Abstract | BACKGROUND: OBJECTIVE: We hypothesized that osteopenia develops early in life, during the natural course of type 1 Gaucher disease (GD1), and that its response to treatment is maximal during this period. METHODS: We examined data from the International Collaborative Gaucher Group (ICGG) Gaucher Registry of patients treated with imiglucerase between the ages of 5 and 50 years. Lumbar spine bone mineral density (BMD) (determined by dual-energy X-ray absorptiometry (DXA) and expressed as Z-scores) at baseline and for up to 10 years on imiglucerase were analyzed in children (ages ≥ 5 to <12 years), adolescents (≥ 12 to <20 years), young adults (≥ 20 to < 30 years), and older adults (≥ 30 to < 50 years). BMD was correlated with other disease characteristics. Pre-treatment, descriptive statistics were applied to 5-year age categories. Non-linear mixed effects regression models were used to analyze DXA Z-scores over time after treatment with imiglucerase. RESULTS: Pre-treatment, low BMD was prevalent in all age groups, most strikingly in adolescents. DXA Z-scores were at or below -1 in 44% of children (n=43), 76% of adolescents (n=41), 54% of young adults (n=56) and 52% of older adults (n=171). The most common GBA1 genotype was N370S heteroallelic. Baseline hematological and visceral manifestations in the 4 age groups were similar. In children with DXA Z-scores ≤-1 at baseline, imiglucerase therapy for 6 years resulted in improvement of mean DXA Z-scores from -1.38 (95% CI -1.73 to -1.03) to -0.73 (95% CI -1.25 to -0.21); in young adults DXA Z-scores improved from -1.95 (95% CI -2.26 to -1.64) to -0.67 (95% CI -1.09 to -0.26). BMD also improved in older adults, but the magnitude of the improvement was lower compared to younger patients. CONCLUSIONS:
Low bone density is common in GD1 with the highest prevalence rate in adolescence, a developmental period critical to attainment of peak bone mass. Imiglucerase results in amelioration of osteopenia in all age groups, with the greatest improvements in younger patients.
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Authors | Pramod K Mistry, Neal J Weinreb, Paige Kaplan, J Alexander Cole, Andrea R Gwosdow, Thomas Hangartner |
Journal | Blood cells, molecules & diseases
(Blood Cells Mol Dis)
Vol. 46
Issue 1
Pg. 66-72
(Jan 15 2011)
ISSN: 1096-0961 [Electronic] United States |
PMID | 21112800
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2010 Elsevier Inc. All rights reserved. |
Chemical References |
- Recombinant Proteins
- Glucosylceramidase
- imiglucerase
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Topics |
- Adolescent
- Adult
- Age of Onset
- Bone Density
- Bone Diseases, Metabolic
(etiology)
- Child
- Child, Preschool
- Enzyme Replacement Therapy
- Female
- Follow-Up Studies
- Gaucher Disease
(complications, drug therapy)
- Glucosylceramidase
(therapeutic use)
- Humans
- Male
- Middle Aged
- Recombinant Proteins
(therapeutic use)
- Registries
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