The Diagnosis and Therapy of Osteoporosis in Gaucher Disease

Gaucher disease is a rare lysosomal storage disorder characterized by the accumulation of glucocerebroside lipids within multiple organs due to a deficiency of the lysosomal enzyme (acid β-glucosidase). It is an inherited autosomal recessive disease. The onset of symptoms can vary depending on disease type and severity, with milder forms presenting in adulthood. The main clinical manifestations include cytopenia, splenomegaly, hepatomegaly, and bone lesions. GD is characterized by several bone manifestations, such as osteopenia/osteoporosis, focal lytic or sclerotic lesions, osteonecrosis acute or chronic bone pain, Erlenmeyer flask deformity, and subchondral joint collapse with secondary degenerative arthritis. In 70-100% of patients affected by Gaucher disease type 1, clinical or radiographic evidence of bone disease occurs. Among bone complications, osteoporosis is very common, but its etiopathogenesis in GD is not completely clear. Results deriving from experimental studies support the hypothesis that there is an aberrant activity of both osteoclasts and osteoblasts due to several factors, resulting in impaired bone turnover. Bone complications represent the main cause of pain, disability, and reduced quality of life in these patients. Therefore, there is a need to enhance awareness among physicians on the skeletal manifestations throughout life of GD patients, in order to improve diagnosis and management of bone complications. In particular, this narrative review focuses on risk of bone fragility in GD, etiopathogenetic hypotheses, epidemiological data, diagnosis, monitoring, and treatment of osteoporosis in patients suffering from Gaucher disease, specifying the challenges not yet addressed.