Skeletal complications of Gaucher disease.
Stowens D W,Teitelbaum S L,Kahn A J,Barranger J A
Gaucher disease is a collection of related disorders of sphingolipid catabolism caused by the deficiency of a specific beta-glucosidase. The inefficiency of this enzyme, glucocerebrosidase, to degrade its natural substrate leads to the accumulation of the complex lipid glucocerebroside in tissue macrophages. The pathogenesis of the disease is, as yet, poorly understood. The manifestations of the disease are protean with hepatosplenomegaly and bone deterioration frequently the predominating signs. The disease most frequently causes disability because of its effects on the skeleton. This review seeks to summarize the current clinical understanding of these complications. Experience with 327 patients reveals that the bone disease in this disorder is extremely variable. The severity of the problems range from asymptomatic persons with neither radiographic, scintigraphic, nor histologic evidence of bone involvement to those whose skeleton is completely devastated by a process of osteopenia, osteonecrosis, and osteosclerosis. These severely affected individuals show the most bizarre deformities in their bones and are subject to pathologic fracture. Most patients fortunately, are less profoundly affected, but many are plagued by bone pain of an arthritic nature or by an acute prostrating bone crisis probably best described as a bone infarction. The accepted etiology that these crises are a result of vascular compromise produced by occlusion of vessels by Gaucher cells is not supported by scintigraphic or histologic studies. Moreover, the vascular hypothesis does not explain the variety of lesions of the skeleton seen in this multifocal bone disease. Preliminary metabolic and endocrinologic studies suggest that this is not a systemic disorder of metabolism which affects bone uniformly. On the contrary, the lesions are multiple and localized, and sometimes much of the skeleton is preserved. These observations suggest that bone is affected because of collections of Gaucher cells scattered throughout its substance and may be the result of a toxic process around these foci. Alternatively, the storage of glucocerebroside in tissue macrophages may disturb the generation of competent osteoclasts and thus result in a failure to maintain a healthy skeleton. Further research is needed to delineate the pathogenesis of this disorder before any effective therapy can be developed.
[Osteoarticular manifestations of Gaucher disease in adults: pathophysiology and treatment].
Javier Rose-Marie,Hachulla Eric
Presse medicale (Paris, France : 1983)
Gaucher disease frequently has severe osteoarticular manifestations that may be disabling. Ischemic phenomena cause the most serious complications and lead to irreversible lesions. Aseptic osteonecrosis of the hip is the most disabling complication; it causes intense early bone pain and often joint collapse and secondary osteoarthritis in young adults. Localized or systemic bone fragility explains osteopenia, osteoporosis, and fractures (vertebral collapse with irreversible kyphosis causing chronic morbidity). Although no double-blind randomized studies have assessed the bone effects of enzyme replacement therapy, it has been shown effective in reducing bone pain in about half of all treatment-naive patients within 1 to 2 years and in improving bone mineral density after 3 years. In open-label trials, substrate reduction therapy (miglustat) reduced both bone pain and bone marrow infiltration. Specific treatment for bone fragility, with bisphosphonates for example, should be considered after rigorous individualized evaluation and assessment of other risk factors.