title: 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.
abstract: Progressive skeletal disease accounts for some of the most debilitating complications of type 1 Gaucher disease. In this 48-month, prospective, non-randomized, open-label study of the effect of enzyme replacement therapy on bone response, 33 imiglucerase-naïve patients (median age 43 years with one or more skeletal manifestations such as osteopenia, history of bone crisis, or other documented bone pathology) received imiglucerase 60 U/kg/2 weeks. Substantial improvements were observed in bone pain (BP), bone crises (BC), and bone mineral density (BMD). Improvements in BP were observed at 3 months (p < 0.001 vs baseline) and continued progressively throughout the study, with 39% of patients reporting pain at 48 months vs 73% at baseline. Eleven of the 13 patients with a pre-treatment history of BC had no recurrences. Biochemical markers for bone formation increased; markers for bone resorption decreased. Steady improvement of spine and femoral neck BMD, measured using dual-energy X-ray absorptiometry was noted. Mean Z score for spine increased from -0.72 +/- 1.302 at baseline to near-normal levels (-0.09 +/- 1.503) by month 48 (p = 0.042) and for femoral neck from -0.59 +/- 1.352 to -0.17 +/- 1.206 (p = 0.035) at month 36. This increase was sustained at 48 months. With imiglucerase treatment, patients should anticipate resolution of BC, rapid improvement in BP, increases in BMD, and decreased skeletal complications.
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA. ksims@partners.org
authors.forename: K B
authors.initials: KB
authors.lastname: Sims
authors.forename: G M
authors.initials: GM
authors.lastname: Pastores
authors.forename: N J
authors.initials: NJ
authors.lastname: Weinreb
authors.forename: J
authors.initials: J
authors.lastname: Barranger
authors.forename: B E
authors.initials: BE
authors.lastname: Rosenbloom
authors.forename: S
authors.initials: S
authors.lastname: Packman
authors.forename: P
authors.initials: P
authors.lastname: Kaplan
authors.forename: H
authors.initials: H
authors.lastname: Mankin
authors.forename: R
authors.initials: R
authors.lastname: Xavier
authors.forename: J
authors.initials: J
authors.lastname: Angell
authors.forename: M A
authors.initials: MA
authors.lastname: Fitzpatrick
authors.forename: D
authors.initials: D
authors.lastname: Rosenthal
mesh_terms: D015519:Bone Density; D001847:Bone Diseases; D001851:Bone Diseases, Metabolic; D015331:Cohort Studies; D005260:Female; D005776:Gaucher Disease / Q000188:drug therapy*; D005962:Glucosylceramidase / Q000627:therapeutic use*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D011446:Prospective Studies; D013131:Spine / Q000378:metabolism*
chemical_list: D005962:Glucosylceramidase; C090568:imiglucerase