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.
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.
Sims
K B
KB
Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA. ksims@partners.org
Pastores
G M
GM
Weinreb
N J
NJ
Barranger
J
J
Rosenbloom
B E
BE
Packman
S
S
Kaplan
P
P
Mankin
H
H
Xavier
R
R
Angell
J
J
Fitzpatrick
M A
MA
Rosenthal
D
D
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*
D005962:Glucosylceramidase; C090568:imiglucerase