Bone pain and fractures are common issues associated with Gaucher disease. But unlike other symptoms of Gaucher disease, bone manifestations of Gaucher disease are often dismissed—especially in young patients. Without timely treatment, Gaucher disease can affect how your bones function and cause debilitating pain and injury.
We turned to Neal Weinreb, MD, FACP, to learn more about how Gaucher disease affects bone function and causes bone symptoms. Dr. Weinreb serves as Regional Coordinator of the International Collaborative Gaucher Group. His career focus is research and management of lysosomal storage disorders including Gaucher disease.
Functions of Bone
To understand how Gaucher disease impacts bone, it’s important to realize the role of bone within the body. When many people think about bones, they picture a skeleton. They may also assume bones are solid like rock or stone. Nonetheless, bone is an active tissue—always changing and remodeling, with many functions including:
- Making and circulating blood: The spongy tissue inside bone (bone marrow) makes blood cells. Blood vessels circulate blood by weaving through the marrow and through small canals in the hard, outer tissue of bones.
- Providing structural support: Bones provide support for the movements of joints, tendons, and ligaments. To stay strong, bones go through a complex process of bone metabolism—a continuous cycle of bone turnover.
How Gaucher Disease Affects Bone Function
There are many ways Gaucher disease disrupts bone function. When Gaucher disease slows down the production of blood cells, it causes hematologic (blood-related) symptoms. But when Gaucher cells disturb the bone’s ability to stay strong and support the body, that’s when bone-related symptoms arise.
Interfering with blood supply
Anytime blood supply fails, it can lead to tissue injury or death—a process known as infarction. When Gaucher cells infiltrate the bone marrow, they interfere with normal blood flow and circulation. They can also interrupt blood supply.
The presence of Gaucher cells initiates a response from the body’s immune system. As a result, fluid and swelling can narrow and block blood vessels. Gaucher cells also release inflammatory chemicals which affect endothelial cells. These cells line blood vessels and introduce a blood clotting process that can block normal blood supply.
“Like any other living tissue, a bone’s ability to be viable depends on getting oxygen and nutrients, which is dependent on blood flow,” Dr. Weinreb says. “Interruption of that vital blood supply can cause temporary or even permanent damage to the bone.”
Disrupting the process of bone modeling and repair
To stay strong, bones are constantly remodeled through a sophisticated and complex process. Specialized macrophage cells called osteoclasts break down and absorb older, worn bone. Other specialized cells called osteoblasts then build and mineralize new bone.
In simple terms, Dr. Weinreb says the process is like sidewalk repair. First, workers (osteoclasts) dig up damaged concrete and get rid of it. When that’s done, the reconstruction crew (osteoblasts) comes in to pour new concrete.
Chemicals secreted by Gaucher cells in the bone marrow can disrupt this balanced process of bone metabolism. “Gaucher cells seem to be toxic to the osteoblast cell,” Dr. Weinreb says. “It keeps those cells from multiplying and maturing, which interferes with bone rebuilding.”
Bone Manifestations of Gaucher Disease
When left untreated, Gaucher disease can cause many symptoms, including various bone-related issues. Bone manifestations often affect people with Gaucher disease type 1 and type 3. These symptoms are also more likely in people who’ve had a splenectomy. Bone symptoms of Gaucher disease can be occasional or chronic. Even so, many people with Gaucher disease experience at least one bone manifestation in their lifetimes.
Bone pain and bone crisis
Many people with Gaucher disease experience chronic bone pain. The pain, caused by reduced blood flow to the bone, is usually dull and often localized to the joints, legs, and back. Approximately 15% to 20% of people with Gaucher disease report having episodes of bone crisis—bone pain that is extreme and acute.
“Individuals seem to be perfectly healthy and functional one day, but then suddenly develop excruciating pain in one site—often the hip or knee,” Dr. Weinreb says. “The main cause is disruption of blood flow and infarction.” A bone crisis also causes an inflammatory response. The result can be warmth and swelling at the site, along with systemic symptoms such as fever.
Avascular necrosis (AVN)
When parts of the bone don’t get enough blood, the tissue deteriorates and dies. The death of bone tissue, known as avascular necrosis (AVN) or osteonecrosis, leads to tiny breaks in the bone and eventual bone collapse. As the condition progresses, AVN produces severe pain—especially in weight-bearing bones. It can cause disability, including joint issues, arthritis, and increased risk of fracture.
According to Dr. Weinreb, the process is not that different from a heart attack (myocardial infarction). Blood supply to the heart stops and if left untreated, the heart muscle dies and cannot fulfill its function. “The same thing can happen with the bones,” Dr. Weinreb says. “Even if bone heals with a scar, it impairs normal bone structure.” That impairment keeps bone from functioning as it should.
Bone weakness and fractures
Without adequate blood supply and remodeling, bones become weak and experience structural changes. Low bone density (osteopenia) may develop and lead to osteoporosis—a bone disease marked by decreased bone strength and high risk of fractures.
Your physician can perform a bone density test. Lower scores indicate higher risk of breakage. Scores between -1 and -2.5 suggest osteopenia. Physicians label scores lower than -2.5 as osteoporosis.
Other risk factors for osteopenia and osteoporosis include:
- Deficiencies in both vitamin D and calcium
- Excessive alcohol use
- Lack of exercise
- Poor nutrition
How Gaucher Disease Treatment Affects Bone Symptoms
Enzyme replacement therapy (ERT) and substrate reduction therapy (SRT) help people with Gaucher disease live more comfortably. But the treatments don’t always ease all bone symptoms. One reason for breakthrough bone symptoms, according to Dr. Weinreb, may be that ERT isn’t delivered as efficiently to bone tissue as it is to the spleen or liver.
The good news is early treatment for Gaucher disease prevents dramatic bone complications that can occur when treatment begins late. There is not yet enough clinical data on SRT’s effect on bone manifestations, but Dr. Weinreb reports that ERT improves:
- AVN: Treatment helps reduce the risk of future episodes of AVN. Still, there are some individuals who develop AVN unpredictably even after years of being on ERT.
- Bone pain: About 50% of people with previous bone pain say ERT continues to make them feel better, even after 10 to 20 years of treatment.
- Osteopenia and osteoporosis: For patients who had osteopenia and osteoporosis before beginning treatment, ERT taken over a period of eight to 10 years improves bone mineral density. It may even help patients get back into the normal range.
What if You Have Bone Pain After Gaucher Disease Treatment?
Even if you are being treated for Gaucher disease, you may still experience episodes of bone pain. If you need help managing bone pain, consider secondary treatment from a specialist such as:
- Occupational therapist
- Pain specialist
- Physical therapist
According to Dr. Weinreb, “They are important potential members of the team when it comes to treating people with Gaucher disease and bone pain.”
How the National Gaucher Foundation Can Help
If you or a loved one lives with Gaucher disease, the National Gaucher Foundation is here for your family. We offer resources to optimize your health with Gaucher disease and connect you with the support you need.
- Orphanet Journal of Rare Diseases: Chronic pain in Gaucher disease: skeletal or neuropathic origin? — https://ojrd.biomedcentral.com/articles/10.1186/s13023-017-0700-7
- National Institute of Arthritis and Musculoskeletal and Skin Diseases: Osteoporosis Overview — https://www.bones.nih.gov/health-info/bone/osteoporosis/overview
- American Academy of Family Physicians: Osteopenia — https://familydoctor.org/condition/osteopenia/
- American College of Rheumatology: Osteonecrosis — https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Osteonecrosis
- National Institute of Arthritis and Musculoskeletal and Skin Diseases: Osteonecrosis — https://www.niams.nih.gov/health-topics/osteonecrosis
- Clinical Cases in Mineral and Bone Metabolism: Clinical manifestations and management of Gaucher disease — https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4625773/