title: Long-term bone mineral density response to enzyme replacement therapy in a retrospective pediatric cohort of Gaucher patients.
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.
authors.affiliation: Regional Coordinator Centre for Rare Diseases, University Hospital Santa Maria della Misericordia, Piazzale Santa Maria della Misericordia 15, 33100, Udine, Italy. ciana.giovanni@aoud.sanita.fvg.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ciana
authors.forename: Laura
authors.initials: L
authors.lastname: Deroma
authors.forename: Anna Martina
authors.initials: AM
authors.lastname: Franzil
authors.forename: Andrea
authors.initials: A
authors.lastname: Dardis
authors.forename: Bruno
authors.initials: B
authors.lastname: Bembi
mesh_terms: D000293:Adolescent; D000328:Adult; D015519:Bone Density / Q000187:drug effects*; D001851:Bone Diseases, Metabolic / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D056947:Enzyme Replacement Therapy; D005260:Female; D005776:Gaucher Disease / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D005962:Glucosylceramidase / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: C070292:alglucerase; D005962:Glucosylceramidase; C090568:imiglucerase