpadronate in children with osteogenesis imperfecta: a 2-year randomised placebo-controlled study. Lancet 363:1427–1431PubMedCrossRefGoogle Scholar
  92. 92.
    Ward LM, Glorieux FH, Rauch F, Verbruggen N, Heyden N, Lombardi A (2005) A randomized, placebo-controlled trial of oral alendronate in children and adolescents with osteogenesis imperfecta. Bone 36Google Scholar
  93. 93.
    Rauch F, Munns CF, Land C, Cheung M, Glorieux FH (2009) Risedronate in the treatment of mild pediatric osteogenesis imperfecta: a randomized placebo-controlled study. J Bone Miner Res 24:1282–1289PubMedCrossRefGoogle Scholar
  94. 94.
    Kroger H, Vainio P, Nieminen J, Kotaniemi A (1995) Comparison of different models for interpreting bone mineral density measurements using DXA and MRI technology. Bone 17:157–159PubMedCrossRefGoogle Scholar
  95. 95.
    Carter DR, Bouxsein ML, Marcus R (1992) New approaches for interpreting projected bone densitometry data. J Bone Miner Res 7:137–145PubMedCrossRefGoogle Scholar
  96. 96.
    Rauch F, Plotkin H, DiMeglio L, Engelbert RH, Henderson RC, Munns C, Wenkert D, Zeitler P (2008) Fracture prediction and the definition of osteoporosis in children and adolescents: the ISCD 2007 Pediatric Official Positions. J Clin Densitom 11:22–28PubMedCrossRefGoogle Scholar
  97. 97.
    Marini JC, Blissett AR (2013) New genes in bone development: what’s new in osteogenesis imperfecta. J Clin Endocrinol Metab 98:3095–3103PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Sillence DO, Rimoin DL (1978) Classification of osteogenesis imperfect. Lancet 1:1041–1042PubMedCrossRefGoogle Scholar
  99. 99.
    Palomo T, Al-Jallad H, Moffatt P, Glorieux FH, Lentle B, Roschger P, Klaushofer K, Rauch F (2014) Skeletal characteristics associated with homozygous and heterozygous WNT1 mutations. Bone 67:63–70PubMedCrossRefGoogle Scholar
  100. 100.
    Mitchell PJ, Cooper C, Dawson-Hughes B, Gordon CM, Rizzoli R (2015) Life-course approach to nutrition. Osteoporos Int 26:2723–2742PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Specker B, Thiex NW, Sudhagoni RG (2015) Does exercise influence pediatric bone? A systematic review. Clin Orthop Relat Res 473:3658–3672PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Golden NH, Abrams SA (2014) Optimizing bone health in children and adolescents. Pediatrics 134:e1229–e1243PubMedCrossRefGoogle Scholar
  103. 103.
    Abrams SA, Coss-Bu JA, Tiosano D (2013) Vitamin D: effects on childhood health and disease. Nat Rev Endocrinol 9:162–170PubMedCrossRefGoogle Scholar
  104. 104.
    Julian-Almarcegui C, Gomez-Cabello A, Huybrechts I, Gonzalez-Aguero A, Kaufman JM, Casajus JA, Vicente-Rodriguez G (2015) Combined effects of interaction between physical activity and nutrition on bone health in children and adolescents: a systematic review. Nutr Rev 73:127–139PubMedCrossRefGoogle Scholar
  105. 105.
    Handel MN, Heitmann BL, Abrahamsen B (2015) Nutrient and food intakes in early life and risk of childhood fractures: a systematic review and meta-analysis. Am J Clin Nutr 102:1182–1195PubMedCrossRefGoogle Scholar
  106. 106.
    Tan VP, Macdonald HM, Kim S, Nettlefold L, Gabel L, Ashe MC, McKay HA (2014) Influence of physical activity on bone strength in children and adolescents: a systematic review and narrative synthesis. J Bone Miner Res 29:2161–2181PubMedCrossRefGoogle Scholar
  107. 107.
    Institute of Medicine (2011) Dietary reference intakes for calcium and vitamin D. The National Academies Press, WashingtonGoogle Scholar
  108. 108.
    Misra M, Pacaud D, Petryk A, Collett-Solberg PF, Kappy M (2008) Vitamin D deficiency in children and its management: review of current knowledge and recommendations. Pediatrics 122:398–417PubMedCrossRefGoogle Scholar
  109. 109.
    Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM (2011) Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96:1911–1930PubMedCrossRefGoogle Scholar
  110. 110.
    Winzenberg T, Powell S, Shaw KA, Jones G (2011) Effects of vitamin D supplementation on bone density in healthy children: systematic review and meta-analysis. BMJ 342:c7254PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Edouard T, Glorieux FH, Rauch F (2011) Predictors and correlates of vitamin D status in children and adolescents with osteogenesis imperfecta. J Clin Endocrinol Metab 96:3193–3198PubMedCrossRefGoogle Scholar
  112. 112.
    Benchimol EI, Ward LM, Gallagher JC, Rauch F, Barrowman N, Warren J, Beedle S, Mack DR (2007) Effect of calcium and vitamin D supplementation on bone mineral density in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 45:538–545PubMedCrossRefGoogle Scholar
  113. 113.
    Kaste SC, Qi A, Smith K, Surprise H, Lovorn E, Boyett J, Ferry RJ Jr, Relling MV, Shurtleff SA, Pui CH, Carbone L, Hudson MM, Ness KK (2014) Calcium and cholecalciferol supplementation provides no added benefit to nutritional counseling to improve bone mineral density in survivors of childhood acute lymphoblastic leukemia (ALL). Pediatr Blood Cancer 61:885–893PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JP (2014) Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ 348:g2035PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Bolland MJ, Avenell A, Baron JA, Grey A, MacLennan GS, Gamble GD, Reid IR (2010) Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ 341:c3691PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Winzenberg T, Shaw K, Fryer J, Jones G (2006) Effects of calcium supplementation on bone density in healthy children: meta-analysis of randomised controlled trials. BMJ 333:775PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Behringer M, Gruetzner S, McCourt M, Mester J (2014) Effects of weight-bearing activities on bone mineral content and density in children and adolescents: a meta-analysis. J Bone Miner Res 29:467–478PubMedCrossRefGoogle Scholar
  118. 118.
    Dubnov-Raz G, Azar M, Reuveny R, Katz U, Weintraub M, Constantini NW (2015) Changes in fitness are associated with changes in body composition and bone health in children after cancer. Acta Paediatr 104:1055–1061PubMedCrossRefGoogle Scholar
  119. 119.
    Hough JP, Boyd RN, Keating JL (2010) Systematic review of interventions for low bone mineral density in children with cerebral palsy. Pediatrics 125:e670–e678PubMedCrossRefGoogle Scholar
  120. 120.
    Mandel K, Atkinson S, Barr RD, Pencharz P (2004) Skeletal morbidity in childhood acute lymphoblastic leukemia. J Clin Oncol 22:1215–1221PubMedCrossRefGoogle Scholar
  121. 121.
    Kalayci AG, Kansu A, Girgin N, Kucuk O, Aras G (2001) Bone mineral density and importance of a gluten-free diet in patients with celiac disease in childhood. Pediatrics 108:E89PubMedCrossRefGoogle Scholar
  122. 122.
    Avgeri M, Papadopoulou A, Platokouki H, Douros K, Rammos S, Nicolaidou P, Aronis S (2008) Assessment of bone mineral density and markers of bone turnover in children under long-term oral anticoagulant therapy. J Pediatr Hematol Oncol 30:592–597PubMedCrossRefGoogle Scholar
  123. 123.
    Modesto W, Bahamondes MV, Bahamondes L (2015) Prevalence of low bone mass and osteoporosis in long-term users of the injectable contraceptive depot medroxyprogesterone acetate. J Womens Health (Larchmt) 24:636–640CrossRefGoogle Scholar
  124. 124.
    Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Vance ML (2011) Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96:1587–1609PubMedCrossRefGoogle Scholar
  125. 125.
    Bodor M, McDonald CM (2013) Why short stature is beneficial in Duchenne muscular dystrophy. Muscle Nerve 48:336–342PubMedCrossRefGoogle Scholar
  126. 126.
    Dubner SE, Shults J, Baldassano RN, Zemel BS, Thayu M, Burnham JM, Herskovitz RM, Howard KM, Leonard MB (2009) Longitudinal assessment of bone density and structure in an incident cohort of children with Crohn’s disease. Gastroenterology 136:123–130PubMedCrossRefGoogle Scholar
  127. 127.
    Dwan K, Phillipi CA, Steiner RD, Basel D (2014) Bisphosphonate therapy for osteogenesis imperfecta. Cochrane Database Syst Rev 7:CD005088Google Scholar
  128. 128.
    Ward L, Tricco AC, Phuong P, Cranney A, Barrowman N, Gaboury I, Rauch F, Tugwell P, Moher D (2007) Bisphosphonate therapy for children and adolescents with secondary osteoporosis. Cochrane Database Syst Rev: CD005324Google Scholar
  129. 129.
    Ward LM, Rauch F (2013) Oral bisphosphonates for paediatric osteogenesis imperfecta? Lancet 282:1388–1389CrossRefGoogle Scholar
  130. 130.
    Glorieux FH, Bishop NJ, Plotkin H, Chabot G, Lanoue G, Travers R (1998) Cyclic administration of pamidronate in children with severe osteogenesis imperfecta. New Eng J Med 339:947–952PubMedCrossRefGoogle Scholar
  131. 131.
    Barros ER, Saraiva GL, de Oliveira TP, Lazaretti-Castro M (2012) Safety and efficacy of a 1-year treatment with zoledronic acid compared with pamidronate in children with osteogenesis imperfecta. J Pediatr Endocrinol Metab 25:485–491PubMedCrossRefGoogle Scholar
  132. 132.
    Grey A, Bolland M, Wattie D, Horne A, Gamble G, Reid IR (2010) Prolonged antiresorptive activity of zoledronate: a randomized, controlled trial. J Bone Miner Res 25:2251–2255PubMedCrossRefGoogle Scholar
  133. 133.
    Ward LM, Denker AE, Porras A, Shugarts S, Kline W, Travers R, Mao C, Rauch F, Maes A, Larson P, Deutsch P, Glorieux FH (2005) Single-dose pharmacokinetics and tolerability of alendronate 35- and 70-milligram tablets in children and adolescents with osteogenesis imperfecta type I. J Clin Endocrinol Metab 90:4051–4056PubMedCrossRefGoogle Scholar
  134. 134.
    Golden NH, Iglesias EA, Jacobson MS, Carey D, Meyer W, Schebendach J, Hertz S, Shenker IR (2005) Alendronate for the treatment of osteopenia in anorexia nervosa: a randomized, double-blind, placebo-controlled trial. J Clin Endocrinol Metab 90:3179–3185PubMedCrossRefGoogle Scholar
  135. 135.
    Bishop N, Adami S, Ahmed SF, Anton J, Arundel P, Burren CP, Devogelaer JP, Hangartner T, Hosszu E, Lane JM, Lorenc R, Makitie O, Munns CF, Paredes A, Pavlov H, Plotkin H, Raggio CL, Reyes ML, Schoenau E, Semler O, Sillence DO, Steiner RD (2013) Risedronate in children with osteogenesis imperfecta: a randomised, double-blind, placebo-controlled trial. Lancet 382:1424–1432PubMedCrossRefGoogle Scholar
  136. 136.
    Bianchi ML, Colombo C, Assael BM, Dubini A, Lombardo M, Quattrucci S, Bella S, Collura M, Messore B, Raia V, Poli F, Bini R, Albanese CV, De Rose V, Costantini D, Romano G, Pustorino E, Magazzu G, Bertasi S, Lucidi V, Traverso G, Coruzzo A, Grzejdziak AD (2013) Treatment of low bone density in young people with cystic fibrosis: a multicentre, prospective, open-label observational study of calcium and calcifediol followed by a randomised placebo-controlled trial of alendronate. Lancet Respir Med 1:377–385PubMedCrossRefGoogle Scholar
  137. 137.
    Rudge S, Hailwood S, Horne A, Lucas J, Wu F, Cundy T (2005) Effects of once-weekly oral alendronate on bone in children on glucocorticoid treatment. Rheumatology (Oxford) 44:813–818CrossRefGoogle Scholar
  138. 138.
    Gatti D, Antoniazzi F, Prizzi R, Braga V, Rossini M, Tato L, Viapiana O, Adami S (2005) Intravenous neridronate in children with osteogenesis imperfecta: a randomized controlled study. J Bone Miner Res 20:758–763PubMedCrossRefGoogle Scholar
  139. 139.
    Ward LM, Rauch F, Whyte MP, D’Astous J, Gates PE, Grogan D, Lester EL, McCall RE, Pressly TA, Sanders JO, Smith PA, Steiner RD, Sullivan E, Tyerman G, Smith-Wright DL, Verbruggen N, Heyden N, Lombardi A, Glorieux FH (2011) Alendronate for the treatment of pediatric osteogenesis imperfecta: a randomized placebo-controlled study. J Clin Endocrinol Metab 96:355–364PubMedCrossRefGoogle Scholar
  140. 140.
    Munns CF, Rauch F, Travers R, Glorieux FH (2005) Effects of intravenous pamidronate treatment in infants with osteogenesis imperfecta: clinical and histomorphometric outcome. J Bone Miner Res 20:1235–1243PubMedCrossRefGoogle Scholar
  141. 141.
    Land C, Rauch F, Munns CF, Sahebjam S, Glorieux FH (2006) Vertebral morphometry in children and adolescents with osteogenesis imperfecta: effect of intravenous pamidronate treatment. Bone 39:901–906PubMedCrossRefGoogle Scholar
  142. 142.
    Astrom E, Jorulf H, Soderhall S (2007) Intravenous pamidronate treatment of infants with severe osteogenesis imperfecta. Arch Dis Child 92:332–338PubMedCrossRefGoogle Scholar
  143. 143.
    Rauch F, Munns C, Land C, Glorieux FH (2006) Pamidronate in children and adolescents with osteogenesis imperfecta: effect of treatment discontinuation. J Clin Endocrinol Metab 91:1268–1274PubMedCrossRefGoogle Scholar
  144. 144.
    Land C, Rauch F, Montpetit K, Ruck-Gibis J, Glorieux FH (2006) Effect of intravenous pamidronate therapy on functional abilities and level of ambulation in children with osteogenesis imperfecta. J Pediatr 148:456–460PubMedCrossRefGoogle Scholar
  145. 145.
    Zeitlin L, Rauch F, Plotkin H, Glorieux FH (2003) Height and weight development during four years of therapy with cyclical intravenous pamidronate in children and adolescents with osteogenesis imperfecta types I, III, and IV. Pediatrics 111:1030–1036PubMedCrossRefGoogle Scholar
  146. 146.
    Vuorimies I, Toiviainen-Salo S, Hero M, Makitie O (2011) Zoledronic acid treatment in children with osteogenesis imperfecta. Horm Res Paediatr 75:346–353PubMedCrossRefGoogle Scholar
  147. 147.
    Ooi HL, Briody J, Biggin A, Cowell CT, Munns CF (2013) Intravenous zoledronic acid given every 6 months in childhood osteoporosis. Horm Res Paediatr 80:179–184PubMedCrossRefGoogle Scholar
  148. 148.
    Gandrud LM, Cheung JC, Daniels MW, Bachrach LK (2003) Low-dose intravenous pamidronate reduces fractures in childhood osteoporosis. J Pediatr Endocrinol Metab 16:887–892PubMedCrossRefGoogle Scholar
  149. 149.
    Steelman J, Zeitler P (2003) Treatment of symptomatic pediatric osteoporosis with cyclic single-day intravenous pamidronate infusions. J Pediatr 142:417–423PubMedCrossRefGoogle Scholar
  150. 150.
    Whyte MP, Wenkert D, Clements KL, McAlister WH, Mumm S (2003) Bisphosphonate-induced osteopetrosis. New Eng J Med 349:457–463PubMedCrossRefGoogle Scholar
  151. 151.
    Rauch F, Cornibert S, Cheung M, Glorieux FH (2007) Long-bone changes after pamidronate discontinuation in children and adolescents with osteogenesis imperfecta. Bone 40:821–827PubMedCrossRefGoogle Scholar
  152. 152.
    Biggin A, Briody JN, Ormshaw E, Wong KK, Bennetts BH, Munns CF (2014) Fracture during intravenous bisphosphonate treatment in a child with osteogenesis imperfecta: an argument for a more frequent, low-dose treatment regimen. Horm Res Paediatr 81:204–210PubMedCrossRefGoogle Scholar
  153. 153.
    Biggin A, Zheng L, Briody JN, Coorey CP, Munns CF (2015) The long-term effects of switching from active intravenous bisphosphonate treatment to low-dose maintenance therapy in children with osteogenesis imperfecta. Horm Res Paediatr 83:183–189PubMedCrossRefGoogle Scholar
  154. 154.
    Brown JP, Morin S, Leslie W, Papaioannou A, Cheung AM, Davison KS, Goltzman D, Hanley DA, Hodsman A, Josse R, Jovaisas A, Juby A, Kaiser S, Karaplis A, Kendler D, Khan A, Ngui D, Olszynski W, Ste-Marie LG, Adachi J (2014) Bisphosphonates for treatment of osteoporosis: expected benefits, potential harms, and drug holidays. Can Fam Physician 60:324–333PubMedPubMedCentralGoogle Scholar
  155. 155.
    Unal E, Abaci A, Bober E, Buyukgebiz A (2006) Efficacy and safety of oral alendronate treatment in children and adolescents with osteoporosis. J Pediatr Endocrinol Metab 19:523–528PubMedGoogle Scholar
  156. 156.
    Khosla S, Burr D, Cauley J, Dempster DW, Ebeling PR, Felsenberg D, Gagel RF, Gilsanz V, Guise T, Koka S, McCauley LK, McGowan J, McKee MD, Mohla S, Pendrys DG, Raisz LG, Ruggiero SL, Shafer DM, Shum L, Silverman SL, Van Poznak CH, Watts N, Woo SB, Shane E (2007) Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 22:1479–1491PubMedCrossRefGoogle Scholar
  157. 157.
    Malmgren B, Astrom E, Soderhall S (2008) No osteonecrosis in jaws of young patients with osteogenesis imperfecta treated with bisphosphonates. J Oral Pathol Med 37:196–200PubMedCrossRefGoogle Scholar
  158. 158.
    Chahine C, Cheung MS, Head TW, Schwartz S, Glorieux FH, Rauch F (2008) Tooth extraction socket healing in pediatric patients treated with intravenous pamidronate. J Pediatr 153:719–720PubMedCrossRefGoogle Scholar
  159. 159.
    Brown JJ, Ramalingam L, Zacharin MR (2008) Bisphosphonate-associated osteonecrosis of the jaw: does it occur in children? Clin Endocrinol (Oxf) 68:863–867CrossRefGoogle Scholar
  160. 160.
    Bhatt RN, Hibbert SA, Munns CF (2014) The use of bisphosphonates in children: review of the literature and guidelines for dental management. Aust Dent J 59:9–19PubMedCrossRefGoogle Scholar
  161. 161.
    Shane E, Burr D, Abrahamsen B, Adler RA, Brown TD, Cheung AM, Cosman F, Curtis JR, Dell R, Dempster DW, Ebeling PR, Einhorn TA, Genant HK, Geusens P, Klaushofer K, Lane JM, McKiernan F, McKinney R, Ng A, Nieves J, O’Keefe R, Papapoulos S, Howe TS, van der Meulen MC, Weinstein RS, Whyte MP (2014) Atypical subtrochanteric and diaphyseal femoral fractures: second report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 29:1–23PubMedCrossRefGoogle Scholar
  162. 162.
    Hegazy A, Kenawey M, Sochett E, Tile L, Cheung AM, Howard AW (2015) Unusual femur stress fractures in children with osteogenesis imperfecta and intramedullary rods on long-term intravenous pamidronate therapy. J Pediatr Orthop Epub ahead of print: 2015 Jun 8 doi: 10.1097/BPO.0000000000000552
  163. 163.
    Munns CF, Rauch F, Zeitlin L, Fassier F, Glorieux FH (2004) Delayed osteotomy but not fracture healing in pediatric osteogenesis imperfecta patients receiving pamidronate. J Bone Miner Res 19:1779–1786PubMedCrossRefGoogle Scholar
  164. 164.
    Anam EA, Rauch F, Glorieux FH, Fassier F, Hamdy R (2015) Osteotomy healing in children with osteogenesis imperfecta receiving bisphosphonate treatment. J Bone Miner Res 30:1362–1368PubMedCrossRefGoogle Scholar
  165. 165.
    Papapoulos SE, Cremers SC (2007) Prolonged bisphosphonate release after treatment in children. New Eng J Med 356:1075–1076PubMedCrossRefGoogle Scholar
  166. 166.
    Djokanovic N, Klieger-Grossmann C, Koren G (2008) Does treatment with bisphosphonates endanger the human pregnancy? J Obstet Gynaecol Can 30:1146–1148PubMedCrossRefGoogle Scholar
  167. 167.
    Green SB, Pappas AL (2014) Effects of maternal bisphosphonate use on fetal and neonatal outcomes. Am J Health Syst Pharm 71:2029–2036PubMedCrossRefGoogle Scholar
  168. 168.
    Levy S, Fayez I, Taguchi N, Han JY, Aiello J, Matsui D, Moretti M, Koren G, Ito S (2009) Pregnancy outcome following in utero exposure to bisphosphonates. Bone 44:428–430PubMedCrossRefGoogle Scholar
  169. 169.
    Munns CF, Rauch F, Ward L, Glorieux FH (2004) Maternal and fetal outcome after long-term pamidronate treatment before conception: a report of two cases. J Bone Miner Res 19:1742–1745PubMedCrossRefGoogle Scholar
  170. 170.
    Faje AT, Fazeli PK, Miller KK, Katzman DK, Ebrahimi S, Lee H, Mendes N, Snelgrove D, Meenaghan E, Misra M, Klibanski A (2014) Fracture risk and areal bone mineral density in adolescent females with anorexia nervosa. Int J Eat Disord 47:458–466PubMedPubMedCentralCrossRefGoogle Scholar
  171. 171.
    Divasta AD, Feldman HA, Gordon CM (2014) Vertebral fracture assessment in adolescents and young women with anorexia nervosa: a case series. J Clin Densitom 17:207–211PubMedCrossRefGoogle Scholar
  172. 172.
    Misra M, Klibanski A (2014) Anorexia nervosa and bone. J Endocrinol 221:R163–R176PubMedPubMedCentralCrossRefGoogle Scholar
  173. 173.
    Nattiv A, Loucks AB, Manore MM, Sanborn CF, Sundgot-Borgen J, Warren MP (2007) American College of Sports Medicine position stand. The female athlete triad. Med Sci Sports Exerc 39:1867–1882PubMedCrossRefGoogle Scholar
  174. 174.
    Saraff V, Hoegler W (2015) Endocrinology and adolescence: osteoporosis in children: diagnosis and management. Eur J Endocrinol 173(6):R185–R1897PubMedCrossRefGoogle Scholar
  175. 175.
    Korula S, Titmuss AT, Biggin A, Munns CF (2015) A practical approach to children with recurrent fractures. Endocr Dev 28:210–225PubMedCrossRefGoogle Scholar
  176. 176.
    Kim MJ, Kim SN, Lee IS, Chung S, Lee J, Yang Y, Lee I, Koh SE (2015) Effects of bisphosphonates to treat osteoporosis in children with cerebral palsy: a meta-analysis. J Pediatr Endocrinol Metab 28(11–12):1343–1350PubMedGoogle Scholar
  177. 177.
    Eghbali-Fatourechi G, Khosla S, Sanyal A, Boyle WJ, Lacey DL, Riggs BL (2003) Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J Clin Invest 111:1221–1230PubMedPubMedCentralCrossRefGoogle Scholar
  178. 178.
    Kostenuik PJ, Nguyen HQ, McCabe J, Warmington KS, Kurahara C, Sun N, Chen C, Li L, Cattley RC, Van G, Scully S, Elliott R, Grisanti M, Morony S, Tan HL, Asuncion F, Li X, Ominsky MS, Stolina M, Dwyer D, Dougall WC, Hawkins N, Boyle WJ, Simonet WS, Sullivan JK (2009) Denosumab, a fully human monoclonal antibody to RANKL, inhibits bone resorption and increases BMD in knock-in mice that express chimeric (murine/human) RANKL. J Bone Miner Res 24:182–195PubMedCrossRefGoogle Scholar
  179. 179.
    Hofbauer LC, Zeitz U, Schoppet M, Skalicky M, Schuler C, Stolina M, Kostenuik PJ, Erben RG (2009) Prevention of glucocorticoid-induced bone loss in mice by inhibition of RANKL. Arthritis Rheum 60:1427–1437PubMedCrossRefGoogle Scholar
  180. 180.
    Dempster DW, Lambing CL, Kostenuik PJ, Grauer A (2012) Role of RANK ligand and denosumab, a targeted RANK ligand inhibitor, in bone health and osteoporosis: a review of preclinical and clinical data. Clin Ther 34:521–536PubMedCrossRefGoogle Scholar
  181. 181.
    Semler O, Netzer C, Hoyer-Kuhn H, Becker J, Eysel P, Schoenau E (2012) First use of the RANKL antibody denosumab in osteogenesis imperfecta type VI. J Musculoskelet Neuronal Interact 12:183–188PubMedGoogle Scholar
  182. 182.
    Karras NA, Polgreen LE, Ogilvie C, Manivel JC, Skubitz KM, Lipsitz E (2013) Denosumab treatment of metastatic giant-cell tumor of bone in a 10-year-old girl. J Clin Oncol 31:e200–e202PubMedPubMedCentralCrossRefGoogle Scholar
  183. 183.
    Lange T, Stehling C, Frohlich B, Klingenhofer M, Kunkel P, Schneppenheim R, Escherich G, Gosheger G, Hardes J, Jurgens H, Schulte TL (2013) Denosumab: a potential new and innovative treatment option for aneurysmal bone cysts. Eur Spine J 22:1417–1422PubMedPubMedCentralCrossRefGoogle Scholar
  184. 184.
    Boyce AM, Chong WH, Yao J, Gafni RI, Kelly MH, Chamberlain CE, Bassim C, Cherman N, Ellsworth M, Kasa-Vubu JZ, Farley FA, Molinolo AA, Bhattacharyya N, Collins MT (2012) Denosumab treatment for fibrous dysplasia. J Bone Miner Res 27:1462–1470PubMedPubMedCentralCrossRefGoogle Scholar
  185. 185.
    Wang HD, Boyce AM, Tsai JY, Gafni RI, Farley FA, Kasa-Vubu JZ, Molinolo AA, Collins MT (2014) Effects of denosumab treatment and discontinuation on human growth plates. J Clin Endocrinol Metab 99:891–897PubMedPubMedCentralCrossRefGoogle Scholar
  186. 186.
    Padhi D, Allison M, Kivitz AJ, Gutierrez MJ, Stouch B, Wang C, Jang G (2014) Multiple doses of sclerostin antibody romosozumab in healthy men and postmenopausal women with low bone mass: a randomized, double-blind, placebo-controlled study. J Clin Pharmacol 54:168–178PubMedCrossRefGoogle Scholar
  187. 187.
    Padhi D, Jang G, Stouch B, Fang L, Posvar E (2011) Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res 26:19–26PubMedCrossRefGoogle Scholar
  188. 188.
    Feurer E, Chapurlat R (2014) Emerging drugs for osteoporosis. Expert Opin Emerg Drugs 19:385–395PubMedCrossRefGoogle Scholar
  189. 189.
    Weintraub JA, Breland CE (2015) Challenges, benefits, and factors to enhance recruitment and inclusion of children in pediatric dental research. Int J Paediatr Dent 25:310–316PubMedPubMedCentralCrossRefGoogle Scholar
  190. 190.
    Makitie O, Doria AS, Henriques F, Cole WG, Compeyrot S, Silverman E, Laxer R, Daneman A, Sochett EB (2005) Radiographic vertebral morphology: a diagnostic tool in pediatric osteoporosis. J Pediatr 146:395–401PubMedCrossRefGoogle Scholar
  191. 191.
    Fung EB, Harmatz PR, Milet M, Coates, T, Thompson, AA, Ranalli, M, Mignaca, R Scher, C Giardina, P Robertson, S, Neumayr, L, Vichinsky, E, The Multi-Center Iron Overload Study Group (2008) Fracture prevalence and relationship to endocrinopathy in iron overloaded patients with sickle cell disease and thalassemia. Bone 43:162–168Google Scholar
  192. 192.
    Dosa NP, Eckrich M, Katz DA, Turk M, Liptak GS (2007) Incidence, prevalence, and characteristics of fractures in children, adolescents, and adults with spina bifida. J Spinal Cord Med 30 Suppl 1:S5–9Google Scholar
  193. 193.
    Nakhla M, Scuccimarri R, Duffy KN, Chedeville G, Campillo S, Duffy CM, Azouz EM, Shenouda N, Sharma AK, Rodd C (2009) Prevalence of Vertebral Fractures in Children with Chronic Rheumatic Diseases at Risk for Osteopenia. J Pediatr 154:438–443Google Scholar
  194. 194.
    Engkakul P, Mahachoklertwattana P, Jaovisidha S, Chuansumrit A, Poomthavorn P, Chitrapazt N, Chuncharunee S (2013) Unrecognized vertebral fractures in adolescents and young adults with thalassemia syndromes. J Pediatr Hematol Oncol 35:212–217Google Scholar
  195. 195.
    Mayranpaa MK, Viljakainen HT, Toiviainen-Salo S, Kallio PE, Makitie O (2012) Impaired bone health and asymptomatic vertebral compressions in fracture-prone children: a case-control study. J Bone Miner Res 27:1413–1424Google Scholar
  196. 196.
    Seikaly MG, Kopanati S, Salhab N, Waber P, Patterson D, Browne R, Herring JA (2005) Impact of alendronate on quality of life in children with osteogenesis imperfecta. J Pediatr Orthop 25:786–791Google Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2016

Authors and Affiliations

  1. 1.Pediatric Bone Health Clinical and Research ProgramsChildren’s Hospital of Eastern OntarioOttawaCanada
  2. 2.Department of PediatricsUniversity of OttawaOttawaCanada
  3. 3.School of Epidemiology, Public Health and Preventive MedicineUniversity of OttawaOttawaCanada

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