Long-term bone mineral density response to enzyme replacement therapy in a retrospective pediatric cohort of Gaucher patients

• Published in: Journal of inherited metabolic disease Vol. 35; no. 6; pp. 1101 - 1106
• Main Authors: Ciana, Giovanni, Deroma, Laura, Franzil, Anna Martina, Dardis, Andrea, Bembi, Bruno
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.11.2012; Springer; Blackwell Publishing Ltd
• Subjects: Adolescent; Adult; Age; Biochemistry; Biological and medical sciences; Bone Density - drug effects; Bone Diseases, Metabolic - drug therapy; Bone Diseases, Metabolic - etiology; Bone Diseases, Metabolic - metabolism; Bone growth; Bone loss; Bone mineral density; Bone turnover; Child; Child, Preschool; Cohort Studies; Densitometry; Enzyme Replacement Therapy; Enzymes; Female; Gaucher Disease - complications; Gaucher Disease - drug therapy; Gaucher Disease - metabolism; Gaucher's disease; Glucosylceramidase - therapeutic use; Human Genetics; Humans; imaging; Internal Medicine; Investigative techniques, diagnostic techniques (general aspects); Long-term effects; Male; Medical genetics; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Original Article; Osteoarticular system. Muscles; Osteopenia; Pediatrics; Puberty; Radiodiagnosis. Nmr imagery. Nmr spectrometry; Retrospective Studies; Siblings; Young Adult; Bone Mineral Density; Enzyme Replacement Therapy; Gauche Disease Patient; Gauche Disease; Asperger Syndrome; Human; Replacement therapy; Nutrition; Enzyme; Metabolic diseases; Enzymopathy; Long term; Retrospective; Genetic disease; Response; Chemotherapy; Treatment; Cohort study; Genetics; Bone mineral density; Child; Long bone; Public health
• ISSN: 0141-8955; 1573-2665
• DOI: 10.1007/s10545-012-9476-z

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.