Abstract
Osteopenia is described as a relevant sign of bone involvement in Gaucher disease (GD) both in pediatric and adult patients. Furthermore, abnormal bone metabolism is considered to play a role in growth and pubertal delay. To analyze the long-term effect of enzyme replacement therapy (ERT) on bone mineral density (BMD), a retrospective observational study was conducted in a cohort of 18 GD pediatric patients (13 males, 5 females; median age 9.2 years). They received biweekly infusions of 20-60 IU/kg of alglucerase/imiglucerase. Clinical, laboratory and imaging parameters were evaluated every 2 years. According to the International Society of Clinical Densitometry guidelines, a Z-score ≤ -2.0 was considered pathological. Nine patients (group P0) began ERT during infancy and nine (group P1) during puberty. At baseline, in three patients (16.6 %; 1P0, 2P1) Z-score was ≤ -2.0 (range -2.47 to -2.25). In patient P0 it normalized after 2 years, while in the 2P1 patients (splenectomized siblings) it persisted abnormal. The remaining 15 patients (83.4 %) always presented a normal value. In group P0, Z-score improved in infancy but showed a significant decrease during puberty, on the contrary it constantly improved in group P1. Furthermore, at baseline group P0 showed a higher median Z-score than group P1: 0.79 (0.38; 1.50) and -1.61 (-2.25; -1.56) respectively. The use of correct BMD standards to interpret bone loss during pediatric age suggests a limited significance of bone loss in these patients. Moreover, the persistence of residual disease activity may affect normal bone growth during puberty in GD populations.
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Andersson H, Kaplan P, Kacena K, Yee J (2008) Eight-year clinical outcomes of long-term enzyme replacement therapy for 884 children with Gaucher disease type 1. Pediatrics 122:1182–1190
Bembi B, Ciana G, Mengel E, Terk MR, Martini C, Wenstrup RJ (2002) Bone complications in children with Gaucher disease. Br J Radiol 75(Suppl 1):A37–A44
Beutler E, Grabowski G (2001) Gaucher disease. In: Scriver C, Beaudet A, Sly E et al (eds) The metabolic and molecular bases of inherited disease. McGraw-Hill, New York, pp 3635–3668
Charrow J, Andersson HC, Kaplan P, Kolodny EH, Mistry P, Pastores G, Rosenbloom BE, Scott CR, Wappner RS, Weinreb NJ, Zimran A (2000) The Gaucher registry: demographics and disease characteristics of 1698 patients with Gaucher disease. Arch Intern Med 160:2835–2843
Ciana G, Addobbati R, Tamaro G, Leopaldi A, Nevyjel M, Ronfani L, Vidoni L, Pittis MG, Bembi B (2005) Gaucher disease and bone: laboratory and skeletal mineral density variations during a long period of enzyme replacement therapy. J Inherit Metab Dis 28:723–732
Deegan PB, Pavlova E, Tindall J, Stein PE, Bearcroft P, Mehta A, Hughes D, Wraith JE, Cox TM (2011) Osseous manifestations of adult Gaucher disease in the era of enzyme replacement therapy. Medicine 90:52–60
El-Beshlawy A, Ragab L, Youssry I, Yakout K, El-Kiki H, Eid K, Mansour IM, Abd El-Hamid S, Yang M, Mistry PK (2006) Enzyme replacement therapy and bony changes in Egyptian paediatric Gaucher disease patients. Inherit Metab Dis 29:92–98
Grabowski GA, Kolodny EH, Weinreb NJ, Charrow J, Pastores GM, Mistry PK (2006) Gaucher disease: phenotypic and genetic variation, Chapter 146.1. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease, 9th edn. McGraw-Hill, New York
Kaplan P, Mazur A, Manor O, Charrow J, Esplin J, Gribble TJ, Wappner RS, Wisch JS, Weinreb NJ (1996) Acceleration of retarded growth in children with Gaucher disease after treatment with alglucerase. J Pediatr 129:149–153
Kelly TL, Specker BL, Binkely T, Zemel BS, Leonard MB, Kalkwarf HJ, Moyer-Mileur LJ, Shepard JA (2005) Pediatric BMD reference database for US white children. Bone 36:S30
Lewiecki EM, Gordon CM, Baim S, Binkley N, Bilezikian JP, Kendler DL, Hans DB, Silverman S, Bishop NJ, Leonard MB, Bianchi ML, Kalkwarf HJ, Langman CB, Plotkin H, Rauch F, Zemel BS (2008) Special report on the 2007 Adult and Pediatric Position Development Conferences of the International Society for Clinical Densitometry. Osteoporos Int 19:1369–1378
Maas M, Hangartner T, Mariani G, McHugh K, Moore S, Grabowski GA, Kaplan P, Vellodi A, Yee J, Steinbach L (2008) Recommendations for the assessment and monitoring of skeletal manifestations in children with Gaucher disease. Skeletal Radiol 37:185–188
Mistry PK, Weinreb NJ, Kaplan P, Cole JA, Gwosdow AR, Hangartner T (2011) Osteopenia in Gaucher disease develops early in life: response to imiglucerase enzyme therapy in children, adolescent and adults. Blood Cells Mol Dis 46:66–72
Pastores GM, Wallenstein S, Desnick RJ, Luckey MM (1996) Bone density in Type 1 Gaucher disease. J Bone Miner Res 11:1801–1807
Poll LW, Koch JA, Willers R, Aerts H, Scherer A, Häussinger D, Mödder U, vom Dahl S (2002) Correlation of bone marrow response with hematological, biochemical, and visceral responses to enzyme replacement therapy of nonneuronopathic (type 1) Gaucher disease in 30 adult patients. Blood Cells Mol Dis 28:209–220
Rosenthal DI, Doppelt SH, Mankin HJ, Dambrosia JM, Xavier RJ, McKusick KA, Rosen BR, Baker J, Niklason LT, Hill SC et al (1995) Enzyme replacement therapy for Gaucher disease: skeletal responses to macrophage-targeted glucocerebrosidase. Pediatrics 96:629–637
Sims KB, Pastores GM, Weinreb NJ, Barranger J, Rosenbloom BE, Packman S, Kaplan P, Mankin H, Xavier R, Angell J, Fitzpatrick MA, Rosenthal D (2008) Improvement of bone disease by imiglucerase (Cerezyme) therapy in patients with skeletal manifestations of type 1 Gaucher disease: results of a 48-month longitudinal cohort study. Clin Genet 73:430–440
Stowens DW, Teitelbaum SL, Kahn AJ, Barranger JA (1985) Skeletal complications of Gaucher disease. Medicine 64:310–322
Walsh JS, Henry YM, Fatayerji D, Eastell R (2009) Lumbar spine peak bone mass and bone turnover in men and women: a longitudinal study. Osteoporos Int 20:355–362
Weinreb NJ, Charrow J, Andersson HC, Kaplan P, Kolodny EH, Mistry P, Pastores G, Rosenbloom BE, Scott CR, Wappner RS, Zimran A (2002) Effectiveness of enzyme replacement therapy in 1028 patients with type 1 Gaucher disease after 2 to 5years of treatment: a report from the Gaucher Registry. Am J Med 113:112–119
Zimran A, Kay A, Gelbart T, Garver P, Thurston D, Saven A, Beutler E (1992) Gaucher disease. Clinical, laboratory, radiologic, and genetic features of 53 patients. Medicine 71:337–353
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We gratefully acknowledge of Giulia Liva for her precious help and support in writing this paper.
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Communicated by: Maurizio Scarpa
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Ciana, G., Deroma, L., Franzil, A.M. et al. Long-term bone mineral density response to enzyme replacement therapy in a retrospective pediatric cohort of Gaucher patients. J Inherit Metab Dis 35, 1101–1106 (2012). https://doi.org/10.1007/s10545-012-9476-z
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DOI: https://doi.org/10.1007/s10545-012-9476-z