Skeletal or bone disease is a common manifestation of Gaucher disease, causing significant disability that impacts the patient’s quality of life. At least 62% of people with Gaucher disease have some form of bone abnormality detectable by imaging tests, studies show.
Gaucher disease is characterized by the accumulation of a fat molecule called glucocerebroside inside cells. This is caused by the lack of the enzyme beta-glucocerebrosidase responsible for its breakdown. The build-up of glucocerebroside and its related compounds, including glucosylsphingosine and glucosylceramide, in the body interfere with bone metabolism, preventing the removal of old bone tissue and the formation of new tissue.
Two main cell types play a central role in bone metabolism: osteoblasts and osteoclasts. In response to signals from cells, osteoblasts build new bone tissue to replace older tissue. Osteoclasts break down the old bone tissue in preparation for the bone regeneration process.
Research has shown that high levels of fat molecules such as glucosylsphingosine and glucosylceramide in people with Gaucher disease interfere with the activities of the osteoblasts and osteoclasts, disturbing the bone metabolism process and resulting in bone disease. Researchers isolated osteoblasts and osteoclasts from Gaucher disease patients and treated them with glucosylceramide to study its impact. Glucosylceramide increased osteoclast activity while slowing osteoblast function, indicating a change in the bone remodeling process.
An overactive immune system and the resulting inflammation also contribute to the damage seen in Gaucher disease. Several immune cells can influence bone growth and regeneration. Many of these immune cells, especially macrophages, are overactive in Gaucher disease patients. Gaucher cells can infiltrate the bone marrow to trigger continuous inflammation and interrupt blood flow, causing osteonecrosis. Pro-inflammatory cytokines — cell signaling molecules released by the activated macrophages — also can stimulate the overproduction of osteoclasts, causing increased bone weakness, and loss of bone minerals leading to porosity.
Although Gaucher disease can impact any of the bones in the body, it primarily affects the femur or the thighbone. “Erlenmeyer flask” deformity of the femur is one of the early signs of bone involvement in Gaucher disease. The middle section of the long bone is narrowed and the wider end portion is expanded, resembling an Erlenmeyer flask.
In addition to Erlenmeyer flask deformity, people Gaucher disease have a number of other bone symptoms. These include:
- Varying levels of bone pain
- Arthritis causing joint pain and damage
- Osteopenia, or reduced bone density causing bone weakness
- Osteoporosis, or porous and fragile bones
- Loss of calcium and minerals
- Frequent fractures
- Osteonecrosis or avascular necrosis, or bone tissue death due to a lack of oxygen
Imaging studies are used to detect bone lesions in Gaucher disease. Magnetic resonance imaging (MRI) is the most commonly used technique. Others include computed tomography (CT), dual-energy X-ray absorptiometry (DEXA), and radionucleotide imaging.
Available treatments for Gaucher disease cannot reverse the bone damage that has already occurred. Enzyme replacement therapy (ERT) can help increase bone mineral density and limit bone loss to slow down disease progression.
The management of bone pain is based on the person’s age, pain intensity, and bone complications. Pain medications like acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs ) such as ibuprofen can help ease mild to moderate pain. Opioids such oxycodone are very rarely prescribed due to the high risk of addiction.
A severe bone injury, such as osteonecrosis of the hip, can only be addressed by orthopedic surgery to correct joint damage and improve range of motion.
Physiotherapy in consultation with a trained physiotherapist can help prevent joint stiffness and maintain mobility. Specific exercise routines, designed based on the patient’s health status, also can help build muscle strength, which in turn can support the bones. Post-surgery physiotherapy is vital to stabilize the bones, help patients gain strength, and increase the range of motion in the joints.
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