Gaucher disease: a systematic review and meta‐analysis of bone complications and their response to treatment

Abstract

Type 1 Gaucher disease (GD1) is an inherited lysosomal storage disease, which is often managed by enzyme replacement therapy (ERT). The bone response to ERT is usually slower than visceral and hematological responses. There is uncertainty as to whether an increase in the dosage of ERT has a beneficial effect. The aim of our study was to determine whether or not there is sufficient evidence to make a definitive statement about the effects of ERT and substrate reduction therapy (SRT) on bone marrow infiltration and bone mineral density (BMD) in GD1. We conducted a systematic review of all studies examining the effects of ERT and SRT on bony complications of GD1 published before July 2008. The studies were identified by a computerized search with use of Medline, Embase, The Cochrane Database of Systematic Reviews, The Cochrane Central Register of Controlled Trials (CCTR), and bibliographies of papers subsequently retrieved from the search. Three hundred studies were grouped according to whether they deal with the natural history of GD1 or therapeutic issues, and 17 studies were included in the review. The results from our systematic review suggest that further investigations, such as better analysis of the Gaucher Registry, are needed on the effects of ERT and SRT on bony complications of GD1. Studies on the effects of the newly identified velaglucerase and the plant-derived glucocerebrosidase on bony complications of GD1 are also needed.

Management of Bone Disease in Gaucher Disease Type 1: Clinical Practice

“…A meta-analysis of clinical studies evaluated the effects of ERT on bone complications from GD, suggesting that the bone marrow fat fraction increases significantly following treatment and that 70% of adults with GD respond to treatment [48]. ERT increases the hyperintense T1-weighted MRI signal in bone marrow and significantly reduces BMB scores in patients with GD [28,49].…”

Retrospective Analysis of Whole-Body Magnetic Resonance Imaging of Bone Manifestations in Long-Term Treated Patients with Gaucher Disease Type 1

“…Several studies have demonstrated the effectiveness of ERT during the first years of treatment, based on MRI analyses [7,18]. Usually, after ERT initiation in Gaucher disease major response occurs within the first years [1,23], following a first order kinetic, while later on only small changes occur.…”

Lysosome-Targeted Octadecyl-Rhodamine B-Liposomes Enhance Lysosomal Accumulation of Glucocerebrosidase in Gaucher‘S Cells In Vitro

“…Velaglucerase alfa (VPRIV™; Shire Human Genetic Therapies, Inc., MA, USA), is one of the therapeutic enzymes available for treatment of Gaucher’s disease [8]. Clinical trials with VPRIV have produced significant improvements in the condition of patients [9].…”