title: Decreased bone density in splenectomized Gaucher patients receiving enzyme replacement therapy.
abstract: 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.affiliation: Developmental and Metabolic Branch, National Institutes of Health, Bethesda, Maryland 20892, USA. RS4e@nih.gov
authors.forename: Raphael
authors.initials: R
authors.lastname: Schiffmann
authors.forename: Henry
authors.initials: H
authors.lastname: Mankin
authors.forename: James M
authors.initials: JM
authors.lastname: Dambrosia
authors.forename: Ramnik J
authors.initials: RJ
authors.lastname: Xavier
authors.forename: Constance
authors.initials: C
authors.lastname: Kreps
authors.forename: Suvimol C
authors.initials: SC
authors.lastname: Hill
authors.forename: Norman W
authors.initials: NW
authors.lastname: Barton
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Rosenthal
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D002117:Calcitriol / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D004798:Enzymes / Q000008:administration & dosage; D005260:Female; D005776:Gaucher Disease / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D005962:Glucosylceramidase / Q000008:administration & dosage*; D006801:Humans; D008161:Lumbosacral Region / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D013156:Splenectomy; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D004798:Enzymes; D005962:Glucosylceramidase; D002117:Calcitriol