11 Skeletal involvement in Gaucher's disease

doi:10.1016/S0950-3536(97)80041-8

Baillière's Clinical Haematology

Volume 10, Issue 4, December 1997, Pages 793-816

https://doi.org/10.1016/S0950-3536(97)80041-8 Get rights and content

Perhaps the most variable of all the symptoms attributed to Gaucher's disease is that of bone involvement, both in the Type 1 and Type 3 forms of the disease. Expression of skeletal involvement in Gaucher patients ranges from asymptomatic disease, with or without radiological signs, to symptomatic disease, which can be severe and engender considerable pain and disability. Herein we discuss the imaging techniques currently available to document the presence and progression of bone involvement as well as the various forms of medical and surgical management that are employed to help the Gaucher patient cope with skeletal disease.

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Gaucher disease (GD), resulting from biallelic mutations in the gene GBA1, is a monogenic recessively inherited Mendelian disorder with a wide range of phenotypic presentations. The more severe forms of the disease, acute neuronopathic GD (GD2) and chronic neuronopathic GD (GD3), also have a continuum of disease severity with an overlap in manifestations and limited genotype-phenotype correlation. In very young patients, assigning a definitive diagnosis can sometimes be challenging. Several recent studies highlight specific features of neuronopathic GD that may provide diagnostic clues. Distinguishing between the different GD types has important therapeutic implications. Currently there are limited treatment options specifically for neuronopathic GD due to the difficulty in delivering therapies across the blood-brain barrier. In this work, we present both classic and newly appreciated aspects of the Gaucher phenotype that can aid in discriminating between acute and chronic neuronopathic GD, and highlight the continuing therapeutic challenges.
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Citation Excerpt :
Although bone crises typically occur in long bones they may also occur in other bones such as the skull or pelvis. Collapse of weight bearing bones may occur especially of the vertebral bodies, calcaneus and femoral head [16] and ‘romantic fractures’ of the ribs have been described [23]. Bone crises in the small bones of the hands and feet also occur but have been described rarely; they have been reported previously in studies of the hands [24] and feet [25] and in series of bone scans in Gaucher disease [7].
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Impact of velaglucerase alfa on bone marrow burden score in adult patients with type 1 Gaucher disease: 7-Year follow-up
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Bone marrow infiltration by substrate-engorged “Gaucher” cells manifests early in Gaucher disease (GD). The impact of velaglucerase alfa on bone marrow burden (BMB) was evaluated as an exploratory assessment.
BMB scores were assessed using T1- and T2-weighted magnetic resonance images of the lumbar spine (LS) and femora among symptomatic GD patients who participated in the 9-month Phase I/II trial and long-term extension study for velaglucerase alfa. A post-hoc assessment of marrow involvement was performed. BMB scores per site are 0–8 (0/1 = normal; 8 = severe infiltration).
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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.

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11 Skeletal involvement in Gaucher's disease

Lancet

Nuclear Medicine and Biology

Clinical Radiology

American Journal of Obstetrics and Gynecology

Lancet

Biochemical Biophysical Research Communications

Surgical Neurology

Journal of Pediatrics

Bilateral total hip replacement in a young woman with Gaucher disease

Harefuah

Pro-inflammatory cytokines and the pathogenesis of Gaucher's disease: increased release of interleukin-6 and interleukin-10

Quarterly Journal of Medicine

Skeletal manifestations and treatment of Gaucher's disease. A review of twenty cases

Journal of Bone and Joint Surgery

Aseptic necrosis in Gaucher's disease

Journal of Bone and Joint Surgery

Replacement therapy for inherited enzyme deficiency: macrophage-targeted glucocerebrosidase for Gaucher's disease

New England Journal of Medicine

Skeletal responses to enzyme replacement therapy in patients with Gaucher disease: What are the goals and expectations of treatment

Gaucher Clinical Perspectives

Bone involvement in Gaucher disease

Aminohydroxypropylidene-bisphosphonate in the treatment of bone lesions in a case of Gaucher's disease type 3

Acta Paediatrica

Effective treatment of painful bone crises in type I Gaucher's disease with high dose prednisolone

Archives of Disease in Childhood

Prophylaxis and treatment of osteoporosis

American Journal of Medicine

Effect of low-dose enzyme replacement therapy on bones in Gaucher disease patients with severe skeletal involvement

Blood, Cells, Molecules and Diseases

Skeletal involvement in a cohort of 266 patients with type I Gaucher disease

Gaucher disease—Norrbottnian type (III)

Acta Paediatrica Scandinavica

Treatment of bone complications in patients with Gaucher disease

Gaucher Clinical Perspectives

Bisphosphonates: pharmacology and use in the treatment of tumor-induced hypercalcaemic and metastatic bone disease

Drugs

Selective effects of glucocerebroside (Gaucher's storage material) on macrophage culture

Journal of Clinical Investigation

Total hip arthroplasty in Gaucher disease

Clinical Orthopedic and Related Research

Gaucher's disease type 1; assessment of bone involvement by CT and scintigraphy

American Journal of Radiology

Spinal cord compression in type I Gaucher disease

Radiology

MR Imaging in adults with Gaucher disease type I: evaluation of marrow involvement and disease activity

Skeletal Radiology

MRI of multiple platyspondyly in Gaucher disease: response to enzyme replacement therapy

Journal of Computer Assisted Tomography

Hemorrhage associated with ‘bone crisis’ in Gaucher disease identified by magnetic resonance imaging

Skeletal Radiology

Quantitative chemical shift imaging of the vertebral bone marrow in patients with Gaucher disease

Radiology

The natural history of osteonecrosis of the femoral head in children and adolescents who have Gaucher disease

Journal of Bone and Joint Surgery

Phenotypic manifestations of Gaucher disease: clinical features in 48 biochemically verified type I patients and comment on type II patients

Total hip replacement in Gaucher's disease

Journal of Bone and Joint Surgery

Gaucher disease: assessment with MR imaging

Radiology

Hip arthroplasties in Gaucher's disease

Journal of Bone and Joint Surgery

The pathology of Gaucher disease

Metabolic bone disease in patients with Gaucher's disease

Scintigraphic findings on 99mTc-MDP, 99mTc-sestamibi and 99mTc-HMPAO images in Gaucher's disease

European Journal of Nuclear Medicine

Chronic Gaucher's disease. Clinical observations on 34 patients

Israel Journal of Medical Sciences

Scintigraphic findings on ^99mTc-MDP, ^99mTc-sestamibi and ^99mTc-HMPAO images in Gaucher's disease