Bone complications in Gaucher disease

Abstract

Purpose: Gaucher disease (GD; OMIM # 230800) is an autosomal recessively inherited lysosomal storage disease. GD is caused by a deficiency of the lysosomal enzyme, glucocerebrosidase (GBA, also called acid ß-glucosidase or GCase), which hydrolyzes glucosylceramide (GlcCer) into ceramide and glucose. As a consequence of mutations in the GBA1 gene located on chromosome 1 (1q21) there is an accumulation of GCase substrate, GlcCer, in macrophages. Bone tissue represents a large systemic compartment of the human body, with an active metabolism that controls mineral deposition and removal, and where several factors may play a role. For these reasons, several non-skeletal diseases may influence bone metabolism. Methods: The present review describes bone skeletal manifestations in the GD and the role of several factors. This manuscript is the result of a review of the literature that focused on the bone manifestations of GD. In particular, relevant studies were identified through a PubMed search strategy. Step 1 consisted of a systematic literature search using the terms: Bone Metabolic Rare Diseases, Hematological Rare Diseases, Gaucher Disease; step 2 involved adding the terms “osteoporosis” or “bone mass”, or “bone turnover” or “bone fragility” or “bone deformity”, or “bone biomarkers”. Results: The skeletal manifestations of GD include a variety of bone pathologies due to various factors. These pathologies include bone infarcts, avascular bone necrosis, cortical thinning, lytic bone lesions, osteosclerosis and fractures due to osteopenia or osteoporosis, and rarely acute osteomyelitis. Conclusions: Bone loss in patients with GD should be managed, whenever possible, at or in close liaison with a center that specializes in the diagnosis, management and therapy of metabolic bone diseases. A multidisciplinary approach is important to better understand the complexity and pathogenesis of bone involvement in GD. In this way it will be possible to refine and standardize the diagnostic and therapeutic approaches to bone disease in GD.