Osteoporosis: Diagnosis and Management

  • Leanne M. Ward
  • Jinhui Ma


Bone health is now recognized as an important facet of child health with sufficient evidence to support standardized approaches to diagnosis, monitoring, treatment, and prevention. Current management strategies are based on monitoring at-risk children to identify and then treat earlier rather than later signs of osteoporosis in those with limited potential for spontaneous recovery. Research studies addressing 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 chapter 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 during routine care. The scope of this chapter 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 provide specific recommendations for monitoring and prevention. This chapter also reviews when a child is a candidate for osteoporosis therapy, which agents and doses should be prescribed, duration of therapy, how the response to therapy is evaluated, and side effects. With this information, the bone health clinician will be poised to diagnose osteoporosis in children, to identify when children need osteoporosis therapy and the clinical outcomes that gauge efficacy and safety of treatment.


Osteoporosis Vertebral fractures Bone fragility Bone density Diagnosis Monitoring Treatment Prevention Bisphosphonates Denosumab Peripheral quantitative computed tomography Dual-energy x-ray absorptiometry Trans-iliac histomorphometry Bone turnover markers Vertebral morphometry 



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; JM: The CHEO Research Institute.

Conflict of Interest

LMW has been a consultant to Novartis, Amgen, and Alexion Pharmaceuticals and has participated in clinical trials sponsored by Novartis and Amgen. JM has no conflicts of interest to disclose.


  1. 1.
    Bachrach LK. Diagnosis and treatment of pediatric osteoporosis. Curr Opin Endocrinol Diabetes Obes. 2014;21:454–60.PubMedCrossRefGoogle Scholar
  2. 2.
    Makitie O. Causes, mechanisms and management of paediatric osteoporosis. Nat Rev Rheumatol. 2013;9:465–75.PubMedCrossRefGoogle Scholar
  3. 3.
    Saraff V, Schneider J, Colleselli V, Ruepp M, Rauchenzauner M, Neururer S, Geiger R, Hogler W. Sex-, age-, and height-specific reference curves for the 6-min walk test in healthy children and adolescents. Eur J Pediatr. 2015;174(6):837–40.PubMedCrossRefGoogle Scholar
  4. 4.
    Bianchi ML, Leonard MB, Bechtold S, Hogler W, 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;17:281–94.PubMedCrossRefGoogle Scholar
  5. 5.
    Ward LM, Konji VN, Ma J. The management of osteoporosis in children. Osteoporos Int. 2016;27:2147–79.PubMedCrossRefGoogle Scholar
  6. 6.
    Rauch F, Glorieux FH. Osteogenesis imperfecta. Lancet. 2004;363:1377–85.PubMedCrossRefGoogle Scholar
  7. 7.
    Ben Amor IM, Roughley P, Glorieux FH, Rauch F. Skeletal clinical characteristics of osteogenesis imperfecta caused by haploinsufficiency mutations in COL1A1. J Bone Miner Res. 2013;28:2001–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Marini JC, Reich A, Smith SM. Osteogenesis imperfecta due to mutations in non-collagenous genes: lessons in the biology of bone formation. Curr Opin Pediatr. 2014;26:500–7.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Rauch F, Lalic L, Roughley P, Glorieux FH. Genotype-phenotype correlations in nonlethal osteogenesis imperfecta caused by mutations in the helical domain of collagen type I. Eur J Hum Genet. 2010;18:642–7.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Pui CH, Evans WE. A 50-year journey to cure childhood acute lymphoblastic leukemia. Semin Hematol. 2013;50:185–96.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    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. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 2010;9:77–93.PubMedCrossRefGoogle Scholar
  12. 12.
    Cummings EA, Ma J, Fernandez CV, Halton J, et al. Incident vertebral fractures in children with leukemia during the four years following diagnosis. J Clin Endocrinol Metab. 2015;100:3408–17.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    LeBlanc CM, Ma J, Taljaard M, Roth J, 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;30:1667–75.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    McMillan HJ, Campbell C, Mah JK. Duchenne muscular dystrophy: Canadian paediatric neuromuscular physicians survey. Can J Neurol Sci Le J Can des Sciences Neurologiques. 2015;37:195–205.CrossRefGoogle Scholar
  15. 15.
    Hyams JS. Biologics in pediatric Crohn’s disease: is it time to move to an earlier therapeutic approach? Expert Rev Clin Immunol. 2014;10:1423–6.PubMedCrossRefGoogle Scholar
  16. 16.
    Thayu M, Leonard MB, Hyams JS, Crandall WV, et al. Improvement in biomarkers of bone formation during infliximab therapy in pediatric Crohn’s disease: results of the REACH study. Clin Gastroenterol Hepatol. 2008;6:1378–84.PubMedCrossRefGoogle Scholar
  17. 17.
    Kessler EA, Becker ML. Therapeutic advancements in juvenile idiopathic arthritis. Best Pract Res Clin Rheumatol. 2014;28:293–313.PubMedCrossRefGoogle Scholar
  18. 18.
    Billiau AD, Loop M, Le PQ, Berthet F, Philippet P, Kasran A, Wouters CH. Etanercept improves linear growth and bone mass acquisition in MTX-resistant polyarticular-course juvenile idiopathic arthritis. Rheumatology (Oxford). 2010;49:1550–8.CrossRefGoogle Scholar
  19. 19.
    Simonini G, Giani T, Stagi S, de Martino M, Falcini F. Bone status over 1 yr of etanercept treatment in juvenile idiopathic arthritis. Rheumatology (Oxford). 2005;44:777–80.CrossRefGoogle Scholar
  20. 20.
    Griffin LM, Thayu M, Baldassano RN, DeBoer MD, Zemel BS, Denburg MR, Denson LA, Shults J, Herskovitz R, Long J, Leonard MB. Improvements in bone density and structure during anti-TNF-alpha therapy in pediatric Crohn’s disease. J Clin Endocrinol Metab. 2015;100:2630–9.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Canalis E, Mazziotti G, Giustina A, Bilezikian JP. Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporos Int. 2007;18:1319–28.PubMedCrossRefGoogle Scholar
  22. 22.
    King WM, Ruttencutter R, Nagaraja HN, Matkovic V, Landoll J, Hoyle C, Mendell JR, Kissel JT. Orthopedic outcomes of long-term daily corticosteroid treatment in Duchenne muscular dystrophy. Neurology. 2007;68:1607–13.PubMedCrossRefGoogle Scholar
  23. 23.
    Halton J, Gaboury I, Grant R, Alos N, et al., Canadian STOPP Consortium. 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;24:1326–1334.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Feber J, Gaboury I, Ni A, Alos N, et al. Skeletal findings in children recently initiating glucocorticoids for the treatment of nephrotic syndrome. Osteoporos Int. 2012;23:751–60.PubMedCrossRefGoogle Scholar
  25. 25.
    Huber AM, Gaboury I, Cabral DA, Lang B, et al. Prevalent vertebral fractures among children initiating glucocorticoid therapy for the treatment of rheumatic disorders. Arthritis Care Res (Hoboken). 2010;62:516–26.CrossRefGoogle Scholar
  26. 26.
    Alos N, Grant RM, Ramsay T, Halton J, et al. High incidence of vertebral fractures in children with acute lymphoblastic leukemia 12 months after the initiation of therapy. J Clin Oncol Off J Am Soc Clin Oncol. 2012;30:2760–7.CrossRefGoogle Scholar
  27. 27.
    Phan V, Blydt-Hansen T, Feber J, Alos N, et al. Skeletal findings in the first 12 months following initiation of glucocorticoid therapy for pediatric nephrotic syndrome. Osteoporos Int. 2014;25:627–37.PubMedCrossRefGoogle Scholar
  28. 28.
    Rodd C, Lang B, Ramsay T, Alos N, et al. Incident vertebral fractures among children with rheumatic disorders 12 months after glucocorticoid initiation: a national observational study. Arthritis Care Res. 2012;64:122–31.CrossRefGoogle Scholar
  29. 29.
    Kilpinen-Loisa P, Paasio T, Soiva M, Ritanen UM, Lautala P, Palmu P, Pihko H, Makitie O. Low bone mass in patients with motor disability: prevalence and risk factors in 59 Finnish children. Dev Med Child Neurol. 2010;52:276–82.PubMedCrossRefGoogle Scholar
  30. 30.
    Bishop N, Arundel P, Clark E, Dimitri P, Farr J, Jones G, Makitie O, Munns CF, Shaw N. Fracture prediction and the definition of osteoporosis in children and adolescents: the ISCD 2013 pediatric official positions. J Clin Densitom. 2014;17:275–80.PubMedCrossRefGoogle Scholar
  31. 31.
    Hogler W, Wehl G, van Staa T, Meister B, Klein-Franke A, Kropshofer G. Incidence of skeletal complications during treatment of childhood acute lymphoblastic leukemia: comparison of fracture risk with the general practice research database. Pediatr Blood Cancer. 2007;48:21–7.PubMedCrossRefGoogle Scholar
  32. 32.
    van Staa TP, Cooper C, Leufkens HG, Bishop N. Children and the risk of fractures caused by oral corticosteroids. J Bone Miner Res. 2003;18:913–8.PubMedCrossRefGoogle Scholar
  33. 33.
    Baty JM, Vogt EC. Bone changes of leukemia in children. Am J Roentgenol. 1935;34:310–3.Google Scholar
  34. 34.
    Helenius I, Remes V, Salminen S, Valta H, 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;21:380–7.PubMedCrossRefGoogle Scholar
  35. 35.
    Valta H, Jalanko H, Holmberg C, Helenius I, Makitie O. Impaired bone health in adolescents after liver transplantation. Am J Transplant. 2008;8:150–7.PubMedGoogle Scholar
  36. 36.
    Valta H, Makitie O, Ronnholm K, Jalanko H. Bone health in children and adolescents after renal transplantation. J Bone Miner Res. 2009;24:1699–708.PubMedCrossRefGoogle Scholar
  37. 37.
    Vautour LM, Melton LJ 3rd, Clarke BL, Achenbach SJ, Oberg AL, McCarthy JT. Long-term fracture risk following renal transplantation: a population-based study. Osteoporos Int. 2004;15:160–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Henderson RC, Berglund LM, May R, Zemel BS, 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;25:520–6.PubMedCrossRefGoogle Scholar
  39. 39.
    Dennison E, Cooper C. Epidemiology of osteoporotic fractures. Horm Res. 2000;54(Suppl 1):58–63.PubMedCrossRefGoogle Scholar
  40. 40.
    McAdam LC, Rastogi A, Macleod K, Douglas Biggar W. Fat embolism syndrome following minor trauma in Duchenne muscular dystrophy. Neuromuscul Disord. 2012;22:1035–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Medeiros MO, Behrend C, King W, Sanders J, Kissel J, Ciafaloni E. Fat embolism syndrome in patients with Duchenne muscular dystrophy. Neurol. 2013;80:1350–2.CrossRefGoogle Scholar
  42. 42.
    Gordon KE, Dooley JM, Sheppard KM, MacSween J, Esser MJ. Impact of bisphosphonates on survival for patients with Duchenne muscular dystrophy. Pediatrics. 2011;127:e353–8.PubMedCrossRefGoogle Scholar
  43. 43.
    Nelson DA, Kleerekoper M, Peterson EL. Reversal of vertebral deformities in osteoporosis: measurement error or “rebound”? J Bone Miner Res. 1994;9:977–82.PubMedCrossRefGoogle Scholar
  44. 44.
    Sbrocchi AM, Rauch F, Jacob P, McCormick A, McMillan HJ, Matzinger MA, Ward LM. The use of intravenous bisphosphonate therapy to treat vertebral fractures due to osteoporosis among boys with Duchenne muscular dystrophy. Osteoporos Int. 2012;23:2703–11.PubMedCrossRefGoogle Scholar
  45. 45.
    Mostoufi-Moab S, Brodsky J, Isaacoff EJ, Tsampalieros A, Ginsberg JP, Zemel B, Shults J, Leonard MB. Longitudinal assessment of bone density and structure in childhood survivors of acute lymphoblastic leukemia without cranial radiation. J Clin Endocrinol Metab. 2012;97:3584–92.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Marinovic D, Dorgeret S, Lescoeur B, Alberti C, Noel M, Czernichow P, Sebag G, Vilmer E, Leger J. Improvement in bone mineral density and body composition in survivors of childhood acute lymphoblastic leukemia: a 1-year prospective study. Pediatrics. 2005;116:e102–8.PubMedCrossRefGoogle Scholar
  47. 47.
    Gurney JG, Kaste SC, Liu W, Srivastava DK, 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;61:1270–6.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Makitie O, Heikkinen R, Toiviainen-Salo S, Henriksson M, Puukko-Viertomies LR, Jahnukainen K. Long-term skeletal consequences of childhood acute lymphoblastic leukemia in adult males: a cohort study. Eur J Endocrinol. 2013;168:281–8.PubMedCrossRefGoogle Scholar
  49. 49.
    Burger H, Van Daele PL, Grashuis K, Hofman A, Grobbee DE, Schutte HE, Birkenhager JC, Pols HA. Vertebral deformities and functional impairment in men and women. J Bone Miner Res. 1997;12:152–7.PubMedCrossRefGoogle Scholar
  50. 50.
    Nevitt MC, Ettinger B, Black DM, Stone K, Jamal SA, Ensrud K, Segal M, Genant HK, Cummings SR. The association of radiographically detected vertebral fractures with back pain and function: a prospective study. Ann Intern Med. 1998;128:793–800.PubMedCrossRefGoogle Scholar
  51. 51.
    Kerkeni S, Kolta S, Fechtenbaum J, Roux C. Spinal deformity index (SDI) is a good predictor of incident vertebral fractures. Osteoporos Int. 2009;20:1547–52.PubMedCrossRefGoogle Scholar
  52. 52.
    Kocks J, Ward K, Mughal Z, Moncayo R, Adams J, Hogler W. Z-score comparability of bone mineral density reference databases for children. J Clin Endocrinol Metab. 2010;95:4652–9.PubMedCrossRefGoogle Scholar
  53. 53.
    Leonard MB, Propert KJ, Zemel BS, Stallings VA, Feldman HI. Discrepancies in pediatric bone mineral density reference data: potential for misdiagnosis of osteopenia. J Pediatr. 2010;135:182–8.CrossRefGoogle Scholar
  54. 54.
    Ma J, Siminoski K, Alos N, Halton J, 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;100:1018–27.PubMedCrossRefGoogle Scholar
  55. 55.
    Genant HK, CY W, van Kuijk C, Nevitt MC. Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res. 1993;8:1137–48.PubMedCrossRefGoogle Scholar
  56. 56.
    Grigoryan M, Guermazi A, Roemer FW, Delmas PD, Genant HK. Recognizing and reporting osteoporotic vertebral fractures. Eur Spine J. 2003;12(Suppl 2):S104–12.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Eastell R, Cedel SL, Wahner HW, Riggs BL, Melton LJ 3rd. Classification of vertebral fractures. J Bone Miner Res. 1991;6:207–15.PubMedCrossRefGoogle Scholar
  58. 58.
    Palomo T, Fassier F, Ouellet J, Sato A, Montpetit K, Glorieux FH, Rauch F. Intravenous bisphosphonate therapy of young children with osteogenesis imperfecta: skeletal findings during follow up throughout the growing years. J Bone Miner Res. 2015;30(12):2150–7.PubMedCrossRefGoogle Scholar
  59. 59.
    Genant HK, Jergas M, Palermo L, Nevitt M, Valentin RS, Black D, Cummings SR. 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. 1996;11:984–96.PubMedCrossRefGoogle Scholar
  60. 60.
    Siminoski K, Lentle B, Matzinger MA, Shenouda N, Ward LM. Observer agreement in pediatric semiquantitative vertebral fracture diagnosis. Pediatr Radiol. 2014;44:457–66.PubMedCrossRefGoogle Scholar
  61. 61.
    Adachi JD, Olszynski WP, Hanley DA, Hodsman AB, et al. Management of corticosteroid-induced osteoporosis. Semin Arthritis Rheum. 2000;29:228–51.PubMedCrossRefGoogle Scholar
  62. 62.
    Vallarta-Ast N, Krueger D, Wrase C, Agrawal S, Binkley N. An evaluation of densitometric vertebral fracture assessment in men. Osteoporos Int. 2007;18:1405–10.PubMedCrossRefGoogle Scholar
  63. 63.
    Spiegel LR, Schneider R, Lang BA, Birdi N, Silverman ED, Laxer RM, Stephens D, Feldman BM. Early predictors of poor functional outcome in systemic-onset juvenile rheumatoid arthritis: a multicenter cohort study. Arthritis Rheum. 2000;43:2402–9.PubMedCrossRefGoogle Scholar
  64. 64.
    Siminoski K, Lee KC, Jen H, Warshawski R, et al. Anatomical distribution of vertebral fractures: comparison of pediatric and adult spines. Osteoporos Int. 2012;23:1999–2008.PubMedCrossRefGoogle Scholar
  65. 65.
    Buehring B, Krueger D, Checovich M, Gemar D, Vallarta-Ast N, Genant HK, Binkley N. Vertebral fracture assessment: impact of instrument and reader. Osteoporos Int. 2010;21:487–94.PubMedCrossRefGoogle Scholar
  66. 66.
    Mayranpaa MK, Helenius I, Valta H, Mayranpaa MI, Toiviainen-Salo S, Makitie O. Bone densitometry in the diagnosis of vertebral fractures in children: accuracy of vertebral fracture assessment. Bone. 2007;41:353–9.PubMedCrossRefGoogle Scholar
  67. 67.
    Glorieux FH, Travers R, Taylor A, Bowen JR, Rauch F, Norman M, Parfitt AM. Normative data for iliac bone histomorphometry in growing children. Bone. 2000;26:103–9.PubMedCrossRefGoogle Scholar
  68. 68.
    Bacchetta J, Wesseling-Perry K, Gilsanz V, Gales B, Pereira RC, Salusky IB. Idiopathic juvenile osteoporosis: a cross-sectional single-centre experience with bone histomorphometry and quantitative computed tomography. Pediatr Rheumatol Online J. 2013;11:6.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Rauch F. Bone biopsy: indications and methods. Endocr Dev. 2009;16:49–57.PubMedCrossRefGoogle Scholar
  70. 70.
    Crabtree NJ, Arabi A, Bachrach LK, Fewtrell M, El-Hajj Fuleihan G, Kecskemethy HH, Jaworski M, Gordon CM. Dual-energy X-ray absorptiometry interpretation and reporting in children and adolescents: the revised 2013 ISCD pediatric official positions. J Clin Densitom. 2014;17:225–42.PubMedCrossRefGoogle Scholar
  71. 71.
    Zemel BS, Stallings VA, Leonard MB, Paulhamus DR, Kecskemethy HH, Harcke HT, Henderson RC. Revised pediatric reference data for the lateral distal femur measured by Hologic discovery/Delphi dual-energy X-ray absorptiometry. J Clin Densitom. 2009;12:207–18.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Greulich WW, Pyle SI. Radiographic atlas of skeletal development of the hand and wrist. 2nd ed. Stanford: Stanford University Press; 1959.Google Scholar
  73. 73.
    Kroger H, Kotaniemi A, Vainio P, Alhava E. Bone densitometry of the spine and femur in children by dual-energy x-ray absorptiometry. Bone Miner. 1992;17:75–85.PubMedCrossRefGoogle Scholar
  74. 74.
    Zemel BS, Kalkwarf HJ, Gilsanz V, Lappe JM, 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;96:3160–9.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Crabtree NJ, Hogler W, Cooper MS, Shaw NJ. Diagnostic evaluation of bone densitometric size adjustment techniques in children with and without low trauma fractures. Osteoporos Int. 2013;24:2015–24.PubMedCrossRefGoogle Scholar
  76. 76.
    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;147:791–6.PubMedCrossRefGoogle Scholar
  77. 77.
    Hogler W, Shaw N. Childhood growth hormone deficiency, bone density, structures and fractures: scrutinizing the evidence. Clin Endocrinol (Oxf). 2010;72:281–9.CrossRefGoogle Scholar
  78. 78.
    Vasikaran S, Cooper C, Eastell R, Griesmacher A, Morris HA, Trenti T, Kanis JA. International Osteoporosis Foundation and International Federation of Clinical Chemistry and Laboratory Medicine position on bone marker standards in osteoporosis. Clin Chem Lab Med. 2011;49:1271–4.PubMedCrossRefGoogle Scholar
  79. 79.
    Rauchenzauner M, Schmid A, Heinz-Erian P, Kapelari K, Falkensammer G, Griesmacher A, Finkenstedt G, Hogler W. 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. 2007;92:443–9.PubMedCrossRefGoogle Scholar
  80. 80.
    Bayer M. Reference values of osteocalcin and procollagen type I N-propeptide plasma levels in a healthy Central European population aged 0-18 years. Osteoporos Int. 2014;25:729–36.PubMedCrossRefGoogle Scholar
  81. 81.
    Morovat A, Catchpole A, Meurisse A, Carlisi A, Bekaert AC, Rousselle O, Paddon M, James T, Cavalier E. IDS iSYS automated intact procollagen-1-N-terminus pro-peptide assay: method evaluation and reference intervals in adults and children. Clin Chem Lab Med. 2013;51:2009–18.PubMedCrossRefGoogle Scholar
  82. 82.
    Huang Y, Eapen E, Steele S, Grey V. Establishment of reference intervals for bone markers in children and adolescents. Clin Biochem. 2011;44:771–8.PubMedCrossRefGoogle Scholar
  83. 83.
    Rauch F, Plotkin H, Travers R, Zeitlin L, Glorieux FH. Osteogenesis imperfecta types I, III, and IV: effect of pamidronate therapy on bone and mineral metabolism. J Clin Endocrinol Metab. 2003;88:986–92.PubMedCrossRefGoogle Scholar
  84. 84.
    Rauch F, Travers R, Plotkin H, Glorieux FH. The effects of intravenous pamidronate on the bone tissue of children and adolescents with osteogenesis imperfecta. J Clin Invest. 2002;110:1293–9.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    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;21:331–7.PubMedCrossRefGoogle Scholar
  86. 86.
    Hartikka H, Makitie O, Mannikko M, Doria AS, Daneman A, Cole WG, Ala-Kokko L, Sochett EB. Heterozygous mutations in the LDL receptor-related protein 5 (LRP5) gene are associated with primary osteoporosis in children. J Bone Miner Res. 2005;20:783–9.PubMedCrossRefGoogle Scholar
  87. 87.
    Fahiminiya S, Majewski J, Roughley P, Roschger P, Klaushofer K, Rauch F. Whole-exome sequencing reveals a heterozygous LRP5 mutation in a 6-year-old boy with vertebral compression fractures and low trabecular bone density. Bone. 2013;57:41–6.PubMedCrossRefGoogle Scholar
  88. 88.
    Whyte MP, Greenberg CR, Salman NJ, Bober MB, et al. Enzyme-replacement therapy in life-threatening hypophosphatasia. NEJM. 2012;366:904–13.PubMedCrossRefGoogle Scholar
  89. 89.
    Faje AT, Fazeli PK, Miller KK, Katzman DK, Ebrahimi S, Lee H, Mendes N, Snelgrove D, Meenaghan E, Misra M, Klibanski A. Fracture risk and areal bone mineral density in adolescent females with anorexia nervosa. Int J Eat Disord. 2014;47:458–66.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Marini JC, Blissett AR. New genes in bone development: what’s new in osteogenesis imperfecta. J Clin Endocrinol Metab. 2013;98:3095–103.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Sillence DO, Rimoin DL. Classification of osteogenesis imperfect. Lancet. 1978;1:1041–2.PubMedCrossRefGoogle Scholar
  92. 92.
    Palomo T, Al-Jallad H, Moffatt P, Glorieux FH, Lentle B, Roschger P, Klaushofer K, Rauch F. Skeletal characteristics associated with homozygous and heterozygous WNT1 mutations. Bone. 2014;67:63–70.PubMedCrossRefGoogle Scholar
  93. 93.
    Mitchell PJ, Cooper C, Dawson-Hughes B, Gordon CM, Rizzoli R. Life-course approach to nutrition. Osteoporos Int. 2005;26:2723–42.CrossRefGoogle Scholar
  94. 94.
    Specker B, Thiex NW, Sudhagoni RG. Does exercise influence Pediatric bone? A systematic review. Clin Orthop Relat Res. 2015;473:3658–72.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Golden NH, Abrams SA. Optimizing bone health in children and adolescents. Pediatrics. 2014;134:e1229–43.PubMedCrossRefGoogle Scholar
  96. 96.
    Abrams SA, Coss-Bu JA, Tiosano D, Vitamin D. Effects on childhood health and disease. Nat Rev Endocrinol. 2013;9:162–70.PubMedCrossRefGoogle Scholar
  97. 97.
    Julian-Almarcegui C, Gomez-Cabello A, Huybrechts I, Gonzalez-Aguero A, Kaufman JM, Casajus JA, Vicente-Rodriguez G. Combined effects of interaction between physical activity and nutrition on bone health in children and adolescents: a systematic review. Nutr Rev. 2015;73:127–39.PubMedCrossRefGoogle Scholar
  98. 98.
    Handel MN, Heitmann BL, Abrahamsen B. Nutrient and food intakes in early life and risk of childhood fractures: a systematic review and meta-analysis. Am J Clin Nutr. 2015;102:1182–95.PubMedCrossRefGoogle Scholar
  99. 99.
    Tan VP, Macdonald HM, Kim S, Nettlefold L, Gabel L, Ashe MC, McKay HA. Influence of physical activity on bone strength in children and adolescents: a systematic review and narrative synthesis. J Bone Miner Res. 2014;29:2161–81.PubMedCrossRefGoogle Scholar
  100. 100.
    Institute of Medicine. Dietary reference intakes for calcium and vitamin D. Washington, DC: The National Academies Press; 2011.Google Scholar
  101. 101.
    Misra M, Pacaud D, Petryk A, Collett-Solberg PF, Kappy M, Vitamin D. Deficiency in children and its management: review of current knowledge and recommendations. Pediatrics. 2008;122:398–417.PubMedCrossRefGoogle Scholar
  102. 102.
    Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:1911–30.PubMedCrossRefGoogle Scholar
  103. 103.
    Winzenberg T, Powell S, Shaw KA, Jones G. Effects of vitamin D supplementation on bone density in healthy children: systematic review and meta-analysis. BMJ. 2011;342:c7254.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Edouard T, Glorieux FH, Rauch F. Predictors and correlates of vitamin D status in children and adolescents with osteogenesis imperfecta. J Clin Endocrinol Metab. 2011;96:31930–8.Google Scholar
  105. 105.
    Benchimol EI, Ward LM, Gallagher JC, Rauch F, Barrowman N, Warren J, Beedle S, Mack DR. Effect of calcium and vitamin D supplementation on bone mineral density in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 2007;45:538–45.PubMedCrossRefGoogle Scholar
  106. 106.
    Kaste SC, Qi A, Smith K, Surprise H, et al. 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. 2014;61:885–93.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JP. Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ. 2014;348:g2035.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Mandel K, Atkinson S, Barr RD, Pencharz P. Skeletal morbidity in childhood acute lymphoblastic leukemia. J Clin Oncol. 2004;22:1215–21.PubMedCrossRefGoogle Scholar
  109. 109.
    Kalayci AG, Kansu A, Girgin N, Kucuk O, Aras G. Bone mineral density and importance of a gluten-free diet in patients with celiac disease in childhood. Pediatrics. 2001;108:E89.PubMedCrossRefGoogle Scholar
  110. 110.
    Avgeri M, Papadopoulou A, Platokouki H, Douros K, Rammos S, Nicolaidou P, Aronis S. Assessment of bone mineral density and markers of bone turnover in children under long-term oral anticoagulant therapy. J Pediatr Hematol Oncol. 2008;30:592–7.PubMedCrossRefGoogle Scholar
  111. 111.
    Modesto W, Bahamondes MV, Bahamondes L. Prevalence of low bone mass and osteoporosis in long-term users of the injectable contraceptive depot medroxyprogesterone acetate. J Womens Health (Larchmt). 2015;24:636–40.CrossRefGoogle Scholar
  112. 112.
    Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Vance ML. Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:1587–609.PubMedCrossRefGoogle Scholar
  113. 113.
    Bodor M, McDonald CM. Why short stature is beneficial in Duchenne muscular dystrophy. Muscle Nerve. 2013;48:336–42.PubMedCrossRefGoogle Scholar
  114. 114.
    Dubner SE, Shults J, Baldassano RN, Zemel BS, Thayu M, Burnham JM, Herskovitz RM, Howard KM, Leonard MB. Longitudinal assessment of bone density and structure in an incident cohort of children with Crohn’s disease. Gastroenterology. 2009;136:123–30.PubMedCrossRefGoogle Scholar
  115. 115.
    Dwan K, Phillipi CA, Steiner RD, Basel D. Bisphosphonate therapy for osteogenesis imperfecta. Cochrane Database Syst Rev. 2014;(7):CD005088.Google Scholar
  116. 116.
    Ward L, Tricco AC, Phuong P, Cranney A, Barrowman N, Gaboury I, Rauch F, Tugwell P, Moher D. Bisphosphonate therapy for children and adolescents with secondary osteoporosis. Cochrane Database Syst Rev. 2007;(4):CD005324.Google Scholar
  117. 117.
    Ward LM, Rauch F. Oral bisphosphonates for paediatric osteogenesis imperfecta? Lancet. 2013;282:1388–9.CrossRefGoogle Scholar
  118. 118.
    Glorieux FH, Bishop NJ, Plotkin H, Chabot G, Lanoue G, Travers R. Cyclic administration of pamidronate in children with severe osteogenesis imperfecta. NEJM. 1998;339:947–52.PubMedCrossRefGoogle Scholar
  119. 119.
    Barros ER, Saraiva GL, de Oliveira TP, Lazaretti-Castro M. Safety and efficacy of a 1-year treatment with zoledronic acid compared with pamidronate in children with osteogenesis imperfecta. J Pediatr Endocrinol Metab. 2012;25:485–91.PubMedCrossRefGoogle Scholar
  120. 120.
    Grey A, Bolland M, Wattie D, Horne A, Gamble G, Reid IR. Prolonged antiresorptive activity of zoledronate: a randomized, controlled trial. J Bone Miner Res. 2010;25:2251–5.PubMedCrossRefGoogle Scholar
  121. 121.
    Ward LM, Denker AE, Porras A, Shugarts S, Kline W, Travers R, Mao C, Rauch F, Maes A, Larson P, Deutsch P, Glorieux FH. 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. 2005;90:4051–6.PubMedCrossRefGoogle Scholar
  122. 122.
    Golden NH, Iglesias EA, Jacobson MS, Carey D, Meyer W, Schebendach J, Hertz S, Shenker IR. Alendronate for the treatment of osteopenia in anorexia nervosa: a randomized, double-blind, placebo-controlled trial. J Clin Endocrinol Metab. 2005;90:3179–85.PubMedCrossRefGoogle Scholar
  123. 123.
    Bishop N, Adami S, Ahmed SF, Anton J, et al. Risedronate in children with osteogenesis imperfecta: a randomised, double-blind, placebo-controlled trial. Lancet. 2013;382:1424–32.PubMedCrossRefGoogle Scholar
  124. 124.
    Rauch F, Munns CF, Land C, Cheung M, Glorieux FH. Risedronate in the treatment of mild pediatric osteogenesis imperfecta: a randomized placebo-controlled study. J Bone Miner Res Off J Am Soc Bone Miner Res. 2009;24:1282–9.CrossRefGoogle Scholar
  125. 125.
    Bianchi ML, Colombo C, Assael BM, Dubini A, et al. 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. 2013;1:377–85.PubMedCrossRefGoogle Scholar
  126. 126.
    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. Rheumatol (Oxford). 2005;44:813–8.CrossRefGoogle Scholar
  127. 127.
    Gatti D, Antoniazzi F, Prizzi R, Braga V, Rossini M, Tato L, Viapiana O, Adami S. Intravenous neridronate in children with osteogenesis imperfecta: a randomized controlled study. J Bone Miner Res. 2005;20:758–63.PubMedCrossRefGoogle Scholar
  128. 128.
    Sakkers R, Kok D, Engelbert R, van Dongen A, Jansen M, Pruijs H, Verbout A, Schweitzer D, Uiterwaal C. Skeletal effects and functional outcome with olpadronate in children with osteogenesis imperfecta: a 2-year randomised placebo-controlled study. Lancet. 2004;363:1427–31.PubMedCrossRefGoogle Scholar
  129. 129.
    Ward LM, Rauch F, Whyte MP, D’Astous J, et al. Alendronate for the treatment of pediatric osteogenesis imperfecta: a randomized placebo-controlled study. J Clin Endocrinol Metab. 2011;96:355–64.PubMedCrossRefGoogle Scholar
  130. 130.
    Munns CF, Rauch F, Travers R, Glorieux FH. Effects of intravenous pamidronate treatment in infants with osteogenesis imperfecta: clinical and histomorphometric outcome. J Bone Miner Res. 2005;20:1235–43.PubMedCrossRefGoogle Scholar
  131. 131.
    Land C, Rauch F, Munns CF, Sahebjam S, Glorieux FH. Vertebral morphometry in children and adolescents with osteogenesis imperfecta: effect of intravenous pamidronate treatment. Bone. 2006;39:901–6.PubMedCrossRefGoogle Scholar
  132. 132.
    Antoniazzi F, Zamboni G, Lauriola S, Donadi L, Adami S, Tato L. Early bisphosphonate treatment in infants with severe osteogenesis imperfecta. J Pediatr. 2006;149:174–9.PubMedCrossRefGoogle Scholar
  133. 133.
    Astrom E, Jorulf H, Soderhall S. Intravenous pamidronate treatment of infants with severe osteogenesis imperfecta. Arch Dis Child. 2007;92:332–8.PubMedCrossRefGoogle Scholar
  134. 134.
    Ward LM, Glorieux FH, Rauch F, Verbruggen N, Heyden N, Lombardi AA. Randomized, placebo-controlled trial of oral alendronate in children and adolescents with osteogenesis imperfecta. Bone. 2005;36:0–18.Google Scholar
  135. 135.
    Rauch F, Munns C, Land C, Glorieux FH. Pamidronate in children and adolescents with osteogenesis imperfecta: effect of treatment discontinuation. J Clin Endocrinol Metab. 2006;91:1268–74.PubMedCrossRefGoogle Scholar
  136. 136.
    Land C, Rauch F, Montpetit K, Ruck-Gibis J, Glorieux FH. Effect of intravenous pamidronate therapy on functional abilities and level of ambulation in children with osteogenesis imperfecta. J Pediatr. 2006;148:456–60.PubMedCrossRefGoogle Scholar
  137. 137.
    Zeitlin L, Rauch F, Plotkin H, Glorieux FH. 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. 2003;111:1030–6.PubMedCrossRefGoogle Scholar
  138. 138.
    Vuorimies I, Toiviainen-Salo S, Hero M, Makitie O. Zoledronic acid treatment in children with osteogenesis imperfecta. Horm Res Paediatr. 2011;75:346–53.PubMedCrossRefGoogle Scholar
  139. 139.
    Ooi HL, Briody J, Biggin A, Cowell CT, Munns CF. Intravenous zoledronic acid given every 6 months in childhood osteoporosis. Horm Res Paediatr. 2013;80:179–84.PubMedCrossRefGoogle Scholar
  140. 140.
    Gandrud LM, Cheung JC, Daniels MW, Bachrach LK. Low-dose intravenous pamidronate reduces fractures in childhood osteoporosis. J Pediatr Endocrinol Metab. 2003;16:887–92.PubMedCrossRefGoogle Scholar
  141. 141.
    Steelman J, Zeitler P. Treatment of symptomatic pediatric osteoporosis with cyclic single-day intravenous pamidronate infusions. J Pediatr. 2003;142:417–23.PubMedCrossRefGoogle Scholar
  142. 142.
    Whyte MP, Wenkert D, Clements KL, McAlister WH, Mumm S. Bisphosphonate-induced osteopetrosis. NEJM. 2003;349:457–63.PubMedCrossRefGoogle Scholar
  143. 143.
    Rauch F, Cornibert S, Cheung M, Glorieux FH. Long-bone changes after pamidronate discontinuation in children and adolescents with osteogenesis imperfecta. Bone. 2007;40:821–7.PubMedCrossRefGoogle Scholar
  144. 144.
    Biggin A, Briody JN, Ormshaw E, Wong KK, Bennetts BH, Munns CF. Fracture during intravenous bisphosphonate treatment in a child with osteogenesis imperfecta: an argument for a more frequent, low-dose treatment regimen. Horm Res Paediatr. 2014;81:204–10.PubMedCrossRefGoogle Scholar
  145. 145.
    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;83:183–9.PubMedCrossRefGoogle Scholar
  146. 146.
    Brown JP, Morin S, Leslie W, Papaioannou A, et al. Bisphosphonates for treatment of osteoporosis: expected benefits, potential harms, and drug holidays. Can Fam Physician. 2014;60:324–33.PubMedPubMedCentralGoogle Scholar
  147. 147.
    Unal E, Abaci A, Bober E, Buyukgebiz A. Efficacy and safety of oral alendronate treatment in children and adolescents with osteoporosis. J Pediatr Endocrinol Metab. 2006;19:523–80.PubMedGoogle Scholar
  148. 148.
    Khosla S, Burr D, Cauley J, Dempster DW, et al. Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2007;22:1479–91.PubMedCrossRefGoogle Scholar
  149. 149.
    Malmgren B, Astrom E, Soderhall S. No osteonecrosis in jaws of young patients with osteogenesis imperfecta treated with bisphosphonates. J Oral Pathol Med. 2008;37:196–200.PubMedCrossRefGoogle Scholar
  150. 150.
    Chahine C, Cheung MS, Head TW, Schwartz S, Glorieux FH, Rauch F. Tooth extraction socket healing in pediatric patients treated with intravenous pamidronate. J Pediatr. 2008;153:719–20.PubMedCrossRefGoogle Scholar
  151. 151.
    Brown JJ, Ramalingam L, Zacharin MR. Bisphosphonate-associated osteonecrosis of the jaw: does it occur in children? Clin Endocrinol. 2008;68:863–7.CrossRefGoogle Scholar
  152. 152.
    Bhatt RN, Hibbert SA, Munns CF. The use of bisphosphonates in children: review of the literature and guidelines for dental management. Aust Dent J. 2014;59:9–19.PubMedCrossRefGoogle Scholar
  153. 153.
    Shane E, Burr D, Abrahamsen B, Adler RA, et al. 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. 2014;29:1–23.PubMedCrossRefGoogle Scholar
  154. 154.
    Hegazy A, Kenawey M, Sochett E, Tile L, Cheung AM, Howard AW. Unusual femur stress fractures in children with osteogenesis imperfecta and intramedullary rods on long-term intravenous pamidronate therapy. J Pediatr Orthop. 2016;36(7):757–61.PubMedCrossRefGoogle Scholar
  155. 155.
    Munns CF, Rauch F, Zeitlin L, Fassier F, Glorieux FH. Delayed osteotomy but not fracture healing in pediatric osteogenesis imperfecta patients receiving pamidronate. J Bone Miner Res. 2004;19:1779–86.PubMedCrossRefGoogle Scholar
  156. 156.
    Anam EA, Rauch F, Glorieux FH, Fassier F, Hamdy R. Osteotomy healing in children with osteogenesis imperfecta receiving bisphosphonate treatment. J Bone Miner Res. 2015;30:1362–8.PubMedCrossRefGoogle Scholar
  157. 157.
    Papapoulos SE, Cremers SC. Prolonged bisphosphonate release after treatment in children. NEJM. 2007;356:1075–6.PubMedCrossRefGoogle Scholar
  158. 158.
    Djokanovic N, Klieger-Grossmann C, Koren G. Does treatment with bisphosphonates endanger the human pregnancy? J Obstet Gynaecol Can. 2008;30:1146–8.PubMedCrossRefGoogle Scholar
  159. 159.
    Green SB, Pappas AL. Effects of maternal bisphosphonate use on fetal and neonatal outcomes. Am J Health Syst Pharm. 2014;71:2029–36.PubMedCrossRefGoogle Scholar
  160. 160.
    Levy S, Fayez I, Taguchi N, Han JY, Aiello J, Matsui D, Moretti M, Koren G, Ito S. Pregnancy outcome following in utero exposure to bisphosphonates. Bone. 2009;44:428–30.PubMedCrossRefGoogle Scholar
  161. 161.
    Munns CF, Rauch F, Ward L, Glorieux FH. Maternal and fetal outcome after long-term pamidronate treatment before conception: a report of two cases. J Bone Miner Res. 2004;19:1742–5.PubMedCrossRefGoogle Scholar
  162. 162.
    Eghbali-Fatourechi G, Khosla S, Sanyal A, Boyle WJ, Lacey DL, Riggs BL. Role of RANK ligand in mediating increased bone resorption in early postmenopausal women. J Clin Invest. 2003;111:1221–30.PubMedPubMedCentralCrossRefGoogle Scholar
  163. 163.
    Kostenuik PJ, Nguyen HQ, McCabe J, Warmington KS, et al. 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. 2009;24:182–95.PubMedCrossRefGoogle Scholar
  164. 164.
    Hofbauer LC, Zeitz U, Schoppet M, Skalicky M, Schuler C, Stolina M, Kostenuik PJ, Erben RG. Prevention of glucocorticoid-induced bone loss in mice by inhibition of RANKL. Arthritis Rheum. 2009;60:1427–37.PubMedCrossRefGoogle Scholar
  165. 165.
    Dempster DW, Lambing CL, Kostenuik PJ, Grauer A. Role of RANK ligand and denosumab, a targeted RANK ligand inhibitor, in bone health and osteoporosis: a review of preclinical and clinical data. Clinical Ther. 2012;34:521–36.CrossRefGoogle Scholar
  166. 166.
    Semler O, Netzer C, Hoyer-Kuhn H, Becker J, Eysel P, Schoenau E. First use of the RANKL antibody denosumab in osteogenesis imperfecta type VI. J Musculoskelet Neuronal Interact. 2012;12:183–8.PubMedGoogle Scholar
  167. 167.
    Karras NA, Polgreen LE, Ogilvie C, Manivel JC, Skubitz KM, Lipsitz E. Denosumab treatment of metastatic giant-cell tumor of bone in a 10-year-old girl. J Clin Oncol. 2013;31:e200–2.PubMedPubMedCentralCrossRefGoogle Scholar
  168. 168.
    Lange T, Stehling C, Frohlich B, Klingenhofer M, et al. Denosumab: a potential new and innovative treatment option for aneurysmal bone cysts. Eur Spine J. 2013;22:1417–22.PubMedPubMedCentralCrossRefGoogle Scholar
  169. 169.
    Boyce AM, Chong WH, Yao J, Gafni RI, et al. Denosumab treatment for fibrous dysplasia. J Bone Miner Res. 2012;27:1462–70.PubMedPubMedCentralCrossRefGoogle Scholar
  170. 170.
    Wang HD, Boyce AM, Tsai JY, Gafni RI, Farley FA, Kasa-Vubu JZ, Molinolo AA, Collins MT. Effects of denosumab treatment and discontinuation on human growth plates. J Clin Endocrinol Metab. 2014;99:891–7.PubMedPubMedCentralCrossRefGoogle Scholar
  171. 171.
    Padhi D, Allison M, Kivitz AJ, Gutierrez MJ, Stouch B, Wang C, Jang G. 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. 2014;54:168–78.PubMedCrossRefGoogle Scholar
  172. 172.
    Padhi D, Jang G, Stouch B, Fang L, Posvar E. Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res. 2011;26:19–26.PubMedCrossRefGoogle Scholar
  173. 173.
    Feurer E, Chapurlat R. Emerging drugs for osteoporosis. Expert Opin Emerg Drugs. 2014;19:385–95.PubMedCrossRefGoogle Scholar
  174. 174.
    Mullard A. Merck & Co. drops osteoporosis drug odanacatib. Nat Rev Drug Discov. 2016;15:669.PubMedGoogle Scholar
  175. 175.
    Weintraub JA, Breland CE. Challenges, benefits, and factors to enhance recruitment and inclusion of children in pediatric dental research. Int J Paediatr Dent. 2015;25:310–6.PubMedPubMedCentralCrossRefGoogle Scholar
  176. 176.
    Makitie O, Doria AS, Henriques F, Cole WG, Compeyrot S, Silverman E, Laxer R, Daneman A, Sochett EB. Radiographic vertebral morphology: a diagnostic tool in pediatric osteoporosis. J Pediatr. 2005;146:395–401.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Pediatrics, Pediatric Bone HealthUniversity of OttawaOttawaCanada
  2. 2.Pediatrics, Division of Endocrinology and MetabolismChildren’s Hospital of Eastern OntarioOttawaCanada
  3. 3.School of Epidemiology, Public Health and Preventive MedicineUniversity of OttawaOttawaCanada
  4. 4.Children’s Hospital of Eastern Ontario Research InstituteOttawaCanada

Personalised recommendations