Advertisement

Treatment of Adolescent Osteoporosis

  • Monica Grover
  • Laura K. Bachrach
Chapter

Abstract

The diagnosis and management of osteoporosis in adolescents differ in several ways from the care of older adults. The diagnosis cannot be based upon low bone mineral density alone. The criteria for osteoporosis in a pediatric patient include a low trauma vertebral fracture or low bone density for age and a significant fracture history (2 or more long bone fractures before age 10 or 3 or more long bone fractures before age 19). Since many vertebral fractures are asymptomatic, radiographic screening is important for youth at high risk. Primary osteoporosis results from heritable disorders, whereas secondary osteoporosis is acquired as a consequence of chronic disease and the medications used for treatment. The myriad disorders linked to bone fragility share one or more common skeletal risk factors including nutritional deficits, reduced mobility, increased inflammatory cytokines, sex steroid or growth hormone deficiency, and osteotoxic drug therapy. The net result is reduced bone formation, which may be compounded by increased bone resorption. Growing children have the potential to restore bone strength if they recover from illness, whereas pharmacologic therapy may be indicated on a compassionate basis for patients with fragility fractures and limited potential to recover spontaneously. Primary care providers can play a critical role by identifying teens at risk for bone fragility, by encouraging optimal nutrition (including protein, calcium, and vitamin D) and physical activity, and by referring to physicians with expertise in pediatric osteoporosis. The goal of this chapter is to educate providers about current consensus and controversy on the use of osteoporosis drugs in adolescents.

Keywords

Pediatric osteoporosis Bisphosphonates DXA Vertebral compression fractures Denosumab 

References

  1. 1.
    Weaver CM, Gordon CM, Janz KF, Kalkwarf HJ, Lappe JM, Lewis R, et al. The National Osteoporosis Foundation’s position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations. Osteoporos Int. 2016;27(4):1281–386.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Rizzoli R, Bianchi ML, Garabédian M, McKay HA, Moreno LA. Maximizing bone mineral mass gain during growth for the prevention of fractures in the adolescents and the elderly. Bone. 2010;46(2):294–305.CrossRefPubMedGoogle Scholar
  3. 3.
    Crabtree NJ, Arabi A, Bachrach LK, Fewtrell M, El-Hajj Fuleihan G, Kecskemethy HH, et al. Dual-energy X-ray absorptiometry interpretation and reporting in children and adolescents: the revised 2013 ISCD Pediatric Official Positions. J Clin Densitom. 2014;17(2):225–42.CrossRefPubMedGoogle Scholar
  4. 4.
    Zemel BS, Leonard MB, Kelly A, Lappe JM, Gilsanz V, Oberfield S, et al. Height adjustment in assessing dual energy x-ray absorptiometry measurements of bone mass and density in children. J Clin Endocrinol Metab. 2010;95(3):1265–73.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Zemel BS, Kalkwarf HJ, Gilsanz V, Lappe JM, Oberfield S, Shepherd JA, et al. Revised reference curves for bone mineral content and areal bone mineral density according to age and sex for black and non-black children: results of the bone mineral density in childhood study. J Clin Endocrinol Metab. 2011;96(10):3160–9.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Bishop N, Arundel P, Clark E, Dimitri P, Farr J, Jones G, et al. Fracture prediction and the definition of osteoporosis in children and adolescents: the ISCD 2013 Pediatric Official Positions. J Clin Densitom. 2014;17(2):275–80.CrossRefPubMedGoogle Scholar
  7. 7.
    Gordon CM, Leonard MB, Zemel BS, Densitometry ISfC. 2013 pediatric position development conference: executive summary and reflections. J Clin Densitom. 2014;17(2):219–24.CrossRefPubMedGoogle Scholar
  8. 8.
    Stone KL, Seeley DG, Lui LY, Cauley JA, Ensrud K, Browner WS, et al. BMD at multiple sites and risk of fracture of multiple types: long-term results from the Study of Osteoporotic Fractures. J Bone Miner Res. 2003;18(11):1947–54.CrossRefPubMedGoogle Scholar
  9. 9.
    Ma J, Siminoski K, Alos N, Halton J, Ho J, Lentle B, et al. The choice of normative pediatric reference database changes spine bone mineral density Z-scores but not the relationship between bone mineral density and prevalent vertebral fractures. J Clin Endocrinol Metab. 2015;100(3):1018–27.CrossRefPubMedGoogle Scholar
  10. 10.
    Sbrocchi AM, Rauch F, Matzinger M, Feber J, Ward LM. Vertebral fractures despite normal spine bone mineral density in a boy with nephrotic syndrome. Pediatr Nephrol. 2011;26(1):139–42.CrossRefPubMedGoogle Scholar
  11. 11.
    LeBlanc CM, Ma J, Taljaard M, Roth J, Scuccimarri R, Miettunen P, et al. Incident vertebral fractures and risk factors in the first three years following glucocorticoid initiation among pediatric patients with rheumatic disorders. J Bone Miner Res. 2015;30(9):1667–75.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Stagi S, Cavalli L, Seminara S, de Martino M, Brandi ML. The ever-expanding conundrum of primary osteoporosis: aetiopathogenesis, diagnosis, and treatment. Ital J Pediatr. 2014;40:55.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Trejo P, Rauch F. Osteogenesis imperfecta in children and adolescents-new developments in diagnosis and treatment. Osteoporos Int. 2016;27(12):3427–37.CrossRefPubMedGoogle Scholar
  14. 14.
    Folkestad L, Hald JD, Ersbøll AK, Gram J, Hermann AP, Langdahl B, et al. Fracture rates and fracture sites in patients with osteogenesis imperfecta: a nationwide register-based cohort study. J Bone Miner Res. 2017;32(1):125–34.CrossRefPubMedGoogle Scholar
  15. 15.
    Bardai G, Moffatt P, Glorieux FH, Rauch F. DNA sequence analysis in 598 individuals with a clinical diagnosis of osteogenesis imperfecta: diagnostic yield and mutation spectrum. Osteoporos Int. 2016;27(12):3607–13.CrossRefPubMedGoogle Scholar
  16. 16.
    Cooper C, Dennison EM, Leufkens HG, Bishop N, van Staa TP. Epidemiology of childhood fractures in Britain: a study using the general practice research database. J Bone Miner Res. 2004;19(12):1976–81.CrossRefPubMedGoogle Scholar
  17. 17.
    Ward L, Tricco AC, Phuong P, Cranney A, Barrowman N, Gaboury I, et al. Bisphosphonate therapy for children and adolescents with secondary osteoporosis. Cochrane Database Syst Rev. 2007;4:CD005324.Google Scholar
  18. 18.
    Bianchi ML. Causes of secondary pediatric osteoporosis. Pediatr Endocrinol Rev. 2013;10(Suppl 2):424–36.PubMedGoogle Scholar
  19. 19.
    Bianchi ML, Leonard MB, Bechtold S, Högler W, Mughal MZ, Schönau E, et al. Bone health in children and adolescents with chronic diseases that may affect the skeleton: the 2013 ISCD Pediatric Official Positions. J Clin Densitom. 2014;17(2):281–94.CrossRefPubMedGoogle Scholar
  20. 20.
    Ward LM, Rauch F, Matzinger MA, Benchimol EI, Boland M, Mack DR. Iliac bone histomorphometry in children with newly diagnosed inflammatory bowel disease. Osteoporos Int. 2010;21(2):331–7.CrossRefPubMedGoogle Scholar
  21. 21.
    Huber AM, Gaboury I, Cabral DA, Lang B, Ni A, Stephure D, et al. Prevalent vertebral fractures among children initiating glucocorticoid therapy for the treatment of rheumatic disorders. Arthritis Care Res (Hoboken). 2010;62(4):516–26.CrossRefGoogle Scholar
  22. 22.
    Halton J, Gaboury I, Grant R, Alos N, Cummings EA, Matzinger M, et al. Advanced vertebral fracture among newly diagnosed children with acute lymphoblastic leukemia: results of the Canadian Steroid-Associated Osteoporosis in the Pediatric Population (STOPP) research program. J Bone Miner Res. 2009;24(7):1326–34.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Rodd C, Lang B, Ramsay T, Alos N, Huber AM, Cabral DA, et al. Incident vertebral fractures among children with rheumatic disorders 12 months after glucocorticoid initiation: a national observational study. Arthritis Care Res (Hoboken). 2012;64(1):122–31.CrossRefGoogle Scholar
  24. 24.
    Ma J, McMillan HJ, Karagüzel G, Goodin C, Wasson J, Matzinger MA, et al. The time to and determinants of first fractures in boys with Duchenne muscular dystrophy. Osteoporos Int. 2017;28(2):597–608.CrossRefPubMedGoogle Scholar
  25. 25.
    Cummings EA, Ma J, Fernandez CV, Halton J, Alos N, Miettunen PM, et al. Incident vertebral fractures in children with leukemia during the four years following diagnosis. J Clin Endocrinol Metab. 2015;100(9):3408–17.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Kerkeni S, Kolta S, Fechtenbaum J, Roux C. Spinal deformity index (SDI) is a good predictor of incident vertebral fractures. Osteoporos Int. 2009;20(9):1547–52.CrossRefPubMedGoogle Scholar
  27. 27.
    Genant HK, CY W, van Kuijk C, Nevitt MC. Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res. 1993;8(9):1137–48.CrossRefPubMedGoogle Scholar
  28. 28.
    Buehring B, Krueger D, Checovich M, Gemar D, Vallarta-Ast N, Genant HK, et al. Vertebral fracture assessment: impact of instrument and reader. Osteoporos Int. 2010;21(3):487–94.CrossRefPubMedGoogle Scholar
  29. 29.
    Offiah A, van Rijn RR, Perez-Rossello JM, Kleinman PK. Skeletal imaging of child abuse (non-accidental injury). Pediatr Radiol. 2009;39(5):461–70.CrossRefPubMedGoogle Scholar
  30. 30.
    Pai B, Shaw N. Understanding rickets. Pediatr Child Health. 2011;21(7):315–21.CrossRefGoogle Scholar
  31. 31.
    Carpenter TO. The expanding family of hypophosphatemic syndromes. J Bone Miner Metab. 2012;30(1):1–9.CrossRefPubMedGoogle Scholar
  32. 32.
    Saraff V, Narayanan VK, Lawson AJ, Shaw NJ, Preece MA, Högler W. A diagnostic algorithm for children with low alkaline phosphatase activities: lessons learned from laboratory screening for hypophosphatasia. J Pediatr. 2016;172:181–6.e1.CrossRefPubMedGoogle Scholar
  33. 33.
    Leonard MB. Glucocorticoid-induced osteoporosis in children: impact of the underlying disease. Pediatrics. 2007;119(Suppl 2):S166–74.CrossRefPubMedGoogle Scholar
  34. 34.
    Griffin LM, Thayu M, Baldassano RN, DeBoer MD, Zemel BS, Denburg MR, et al. Improvements in bone density and structure during anti-TNF-α therapy in pediatric Crohn’s disease. J Clin Endocrinol Metab. 2015;100(7):2630–9.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Billiau AD, Loop M, Le PQ, Berthet F, Philippet P, Kasran A, et al. Etanercept improves linear growth and bone mass acquisition in MTX-resistant polyarticular-course juvenile idiopathic arthritis. Rheumatology (Oxford). 2010;49(8):1550–8.CrossRefGoogle Scholar
  36. 36.
    Vahle JL, Long GG, Sandusky G, Westmore M, Ma YL, Sato M. Bone neoplasms in F344 rats given teriparatide [rhPTH(1-34)] are dependent on duration of treatment and dose. Toxicol Pathol. 2004;32(4):426–38.CrossRefPubMedGoogle Scholar
  37. 37.
    Ward LM, Konji VN, Ma J. The management of osteoporosis in children. Osteoporos Int. 2016;27(7):2147–79.CrossRefPubMedGoogle Scholar
  38. 38.
    Rauch F, Travers R, Glorieux FH. Pamidronate in children with osteogenesis imperfecta: histomorphometric effects of long-term therapy. J Clin Endocrinol Metab. 2006;91(2):511–6.CrossRefPubMedGoogle Scholar
  39. 39.
    Mostoufi-Moab S, Brodsky J, Isaacoff EJ, Tsampalieros A, Ginsberg JP, Zemel B, et al. Longitudinal assessment of bone density and structure in childhood survivors of acute lymphoblastic leukemia without cranial radiation. J Clin Endocrinol Metab. 2012;97(10):3584–92.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Phillipi CA, Remmington T, Steiner RD. Bisphosphonate therapy for osteogenesis imperfecta. Cochrane Database Syst Rev. 2008;4:CD005088.Google Scholar
  41. 41.
    Sbrocchi AM, Forget S, Laforte D, Azouz EM, Rodd C. Zoledronic acid for the treatment of osteopenia in pediatric Crohn’s disease. Pediatr Int. 2010;52(5):754–61.CrossRefPubMedGoogle Scholar
  42. 42.
    Sbrocchi AM, Rauch F, Jacob P, McCormick A, McMillan HJ, Matzinger MA, et al. The use of intravenous bisphosphonate therapy to treat vertebral fractures due to osteoporosis among boys with Duchenne muscular dystrophy. Osteoporos Int. 2012;23(11):2703–11.CrossRefPubMedGoogle Scholar
  43. 43.
    Rudge S, Hailwood S, Horne A, Lucas J, Wu F, Cundy T. Effects of once-weekly oral alendronate on bone in children on glucocorticoid treatment. Rheumatology (Oxford). 2005;44(6):813–8.CrossRefGoogle Scholar
  44. 44.
    Houston C, Mathews K, Shibli-Rahhal A. Bone density and alendronate effects in Duchenne muscular dystrophy patients. Muscle Nerve. 2014;49(4):506–11.CrossRefPubMedGoogle Scholar
  45. 45.
    Kim MJ, Kim SN, Lee IS, Chung S, Lee J, Yang Y, et al. Effects of bisphosphonates to treat osteoporosis in children with cerebral palsy: a meta-analysis. J Pediatr Endocrinol Metab. 2015;28(11–12):1343–50.PubMedGoogle Scholar
  46. 46.
    George S, Weber DR, Kaplan P, Hummel K, Monk HM, Levine MA. Short-term safety of zoledronic acid in young patients with bone disorders: an extensive institutional experience. J Clin Endocrinol Metab. 2015;100(11):4163–71.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Ooi HL, Briody J, Biggin A, Cowell CT, Munns CF. Intravenous zoledronic acid given every 6 months in childhood osteoporosis. Horm Res Paediatr. 2013;80(3):179–84.CrossRefPubMedGoogle Scholar
  48. 48.
    Ward LM, Rauch F, Whyte MP, D’Astous J, Gates PE, Grogan D, et al. Alendronate for the treatment of pediatric osteogenesis imperfecta: a randomized placebo-controlled study. J Clin Endocrinol Metab. 2011;96(2):355–64.CrossRefPubMedGoogle Scholar
  49. 49.
    Bishop N, Adami S, Ahmed SF, Antón J, Arundel P, Burren CP, et al. Risedronate in children with osteogenesis imperfecta: a randomised, double-blind, placebo-controlled trial. Lancet. 2013;382(9902):1424–32.CrossRefPubMedGoogle Scholar
  50. 50.
    Djokanovic N, Klieger-Grossmann C, Koren G. Does treatment with bisphosphonates endanger the human pregnancy? J Obstet Gynaecol Can. 2008;30(12):1146–8.CrossRefPubMedGoogle Scholar
  51. 51.
    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(11):1779–86.CrossRefPubMedGoogle Scholar
  52. 52.
    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(8):1362–8.CrossRefPubMedGoogle Scholar
  53. 53.
    Vasanwala RF, Sanghrajka A, Bishop NJ, Högler W. Recurrent proximal femur fractures in a teenager with osteogenesis imperfecta on continuous bisphosphonate therapy: are we overtreating? J Bone Miner Res. 2016;31(7):1449–54.CrossRefPubMedGoogle Scholar
  54. 54.
    Shane E, Burr D, Abrahamsen B, Adler RA, Brown TD, Cheung AM, 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):1–23.CrossRefPubMedGoogle Scholar
  55. 55.
    Nicolaou N, Agrawal Y, Padman M, Fernandes JA, Bell MJ. Changing pattern of femoral fractures in osteogenesis imperfecta with prolonged use of bisphosphonates. J Child Orthop. 2012;6(1):21–7.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Trejo P, Fassier F, Glorieux FH, Rauch F. Diaphyseal femur fractures in osteogenesis imperfecta: characteristics and relationship with bisphosphonate treatment. J Bone Miner Res. 2017;32(5):1034–9.CrossRefPubMedGoogle Scholar
  57. 57.
    Glorieux FH, Bishop NJ, Plotkin H, Chabot G, Lanoue G, Travers R. Cyclic administration of pamidronate in children with severe osteogenesis imperfecta. N Engl J Med. 1998;339(14):947–52.CrossRefPubMedGoogle Scholar
  58. 58.
    Brown JP, Morin S, Leslie W, Papaioannou A, Cheung AM, Davison KS, et al. Bisphosphonates for treatment of osteoporosis: expected benefits, potential harms, and drug holidays. Can Fam Physician. 2014;60(4):324–33.PubMedPubMedCentralGoogle Scholar
  59. 59.
    Biggin A, Zheng L, Briody JN, Coorey CP, Munns CF. The long-term effects of switching from active intravenous bisphosphonate treatment to low-dose maintenance therapy in children with osteogenesis imperfecta. Horm Res Paediatr. 2015;83(3):183–9.CrossRefPubMedGoogle Scholar
  60. 60.
    Whyte MP, Wenkert D, Clements KL, McAlister WH, Mumm S. Bisphosphonate-induced osteopetrosis. N Engl J Med. 2003;349(5):457–63.CrossRefPubMedGoogle Scholar
  61. 61.
    Huang Y, Eapen E, Steele S, Grey V. Establishment of reference intervals for bone markers in children and adolescents. Clin Biochem. 2011;44(10–11):771–8.CrossRefPubMedGoogle Scholar
  62. 62.
    Tuchman S, Thayu M, Shults J, Zemel BS, Burnham JM, Leonard MB. Interpretation of biomarkers of bone metabolism in children: impact of growth velocity and body size in healthy children and chronic disease. J Pediatr. 2008;153(4):484–90.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    McCloskey EV, Vasikaran S, Cooper C, Members FPDC. Official Positions for FRAX® clinical regarding biochemical markers from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX®. J Clin Densitom. 2011;14(3):220–2.CrossRefPubMedGoogle Scholar
  64. 64.
    McDonald DG, Kinali M, Gallagher AC, Mercuri E, Muntoni F, Roper H, et al. Fracture prevalence in Duchenne muscular dystrophy. Dev Med Child Neurol. 2002;44(10):695–8.CrossRefPubMedGoogle Scholar
  65. 65.
    Mayo AL, Craven BC, McAdam LC, Biggar WD. Bone health in boys with Duchenne Muscular Dystrophy on long-term daily deflazacort therapy. Neuromuscul Disord. 2012;22(12):1040–5.CrossRefPubMedGoogle Scholar
  66. 66.
    King WM, Ruttencutter R, Nagaraja HN, Matkovic V, Landoll J, Hoyle C, et al. Orthopedic outcomes of long-term daily corticosteroid treatment in Duchenne muscular dystrophy. Neurology. 2007;68(19):1607–13.CrossRefPubMedGoogle Scholar
  67. 67.
    Henderson RC, Berglund LM, May R, Zemel BS, Grossberg RI, Johnson J, et al. The relationship between fractures and DXA measures of BMD in the distal femur of children and adolescents with cerebral palsy or muscular dystrophy. J Bone Miner Res. 2010;25(3):520–6.CrossRefPubMedGoogle Scholar
  68. 68.
    Srinivasan R, Rawlings D, Wood CL, Cheetham T, Moreno AC, Mayhew A, et al. Prophylactic oral bisphosphonate therapy in duchenne muscular dystrophy. Muscle Nerve. 2016;54(1):79–85.CrossRefPubMedGoogle Scholar
  69. 69.
    Brown JP, Reid IR, Wagman RB, Kendler D, Miller PD, Jensen JE, et al. Effects of up to 5 years of denosumab treatment on bone histology and histomorphometry: the FREEDOM study extension. J Bone Miner Res. 2014;29(9):2051–6.CrossRefPubMedGoogle Scholar
  70. 70.
    Hoyer-Kuhn H, Netzer C, Koerber F, Schoenau E, Semler O. Two years’ experience with denosumab for children with osteogenesis imperfecta type VI. Orphanet J Rare Dis. 2014;9:145.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Hoyer-Kuhn H, Franklin J, Allo G, Kron M, Netzer C, Eysel P, et al. Safety and efficacy of denosumab in children with osteogenesis imperfect – a first prospective trial. J Musculoskelet Neuronal Interact. 2016;16(1):24–32.PubMedPubMedCentralGoogle Scholar
  72. 72.
    Setsu N, Kobayashi E, Asano N, Yasui N, Kawamoto H, Kawai A, et al. Severe hypercalcemia following denosumab treatment in a juvenile patient. J Bone Miner Metab. 2016;34(1):118–22.CrossRefPubMedGoogle Scholar
  73. 73.
    Anastasilakis AD, Polyzos SA, Makras P, Aubry-Rozier B, Kaouri S, Lamy O. Clinical features of 24 patients with rebound-associated vertebral fractures after denosumab discontinuation: systematic review and additional cases. J Bone Miner Res. 2017;32(6):1291–6.CrossRefPubMedGoogle Scholar
  74. 74.
    Feurer E, Chapurlat R. Emerging drugs for osteoporosis. Expert Opin Emerg Drugs. 2014;19(3):385–95.CrossRefPubMedGoogle Scholar
  75. 75.
    Rauch F, Cornibert S, Cheung M, Glorieux FH. Long bone changes after pamidronate discontinuation in children and adolescents with osteogenesis imperfecta. Bone. 2007;40(4):821–7.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Pediatrics, Division of EndocrinologyStanford University School of MedicineStanfordUSA

Personalised recommendations