Therapeutic approaches to bone pathology in Gaucher disease: past, present and future

Abstract

Enzyme replacement therapy (ERT) is effective for the treatment of the systemic manifestations of Gaucher disease (GD) and can have a significant impact on skeletal manifestations. Bone involvement is broad and can occur in otherwise clinically asymptomatic individuals. The heterogeneity in GD-related bone disease may implicate multiple pathological processes such as disruption of coordinated bone cell activity, in addition to the physical impact of Gaucher cells causing vascular occlusion. Accumulated data suggests that earlier treatment initiation decreases skeletal complications and that bone disease may require a longer duration of treatment and higher dose than is necessary for organ involvement and hematopoietic manifestations. However, in some patients, bone manifestations persist and even worsen despite ERT, regardless of dose or duration of treatment. Treating skeletal disease should be considered of equal importance as treating visceral and hematologic manifestations. When treatment decisions involve multiple enzyme preparations and other therapeutic modalities such small molecules, the choice should be tailored on an individual basis with continuing evaluation.