Skeletal aspects of Gaucher disease: a review

In Gaucher disease, a genetic deficiency in the activity of the lysosomal enzyme beta-glucocerebrosidase (acid beta-glucosidase) causes monocytes and macrophages to store excessive amounts of glucocerebroside in lysosomes. The resulting distended cells are called Gaucher cells, and the pathology associated with this condition stems from the accumulation of Gaucher cells in organ systems. The skeletal manifestations are probably the most disabling aspect of the disease. Patients commonly experience bone pain, some suffer bone crises, and up to 20% have impaired mobility. Radiological findings include Erlenmeyer flask deformity, osteopenia, osteosclerosis, osteonecrosis, fractures and bone marrow infiltration. Findings from the Gaucher Registry show that nearly all patients with Gaucher disease have radiological evidence of skeletal involvement, and the majority have a history of serious skeletal complications. Skeletal involvement follows three basic processes: focal disease (irreversible lesions such as osteonecrosis and osteosclerosis), local disease (reversible abnormalities adjacent to heavily involved marrow such as cortical thinning and long bone deformity) and generalized osteopenia. Infarctions are involved in some of the skeletal manifestations, but the mechanisms causing high rates of bone turnover and failure of remodelling are not known. The availability of a beta-glucocerebrosidase-deficient mouse model of Gaucher disease with long-term survival should help elucidate the skeletal pathology in Gaucher disease and may ultimately lead to improved management of skeletal complications.