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Bone problems in childhood cancer patients

Author
Susan R Rose, MD
Section Editors
David G Poplack, MD
Mitchell E Geffner, MD
Deputy Editor
Alison G Hoppin, MD

INTRODUCTION

Children and adolescents may experience bone problems and endocrine problems during and after therapy for oncologic problems. The bone problems, which may be acute or chronic, and symptomatic or asymptomatic, will be discussed in this topic review.

The related endocrine problems will be discussed briefly here, and in detail separately. (See "Endocrinopathies in the childhood cancer survivor".)

PATHOPHYSIOLOGY

Normal bone formation — Bone forms by deposition of osteoid through osteoblast activity. Resorption of osteoid occurs through osteoclast activity. Resorption actively occurs even in growing children. This allows bone remodeling as bones increase in circumference and length. Length is added to bones in the epiphyseal plate, a metabolically active zone in which chondrocytes and cartilage are converted to osteocytes and calcified matrix. The relatively faster rate of bone formation compared with rate of bone resorption leads to growth in bone size and increase in bone mineral density (BMD). Bone strength and fracture risk are related to bone size, BMD, and microstructural architecture. (See "Normal skeletal development and regulation of bone formation and resorption".)

Both bone size and BMD increase gradually through the childhood years with more rapid increases during puberty [1]. Calcium is added to bone most rapidly between ages 9 and 15 years in girls, and between ages 10 and 18 years in boys [2]. After adult height is achieved, bone size remains stable, but BMD continues to increase until age reaches the mid-to-late 20s (peak bone mass). Subsequently, bone mass and BMD decline very gradually throughout the rest of adult life. If peak bone mass is reduced, osteoporosis and fractures may occur earlier in adult life. Bone growth and remodeling are regulated by endogenous hormones, including growth hormone, sex steroids, growth factors, and cytokines, as well as exogenous factors such as nutrition and weight-bearing exercise [3].

Effects of cancer — Childhood cancer can affect bone metabolism and growth through a variety of mechanisms. The relative contributions of these factors to bone disease in a particular patient, and the contribution of genetics, are often unclear.

                         

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Literature review current through: Nov 2016. | This topic last updated: Fri Apr 01 00:00:00 GMT+00:00 2016.
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References
Top
  1. Camacho-Hübner C. Normal Physiology of Growth Hormone and Insulin-Like Growth Factors in Childhood. In: Endotext [Internet], De Groot LJ, Beck-Peccoz P, Chrousos G, et al. (Eds), Dept of Endocrinology, St. Bartholomew's Hospital, London 2010. (accessed May 6, 2015)
  2. Abrams SA. Calcium turnover and nutrition through the life cycle. Proc Nutr Soc 2001; 60:283.
  3. Lui JC, Nilsson O, Baron J. Recent research on the growth plate: Recent insights into the regulation of the growth plate. J Mol Endocrinol 2014; 53:T1.
  4. Sinha A, Avery P, Turner S, et al. Vitamin D status in paediatric patients with cancer. Pediatr Blood Cancer 2011; 57:594.
  5. Choudhary A, Chou J, Heller G, Sklar C. Prevalence of vitamin D insufficiency in survivors of childhood cancer. Pediatr Blood Cancer 2013; 60:1237.
  6. Lackner H, Benesch M, Moser A, et al. Aseptic osteonecrosis in children and adolescents treated for hemato-oncologic diseases: a 13-year longitudinal observational study. J Pediatr Hematol Oncol 2005; 27:259.
  7. Bürger B, Beier R, Zimmermann M, et al. Osteonecrosis: a treatment related toxicity in childhood acute lymphoblastic leukemia (ALL)--experiences from trial ALL-BFM 95. Pediatr Blood Cancer 2005; 44:220.
  8. Aricò M, Boccalatte MF, Silvestri D, et al. Osteonecrosis: An emerging complication of intensive chemotherapy for childhood acute lymphoblastic leukemia. Haematologica 2003; 88:747.
  9. Niinimäki RA, Harila-Saari AH, Jartti AE, et al. Osteonecrosis in children treated for lymphoma or solid tumors. J Pediatr Hematol Oncol 2008; 30:798.
  10. Högler W, Wehl G, van Staa T, et al. 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.
  11. Fan C, Foster BK, Wallace WH, Xian CJ. Pathobiology and prevention of cancer chemotherapy-induced bone growth arrest, bone loss, and osteonecrosis. Curr Mol Med 2011; 11:140.
  12. Girard P, Auquier P, Barlogis V, et al. Symptomatic osteonecrosis in childhood leukemia survivors: prevalence, risk factors and impact on quality of life in adulthood. Haematologica 2013; 98:1089.
  13. Salem KH, Brockert AK, Mertens R, Drescher W. Avascular necrosis after chemotherapy for haematological malignancy in childhood. Bone Joint J 2013; 95-B:1708.
  14. Mattano LA Jr, Sather HN, Trigg ME, Nachman JB. Osteonecrosis as a complication of treating acute lymphoblastic leukemia in children: a report from the Children's Cancer Group. J Clin Oncol 2000; 18:3262.
  15. Wiesmann A, Pereira P, Böhm P, et al. Avascular necrosis of bone following allogeneic stem cell transplantation: MR screening and therapeutic options. Bone Marrow Transplant 1998; 22:565.
  16. Kawedia JD, Kaste SC, Pei D, et al. Pharmacokinetic, pharmacodynamic, and pharmacogenetic determinants of osteonecrosis in children with acute lymphoblastic leukemia. Blood 2011; 117:2340.
  17. Kadan-Lottick NS, Dinu I, Wasilewski-Masker K, et al. Osteonecrosis in adult survivors of childhood cancer: a report from the childhood cancer survivor study. J Clin Oncol 2008; 26:3038.
  18. Faraci M, Calevo MG, Lanino E, et al. Osteonecrosis after allogeneic stem cell transplantation in childhood. A case-control study in Italy. Haematologica 2006; 91:1096.
  19. Mattano LA Jr, Devidas M, Nachman JB, et al. Effect of alternate-week versus continuous dexamethasone scheduling on the risk of osteonecrosis in paediatric patients with acute lymphoblastic leukaemia: results from the CCG-1961 randomised cohort trial. Lancet Oncol 2012; 13:906.
  20. Relling MV, Yang W, Das S, et al. Pharmacogenetic risk factors for osteonecrosis of the hip among children with leukemia. J Clin Oncol 2004; 22:3930.
  21. Armstrong GT, Sklar CA, Hudson MM, Robison LL. Long-term health status among survivors of childhood cancer: does sex matter? J Clin Oncol 2007; 25:4477.
  22. Niinimäki RA, Harila-Saari AH, Jartti AE, et al. High body mass index increases the risk for osteonecrosis in children with acute lymphoblastic leukemia. J Clin Oncol 2007; 25:1498.
  23. Karol SE, Yang W, Van Driest SL, et al. Genetics of glucocorticoid-associated osteonecrosis in children with acute lymphoblastic leukemia. Blood 2015; 126:1770.
  24. Karol SE, Mattano LA Jr, Yang W, et al. Genetic risk factors for the development of osteonecrosis in children under age 10 treated for acute lymphoblastic leukemia. Blood 2016; 127:558.
  25. Wang KZ, Mao LZ, Hu CG. [Experimental study on mechanism of steroid-induced avascular necrosis of femoral head]. Zhonghua Wai Ke Za Zhi 1994; 32:515.
  26. Ribeiro RC, Fletcher BD, Kennedy W, et al. Magnetic resonance imaging detection of avascular necrosis of the bone in children receiving intensive prednisone therapy for acute lymphoblastic leukemia or non-Hodgkin lymphoma. Leukemia 2001; 15:891.
  27. Sansgiri RK, Neel MD, Soto-Fourier M, Kaste SC. Unique MRI findings as an early predictor of osteonecrosis in pediatric acute lymphoblastic leukemia. AJR Am J Roentgenol 2012; 198:W432.
  28. Kaste SC. Skeletal toxicities of treatment in children with cancer. Pediatr Blood Cancer 2008; 50:469.
  29. Leblicq C, Laverdière C, Décarie JC, et al. Effectiveness of pamidronate as treatment of symptomatic osteonecrosis occurring in children treated for acute lymphoblastic leukemia. Pediatr Blood Cancer 2013; 60:741.
  30. Castro FP Jr, Barrack RL. Core decompression and conservative treatment for avascular necrosis of the femoral head: a meta-analysis. Am J Orthop (Belle Mead NJ) 2000; 29:187.
  31. Karimova EJ, Rai SN, Howard SC, et al. Femoral head osteonecrosis in pediatric and young adult patients with leukemia or lymphoma. J Clin Oncol 2007; 25:1525.
  32. Aigner N, Petje G, Schneider W, et al. Juvenile bone-marrow oedema of the acetabulum treated by iloprost. J Bone Joint Surg Br 2002; 84:1050.
  33. Bernbeck B, Krauth KA, Scherer A, et al. Aseptic osteonecrosis in a child with nephroblastoma healed by hyperbaric oxygen therapy. Med Pediatr Oncol 2002; 39:47.
  34. Niinimäki T, Harila-Saari A, Niinimäki R. The diagnosis and classification of osteonecrosis in patients with childhood leukemia. Pediatr Blood Cancer 2015; 62:198.
  35. Te Winkel ML, Pieters R, Wind EJ, et al. Management and treatment of osteonecrosis in children and adolescents with acute lymphoblastic leukemia. Haematologica 2014; 99:430.
  36. Seller K, Raab P, Wild A, Krauspe R. Risk-benefit analysis of prophylactic pinning in slipped capital femoral epiphysis. J Pediatr Orthop B 2001; 10:192.
  37. Liu SC, Tsai CC, Huang CH. Atypical slipped capital femoral epiphysis after radiotherapy and chemotherapy. Clin Orthop Relat Res 2004; :212.
  38. Viana MB, Vilela MI. Height deficit during and many years after treatment for acute lymphoblastic leukemia in children: a review. Pediatr Blood Cancer 2008; 50:509.
  39. Caruso-Nicoletti M, Mancuso M, Spadaro G, et al. Growth and growth hormone in children during and after therapy for acute lymphoblastic leukaemia. Eur J Pediatr 1993; 152:730.
  40. Ahmed SF, Wallace WH, Crofton PM, et al. Short-term changes in lower leg length in children treated for acute lymphoblastic leukaemia. J Pediatr Endocrinol Metab 1999; 12:75.
  41. van Leeuwen BL, Kamps WA, Jansen HW, Hoekstra HJ. The effect of chemotherapy on the growing skeleton. Cancer Treat Rev 2000; 26:363.
  42. Xian CJ, Cool JC, Scherer MA, et al. Cellular mechanisms for methotrexate chemotherapy-induced bone growth defects. Bone 2007; 41:842.
  43. Bongers ME, Francken AB, Rouwé C, et al. Reduction of adult height in childhood acute lymphoblastic leukemia survivors after prophylactic cranial irradiation. Pediatr Blood Cancer 2005; 45:139.
  44. Davies HA, Didcock E, Didi M, et al. Disproportionate short stature after cranial irradiation and combination chemotherapy for leukaemia. Arch Dis Child 1994; 70:472.
  45. Arikoski P, Komulainen J, Riikonen P, et al. Alterations in bone turnover and impaired development of bone mineral density in newly diagnosed children with cancer: a 1-year prospective study. J Clin Endocrinol Metab 1999; 84:3174.
  46. te Winkel ML, Pieters R, Hop WC, et al. Bone mineral density at diagnosis determines fracture rate in children with acute lymphoblastic leukemia treated according to the DCOG-ALL9 protocol. Bone 2014; 59:223.
  47. Wasilewski-Masker K, Kaste SC, Hudson MM, et al. Bone mineral density deficits in survivors of childhood cancer: long-term follow-up guidelines and review of the literature. Pediatrics 2008; 121:e705.
  48. Kaste SC, Jones-Wallace D, Rose SR, et al. Bone mineral decrements in survivors of childhood acute lymphoblastic leukemia: frequency of occurrence and risk factors for their development. Leukemia 2001; 15:728.
  49. Muszynska-Roslan K, Panasiuk A, Latoch E, et al. Little evidence of low bone mass in acute lymphoblastic leukemia survivors. J Clin Densitom 2012; 15:108.
  50. Mostoufi-Moab S, Brodsky J, Isaacoff EJ, et al. Longitudinal assessment of bone density and structure in childhood survivors of acute lymphoblastic leukemia without cranial radiation. J Clin Endocrinol Metab 2012; 97:3584.
  51. Gordon CM, Leonard MB, Zemel BS, International Society for Clinical Densitometry. 2013 Pediatric Position Development Conference: executive summary and reflections. J Clin Densitom 2014; 17:219.
  52. Aldhafiri F, Al-Nasser A, Al-Sugair A, et al. Importance of adjusting dual-energy X-ray output for body size: an example from survivors of childhood acute lymphoblastic leukemia. J Pediatr Hematol Oncol 2013; 35:e27.
  53. Stein E, Shane E. Secondary osteoporosis. Endocrinol Metab Clin North Am 2003; 32:115.
  54. Kaste SC, Chesney RW, Hudson MM, et al. Bone mineral status during and after therapy of childhood cancer: an increasing population with multiple risk factors for impaired bone health. J Bone Miner Res 1999; 14:2010.
  55. Haddy TB, Mosher RB, Reaman GH. Osteoporosis in survivors of acute lymphoblastic leukemia. Oncologist 2001; 6:278.
  56. Nysom K, Holm K, Michaelsen KF, et al. Bone mass after treatment of malignant lymphoma in childhood. Med Pediatr Oncol 2001; 37:518.
  57. Bhatia S, Ramsay NK, Weisdorf D, et al. Bone mineral density in patients undergoing bone marrow transplantation for myeloid malignancies. Bone Marrow Transplant 1998; 22:87.
  58. Perkins JL, Kunin-Batson AS, Youngren NM, et al. Long-term follow-up of children who underwent hematopoeitic cell transplant (HCT) for AML or ALL at less than 3 years of age. Pediatr Blood Cancer 2007; 49:958.
  59. Athanassiadou F, Tragiannidis A, Rousso I, et al. Evaluation of bone metabolism in children with acute lymphoblastic leukemia after induction chemotherapy treatment. Pediatr Hematol Oncol 2005; 22:285.
  60. Müller HL, Schneider P, Bueb K, et al. Volumetric bone mineral density in patients with childhood craniopharyngioma. Exp Clin Endocrinol Diabetes 2003; 111:168.
  61. Kelly KM, Thornton JC, Hughes D, et al. Total body bone measurements: a cross-sectional study in children with acute lymphoblastic leukemia during and following completion of therapy. Pediatr Blood Cancer 2009; 52:33.
  62. Odame I, Duckworth J, Talsma D, et al. Osteopenia, physical activity and health-related quality of life in survivors of brain tumors treated in childhood. Pediatr Blood Cancer 2006; 46:357.
  63. Davies JH, Evans BA, Jones E, et al. Osteopenia, excess adiposity and hyperleptinaemia during 2 years of treatment for childhood acute lymphoblastic leukaemia without cranial irradiation. Clin Endocrinol (Oxf) 2004; 60:358.
  64. Thomas IH, Donohue JE, Ness KK, et al. Bone mineral density in young adult survivors of acute lymphoblastic leukemia. Cancer 2008; 113:3248.
  65. Muszynska-Roslan K, Konstantynowicz J, Panasiuk A, Krawczuk-Rybak M. Is the treatment for childhood solid tumors associated with lower bone mass than that for leukemia and Hodgkin disease? Pediatr Hematol Oncol 2009; 26:36.
  66. Hesseling PB, Hough SF, Nel ED, et al. Bone mineral density in long-term survivors of childhood cancer. Int J Cancer Suppl 1998; 11:44.
  67. Alos N, Grant RM, Ramsay T, et al. High incidence of vertebral fractures in children with acute lymphoblastic leukemia 12 months after the initiation of therapy. J Clin Oncol 2012; 30:2760.
  68. Pirker-Frühauf UM, Friesenbichler J, Urban EC, et al. Osteoporosis in children and young adults: a late effect after chemotherapy for bone sarcoma. Clin Orthop Relat Res 2012; 470:2874.
  69. Kadan-Lottick N, Marshall JA, Barón AE, et al. Normal bone mineral density after treatment for childhood acute lymphoblastic leukemia diagnosed between 1991 and 1998. J Pediatr 2001; 138:898.
  70. Nysom K, Holm K, Michaelsen KF, et al. Bone mass after allogeneic BMT for childhood leukaemia or lymphoma. Bone Marrow Transplant 2000; 25:191.
  71. Benmiloud S, Steffens M, Beauloye V, et al. Long-term effects on bone mineral density of different therapeutic schemes for acute lymphoblastic leukemia or non-Hodgkin lymphoma during childhood. Horm Res Paediatr 2010; 74:241.
  72. Chemaitilly W, Li Z, Huang S, et al. Anterior hypopituitarism in adult survivors of childhood cancers treated with cranial radiotherapy: a report from the St Jude Lifetime Cohort study. J Clin Oncol 2015; 33:492.
  73. Mattano L. The skeletal remains: porosis and necrosis of bone in the marrow transplantation setting. Pediatr Transplant 2003; 7 Suppl 3:71.
  74. Le Meignen M, Auquier P, Barlogis V, et al. Bone mineral density in adult survivors of childhood acute leukemia: impact of hematopoietic stem cell transplantation and other treatment modalities. Blood 2011; 118:1481.
  75. Mandel K, Atkinson S, Barr RD, Pencharz P. Skeletal morbidity in childhood acute lymphoblastic leukemia. J Clin Oncol 2004; 22:1215.
  76. Strauss AJ, Su JT, Dalton VM, et al. Bony morbidity in children treated for acute lymphoblastic leukemia. J Clin Oncol 2001; 19:3066.
  77. Alikasifoglu A, Yetgin S, Cetin M, et al. Bone mineral density and serum bone turnover markers in survivors of childhood acute lymphoblastic leukemia: comparison of megadose methylprednisolone and conventional-dose prednisolone treatments. Am J Hematol 2005; 80:113.
  78. Holzer G, Krepler P, Koschat MA, et al. Bone mineral density in long-term survivors of highly malignant osteosarcoma. J Bone Joint Surg Br 2003; 85:231.
  79. Fan C, Georgiou KR, King TJ, Xian CJ. Methotrexate toxicity in growing long bones of young rats: a model for studying cancer chemotherapy-induced bone growth defects in children. J Biomed Biotechnol 2011; 2011:903097.
  80. Hudson MM, Landier W, Bhatia S. Long-term follow-up guidelines for surviviros of childhood, adolescent, and young adult cancers. In: Children's Oncology Group, ed. Version 2. www.survivorshipguidelines.org (Accessed on January 19, 2010).
  81. Mäkitie O, Heikkinen R, Toiviainen-Salo S, et al. Long-term skeletal consequences of childhood acute lymphoblastic leukemia in adult males: a cohort study. Eur J Endocrinol 2013; 168:281.
  82. Lim JS, Kim DH, Lee JA, et al. Young age at diagnosis, male sex, and decreased lean mass are risk factors of osteoporosis in long-term survivors of osteosarcoma. J Pediatr Hematol Oncol 2013; 35:54.
  83. Frisk P, Arvidson J, Ljunggren O, Gustafsson J. Decreased bone mineral density in young adults treated with SCT in childhood: the role of 25-hydroxyvitamin D. Bone Marrow Transplant 2012; 47:657.
  84. Gleeson HK, Shalet SM. The impact of cancer therapy on the endocrine system in survivors of childhood brain tumours. Endocr Relat Cancer 2004; 11:589.
  85. Gómez JM. The role of insulin-like growth factor I components in the regulation of vitamin D. Curr Pharm Biotechnol 2006; 7:125.
  86. Keilholz U, Max R, Scheibenbogen C, et al. Endocrine function and bone metabolism 5 years after autologous bone marrow/blood-derived progenitor cell transplantation. Cancer 1997; 79:1617.
  87. Leonard MB. Assessment of bone health in children and adolescents with cancer: promises and pitfalls of current techniques. Med Pediatr Oncol 2003; 41:198.
  88. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011; 96:1911.
  89. Weilbaecher KN. Mechanisms of osteoporosis after hematopoietic cell transplantation. Biol Blood Marrow Transplant 2000; 6:165.
  90. Howell SJ, Radford JA, Adams JE, Shalet SM. The impact of mild Leydig cell dysfunction following cytotoxic chemotherapy on bone mineral density (BMD) and body composition. Clin Endocrinol (Oxf) 2000; 52:609.
  91. Sklar C, Whitton J, Mertens A, et al. Abnormalities of the thyroid in survivors of Hodgkin's disease: data from the Childhood Cancer Survivor Study. J Clin Endocrinol Metab 2000; 85:3227.
  92. Wren TA, Kalkwarf HJ, Zemel BS, et al. Longitudinal tracking of dual-energy X-ray absorptiometry bone measures over 6 years in children and adolescents: persistence of low bone mass to maturity. J Pediatr 2014; 164:1280.
  93. Fewtrell MS, Gordon I, Biassoni L, Cole TJ. Dual X-ray absorptiometry (DXA) of the lumbar spine in a clinical paediatric setting: does the method of size-adjustment matter? Bone 2005; 37:413.
  94. Position statement, the International Society for Clinical Densitometry. www.iscd.org. (Accessed on March 12, 2009).
  95. Mora S, Pitukcheewanont P, Kaufman FR, et al. Biochemical markers of bone turnover and the volume and the density of bone in children at different stages of sexual development. J Bone Miner Res 1999; 14:1664.
  96. Watsky MA, Carbone LD, An Q, et al. Bone turnover in long-term survivors of childhood acute lymphoblastic leukemia. Pediatr Blood Cancer 2014; 61:1451.
  97. Sweet MG, Sweet JM, Jeremiah MP, Galazka SS. Diagnosis and treatment of osteoporosis. Am Fam Physician 2009; 79:193.
  98. Ross AC, Manson JE, Abrams SA, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 2011; 96:53.
  99. Zhang FF, Saltzman E, Kelly MJ, et al. Comparison of childhood cancer survivors' nutritional intake with US dietary guidelines. Pediatr Blood Cancer 2015; 62:1461.
  100. Golden NH, Abrams SA, Committee on Nutrition. Optimizing bone health in children and adolescents. Pediatrics 2014; 134:e1229.
  101. Kelly AK. Physical activity prescription for childhood cancer survivors. Curr Sports Med Rep 2011; 10:352.
  102. Joyce ED, Nolan VG, Ness KK, et al. Association of muscle strength and bone mineral density in adult survivors of childhood acute lymphoblastic leukemia. Arch Phys Med Rehabil 2011; 92:873.
  103. Gonc EN, Kandemir N. Long-term effects of growth hormone (GH) on bone mineral status and bone turnover markers in patients with isolated GH deficiency and multiple pituitary hormone deficiency. Clin Endocrinol (Oxf) 2007; 66:672.
  104. van den Heijkant S, Hoorweg-Nijman G, Huisman J, et al. Effects of growth hormone therapy on bone mass, metabolic balance, and well-being in young adult survivors of childhood acute lymphoblastic leukemia. J Pediatr Hematol Oncol 2011; 33:e231.
  105. Gurney JG, Kaste SC, Liu W, 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.
  106. Pluijm S, den Hoed M, van den Heuvel-Eibrink MM. Catch-up of bone mineral density among long-term survivors of childhood cancer? Letter to the editor: Response to the article of Gurney et al. 2014. Pediatr Blood Cancer 2015; 62:369.
  107. Theriault RL, Lipton A, Hortobagyi GN, et al. Pamidronate reduces skeletal morbidity in women with advanced breast cancer and lytic bone lesions: a randomized, placebo-controlled trial. Protocol 18 Aredia Breast Cancer Study Group. J Clin Oncol 1999; 17:846.
  108. Lethaby C, Wiernikowski J, Sala A, et al. Bisphosphonate therapy for reduced bone mineral density during treatment of acute lymphoblastic leukemia in childhood and adolescence: a report of preliminary experience. J Pediatr Hematol Oncol 2007; 29:613.
  109. Wiernikowski JT, Barr RD, Webber C, et al. Alendronate for steroid-induced osteopenia in children with acute lymphoblastic leukaemia or non-Hodgkin's lymphoma: results of a pilot study. J Oncol Pharm Pract 2005; 11:51.
  110. Bachrach LK. Diagnosis and treatment of pediatric osteoporosis. Curr Opin Endocrinol Diabetes Obes 2014; 21:454.
  111. Padhye B, Dalla-Pozza L, Little DG, Munns CF. Use of zoledronic acid for treatment of chemotherapy related osteonecrosis in children and adolescents: a retrospective analysis. Pediatr Blood Cancer 2013; 60:1539.
  112. Shi CG, Zhang Y, Yuan W. Efficacy of Bisphosphonates on Bone Mineral Density and Fracture Rate in Patients With Osteogenesis Imperfecta: A Systematic Review and Meta-analysis. Am J Ther 2016; 23:e894.
  113. 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.
  114. Papapoulos SE, Cremers SC. Prolonged bisphosphonate release after treatment in children. N Engl J Med 2007; 356:1075.
  115. Ward L, Tricco AC, Phuong P, et al. Bisphosphonate therapy for children and adolescents with secondary osteoporosis. Cochrane Database Syst Rev 2007; :CD005324.
  116. Bachrach LK, Ward LM. Clinical review 1: Bisphosphonate use in childhood osteoporosis. J Clin Endocrinol Metab 2009; 94:400.