Abstract
Pediatric nephrology and rheumatology patients with steroid-induced osteopenia are at risk of skeletal fracture. Bisphosphonate therapy has not been routinely advocated as a primary or secondary intervention for steroid-associated fractures in this population. This case control study evaluates the role of pamidronate therapy as a secondary fracture intervention. Children with symptomatic pathological fractures of the axial spine or ribs were treated with pamidronate 1 mg/kg/dose (n=17) IV at 60-day intervals for 1 yr (n=15) or 2 yr (n=2). Bone mineral density of L1–L4 (BMD) was assessed prior to treatment and at six-month intervals, and compared to 17 disease-age-gender-steroid dose-matched control patients. Alkaline phosphatase, calcium, phosphate, PTH, renal biochemistry, and 24-hr urine collections for CrCl, N-telopeptide/creatinine ratio, phosphate excretion, and calcium excretion were obtained every two months in the pamidronate population. Pamidronate caused a first exposure transient flu-like illness lasting <24 h in three patients and one patient had a new pathological fracture. No adverse events of hypocalcemia, allergic reaction or thrombophlebitis were noted. All patients reported improvement of skeletal pain. Despite ongoing steroid treatment, pamidronate significantly increased L1–L4 BMD Z-scores (mean±SE) relative to baseline (pamidronate vs control: 0–6 months: 0.27±0.14 vs −0.82±0.31; 0–12 months: 0.63±0.17 vs −0.46±0.27; 0–18 months: 0.55±0.32 vs 0.17±0.27; 0–24 months: 0.15±0.21 vs −0.23±0.22; 0–30 or 36 months: 0.77±0.71 vs −0.68±0.25) with repeated measures ANOVA assessment (F=11.27, p=0.0057). This study supports the safety and efficacy of pamidronate in steroid-induced fractures in pediatric nephrology and rheumatology patients.
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Warady BA, Hébert D, Sullivan EK, Alexander SR, Tejani A (1997) Renal transplantation, chronic dialysis, and chronic renal insufficiency in children and adolescents. The 1995 Annual Report of the North American Pediatric Transplant Cooperative Study. Pediatr Nephrol 11:49–64
Cushing H (1932) The basophil adenomas of the pituitary body and their clinical manifestations (pituitary basophilism). B Johns Hopkins Hosp 50:137
Lukert BP, Raisz LG (1990) Glucocorticoid-induced osteoporosis: pathogenesis and management. Ann Intern Med 112:352–364
Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, Bauer DC, Genant HK, Haskell WL, Marcus R, Ott SM, Torner JC, Quandt SA, Reiss TF, Ensrud KE (1997) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 348:1535–1541
Bone HG, Downs RW Jr, Tucci JR, Harris ST, Weinstein RS, Licata AA, McClung MR, Kimmel DB, Gertz BJ, Hale E, Polvino WJ (1997) Dose-response relationships for alendronate treatment in osteoporotic elderly women. J Clin Endocr Metab 82:265–274
Liberman UA, Weiss SR, Broll J, Minne HW, Quan H, Bell NH, Rodriguez-Portales J, Downs RW Jr, Dequeker J, Favus M (1995) Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. New Engl J Med 333:1437–43
Tobias JH (1997) How do bisphosphonates prevent fractures? Ann Rheum Dis 56:510–511
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
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
Hoekman K, Papapoulos SE, Peters AC, Bijvoet OL (1985) Characteristics and bisphosphonate treatment of a patient with juvenile osteoporosis. J Clin Endocr Metab 61:952–956
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
Fujiwara I, Ogawa E, Igarashi Y, Ohba M, Asanuma A (1998) Intravenous pamidronate treatment in osteogenesis imperfecta. Eur J Pediatr 157:261–262
Huaux JP, Lokietek W (1998) Is APD a promising drug in the treatment of severe osteogenesis imperfecta? J Pediatr Orthop 8:71–72
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
Devogelaer JP, Malghem J, Maldague B, Nagant de Deuxchaisnes C (1987) Radiological manifestations of bisphosphonate treatment with APD in a child suffering from osteogenesis imperfecta. Skeletal Radiol 16:360–363
Plotkin H, Rauch F, Bishop NJ, Montpetit K, Ruck-Gibis J, Travers R, Glorieux FH (2000) Pamidronate treatment of severe osteogenesis in children under 3 years of age. J Clin Endocr Metab 85:1846–1850
Rice A, Rivkees S (1999) Etidronate therapy for hypercalcemia in subcutaneous fat necrosis of the newborn. J Pediatr 134:349–351
Attard TM, Dhawan A, Kaufman SS, Collier DS, Langnas AN (1998) Use of disodium pamidronate in children with hypercalcemia awaiting liver transplantation. Pediatr Transpl 2:157–159
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
Rawlinson PS, Green RH, Coggins AM, Boyle IT, Gibson BE (1991) Malignant osteoporosis: hypercalcaemia after bone marrow transplantation. Arch Dis Child 66:638–639
Boudailliez BR, Pautard BJ, Sebert JL, Kremp O, Piussan CX (1990) Leukaemia-associated hypercalcemia in a 10-year-old boy: effectiveness of aminohydroxypropylidene bisphosphonate. Pediatr Nephrol 4:510–511
Young G, Shende A (1998) Use of pamidronate in the management of acute cancer-related hypercalcemia in children. Med Pediatr Oncol 30:117–121
Varache N, Audran M, Clochon P, Lortholary A, Bouachour G, Alquier P, Basle MF (1991) Aminohydroxyprophylidene bisphosphonate (AHPrBP) treatment of severe immobilization hypercalcemia in a young patient. Clin Rheumatol 10:328–332
McIntyre HD, Cameron DP, Urquhart SM, Davies WE (1989) Immobilization hypercalcemia responding to intravenous pamidronate sodium therapy. Postgrad Med J 65:244–246
Sellers E, Sharma A, Rodd C (1998) The use of pamidronate in three children with renal disease. Pediatr Nephrol 12:778–781
Jansson S, Tissell LE, Lindstedt G, Lundberg PA (1991) Disodium pamidronate in the preoperative treatment of hypercalcemia in patients with primary hyperparathyroidism. Surgery 110:480–486
Liens D, Delmas PD, Meunier PJ (1994) Long-term effects of intravenous pamidronate in fibrous dysplasia of bone. Lancet 343:953–954
Lala R, Matarazzo P, Bertelloni S, Buzi F, Rignon F, de Sanctis C (2000) Pamidronate treatment of bone fibrous dysplasia in nine children with McCune-Albright syndrome. Acta Paediatr 89:188–193
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
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
Bassett CAL, Donath A, Macagno F, Preisig R, Fleisch H, Francis MD (1969) Diphosphonates in the treatment of myositis ossificans. Lancet 2:845
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
Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, Bauer DC, Genant HK, Haskell WL, Marcus R, Ott SM, Torner JC, Quandt SA, Reiss TF, Ensrud KE (1996) Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 348:1535–1541
Kleerekoper M, Avioli LV (1996) Evaluation and treatment of postmenopausal osteoporosis. In: Favus MJ (ed) Primer on the metabolic bone diseases and disorders of mineral metabolism, 3rd edn. Lippincott-Raven, Philadelphia, PA, pp 264–271
Bell NH, Johnson RH (1997) Bisphosphonates in the treatment of osteoporosis. Endocrine 6:203–206
De Groen PC, Lubbe DF, Hirsch LJ et al. (1996) Esophagitis associated with the use of alendronate. New Engl J Med 335:1016–1021
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
Gandrud LM, Cheung JC, Daniels MW, Bachrach LK (2003) Low-dose intravenous pamidronate reduces fractures in childhood osteoporosis. J Pediatr Endocr Metab 16(6):887–92
Shaw NJ, Boivin CM, Crabtree NJ (2000) Intravenous pamidronate in juvenile osteoporosis. Arch Dis Child 83(2):143–5
Steelman J, Zeitler P (2003) Treatment of symptomatic pediatric osteoporosis with cyclic single-day intravenous pamidronate infusions. J Pediatr 142(4):417–23
Noguera A, Ros JB, Pavia C, Alcover E, Valls C, Villaronga M, Gonzalez E (2003) Bisphosphonates, a new treatment for glucocorticoid-induced osteoporosis in children. J Pediatr Endocr Metab 16(4):529–36
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This study was presented in part at the IPNA Seventh Symposium of Growth and Development in Children with Chronic Kidney Disease: The Molecular Basis of Skeletal Growth, 1–3 April 2004, Heidelberg, Germany
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Acott, P.D., Wong, J.A., Lang, B.A. et al. Pamidronate treatment of pediatric fracture patients on chronic steroid therapy. Pediatr Nephrol 20, 368–373 (2005). https://doi.org/10.1007/s00467-004-1790-8
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DOI: https://doi.org/10.1007/s00467-004-1790-8