Document Detail


Decreased bone density in splenectomized Gaucher patients receiving enzyme replacement therapy.
MedLine Citation:
PMID:  12064924     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Little is known about the effect of enzyme replacement therapy (ERT) on the bone abnormalities in Gaucher disease. Splenectomized Gaucher patients tend to suffer the most severe skeletal complications. We hypothesized that vitamin D supplementation would act synergistically with glucocerebrosidase infusions to increase bone density in splenectomized Gaucher patients. In a 24-month study, 29 splenectomized Gaucher patients were randomized to three groups: Group 1, calcitriol (1,25-dihydroxyvitamin D3; 0.25-3.0 microg/day) alone for the first 6 months with the addition of ceredase/cerezyme at 60 IU/kg every 2 weeks during months 7-12; Group 2, calcitriol together with ceredase/cerezyme at 60 IU/kg every 2 weeks during months 1-6; and Group 3, enzyme only at 60 IU/kg body wt every 2 weeks. In all three groups, enzyme dose was halved after the first 6 months of therapy. The primary outcome measure was bone mineral density of the lumbar spine measured by single-energy quantitative CT. Bone density by single-energy CT (P = 0.001) and by dual-energy CT (P = 0.06) declined overall, but there was no significant difference between the groups. Calcitriol had no significant effect on bone density. Fat fraction in lumbar spine increased (P = 0.000) and skeletal MRI scores improved. Bone-specific alkaline phosphatase (P = 0.002) and serum osteocalcin increased (P = 0.008), while blood cyclic AMP and urinary deoxypyridinoline did not change appreciably. Hemoglobin, platelet counts, and liver volume significantly improved. We conclude that ERT alone, or in combination with calcitriol, cannot repair the bone composition in splenectomized adult Gaucher patients. Alternatively, measuring trabecular bone density may be an inadequate marker of clinical efficacy for treating skeletal involvement in Gaucher disease.
Authors:
Raphael Schiffmann; Henry Mankin; James M Dambrosia; Ramnik J Xavier; Constance Kreps; Suvimol C Hill; Norman W Barton; Daniel I Rosenthal
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial    
Journal Detail:
Title:  Blood cells, molecules & diseases     Volume:  28     ISSN:  1079-9796     ISO Abbreviation:  Blood Cells Mol. Dis.     Publication Date:    2002 Mar-Apr
Date Detail:
Created Date:  2002-06-14     Completed Date:  2003-08-05     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  9509932     Medline TA:  Blood Cells Mol Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  288-96     Citation Subset:  IM    
Affiliation:
Developmental and Metabolic Branch, National Institutes of Health, Bethesda, Maryland 20892, USA. RS4e@nih.gov
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MeSH Terms
Descriptor/Qualifier:
Adult
Biological Markers / analysis
Bone Density / drug effects*,  physiology
Calcitriol / administration & dosage
Drug Therapy, Combination
Enzymes / administration & dosage
Female
Gaucher Disease / complications,  drug therapy*,  physiopathology*
Glucosylceramidase / administration & dosage*
Humans
Lumbosacral Region / physiopathology
Male
Middle Aged
Splenectomy
Treatment Outcome
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Enzymes; 32222-06-3/Calcitriol; EC 3.2.1.45/Glucosylceramidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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