OBJECTIVE: Eliglustat is an investigational oral substrate reduction therapy for 
Gaucher disease type 1 (GD1). Its skeletal effects were evaluated by prospective 
monitoring of bone mineral density (BMD), fractures, marrow infiltration by 
Gaucher cells, focal bone lesions, and infarcts during an open-label, 
multi-site, single-arm phase 2 trial (NCT00358150).
MATERIALS AND METHODS: Institutional review board approval and patient informed 
consent were obtained. Eliglustat (50 or 100 mg) was self-administered by mouth 
twice daily; 19 patients completed 4 years of treatment. All were skeletally 
mature (age range, 18-55 years). DXA and MRI assessments were conducted at 
baseline and annually thereafter. X-rays were obtained annually until month 24, 
and then every other year.
RESULTS: Lumbar spine BMD increased significantly (p = 0.02; n = 15) by a mean 
(SD) of 9.9% (14.2%) from baseline to year 4; corresponding T-scores increased 
significantly (p = 0.01) from a mean (SD) of -1.6 (1.1) to -0.9 (1.3). Mean 
femur T-score remained normal through 4 years. Femur MRI showed that 10/18 (56%) 
patients had decreased Gaucher cell infiltration compared to baseline; one 
patient with early improvement had transient worsening at year 4. There were no 
lumbar spine or femoral fractures and no reported bone crises during the study. 
At baseline, 8/19 (42%) patients had focal bone lesions, which remained stable, 
and 7/19 (37%) patients had bone infarctions, which improved in one patient by 
year 2. At year 4, one new asymptomatic, indeterminate bone lesion was 
discovered that subsequently resolved.
CONCLUSIONS: Eliglustat may be a therapeutic option for treating the skeletal 
manifestations of GD1.