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The role of bisphosphonates in diseases of childhood

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Abstract

Bisphosphonates are synthetic analogues of pyrophosphate that inhibit bone resorption by their action on osteoclasts. In recent years, bisphosphonates have been used in children for treatment of a growing number of disorders associated primarily with generalized or localized osteoporosis, metabolic bone diseases, heterotopic calcification in soft tissues, and for resistant hypercalcemia. In the present review we discuss the pharmacological aspects of bisphosphonates and related bone pathophysiology, review the pediatric literature on the role of bisphosphonates in childhood diseases and our experience with these drugs. The theoretical concerns of possible adverse effects of these drugs on the growing skeleton have not materialized in the limited pediatric clinical experience. Bisphosphonates provide the pediatrician with an opportunity to treat mineral and bone disorders of childhood which until recently did not have satisfactory therapy, at the same time, being aware of the theoretical concerns on microdamage accumulation in bone, bone quality and teratogenic potential of these drugs

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References

  1. Akyuz C, Yalcin B, Kutluk T, Cila A, Buyukpamukcu M (1999) Brief report: medulloblastoma with widespread skeletal metastases presenting with hypercalcemia. Med Pediatr Oncol 33: 126–128

    Article  CAS  PubMed  Google Scholar 

  2. Amin S, LaValley MP, Simms RW, Felson DT (1999) The role of vitamin D in corticosteroid-induced osteoporosis: a meta-analytic approach. Arthritis Rheum 42: 1740–1751

    Article  CAS  PubMed  Google Scholar 

  3. Antoniazzi F, Mottes M, Fraschini P, Brunelli PC, Tato L (2000) Osteogenesis imperfecta: practical treatment guidelines. Paediatr Drugs 2: 465–488

    CAS  PubMed  Google Scholar 

  4. Aris RM, Lester GE, Renner JB, Winders A, Denene Blackwood A, Lark RK, Ontjes DA (2000) Efficacy of pamidronate for osteoporosis in patients with cystic fibrosis following lung transplantation. Am J Respir Crit Care Med 162: 941–946

    Google Scholar 

  5. Astrom E, Soderhall S (1998) Beneficial effect of bisphosphonate during five years of treatment of severe osteogenesis imperfecta. Acta Paediatr 87: 64–68

    Article  CAS  PubMed  Google Scholar 

  6. Attard TM, Dhawan A, Kaufman SS, Collier DS, Langnas AN (1998) Use of disodium pamidronate in children with hypercalcemia awaiting liver transplantation. Pediatr Transplantation 2: 157–159

    CAS  Google Scholar 

  7. Bassett CA, Donath A, Macagno F, Preisig R, Fleisch H, Francis MD (1969) Diphosphonates in the treatment of myositis ossificans. Lancet 2: 845

    CAS  PubMed  Google Scholar 

  8. Bembi B, Agosti E, Boehm P, Nassimbeni G, Zanatta M, Vidoni L (1994) Aminohydroxypropylidene-biphosphonate in the treatment of bone lesions in a case of Gaucher's disease type 3. Acta Paediatr 83: 122–124

    CAS  PubMed  Google Scholar 

  9. Bembi B, Parma A, Bottega M, Ceschel S, Zanatta M, Martini C, Ciana G (1997) Intravenous pamidronate treatment in osteogenesis imperfecta. J Pediatr 131: 622–625

    CAS  PubMed  Google Scholar 

  10. Bianchi ML, Cimaz R, Bardare M, Zulian F, Lepore L, Boncompagni A, Galbiati E, Corona F, Luisetto G, Giuntini D, Picco P, Brandi ML, Falcini F (2000) Efficacy and safety of alendronate for the treatment of osteoporosis in diffuse connective tissue diseases in children: a prospective multicenter study. Arthritis Rheum 43: 1960–1966

    Article  CAS  PubMed  Google Scholar 

  11. Bishop NJ, Williams DM, Compston JC, Stirling DM, Prentice A (1995) Osteoporosis in severe congenital neutropenia treated with granulocyte colony-stimulating factor. Br J Haematol 89: 927–928

    CAS  PubMed  Google Scholar 

  12. Brumsen C, Hamdy NA, Papapoulos SE (1997) Long-term effects of bisphosphonates on the growing skeleton. Studies of young patients with severe osteoporosis. Medicine (Baltimore) 76: 266–283

    Google Scholar 

  13. Buckmaster A, Rodda C, Cowell CT, Ogle G, Dorney S (1997) The use of pamidronate in PTHrP associated hypercalcaemia in infancy. J Pediatr Endocrinol Metab 10: 301–304

    CAS  PubMed  Google Scholar 

  14. Buyse G, Silberstein J, Goemans N, Casaer P (1995) Fibrodysplasia ossificans progressiva: still turning into wood after 300 years? Eur J Pediatr 154: 694–699

    CAS  PubMed  Google Scholar 

  15. Carano A, Teitelbaum SL, Konsek JD, Schlesinger PH, Blair HC (1990) Bisphosphonates directly inhibit the bone resorption activity of isolated avian osteoclasts in vitro. J Clin Invest 85: 456–461

    CAS  PubMed  Google Scholar 

  16. Cassinelli HR, Mautalen CA, Heinrich JJ, Miglietta A, Bergada C (1992) Familial idiopathic hyperphosphatasia (FIH): response to long-term treatment with pamidronate (APD). Bone Miner 19: 175–184

    CAS  PubMed  Google Scholar 

  17. Chavassieux PM, Arlot ME, Reda C, Wei L, Yates AJ, Meunier PJ (1997) Histomorphometric assessment of the long-term effects of alendronate on bone quality and remodeling in patients with osteoporosis. J Clin Invest 100: 1475–1480

    CAS  PubMed  Google Scholar 

  18. Conway SP (2001) Impact of lung inflammation on bone metabolism in adolescents with cystic fibrosis. Paediatr Respir Rev 2: 324–331

    Article  CAS  PubMed  Google Scholar 

  19. Cranney A, Tugwell P, Adachi J, Weaver B, Zytaruk N, Papaioannou A, Robinson V, Shea B, Wells G, Guyatt G (2002) Meta-analyses of therapies for postmenopausal osteoporosis. III. Meta-analysis of risedronate for the treatment of postmenopausal osteoporosis. Endocr Rev 23: 517–523

    Article  CAS  PubMed  Google Scholar 

  20. Cranney A, Wells G, Willan A, Griffith L, Zytaruk N, Robinson V, Black D, Adachi J, Shea B, Tugwell P, Guyatt G (2002) Meta-analyses of therapies for postmenopausal osteoporosis. II. Meta-analysis of alendronate for the treatment of postmenopausal women. Endocr Rev 23: 508–516

    Article  CAS  PubMed  Google Scholar 

  21. De Schepper J, de Pont S, Smitz J, De Coster D, Schots R, Otten J (1999) Metabolic disturbances after a single dose of 30 mg pamidronate for leukaemia-associated hypercalcaemia in a 11-year-old boy. Eur J Pediatr 158: 765–766

    Article  PubMed  Google Scholar 

  22. Demir E, Bereket A, Ozkan B, Topcu M (2000) Effect of alendronate treatment on the clinical picture and bone turnover markers in chronic idiopathic hyperphosphatasia. J Pediatr Endocrinol Metab 13: 217–221

    CAS  PubMed  Google Scholar 

  23. Drake WM, Kendler DL, Brown JP (2001) Consensus statement on the modern therapy of Paget's disease of bone from a Western Osteoporosis Alliance symposium. Biannual Foothills Meeting on Osteoporosis, Calgary, Alberta, Canada, September 9–10, 2000. Clin Ther 23: 620–626

    Article  CAS  PubMed  Google Scholar 

  24. Drake WM, Hiorns MP, Kendler DL (2003) Hadju-Cheney syndrome: response to therapy with bisphosphonates in two patients. J Bone Miner Res 18: 131–133

    CAS  PubMed  Google Scholar 

  25. Dunlop DJ, Soukop M, McEwan HP (1990) Antenatal administration of aminopropylidene diphosphonate. Ann Rheum Dis 49: 955

    CAS  Google Scholar 

  26. Eyre DR (1996) Biochemical markers of bone turnover. In: Favus MJ (ed) Primer on the metabolic bone diseases and disorders of mineral metabolism, 3rd edn. Lippincott-Raven, Philadelphia, pp 114–119

  27. Ezra A, Golomb G (2000) Administration routes and delivery systems of bisphosphonates for the treatment of bone resorption. Adv Drug Deliv Rev 42: 175–195

    Article  CAS  PubMed  Google Scholar 

  28. Falcini F, Trapani S, Ermini M, Brandi ML (1996) Intravenous administration of alendronate counteracts the in vivo effects of glucocorticoids on bone remodeling. Calcif Tissue Int 58: 166–169

    Article  CAS  PubMed  Google Scholar 

  29. Falk MJ, Heeger S, Lynch KA, DeCaro KR, Bohach D, Gibson KS, Warman ML (2003) Intravenous bisphosphonate therapy in children with osteogenesis imperfecta. Pediatrics 111: 573–578

    PubMed  Google Scholar 

  30. Flanagan AM, Chambers TJ (1991) Inhibition of bone resorption by bisphosphonates: interactions between bisphosphonates, osteoclasts, and bone. Calcif Tissue Int 49: 407–415

    CAS  PubMed  Google Scholar 

  31. Fleisch H (2001) Can bisphosphonates be given to patients with fractures? J Bone Miner Res 16: 437–440

    CAS  PubMed  Google Scholar 

  32. Fraunfelder FW, Fraunfelder FT, Jensvold B (2003) Scleritis and other ocular side effects associated with pamidronate disodium. Am J Opthalmol 135: 219–222

    Article  CAS  Google Scholar 

  33. Fujiwara I, Ogawa E, Igarashi Y, Ohba M, Asanuma A (1998) Intravenous pamidronate treatment in osteogenesis imperfecta. Eur J Pediatr 157: 261–262

    CAS  Google Scholar 

  34. Garnero P, Shih WJ, Gineyts E, Karpf DB, Delmas PD (1994) Comparison of new biochemical markers of bone turnover in late postmenopausal osteoporotic women in response to alendronate treatment. J Clin Endocrinol Metab 79: 1693–1700

    CAS  PubMed  Google Scholar 

  35. Geusens P, Menten J, Vosse D, Vanhoof J, van der Linden S (2001) Recovery from severe glucocorticoid-induced osteoporosis in an adolescent boy. J Clin Densitom 4: 389–394

    CAS  PubMed  Google Scholar 

  36. Giraud F, Meunier PJ (2002) Effect of cyclical intravenous pamidronate therapy in children with osteogenesis imperfecta. Open-label study in seven patients. Joint Bone Spine 69: 486–490

    Article  PubMed  Google Scholar 

  37. Glorieux FH, Bishop NJ, Plotkin H, Chabot G, Lanoue G, Travers R (1998) Cyclic administration of pamindronate in children with severe osteogenesis imperfecta. N Engl J Med 339: 947–952

    Google Scholar 

  38. Go T (2001) Low-dose oral etidronate therapy for immobilization hypercalcaemia associated with Guillain-Barre syndrome. Acta Paediatr 90: 1202–1204

    Article  CAS  PubMed  Google Scholar 

  39. Gonzalez E, Pavia C, Ros J, Villaronga M, Valls C, Escola J (2001) Efficacy of low dose schedule pamidronate infusion in children with osteogenesis imperfecta. J Pediatr Endocrinol Metab 14: 529–533

    CAS  PubMed  Google Scholar 

  40. Harris ST, Eriksen EF, Davidson M, Ettinger MP, Moffett Jr AH Jr, Baylink DJ, Crusan CE, Chines AA (2001) Effect of combined risedronate and hormone replacement therapies on bone mineral density in postmenopausal women. J Clin Endocrinol Metab 86: 1890–1897

    CAS  PubMed  Google Scholar 

  41. Haworth CS, Selby PL, Webb AK, Mawer EB, Adams JE, Freemont TJ (1998) Severe bone pain after intravenous pamidronate in adult patients with cystic fibrosis. Lancet 352: 1753–1754

    CAS  PubMed  Google Scholar 

  42. Haworth CS, Selby PL, Adams JE, Mawer EB, Horrocks AW, Webb AK (2001) Effect of intravenous pamidronate on bone mineral density in adults with cystic fibrosis. Thorax 56: 314–316

    Article  CAS  PubMed  Google Scholar 

  43. Henderson RC, Lark RK, Kecskemethy HH, Miller F, Harcke HT, Bachrach SJ (2002) Bisphosphonates to treat osteopenia in children with quadriplegic cerebral palsy: a randomized, placebo-controlled clinical trial. J Pediatr 141: 644–651

    Article  CAS  PubMed  Google Scholar 

  44. Hirano T, Turner CH, Forwood MR, Johnston CC, Burr DB (2000) Does suppression of bone turnover impair mechanical properties by allowing microdamage accumulation? Bone 27: 13–20

    Article  CAS  PubMed  Google Scholar 

  45. Hoekman K, Papapoulos SE, Peters AC, Bijvoet OL (1985) Characteristics and bisphosphonate treatment of a patient with juvenile osteoporosis. J Clin Endocrinol Metab 61: 952–956

    Google Scholar 

  46. Homik JE, Cranney A, Shea B, Tugwell P, Wells G, Adachi JD, Suarez-Almazor ME (1999) A meta-analysis on the use of bisphosphonates in corticosteroid induced osteoporosis. J Rheumatol 26: 1148–1157

    CAS  PubMed  Google Scholar 

  47. Huaux JP, Lokietek W (1988) Is APD a promising drug in the treatment of severe osteogenesis imperfecta? J Pediatr Orthop 8: 71–72

    CAS  PubMed  Google Scholar 

  48. Hughes DE, Wright KR, Uy HL, Sasaki A, Yoneda T, Roodman GD, Mundy GR, Boyce BF (1995) Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. J Bone Miner Res 10: 1478–1487

    CAS  PubMed  Google Scholar 

  49. Hurvitz EA, Mandac BR, Davidoff G, Johnson JH, Nelson VS (1992) Risk factors for heterotopic ossification in children and adolescents with severe traumatic brain injury. Arch Phys Med Rehabil 73: 459–462

    CAS  PubMed  Google Scholar 

  50. Illidge TM, Hussey M, Godden CW (1996) Malignant hypercalcaemia in pregnancy and antenatal administration of intravenous pamidronate. Clin Oncol (R Coll Radiol) 8: 257–258

    Google Scholar 

  51. Julian BA, Laskow DA, Dubovsky J, Dubovsky EV, Curtis JJ, Quarles LD (1991) Rapid loss of vertebral mineral density after renal transplantation. N Engl J Med 325: 544–550

    CAS  PubMed  Google Scholar 

  52. Kauffman RP, Overton TH, Shiflett M, Jennings JC (2001) Osteoporosis in children and adolescent girls: case report of idiopathic juvenile osteoporosis and review of the literature. Obstet Gynecol Surv 56: 492–504

    Article  CAS  PubMed  Google Scholar 

  53. Khan N, Licata A, Rogers D (2001) Intravenous bisphosphonate for hypercalcemia accompanying subcutaneous fat necrosis: a novel treatment approach. Clin Pediatr (Phila) 40: 217–219

    Google Scholar 

  54. Kutluk MT, Hazar V, Akyuz C, Varan A, Buyukpamukcu M (1997) Childhood cancer and hypercalcemia: report of a case treated with pamidronate. J Pediatr 130: 828–831

    CAS  PubMed  Google Scholar 

  55. Landman JO, Hamdy NA, Pauwels EK, Papapoulos SE (1995) Skeletal metabolism in patients with osteoporosis after discontinuation of long-term treatment with oral pamidronate. J Clin Endocrinol Metab 80: 3465–3468

    Google Scholar 

  56. Landsmeer-Beker EA, Massa GG, Maaswinkel-Mooy PD, van de Kamp JJ, Papapoulos SE (1997) Treatment of osteogenesis imperfecta with the bisphosphonate olpadronate (dimethylaminohydroxypropylidene bisphosphonate). Eur J Pediatr 156: 792–794

    Article  CAS  PubMed  Google Scholar 

  57. Lanza FL (1998) Bisphosphonates: oesophageal and gastric toxicity—fact or fiction. Ital J Gastroenterol Hepatol 30: 143–145

    CAS  PubMed  Google Scholar 

  58. Lee YS, Low SL, Lim LA, Loke KY (2001) Cyclic pamidronate infusion improves bone mineralisation and reduces fracture incidence in osteogenesis imperfecta. Eur J Pediatr 160: 641–644

    CAS  PubMed  Google Scholar 

  59. Leonard MB, Propert KJ, Zemel BS, Stallings VA, Feldman HI (1999) Discrepancies in pediatric bone mineral density reference data: potential for misdiagnosis of osteopenia. J Pediatr 135: 182–188

    CAS  PubMed  Google Scholar 

  60. Lepore L, Pennesi M, Barbi E, Pozzi R (1991) Treatment and prevention of osteoporosis in juvenile chronic arthritis with disodium clodronate. Clin Exp Rheumatol 9[Suppl 6]: 33–35

  61. Liens D, Delmas PD, Meunier PJ (1994) Long-term effects of intravenous pamidronate in fibrous dysplasia of bone. Lancet 343: 953–954

    CAS  PubMed  Google Scholar 

  62. Lindhout D, Golding RP, Taets van Amerongen AH (1985) Fibrodysplasia ossificans progressiva: current concepts and the role of CT in acute changes. Pediatr Radiol 15: 211–213

    CAS  PubMed  Google Scholar 

  63. Loh K, Matthay KK, Hoover M, Bracho FA, Cortez AB, Conte FA, Albanese CT, Miller TR, Price DC, Flores AJ, Kaviani A, Shoback D (1998) Hypercalcemia in malignant paraganglioma due to parathyroid hormone-related protein. Horm Res 50: 217–221

    Article  CAS  PubMed  Google Scholar 

  64. Looker AC, Bauer DC, Chesnut CH 3rd, Gundberg CM, Hochberg MC, Klee G, Kleerekoper M, Watts NB, Bell NH (2000) Clinical use of biochemical markers of bone remodeling: current status and future directions. Osteoporos Int 11: 467–480

    CAS  PubMed  Google Scholar 

  65. Lteif AN, Zimmerman D (1998) Bisphosphonates for treatment of childhood hypercalcemia. Pediatrics 102: 990–993

    CAS  PubMed  Google Scholar 

  66. Markowitz GS, Appel GB, Fine PL, Fenves AZ, Loon NR, Jagannath S, Kuhn JA, Dratch AD, D'Agati VD (2001) Collapsing focal segmental glomerulosclerosis following treatment with high-dose pamidronate. J Am Soc Nephrol 12: 1164–1172

    CAS  PubMed  Google Scholar 

  67. Mashiba T, Hirano T, Turner CH, Forwood MR, Johnston CC, Burr DB (2000) Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib. J Bone Miner Res 15: 613–620

    CAS  PubMed  Google Scholar 

  68. Mashiba T, Turner CH, Hirano T, Forwood MR, Jacob DS, Johnston CC, Burr DB (2001) Effects of high-dose etidronate treatment on microdamage accumulation and biomechanical properties in beagle bone before occurrence of spontaneous fractures. Bone 29: 271–278

    Article  CAS  PubMed  Google Scholar 

  69. Matarazzo P, Lala R, Masi G, Andreo M, Altare F, de Sanctis C (2002) Pamidronate treatment in bone fibrous dysplasia in children and adolescents with McCune-Albright syndrome. J Pediatr Endocrinol Metab 15[Suppl 3]: 929–937

  70. McCarthy EA, Raggio CL, Hossack MD, Miller EA, Jain S, Boskey AL, Camacho NP (2002) Alendronate treatment for infants with osteogenesis imperfecta: demonstration of efficacy in a mouse model. Pediatr Res 52: 660–670

    Article  CAS  PubMed  Google Scholar 

  71. Meradji M, de Villeneuve VH, Huber J, de Bruijn WC, Pearse RG (1978) Idiopathic infantile arterial calcification in siblings: radiologic diagnosis and successful treatment. J Pediatr 92: 401–405

    CAS  PubMed  Google Scholar 

  72. Molgaard C, Thomsen BL, Prentice A, Cole TJ, Michaelsen KF (1997) Whole body bone mineral content in healthy children and adolescents. Arch Dis Child 76: 9-15

    CAS  Google Scholar 

  73. Mora S, Prinster C, Proverbio MC, Bellini A, de Poli SC, Weber G, Abbiati G, Chiumello G (1998) Urinary markers of bone turnover in healthy children and adolescents: age-related changes and effect of puberty. Calcif Tissue Int 63: 369–374

    Article  CAS  PubMed  Google Scholar 

  74. Morabito N, Lasco A, Gaudio A, Crisafulli A, Di Pietro C, Meo A, Frisina N (2002) Bisphosphonates in the treatment of thalassemia-induced osteoporosis. Osteoporos Int 13: 644–649

    Article  Google Scholar 

  75. Nishikawa M, Yamamoto M, Murakami T, Akatsu T, Kugai N, Nagata N (1998) A third-generation bisphosphonate, YM175, inhibits osteoclast formation in murine cocultures by inhibiting proliferation of precursor cells via supporting cell-dependent mechanisms. J Bone Miner Res 13: 986–995

    CAS  PubMed  Google Scholar 

  76. Nucci A, Queiroz LD, Santos AD, Camargo EE, Moura-Ribeiro MV (2000) Fibrodysplasia ossificans progressiva: case report. Arq Neuropsiquiatr 58: 342–347

    CAS  PubMed  Google Scholar 

  77. Oguz A, Karadeniz C, Caglar E, Caglar Citak E, Ataoglu O (1999) The use of etidronate in therapy-resistant hypercalcemia. Acta Oncol 38: 125–127

    Article  CAS  PubMed  Google Scholar 

  78. Oliveri MB, Mautalen C, Mega M, Rossi E (1994) Congenital erythropoietic porphyria: skeletal manifestations and effect of pamidronate treatment. Bone 15: 101–104

    CAS  PubMed  Google Scholar 

  79. O'Sullivan M, Zacharin M (2002) Intramedullary rodding and bisphosphonate treatment of polyostotic fibrous dysplasia associated with the McCune-Albright syndrome. J Pediatr Orthop 22: 255–260

    Article  PubMed  Google Scholar 

  80. Patlas N, Golomb G, Yaffe P, Pinto T, Breuer E, Ornoy A (1999) Transplacental effects of bisphosphonates on fetal skeletal ossification and mineralization in rats. Teratology 60: 68–73

    Article  CAS  PubMed  Google Scholar 

  81. Pecherstorfer M, Herrmann Z, Body JJ, Manegold C, Degardin M, Clemens MR, Thurlimann B, Tubiana-Hulin M, Steinhauer EU, van Eijkeren M, Huss HJ, Thiebaud D (1996) Randomized phase II trial comparing different doses of the bisphosphonate ibandronate in the treatment of hypercalcemia of malignancy. J Clin Oncol 14: 268–276

    CAS  PubMed  Google Scholar 

  82. Pfeilschifter J, Ziegler R (1998) Wirkung von pamidronat auf beschwerdebild und knochenstoffwechsel bei fibroser dysplasie und McCune-Albright-Syndrom. Med Klin 93: 352–359

    CAS  PubMed  Google Scholar 

  83. Plotkin H, Rauch F, Bishop NJ, Montpetit K, Ruck-Gibis J, Travers R, Glorieux FH (2000) Pamidronate treatment of severe osteogenesis imperfecta in children under 3 years of age. J Clin Endocrinol Metab 85: 1846–1850

    Google Scholar 

  84. Profumo RJ, Reese JC, Foy TM, Garibaldi LR, Kane RE (1994) Severe immobilization-induced hypercalcemia in a child after liver transplantation successfully treated with pamidronate. Transplantation 57: 301–303

    Google Scholar 

  85. Pullon HW, Bellingham AJ, Humphreys S, Cundy TF (1991) The osteodystrophy of congenital erythropoietic porphyria. Bone 12: 89–92

    CAS  PubMed  Google Scholar 

  86. Rauch F, Travers R, Parfitt AM, Glorieux FH (2000) Static and dynamic bone histomorphometry in children with osteogenesis imperfecta. Bone 26: 581–589

    Article  CAS  PubMed  Google Scholar 

  87. Rauch F, Travers R, Plotkin H, Glorieux FH (2002) The effects of intravenous pamidronate on the bone tissue of children and adolescents with osteogenesis imperfecta. J Clin Invest 110: 1293–1299

    Article  CAS  PubMed  Google Scholar 

  88. Rawlinson PS, Green RH, Coggins AM, Boyle IT, Gibson BE (1991) Malignant osteopetrosis: hypercalcaemia after bone marrow transplantation. Arch Dis Child 66: 638–639

    CAS  PubMed  Google Scholar 

  89. Rice AM, Rivkees SA (1999) Etidronate therapy for hypercalcemia in subcutaneous fat necrosis of the newborn. J Pediatr 134: 349–351

    CAS  PubMed  Google Scholar 

  90. Rodan GA (1998) Mechanisms of action of bisphosphonates. Annu Rev Pharmacol Toxicol 38: 375–388

    Article  CAS  PubMed  Google Scholar 

  91. Rodd C (2001) Bisphosphonates in dialysis and transplantation patients: efficacy and safety issues. Perit Dial Int 21[Suppl 3]: S256–S260

    Google Scholar 

  92. Rogers JG, Geho WB (1979) Fibrodysplasia ossificans progressiva. A survey of forty-two cases. J Bone Joint Surg Am 61: 909–914

    CAS  PubMed  Google Scholar 

  93. Rogers JG, Dorst JP, Geho WB (1977) Use and complications of high-dose disodium etidronate therapy in fibrodysplasia ossificans progressiva. J Pediatr 91: 1011–1014

    CAS  PubMed  Google Scholar 

  94. Roldan EJ, Pasqualini T, Plantalech L (1999) Bisphosphonates in children with osteogenesis imperfecta may improve bone mineralization but not bone strength. Report of two patients. J Pediatr Endocrinol Metab 12: 555–559

    Google Scholar 

  95. Rossini M, Gatti D, Zamberlan N, Braga V, Dorizzi R, Adami S (1994) Long-term effects of a treatment course with oral alendronate of postmenopausal osteoporosis. J Bone Miner Res 9: 1833–1837

    CAS  PubMed  Google Scholar 

  96. Rowe DJ, Hausmann E (1980) The effects of calcitonin and colchicine on the cellular response to diphosphonate. Br J Exp Pathol 61: 303–309

    CAS  PubMed  Google Scholar 

  97. Russell RG, Croucher PI, Rogers MJ (1999) Bisphosphonates: pharmacology, mechanisms of action and clinical uses. Osteoporos Int 9[Suppl 2]: S66–S80

    Google Scholar 

  98. Saha H, Castren-Kortekangas P, Ojanen S, Juhakoski A, Tuominen J, Tokola O, Pasternack A (1994) Pharmacokinetics of clodronate in renal failure. J Bone Miner Res 9: 1953–1958

    CAS  PubMed  Google Scholar 

  99. Sakamoto O, Yoshinari M, Rikiishi T, Fujiwara I, Imaizumi M, Tsuchiya S, Iinuma K (2001) Hypercalcemia due to all-trans retinoic acid therapy for acute promyelocytic leukemia: a case report of effective treatment with bisphosphonate. Pediatr Int 43: 688–690

    Article  CAS  PubMed  Google Scholar 

  100. Samuel R, Katz K, Papapoulos SE, Yosipovitch Z, Zaizov R, Liberman UA (1994) Aminohydroxy propylidene bisphosphonate (APD) treatment improves the clinical skeletal manifestations of Gaucher's disease. Pediatrics 94: 385–389

    CAS  PubMed  Google Scholar 

  101. Sato M, Grasser W, Endo N, Akins R, Simmons H, Thompson DD, Golub E, Rodan GA (1991) Bisphosphonate action. Alendronate localization in rat bone and effects on osteoclast ultrastructure. J Clin Invest 88: 2095–2105

    CAS  PubMed  Google Scholar 

  102. Schibler D, Russell RG, Fleisch H (1968) Inhibition by pyrophosphate and polyphosphate of aortic calcification induced by vitamin D3 in rats. Clin Sci 35: 363–372

    CAS  PubMed  Google Scholar 

  103. Schmid I, Stachel D, Schon C, Bauer M, Haas RJ (2001) Pamidronate and calcitonin as therapy of acute cancer-related hypercalcemia in children. Klin Padiatr 213: 30–34

    Article  CAS  PubMed  Google Scholar 

  104. Sellers E, Sharma A, Rodd C (1998) The use of pamidronate in three children with renal disease. Pediatr Nephrol 12: 778–781

    Article  CAS  PubMed  Google Scholar 

  105. Shaw NJ, White CP, Fraser WD, Rosenbloom L (1994) Osteopenia in cerebral palsy. Arch Dis Child 71: 235–238

    CAS  PubMed  Google Scholar 

  106. Silverman SL, Hurvitz EA, Nelson VS, Chiodo A (1994) Rachitic syndrome after disodium etidronate therapy in an adolescent. Arch Phys Med Rehabil 75: 118–120

    CAS  PubMed  Google Scholar 

  107. Smith R, Russell RGG, Bishop M (1971) Diphosphonates and Paget's disease of bone. Lancet 1: 945–947

    CAS  Google Scholar 

  108. Srivastava T, Alon US (1999) Bisphosphonates: from grandparents to grandchildren. Clin Pediatr (Phila) 38: 687–702

    Google Scholar 

  109. Stover SL, Hahn HR, Miller JM 3rd (1976) Disodium etidronate in the prevention of heterotopic ossification following spinal cord injury. Paraplegia 14: 146–156

    CAS  PubMed  Google Scholar 

  110. Taggart H, Bolognese MA, Lindsay R, Ettinger MP, Mulder H, Josse RG, Roberts A, Zippel H, Adami S, Ernst TF, Stevens KP (2002) Upper gastrointestinal tract safety of risedronate: a pooled analysis of 9 clinical trials. Mayo Clin Proc 77: 262–270

    CAS  PubMed  Google Scholar 

  111. Teramoto S, Matsuse T, Ouchi Y (1999) Increased cytokines and pamidronate-induced bone pain in adults with cystic fibrosis. Lancet 353: 750

    Article  CAS  Google Scholar 

  112. Thiaville A, Smets A, Clercx A, Perlmutter N (1994) Idiopathic infantile arterial calcification: a surviving patient with renal artery stenosis. Pediatr Radiol 24: 506–508

    CAS  PubMed  Google Scholar 

  113. Van Beek E, Hoekstra M, van de Ruit M, Lowik C, Papapoulos S (1994) Structural requirements for biphosphonates actions in vitro. J Bone Miner Res 9: 1875–1882

    PubMed  Google Scholar 

  114. Van Dyck M, Proesmans W, Van Hollebeke E, Marchal G, Moerman P (1989) Idiopathic infantile arterial calcification with cardiac, renal and central nervous system involvement. Eur J Pediatr 148: 374–377

    PubMed  Google Scholar 

  115. Van Persijn van Meerten EL, Kroon HM, Papapoulos SE (1992) Epi- and metaphyseal changes in children caused by administration of bisphosphonates. Radiology 184: 249–254

    PubMed  Google Scholar 

  116. Vera J, Lucaya J, Garcia Conesa JA, Aso C, Balaguer A (1990) Idiopathic infantile arterial calcification: unusual features. Pediatr Radiol 20: 585–587

    CAS  PubMed  Google Scholar 

  117. Vichinsky EP (1998) The morbidity of bone disease in thalassemia. Ann N Y Acad Sci 850: 344–348

    CAS  PubMed  Google Scholar 

  118. Wiadrowski TP, Marshman G (2001) Subcutaneous fat necrosis of the newborn following hypothermia and complicated by pain and hypercalcaemia. Australas J Dermatol 42: 207–210

    Article  CAS  PubMed  Google Scholar 

  119. Williams CJ, Smith RA, Ball RJ, Wilkinson H (1997) Hypercalcaemia in osteogenesis imperfecta treated with pamidronate. Arch Dis Child 76: 169–1670

    CAS  PubMed  Google Scholar 

  120. Yamaguchi K, Grant J, Noble-Jamieson G, Jamieson N, Barnes ND, Compston JE (1995) Hypercalcaemia in primary oxalosis: role of increased bone resorption and effects of treatment with pamidronate. Bone 16: 61–67

    Article  CAS  PubMed  Google Scholar 

  121. Young G, Shende A (1998) Use of pamidronate in the management of acute cancer-related hypercalcemia in children. Med Pediatr Oncol 30: 117–121

    Article  PubMed  Google Scholar 

  122. Zacharin M, Cundy T (2000) Osteoporosis pseudoglioma syndrome: treatment of spinal osteoporosis with intravenous bisphosphonates. J Pediatr 137: 410–415

    Article  CAS  PubMed  Google Scholar 

  123. Zacharin M, Bateman J (2002) Pamidronate treatment of osteogenesis imperfecta: lack of correlation between clinical severity, age at onset of treatment, predicted collagen mutation and treatment response. J Pediatr Endocrinol Metab 15: 163–174

    CAS  PubMed  Google Scholar 

  124. Zimolo Z, Wesolowski G, Rodan GA (1995) Acid extrusion is induced by osteoclast attachment to bone. Inhibition by alendronate and calcitonin. J Clin Invest 96: 2277–2283

    CAS  PubMed  Google Scholar 

  125. Zurutuza L, Muller F, Gibrat JF, Taillandier A, Simon-Bouy B, Serre JL, Mornet E (1999) Correlations of genotype and phenotype in hypophosphatasia. Hum Mol Genet 8: 1039–1046

    CAS  PubMed  Google Scholar 

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  1. Section of Nephrology, The Children's Mercy Hospital, 2401 Gillham Road, Kansas City, MO 64108, USA

    Tarak Srivastava & Uri S. Alon

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  1. Tarak Srivastava
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  2. Uri S. Alon
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Correspondence to Uri S. Alon.

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Supported by the Sam and Helen Kaplan Research Fund in Pediatric Nephrology

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Srivastava, T., Alon, U.S. The role of bisphosphonates in diseases of childhood. Eur J Pediatr 162, 735–751 (2003). https://doi.org/10.1007/s00431-003-1298-4

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