Gaucher disease: alendronate disodium improves bone mineral density in adults receiving enzyme therapy

Abstract

Symptomatic patients with Gaucher disease (GD) (acid ␤-glucosidase [Gcase] deficiency) are treated with injectable human recombinant GCase. Treatment results in significant decreases in lipid storage in liver, spleen, and bone marrow, but the generalized osteopenia and focal bone lesions present in many adult patients are refractory to treatment. A double-blind, 2-arm, placebo-controlled trial of alendronate (40 mg/d) was performed in adults with GD who had been treated with enzyme for at least 24 months. Primary therapeutic endpoints were improvements in (1) bone mineral density (BMD) and content (BMC) at the lumbar spine, and (2) focal lesions in x-rays of long bones assessed by a blinded reviewer. There were 34 patients with GD type 1 (age range, 18-50 years) receiving enzyme therapy who were randomized for this study. After 18 months, ⌬BMD at the lumbar spine was 0.068 ؎ 0.21 and 0.015 ؎ 0.034 for alendronate and placebo groups, respectively (P ‫؍‬ .001). Long-bone x-rays showed no change in focal lesions or bone deformities in any subject in either arm. Alendronate is a useful adjunctive therapy in combination with enzyme replacement therapy (ERT) for the treatment of GD-related osteopenia in adults, but it cannot be expected to improve focal

Individualization of long-term enzyme replacement therapy for Gaucher disease

“…However, alternative strategies should also be considered such as adjuvant therapy with bisphosphonates for adults who fail to achieve significant improvement in osteopenia in the expected time frame. 12 …”

“…Adult patients with severe osteopenia/osteoporosis may benefit from the use of adjunctive treatments (e.g., bisphosphonates). 12 The use of bone antiresorptive agents in affected children is currently under investigation.…”

Risk factors for fractures and avascular osteonecrosis in type 1 Gaucher disease: A study from the International Collaborative Gaucher Group (ICGG) Gaucher Registry

“…(13) The addition of oral alendronate (40 mg/d) to imiglucerasetreated GD1 patients substantially increased the rapidity and magnitude of the bone mineral density response in premenopausal women and in men to age 70 years. (34) However, a benefit in terms of fracture outcome was not investigated within the time frame of the study, and a role for bisphosphonate therapy for GD1-related osteopenia/osteoporosis, although commonly prescribed, remains conjectural. In an uncontrolled case study, the 10-year probability of a new fracture in elderly GD1 women treated with imiglucerase was twofold to threefold greater than that expected in comparably aged osteoporotic women without Anemia is defined according to age and gender norms for hemoglobin concentrations as follows: <12 g/dL for males older than 12 years; <11 g/dL for females older than 12 years; <10.5 g/dL for children ages >2 to 12 years; <9.5 g/dL for children ages 6 months to 2 years; and <10.1 g/dL for children younger than 6 months of age.…”

Improvement in hematological, visceral, and skeletal manifestations of Gaucher disease type 1 with oral eliglustat tartrate (Genz-112638) treatment: 2-year results of a phase 2 study

“…A mean increase in BMD of ϳ 8% was previously reported in osteopenic adult GD1 patients after 2 years of treatment with a high dose of alendronate in conjunction with ERT, whereas ERT plus placebo did not significantly change BMD. 10 None of the 16 phase 2 patients in this analysis received bisphosphonates during or for 3 months before the study. It is also noteworthy that the phase 2 data include responses in patients with normal as well as abnormal baseline lumbar spine BMD.…”