A Prematurely Halted, Randomized, Controlled Clinical Trial of Alendronate Treatment in Patients with Gaucher Disease

Abstract

Overview: Most symptomatic patients with Gaucher disease (GD) are treated with periodic injections of recombinant glucocerebrosidase (GC). This therapy results in decreases in glucosylceramide storage in the liver and spleen, but signs and symptoms of osteopenia have proven refractory to enzyme therapy.

The purpose of this investigation was to determine whether the osteopenia of GD can be corrected by bone anti-resorptive therapy in patients who are receiving enzyme therapy. We initiated a two-year, double-blind, two-arm, placebo -controlled trial of alendronate , at a dose of 40 mg/day, in adults with GD who had been treated for at least six months with GC enzyme therapy. Therapeutic outcome was monitored by dual-energy x-ray absorptiometry (DXA) measurements of both bone mineral density (BMD) and bone mineral content (BMC) at the lumbar spine and whole body DXA scans at entry into the study and at six-month intervals until the end of the study.

Data were collected on 31 patients. Because a large group difference became apparent after six months of treatment, the group randomization code was broken. It was found that 16 patients had been randomized to alendronate and 15 to placebo .

Approach: Due to the small sample sizes, a longitudinal model was not applied to the dataset. Instead, we calculated the mean of the measured variables between the second visit and the most recent visit and the differences between this mean and baseline measurements for each individual. A paired t test was used to check whether the resulting differences were qualitatively different from zero, and a two-sample t test was applied to determine whether BMD improved in patients assigned to alendronate compared to those assigned to placebo . In another statistical approach, we calculated linear regressions to obtain the change in slopes of the outcome parameters in the two groups over time for patients who had more than one visit.

Results: Lumbar spine BMC and BMD increased significantly in the alendronate group after the first six months of treatment compared to baseline measurements. Compared to the placebo group, the alendronate group also had significantly greater increases in total body BMC and BMD after six months of treatment.

Conclusion: Given the significant increments in lumbar and total body BMD and BMC in the patients assigned to alendronate versus placebo , it is reasonable to conclude that patients with the osteopenia of Gaucher disease should be treated with alendronate or a similar bone anti-resorptive agent unless there are sound reasons not to do so.