The more we learn about Gaucher disease, the more we understand how it affects complex cellular interactions among various body systems. As familiarity with Gaucher disease grows, more people recognize the hallmark symptoms of this disorder, such as spleen and liver enlargement and problems with certain blood components. But difficult-to-treat bone disorders are also common among Gaucher disease patients.

Patient-specific treatments like enzyme replacement therapy (ERT) may dramatically improve many symptoms in people living with Gaucher disease—except for symptoms caused by bone changes. However, current research sheds light on therapies which may be effective in slowing or stopping damage occurring to bone.

Skeletal System Involvement in Gaucher Disease

According to some research, as many as 62% of Gaucher disease patients worldwide have some kind of bone disease detectable by radiological tests, such as magnetic resonance imaging (MRI). Patients frequently experience a range of bone symptoms and signs, including:

• Avascular necrosis (AVN)
• Bone pain, which may be severe
• Joint pain, arthritis, and joint damage
• Osteopenia and osteoporosis
• Spontaneous fractures 

People living with Gaucher disease type I or type III commonly experience skeletal system involvement as a result of their disease. One of the earliest signs, the “Erlenmeyer flask” deformity, affects a large proportion of people with Gaucher disease. This deformity—characterized by narrowing of the shafts of long bones and flaring of the wider portions of long bones—primarily affects the femur, or thighbone. However, it’s possible for this bone abnormality to affect any of the long bones in the body.

Understanding How Gaucher Disease Affects Bones

To understand how Gaucher disease causes bone symptoms, it’s necessary to understand how bones form and regenerate. Bone is a living tissue, constantly being built and broken down by specialized cells throughout an individual’s lifetime. Certain cells, called osteoblasts, build new bone in response to cellular signals. They replace older, worn-down bone tissue in a process called bone remodeling. Other specialized bone cells, called osteoclasts, break down and absorb old bone tissue during the remodeling process. Complete bone remodeling occurs about once every 10 years.

The mechanisms by which Gaucher disease affects bone cells are not completely understood, but current research points to impairments in osteoblast formation and action. Additionally, osteoclasts become more active and seem to work overtime. This means osteoclasts destroy bone tissue faster than osteoblasts can replace it. As a result, bones lose bone mineral density and start to thin, increasing the potential for problems like osteoporosis and fractures.

Chemical Compounds and Bone Remodeling

Researchers think the accumulation of certain chemical compounds related to glucocerebroside, called glucosylceramide (Gb1) and glucosylsphingosine (Lyso-Gb1), contribute to the process of abnormal bone remodeling in people living with Gaucher disease. Like glucocerebroside, Lyso-Gb1 builds up in the body, preventing various enzymes and other cellular products from stimulating new bone formation.

Gaucher Disease Cells Linked to Bone Disorders

Other research indicates Gaucher disease cells themselves may trigger the accumulation of white blood cells and other immune system cells within bone tissue. When white blood cells gather together in large numbers, they release chemicals into the surrounding tissues. These chemicals cause inflammation and can ultimately interrupt blood flow to the bone tissue. Under normal circumstances, this process is self-limiting and stops before any damage to the bone occurs.

However, Gaucher disease cells seem to continuously stimulate the body’s immune system. This results in continuous inflammation and unchecked interruption in blood supply to the bone. Complications like AVN, in which bone tissue dies, are more likely when white blood cells compromise the bone’s blood supply. Implementing natural ways to boost your immune system and reduce inflammation may provide benefit.

Treatment Challenges for Those with Gaucher Disease

Bone involvement in Gaucher disease poses unique challenges to patients and clinicians. Dr. Neal Weinreb, Voluntary Associate Professor of Human Genetics and Hematology at the University of Miami Miller School of Medicine, member of the North American Scientific Advisory Board of the International Collaborative Gaucher Group, and member of the Medical Advisory Board for NGF, says: “Pain is very nonspecific, which makes it difficult to evaluate in patients. In those with Gaucher disease, especially those with a new diagnosis, their symptoms may be so mild that doctors initially withhold treatments like ERT. Sometimes these people get used to symptoms, like mild bone pain, and are unaware they could feel better.”

“But even if a person receives treatment, pain can acquire its own difficult characteristics, especially if it’s been present for a long time without being addressed. This makes pain much harder to treat. Many people with Gaucher disease experience chronic pain, which can lead to other complications like depression. This, in turn, has a huge negative impact on a person’s quality of life. Unfortunately, in these situations, standard pain management usually doesn’t affect outcomes all that well.”

Bone tissue also does not respond to standard Gaucher disease therapies, such as ERT, as well as other organs do. While ERT may help slow the progression of bone loss and damage by boosting bone mineral density, enzyme therapy cannot reverse bone injuries that have already occurred.

New Medications May Be Key to Normalizing Bone Remodeling

Thanks to our evolving understanding of how Gaucher disease affects bone, research now focuses on the bone remodeling process in an attempt to slow down rates of bone loss. Currently, research efforts center around medications to stabilize bone remodeling by inhibiting the actions of osteoclasts or stimulating osteoblasts to form new bone.

Putting the Brakes on Bone Destruction

A certain class of drugs, bisphosphonates, slow down the process of bone destruction by osteoclasts. Many treatments for osteoporosis center around this drug class. “Bisphosphonates have some benefit in younger people with Gaucher disease, but we’re not sure whether these should be taken long term,” says Dr. Weinreb. “Once these drugs are in the body, they stay there for a long time. We’re not sure what the consequences of that are. Right now, the tendency is to treat patients for as many as five years, then stop treatment to see how the patient responds.”

Helping Osteoblasts Make New Bone

Medications that stimulate osteoblasts directly may also help people living with Gaucher disease avoid bone disorders. Forteo®, which was approved by the FDA in 2002 and is primarily prescribed for osteoporosis, is injected into the body once each day. This drug helps build new bone and improves bone strength, but people cannot use it indefinitely due to the risk of certain complications, like bone cancer. Research shows that people with Gaucher disease who use Forteo® do benefit, but once therapy doctors discontinue the medication, that benefit rapidly declines.

Still, doctors and researchers alike hope to find a long-term-use medication that promotes the actions of osteoblasts. Newer drugs targeting sclerostin, a protein which stops osteoblasts from forming new bone, may offer hope for people living with bone manifestations of Gaucher disease. While animal models and clinical trials show promise, these drugs, called antisclerostin monoclonal antibodies, currently carry a high risk for side effects and aren’t yet approved for clinical use in humans.

Taking Action Early to Help Prevent Bone Problems

“The big take-away for people with Gaucher disease, especially if they’re younger, is that bone loss is a process that may occur without any symptoms. If you or a loved one is diagnosed with Gaucher disease, you should have testing done to evaluate bone mineral density,” says Dr. Weinreb.

Doctors can easily evaluate bone mineral density using a test called bone densitometry, also known as a DEXA scan. This procedure requires no special preparation and is beneficial for measuring bone mineral density in both children and adults. While a DEXA scan measures bone mineral density at the hip, wrist, and spine in adult patients, the test provides important information about bone mineral density throughout a child’s entire body.

“Find a testing center where they know how to perform DEXA scans properly—somewhere with radiology experience,” says Dr. Weinreb. “It’s in the overall benefit of Gaucher disease patients to see practitioners with a lot of experience and knowledge. Diagnosing Gaucher disease complications like bone mineral loss early helps determine the best course of treatment. And early treatment with ERT may help to drastically slow the progression of bone loss and damage.”

Dr. Weinreb also notes, “If you have Gaucher disease and experience significant bone pain issues, it’s advisable to work with a qualified pain management specialist, who is preferably a member of or known to your Gaucher disease treatment team. This provides you with the most support possible while dealing with this rare disease and its possible complications.”