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Skeletal Assessments

Assessment of skeletal pathology requires multiple imaging methods: MRI to assess bone marrow infiltration, plain radiography to detect fractures, and dual X-ray absorptiometry (DEXA) of lumbar spine and femoral neck to measure bone mineral density (BMD). T1-weighted MRI detects and quantifies marrow infiltration, whereas T2 MRI identifies lesions, active bone infarcts, osteonecrosis, and osteomyelitis.

Potential Bone Disease Caused by Type 1 Gaucher Disease

Most patients with nonneuronopathic Gaucher disease have skeletal pathology, which is often the most debilitating feature.

Bone disease in type 1 Gaucher disease is multifaceted. Three, often coexistent, pathologic presentations have been identified: focal disease (lytic and/or sclerotic lesions associated with infarction, thrombosis, and inflammatory processes that can progress to osteonecrosis), local disease (remodeling defects and long bone deformities such as Erlenmeyer flask deformity, and cortical bone thinning), and generalized osteopenia and osteoporosis. Osteoporosis is associated with an increased risk of pathologic fracture.

The functional effects of these osseous manifestations of Gaucher disease can include loss of skeletal function (due to fractures and joint deterioration) and various combinations and fluctuations of acute and chronic bone pain. Chronic bone pain is usually either dull and achy, or localized and intense. Acute, excruciating episodic bone pain is characteristic of Gaucher bone crises, which typically causes debilitation lasting several days or longer. Bone crises may also be accompanied by swelling, tenderness, periosteal elevation, leukocytosis, and fever, and can mimic osteomyelitis.

Bone Marrow Infiltration

(Image 1) X-ray verses MRI of the femur

While plain radiography is useful for monitoring bone disease, it is a relatively insensitive technique for evaluating the burden of bone disease compared to Magnetic Resonance Imaging (MRI). In Image 1, the left image, a plain radiograph of the femur shows little evidence of skeletal disease. However, MRI (shown on right) reveals quite extensive marrow infiltration indicating significant bone involvement.

Erlenmeyer Flask Deformity and Osteosclerosis

(Image 2) Erlenmeyer Flask Deformity

Erlenmeyer flask deformity is commonly seen in Gaucher patients. It is observed mainly at the distal femur and proximal tibia and is due to a remodeling failure following the synthesis of new bone in the metaphyseal region. This leads to the characteristic exaggeration of the normal flare shown in Image 2.

Osteosclerosis, both diffuse and localized, may be seen in patients with severe disease. It is shown on this radiograph as hyperdense (or hyperopaque) areas.

Osteonecrosis

(Image 3) Left: Avascular Necrosis of the humeral head. Right: Cross section showing marrow replacement and bone necrosis of the femur

The image on the left shows osteonecrosis (also termed avascular necrosis) that led to a joint collapse. This is often seen on radiographs as a wedge-shaped infarction commonly in the weight-bearing portion of the femoral or humeral heads. It is associated with pain. Osteonecrosis shows as a deformation of the head and acetabulum. In the long bones it often progresses silently. Bone crises often signal medullary or corticomedullary infarction and pathologic fractures may be observed in the affected areas.

The image on the right is a cross section showing marrow replacement and bone necrosis.

Osteopenia / Pathologic Fracture

(Image 4) Left: Osteopenia of the femur Right: Fracture in the humeral shaft

As shown on the left, bone mineral damage can manifest in a number of complications. A reduction in bone density results from diffuse cortical and trabecular bone loss (osteopenia) and leads to a general weakening of the skeleton. In addition to the generalized loss, localized areas of bone loss can be seen, affecting mainly the diaphyses of long bones and the vertebrae. These so-called lytic areas are particularly prone to fracture and represent significant bone disease.

The weakened bone of a Gaucher patient is prone to fracture. The right-hand image shows a fracture in the humeral shaft of a 22-year-old female patient.

Bone Disease Affects Most Patients With Gaucher Disease* – Gaucher Registry Data

Data on the history of bone symptoms and radiological bone disease were available for a subset of patients participating in the Gaucher Registry. The total number of patients for each manifestation is the number for whom information was available on that specific manifestation; the number of patients experiencing the manifestation is a subset of that total number. More than one radiological sign could be reported for an individual patient.

Important Safety Information

Approximately 15% of patients have developed immune responses (antibodies). These patients have a higher risk of an allergic reaction (hypersensitivity). Use Cerezyme® (imiglucerase for injection) carefully if you have had an allergic reaction to the product in the past. Symptoms suggestive of allergic reaction happened in 6.6% of patients, and include anaphylactoid reaction (a serious allergic reaction), itching, flushing, hives, an accumulation of fluid under the skin, chest discomfort, shortness of breath, coughing, cyanosis (a bluish discoloration of the skin due to diminished oxygen), and low blood pressure. Side effects related to Cerezyme administration have been reported in less than 15% of patients. Each of the following events occurred in less than 2% of the total patient population. Reported side effects include nausea, vomiting, abdominal pain, diarrhea, rash, fatigue, headache, fever, dizziness, chills, backache, and rapid heart rate. Because Cerezyme therapy is administered by intravenous infusion, reactions at the site of injection may occur: discomfort, itching, burning, swelling or uninfected abscess. Cerezyme is available by prescription only. For more information, consult your physician. To learn more, please see full product information (PDF), or contact Genzyme at 1-800-745-4447.

Charrow J, Andersson HC, Kaplan P, et al. The Gaucher registry: demographics and disease characteristics of 1698 patients with Gaucher disease. Arch Intern Med. 2000;160:2835-2843.

Wenstrup RJ, Roca-Espiau M, Weinreb NJ, et al. Skeletal aspects of Gaucher disease: a review. Br J Radiol. 2002;75(suppl 1):A2-A12.

Weinreb NJ, Aggio MC, Andersson HC, et al. Gaucher disease type 1: Revised recommendations on evaluations and monitoring for adult patients. Semin Hematol. 2004;41(4 suppl 5):15-22.