Skip to main content
Top
Published in: Current Osteoporosis Reports 4/2017

01-08-2017 | Pediatrics (L Ward and E Imel, Section Editors)

Denosumab: an Emerging Therapy in Pediatric Bone Disorders

Author: Alison M. Boyce

Published in: Current Osteoporosis Reports | Issue 4/2017

Login to get access

Abstract

Purpose of Review

Denosumab is an inhibitor of receptor activator of nuclear factor kappa-B ligand (RANKL), and has emerged as an important novel therapy for skeletal disorders. This article examines the use of denosumab in children.

Recent Findings

Considerable safety and efficacy data exists for denosumab treatment of adults with osteoporosis, bone metastases, and giant cell tumors. Pediatric data is limited; however, evidence suggests denosumab may be beneficial in decreasing bone turnover, increasing bone density, and preventing growth of certain skeletal neoplasms in children. Denosumab’s effect on bone turnover is rapidly reversible after drug discontinuation, representing a key difference from bisphosphonates. Rebound increased bone turnover has led to severe hypercalcemia in several pediatric patients.

Summary

Denosumab is a promising therapy for pediatric skeletal disorders. At present, safety concerns related to rebounding bone turnover and mineral homeostasis impact use of denosumab in children. Research is needed to determine if and how these effects can be mitigated.
Literature
5.
go back to reference Lacey DL, Timms E, Tan HL, et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998;93(2):165–76.CrossRefPubMed Lacey DL, Timms E, Tan HL, et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998;93(2):165–76.CrossRefPubMed
6.
go back to reference Hsu H, Lacey DL, Dunstan CR, et al. Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proc Natl Acad Sci U S A. 1999;96(7):3540–5.CrossRefPubMedCentralPubMed Hsu H, Lacey DL, Dunstan CR, et al. Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proc Natl Acad Sci U S A. 1999;96(7):3540–5.CrossRefPubMedCentralPubMed
7.
go back to reference Simonet WS, Lacey DL, Dunstan CR, et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 1997;89(2):309–19.CrossRefPubMed Simonet WS, Lacey DL, Dunstan CR, et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 1997;89(2):309–19.CrossRefPubMed
11.
go back to reference Zheng S, Gaitonde P, Andrew MA, Gibbs MA, Lesko LJ, Schmidt S. Model-based assessment of dosing strategies in children for monoclonal antibodies exhibiting target-mediated drug disposition. CPT Pharm Systems Pharmacol. 2014;3:e138. doi:10.1038/psp.2014.38.CrossRef Zheng S, Gaitonde P, Andrew MA, Gibbs MA, Lesko LJ, Schmidt S. Model-based assessment of dosing strategies in children for monoclonal antibodies exhibiting target-mediated drug disposition. CPT Pharm Systems Pharmacol. 2014;3:e138. doi:10.​1038/​psp.​2014.​38.CrossRef
12.
go back to reference •• Cummings SR, San Martin J, MR MC, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361(8):756–65. doi:10.1056/NEJMoa0809493. The pivotal FREEDOM study was the first randomized, placebo-controlled trial of denosumab to demonstrate a decrease in vertebral and non-vertebral fractures in adults with osteoporosis.CrossRefPubMed •• Cummings SR, San Martin J, MR MC, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361(8):756–65. doi:10.​1056/​NEJMoa0809493. The pivotal FREEDOM study was the first randomized, placebo-controlled trial of denosumab to demonstrate a decrease in vertebral and non-vertebral fractures in adults with osteoporosis.CrossRefPubMed
13.
go back to reference Nakamura T, Matsumoto T, Sugimoto T, et al. Clinical Trials Express: fracture risk reduction with denosumab in Japanese postmenopausal women and men with osteoporosis: denosumab fracture intervention randomized placebo controlled trial (DIRECT). J Clin Endocrinol Metab. 2014;99(7):2599–607. doi:10.1210/jc.2013-4175.CrossRefPubMedPubMedCentral Nakamura T, Matsumoto T, Sugimoto T, et al. Clinical Trials Express: fracture risk reduction with denosumab in Japanese postmenopausal women and men with osteoporosis: denosumab fracture intervention randomized placebo controlled trial (DIRECT). J Clin Endocrinol Metab. 2014;99(7):2599–607. doi:10.​1210/​jc.​2013-4175.CrossRefPubMedPubMedCentral
15.
go back to reference Brown JP, Prince RL, Deal C, et al. Comparison of the effect of denosumab and alendronate on bone mineral density and biochemical markers of bone turnover in postmenopausal women with low bone mass: a randomized, blinded, phase 3 trial. J Bone Miner Res Off J Am Soc Bone Miner Res. 2009;1–34. doi:10.1359/jbmr.080910. Brown JP, Prince RL, Deal C, et al. Comparison of the effect of denosumab and alendronate on bone mineral density and biochemical markers of bone turnover in postmenopausal women with low bone mass: a randomized, blinded, phase 3 trial. J Bone Miner Res Off J Am Soc Bone Miner Res. 2009;1–34. doi:10.​1359/​jbmr.​080910.
16.
go back to reference Kendler DL, Roux C, Benhamou CL, et al. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. J Bone Miner Res Off J Am Soc Bone Miner Res. 2010;25(1):72–81. doi:10.1359/jbmr.090716.CrossRef Kendler DL, Roux C, Benhamou CL, et al. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. J Bone Miner Res Off J Am Soc Bone Miner Res. 2010;25(1):72–81. doi:10.​1359/​jbmr.​090716.CrossRef
17.
go back to reference Freemantle N, Satram-Hoang S, Tang ET, et al. Final results of the DAPS (Denosumab Adherence Preference Satisfaction) study: a 24-month, randomized, crossover comparison with alendronate in postmenopausal women. Osteoporos Int J Established Result Coop Eur Found Osteoporos Natl Osteoporos Found U S A. 2012;23(1):317–26. doi:10.1007/s00198-011-1780-1.CrossRef Freemantle N, Satram-Hoang S, Tang ET, et al. Final results of the DAPS (Denosumab Adherence Preference Satisfaction) study: a 24-month, randomized, crossover comparison with alendronate in postmenopausal women. Osteoporos Int J Established Result Coop Eur Found Osteoporos Natl Osteoporos Found U S A. 2012;23(1):317–26. doi:10.​1007/​s00198-011-1780-1.CrossRef
18.
go back to reference Papapoulos S, Lippuner K, Roux C, et al. The effect of 8 or 5 years of denosumab treatment in postmenopausal women with osteoporosis: results from the FREEDOM Extension study. Osteoporos Int J Established Result Coop Eur Found Osteoporos Natl Osteoporos Found U S A. 2015;26(12):2773–83. doi:10.1007/s00198-015-3234-7.CrossRef Papapoulos S, Lippuner K, Roux C, et al. The effect of 8 or 5 years of denosumab treatment in postmenopausal women with osteoporosis: results from the FREEDOM Extension study. Osteoporos Int J Established Result Coop Eur Found Osteoporos Natl Osteoporos Found U S A. 2015;26(12):2773–83. doi:10.​1007/​s00198-015-3234-7.CrossRef
20.
go back to reference Ellis GK, Bone HG, Chlebowski R, et al. Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2008;26(30):4875–82. doi:10.1200/jco.2008.16.3832.CrossRef Ellis GK, Bone HG, Chlebowski R, et al. Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2008;26(30):4875–82. doi:10.​1200/​jco.​2008.​16.​3832.CrossRef
21.
go back to reference Prolia [package insert]. Thousand Oaks, CA. 2016;Amgen, Inc. Prolia [package insert]. Thousand Oaks, CA. 2016;Amgen, Inc.
22.
go back to reference Stopeck AT, Lipton A, Body JJ, et al. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J Clin Oncol Off J Am Soc Clin Oncol. 2010;28(35):5132–9. doi:10.1200/jco.2010.29.7101.CrossRef Stopeck AT, Lipton A, Body JJ, et al. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J Clin Oncol Off J Am Soc Clin Oncol. 2010;28(35):5132–9. doi:10.​1200/​jco.​2010.​29.​7101.CrossRef
24.
go back to reference Henry DH, Costa L, Goldwasser F, et al. Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol Off J Am Soc Clin Oncol. 2011;29(9):1125–32. doi:10.1200/jco.2010.31.3304.CrossRef Henry DH, Costa L, Goldwasser F, et al. Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol Off J Am Soc Clin Oncol. 2011;29(9):1125–32. doi:10.​1200/​jco.​2010.​31.​3304.CrossRef
25.
go back to reference Xgeva [package insert]. Thousand Oaks, CA. 2016;Amgen, Inc. Xgeva [package insert]. Thousand Oaks, CA. 2016;Amgen, Inc.
28.
go back to reference Diel IJ, Body JJ, Stopeck AT, et al. The role of denosumab in the prevention of hypercalcaemia of malignancy in cancer patients with metastatic bone disease. Eur J Cancer (Oxford, England: 1990). 2015;51(11):1467–75. doi:10.1016/j.ejca.2015.04.017.CrossRef Diel IJ, Body JJ, Stopeck AT, et al. The role of denosumab in the prevention of hypercalcaemia of malignancy in cancer patients with metastatic bone disease. Eur J Cancer (Oxford, England: 1990). 2015;51(11):1467–75. doi:10.​1016/​j.​ejca.​2015.​04.​017.CrossRef
32.
go back to reference •• Chawla S, Henshaw R, Seeger L, et al. Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant cell tumour of bone: interim analysis of an open-label, parallel-group, phase 2 study. Lancet Oncol. 2013;14(9):901–8. doi:10.1016/s1470-2045(13)70277-8. This open-label study in giant cell tumors included adults and ten skeletally mature adolescents, and demonstrated improvement in tumor progression and skeletal morbidity.CrossRefPubMed •• Chawla S, Henshaw R, Seeger L, et al. Safety and efficacy of denosumab for adults and skeletally mature adolescents with giant cell tumour of bone: interim analysis of an open-label, parallel-group, phase 2 study. Lancet Oncol. 2013;14(9):901–8. doi:10.​1016/​s1470-2045(13)70277-8. This open-label study in giant cell tumors included adults and ten skeletally mature adolescents, and demonstrated improvement in tumor progression and skeletal morbidity.CrossRefPubMed
33.
go back to reference Martin-Broto J, Cleeland CS, Glare PA, et al. Effects of denosumab on pain and analgesic use in giant cell tumor of bone: interim results from a phase II study. Acta Oncol (Stockholm, Sweden). 2014;53(9):1173–9. doi:10.3109/0284186x.2014.910313.CrossRef Martin-Broto J, Cleeland CS, Glare PA, et al. Effects of denosumab on pain and analgesic use in giant cell tumor of bone: interim results from a phase II study. Acta Oncol (Stockholm, Sweden). 2014;53(9):1173–9. doi:10.​3109/​0284186x.​2014.​910313.CrossRef
34.
go back to reference 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 Off J Am Soc Clin Oncol. 2013;31(12):e200–2. doi:10.1200/jco.2012.46.4255.CrossRef 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 Off J Am Soc Clin Oncol. 2013;31(12):e200–2. doi:10.​1200/​jco.​2012.​46.​4255.CrossRef
35.
go back to reference Gossai N, Hilgers MV, Polgreen LE, Greengard EG. Critical hypercalcemia following discontinuation of denosumab therapy for metastatic giant cell tumor of bone. Pediatr Blood Cancer. 2015;62(6):1078–80. doi:10.1002/pbc.25393.CrossRefPubMed Gossai N, Hilgers MV, Polgreen LE, Greengard EG. Critical hypercalcemia following discontinuation of denosumab therapy for metastatic giant cell tumor of bone. Pediatr Blood Cancer. 2015;62(6):1078–80. doi:10.​1002/​pbc.​25393.CrossRefPubMed
39.
40.
go back to reference Glorieux FH, Ward LM, Rauch F, Lalic L, Roughley PJ, Travers R. Osteogenesis imperfecta type VI: a form of brittle bone disease with a mineralization defect. J Bone Miner Res Off J Am Soc Bone Miner Res. 2002;17(1):30–8. doi:10.1359/jbmr.2002.17.1.30.CrossRef Glorieux FH, Ward LM, Rauch F, Lalic L, Roughley PJ, Travers R. Osteogenesis imperfecta type VI: a form of brittle bone disease with a mineralization defect. J Bone Miner Res Off J Am Soc Bone Miner Res. 2002;17(1):30–8. doi:10.​1359/​jbmr.​2002.​17.​1.​30.CrossRef
41.
go back to reference 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(3):183–8.PubMed 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(3):183–8.PubMed
44.
go back to reference Hoyer-Kuhn H, Franklin J, Allo G, 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.PubMedPubMedCentral Hoyer-Kuhn H, Franklin J, Allo G, 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.PubMedPubMedCentral
46.
go back to reference Grasemann C, Schundeln MM, Hovel M, et al. Effects of RANK-ligand antibody (denosumab) treatment on bone turnover markers in a girl with juvenile Paget’s disease. J Clin Endocrinol Metab. 2013;98(8):3121–6. doi:10.1210/jc.2013-1143.CrossRefPubMed Grasemann C, Schundeln MM, Hovel M, et al. Effects of RANK-ligand antibody (denosumab) treatment on bone turnover markers in a girl with juvenile Paget’s disease. J Clin Endocrinol Metab. 2013;98(8):3121–6. doi:10.​1210/​jc.​2013-1143.CrossRefPubMed
47.
48.
go back to reference • Wang HD, Boyce AM, Tsai JY, et al. Effects of denosumab treatment and discontinuation on human growth plates. J Clin Endocrinol Metab. 2014;99(3):891–7. doi:10.1210/jc.2013-3081. This study provided histopathologic evidence that denosumab treatment did not appear to adversely affect growth plates in a growing child.CrossRefPubMedPubMedCentral • Wang HD, Boyce AM, Tsai JY, et al. Effects of denosumab treatment and discontinuation on human growth plates. J Clin Endocrinol Metab. 2014;99(3):891–7. doi:10.​1210/​jc.​2013-3081. This study provided histopathologic evidence that denosumab treatment did not appear to adversely affect growth plates in a growing child.CrossRefPubMedPubMedCentral
49.
50.
go back to reference Lange T, Stehling C, Frohlich B, et al. Denosumab: a potential new and innovative treatment option for aneurysmal bone cysts. Eur Spine J Off Publ Eur Spine Soc Eur Spinal Deformity Soc Eur Sect Cervical Spine Res Soc. 2013;22(6):1417–22. doi:10.1007/s00586-013-2715-7.CrossRef Lange T, Stehling C, Frohlich B, et al. Denosumab: a potential new and innovative treatment option for aneurysmal bone cysts. Eur Spine J Off Publ Eur Spine Soc Eur Spinal Deformity Soc Eur Sect Cervical Spine Res Soc. 2013;22(6):1417–22. doi:10.​1007/​s00586-013-2715-7.CrossRef
51.
go back to reference Pelle DW, Ringler JW, Peacock JD, et al. Targeting receptor-activator of nuclear kappaB ligand in aneurysmal bone cysts: verification of target and therapeutic response. Transl Res J Lab Clin Med. 2014;164(2):139–48. doi:10.1016/j.trsl.2014.03.005.CrossRef Pelle DW, Ringler JW, Peacock JD, et al. Targeting receptor-activator of nuclear kappaB ligand in aneurysmal bone cysts: verification of target and therapeutic response. Transl Res J Lab Clin Med. 2014;164(2):139–48. doi:10.​1016/​j.​trsl.​2014.​03.​005.CrossRef
52.
go back to reference 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(5 Pt 1):1030–6.CrossRefPubMed 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(5 Pt 1):1030–6.CrossRefPubMed
53.
go back to reference 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: JPEM. 2006;19(4):523–8.PubMed 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: JPEM. 2006;19(4):523–8.PubMed
54.
go back to reference Palomo T, Fassier F, Ouellet J, et al. Intravenous bisphosphonate therapy of young children with osteogenesis imperfecta: skeletal findings during follow up throughout the growing years. J Bone Miner Res Off J Am Soc Bone Miner Res. 2015;30(12):2150–7. doi:10.1002/jbmr.2567.CrossRef Palomo T, Fassier F, Ouellet J, et al. Intravenous bisphosphonate therapy of young children with osteogenesis imperfecta: skeletal findings during follow up throughout the growing years. J Bone Miner Res Off J Am Soc Bone Miner Res. 2015;30(12):2150–7. doi:10.​1002/​jbmr.​2567.CrossRef
56.
go back to reference Kong YY, Yoshida H, Sarosi I, et al. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature. 1999;397(6717):315–23. doi:10.1038/16852.CrossRefPubMed Kong YY, Yoshida H, Sarosi I, et al. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature. 1999;397(6717):315–23. doi:10.​1038/​16852.CrossRefPubMed
58.
59.
go back to reference Khan AA, Morrison A, Hanley DA, et al. Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. J Bone Miner Res Off J Am Soc Bone Miner Res. 2015;30(1):3–23. doi:10.1002/jbmr.2405.CrossRef Khan AA, Morrison A, Hanley DA, et al. Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. J Bone Miner Res Off J Am Soc Bone Miner Res. 2015;30(1):3–23. doi:10.​1002/​jbmr.​2405.CrossRef
60.
go back to reference Selga J, Nunez JH, Minguell J, Lalanza M, Garrido M. Simultaneous bilateral atypical femoral fracture in a patient receiving denosumab: case report and literature review. Osteoporos Int J Established Result Coop Eur Found Osteoporos Natl Osteoporos Found U S A. 2016;27(2):827–32. doi:10.1007/s00198-015-3355-z.CrossRef Selga J, Nunez JH, Minguell J, Lalanza M, Garrido M. Simultaneous bilateral atypical femoral fracture in a patient receiving denosumab: case report and literature review. Osteoporos Int J Established Result Coop Eur Found Osteoporos Natl Osteoporos Found U S A. 2016;27(2):827–32. doi:10.​1007/​s00198-015-3355-z.CrossRef
61.
go back to reference Gerstenfeld LC, Sacks DJ, Pelis M, et al. Comparison of effects of the bisphosphonate alendronate versus the RANKL inhibitor denosumab on murine fracture healing. J Bone Miner Res Off J Am Soc Bone Miner Res. 2009;24(2):196–208. doi:10.1359/jbmr.081113.CrossRef Gerstenfeld LC, Sacks DJ, Pelis M, et al. Comparison of effects of the bisphosphonate alendronate versus the RANKL inhibitor denosumab on murine fracture healing. J Bone Miner Res Off J Am Soc Bone Miner Res. 2009;24(2):196–208. doi:10.​1359/​jbmr.​081113.CrossRef
62.
go back to reference Bone HG, Bolognese MA, Yuen CK, et al. Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass. J Clin Endocrinol Metab. 2011;96(4):972–80. doi:10.1210/jc.2010-1502.CrossRefPubMed Bone HG, Bolognese MA, Yuen CK, et al. Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass. J Clin Endocrinol Metab. 2011;96(4):972–80. doi:10.​1210/​jc.​2010-1502.CrossRefPubMed
63.
go back to reference Koldkjaer Solling AS, Harslof T, Kaal A, Rejnmark L, Langdahl B. Hypercalcemia after discontinuation of long-term denosumab treatment. Osteoporos Int J Established Result Coop Eur Found Osteoporos Natl Osteoporos Found U S A. 2016;27(7):2383–6. doi:10.1007/s00198-016-3535-5.CrossRef Koldkjaer Solling AS, Harslof T, Kaal A, Rejnmark L, Langdahl B. Hypercalcemia after discontinuation of long-term denosumab treatment. Osteoporos Int J Established Result Coop Eur Found Osteoporos Natl Osteoporos Found U S A. 2016;27(7):2383–6. doi:10.​1007/​s00198-016-3535-5.CrossRef
65.
go back to reference van Persijn van Meerten EL, Kroon HM, Papapoulos SE. Epi- and metaphyseal changes in children caused by administration of bisphosphonates. Radiology. 1992;184(1):249–54.CrossRefPubMed van Persijn van Meerten EL, Kroon HM, Papapoulos SE. Epi- and metaphyseal changes in children caused by administration of bisphosphonates. Radiology. 1992;184(1):249–54.CrossRefPubMed
66.
go back to reference Rauch F, Travers R, Munns C, Glorieux FH. Sclerotic metaphyseal lines in a child treated with pamidronate: histomorphometric analysis. J Bone Miner Res Off J Am Soc Bone Miner Res. 2004;19(7):1191–3. doi:10.1359/jbmr.040303.CrossRef Rauch F, Travers R, Munns C, Glorieux FH. Sclerotic metaphyseal lines in a child treated with pamidronate: histomorphometric analysis. J Bone Miner Res Off J Am Soc Bone Miner Res. 2004;19(7):1191–3. doi:10.​1359/​jbmr.​040303.CrossRef
67.
go back to reference Brown JP, Roux C, Torring O, et al. Discontinuation of denosumab and associated fracture incidence: analysis from the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) trial. J Bone Miner Res Off J Am Soc Bone Miner Res. 2013;28(4):746–52. doi:10.1002/jbmr.1808.CrossRef Brown JP, Roux C, Torring O, et al. Discontinuation of denosumab and associated fracture incidence: analysis from the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) trial. J Bone Miner Res Off J Am Soc Bone Miner Res. 2013;28(4):746–52. doi:10.​1002/​jbmr.​1808.CrossRef
68.
go back to reference Aubry-Rozier B, Gonzalez-Rodriguez E, Stoll D, Lamy O. Severe spontaneous vertebral fractures after denosumab discontinuation: three case reports. Osteoporos Int J Established Result Coop Eur Found Osteoporos Natl Osteoporos Found U S A. 2016;27(5):1923–5. doi:10.1007/s00198-015-3380-y.CrossRef Aubry-Rozier B, Gonzalez-Rodriguez E, Stoll D, Lamy O. Severe spontaneous vertebral fractures after denosumab discontinuation: three case reports. Osteoporos Int J Established Result Coop Eur Found Osteoporos Natl Osteoporos Found U S A. 2016;27(5):1923–5. doi:10.​1007/​s00198-015-3380-y.CrossRef
69.
go back to reference Lamy O, Gonzalez-Rodriguez E, Stoll D, Hans D, Aubry-Rozier B. Severe rebound-associated vertebral fractures after denosumab discontinuation: nine clinical cases report. J Clin Endocrinol Metab. 2016:jc20163170. doi:10.1210/jc.2016-3170.CrossRef Lamy O, Gonzalez-Rodriguez E, Stoll D, Hans D, Aubry-Rozier B. Severe rebound-associated vertebral fractures after denosumab discontinuation: nine clinical cases report. J Clin Endocrinol Metab. 2016:jc20163170. doi:10.​1210/​jc.​2016-3170.CrossRef
71.
go back to reference Popp AW, Zysset PK, Lippuner K. Rebound-associated vertebral fractures after discontinuation of denosumab-from clinic and biomechanics. Osteoporos Int: J Established Result Coop Eur Found Osteoporos Natl Osteoporos Found U S A. 2016;27(5):1917–21. doi:10.1007/s00198-015-3458-6.CrossRef Popp AW, Zysset PK, Lippuner K. Rebound-associated vertebral fractures after discontinuation of denosumab-from clinic and biomechanics. Osteoporos Int: J Established Result Coop Eur Found Osteoporos Natl Osteoporos Found U S A. 2016;27(5):1917–21. doi:10.​1007/​s00198-015-3458-6.CrossRef
72.
73.
74.
go back to reference Block GA, Bone HG, Fang L, Lee E, Padhi D. A single-dose study of denosumab in patients with various degrees of renal impairment. J Bone Miner Res Off J Am Soc Bone Miner Res. 2012;27(7):1471–9. doi:10.1002/jbmr.1613.CrossRef Block GA, Bone HG, Fang L, Lee E, Padhi D. A single-dose study of denosumab in patients with various degrees of renal impairment. J Bone Miner Res Off J Am Soc Bone Miner Res. 2012;27(7):1471–9. doi:10.​1002/​jbmr.​1613.CrossRef
75.
go back to reference Watts NB, Roux C, Modlin JF, et al. Infections in postmenopausal women with osteoporosis treated with denosumab or placebo: coincidence or causal association? Osteoporos Int J Established Result Coop Eur Found Osteoporos Natl Osteoporos Found U S A. 2012;23(1):327–37. doi:10.1007/s00198-011-1755-2.CrossRef Watts NB, Roux C, Modlin JF, et al. Infections in postmenopausal women with osteoporosis treated with denosumab or placebo: coincidence or causal association? Osteoporos Int J Established Result Coop Eur Found Osteoporos Natl Osteoporos Found U S A. 2012;23(1):327–37. doi:10.​1007/​s00198-011-1755-2.CrossRef
76.
go back to reference Fata JE, Kong YY, Li J, et al. The osteoclast differentiation factor osteoprotegerin-ligand is essential for mammary gland development. Cell. 2000;103(1):41–50.CrossRefPubMed Fata JE, Kong YY, Li J, et al. The osteoclast differentiation factor osteoprotegerin-ligand is essential for mammary gland development. Cell. 2000;103(1):41–50.CrossRefPubMed
Metadata
Title
Denosumab: an Emerging Therapy in Pediatric Bone Disorders
Author
Alison M. Boyce
Publication date
01-08-2017
Publisher
Springer US
Published in
Current Osteoporosis Reports / Issue 4/2017
Print ISSN: 1544-1873
Electronic ISSN: 1544-2241
DOI
https://doi.org/10.1007/s11914-017-0380-1

Other articles of this Issue 4/2017

Current Osteoporosis Reports 4/2017 Go to the issue

Osteoimmunology (M Humphrey and M. Nakamura, Section Editors)

Gut Microbiome and Bone: to Build, Destroy, or Both?

Osteocytes (T Bellido and J Klein-Nulend, Section Editors)

Osteocyte Mechanobiology