Bone disease in patients with Gaucher disease

Abstract

Gaucher disease is an inborn error of metabolism due to a deficiency of the lysosomal enzyme glucocerebrosidase. As a result of this deficiency, the substrate glucocerebroside accumulates in the liver, spleen, bone and bone marrow. Bone involvement can lead to abnormalities in bone growth, bone remodeling, bone infarcts, aseptic necrosis, osteonecrosis, increased fracture risk and lytic bone lesions. Patients may experience bone pain and bone crises related to bone infarcts. There is evidence of abnormal bone metabolism in both bone resorption and bone formation based upon biochemical abnormalities found in patients. In addition, both immunological and coagulation abnormalities have in part been implicated in the causation of bone disease. Treatment with enzyme replacement therapy and substrate reduction therapy has led to improvement in both the symptoms and the radiographic abnormalities seen in these patients. It is unknown whether these treatments lower fracture risk.

Keywords:

• D-dimer
• gaucher
• glucocerebrosidase
• glucocerebroside
• macrophage
• osteocalcin
• telopeptide

Financial & competing interests disclosure

NJ Weinreb received a research grant from Genzyme – a Sanofi company and takes part in advisory boards for Genzyme, Shire, Pfizer, Synageva. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Gaucher disease (GD) is an inborn error of metabolism due to a deficiency of the lysosomal enzyme glucocerebrosidase.

• There are three types of GD with types 2 and 3 characterized by significant neurological impairment.

• Skeletal involvement can be severe and lead to significant morbidity.

• Treatment of GD with enzyme replacement therapy has markedly changed the natural history of the disease, especially for patients with type 1 disease.

• Normal bone physiology and homeostasis are a complex process that necessitates a balance between bone resorption and new bone formation.

• There is evidence using bone biomarkers that bone metabolism is impaired in GD.

• Enzyme replacement therapy and substrate reduction therapy have been shown to improve both the symptoms of bone disease as well as the abnormal imaging findings.

• There are both immunological and coagulation abnormalities described in GD that may impact bone metabolism.