Osteosclerotic myeloma is a rare form of multiple myeloma, representing only about 1 percent to 3 percent of all multiple myeloma cases. Multiple myeloma is a type of blood cancer that affects plasma cells, a kind of white blood cell located in the bone marrow. Healthy plasma cells help fight infections by making antibodies.

Osteosclerotic myeloma is distinguished by sclerosis (a hardening or thickening of bone tissue) instead of the osteolysis (bone thinning or breakdown) seen in most cases of multiple myeloma. Typical multiple myeloma often causes bone thinning, but osteosclerotic lesions are denser and can sometimes occur alongside these bone-destroying lesions.

In this article, we’ll discuss osteosclerotic myeloma, including its possible causes, symptoms, and treatment options. Each case of myeloma has specific details and circumstances, so it’s essential to work closely with your oncologist (cancer doctor) for tailored advice and care.

What Causes Osteosclerotic Myeloma?

The exact cause of osteosclerotic myeloma is still unclear, but researchers believe that genetic factors may play a significant role. Many individuals with the condition show mutations (changes) in genes that influence cytokines — chemical messengers that help the immune system communicate. These mutations may affect the production of substances like vascular endothelial growth factor (VEGF), immunoglobulins (antibodies), and other cytokines involved in cancer development. However, the exact genetic triggers remain unclear.

Osteosclerotic Myeloma and POEMS Syndrome

In most cases, osteosclerotic myeloma is linked to a condition called POEMS syndrome. Only a small number of cases of osteosclerotic myeloma without POEMS syndrome have been documented.

The terms “osteosclerotic myeloma,” “Crow-Fukase syndrome,” and “POEMS syndrome” are often used interchangeably because they frequently occur together. However, they are not synonymous. Crow-Fukase syndrome is another name for POEMS syndrome. Osteosclerotic myeloma refers to a plasma cell cancer that primarily affects the bones and can occur with or without POEMS syndrome.

POEMS syndrome is an uncommon disorder characterized by a mix of health issues. The name POEMS represents its five key features:

• P — Polyneuropathy, damage or disease affecting the nerves, leading to weakness, tingling, or numbness in the hands and feet
• O — Organomegaly, enlargement of organs such as the liver, spleen, or lymph nodes
• E — Endocrinopathy, problems with hormone-producing glands, such as the thyroid or adrenal glands
• M — Monoclonal gammopathy, the presence of abnormal proteins in the blood, produced by plasma cells
• S — Skin abnormalities, changes in the skin, like thickening, darkening, or unusual hair growth

Some risk factors may worsen outcomes for individuals with this condition, including:

• Low levels of serum albumin, a protein made by the liver that helps maintain body fluid balance
• Older age at diagnosis, which can affect the body’s ability to recover
• Pleural effusion, a buildup of fluid around the lungs that can impair breathing
• Hypertension (high blood pressure) or damaged blood vessels in the lungs
• High VEGF levels, which are associated with abnormal blood vessel growth
• Kidney disease, a common complication in people living with multiple myeloma

Signs and Symptoms of Osteosclerotic Myeloma

Osteosclerotic myeloma is characterized by sclerotic lesions (damaged areas of bone) that are much harder or denser than regular bone. Common symptoms include:

• Weakness in the arms and legs that worsens over time
• Enlarged organs including spleen, liver, and/or lymph nodes
• Skin changes such as darkening of the skin, thickened or hardened skin, or excessive hair growth
• Optic nerve swelling, which can affect vision
• Hormone problems, such as hormonal imbalances, infertility, and type 2 diabetes
• Retention of fluids in the ankles, abdomen, or lungs
• Bone scars visible by X-ray
• High levels of platelets seen in blood counts, which may increase the risk of clotting
• Decreased lung function, lung fibrosis

Diagnosis of Osteosclerotic Myeloma

The symptoms of osteosclerotic myeloma can vary widely and often overlap with other conditions, making diagnosis challenging. Misdiagnosis is common, and because osteosclerotic myeloma is so rare, diagnosis is often delayed. On average, individuals with this condition wait 13 to 18 months from the onset of symptoms to receive a correct diagnosis.

To diagnose osteosclerotic myeloma, doctors use a combination of major and minor criteria, with three major criteria (including two mandatory ones) and at least one minor criterion required.

Major Criteria

To be diagnosed with osteosclerotic myeloma, a person must be diagnosed with both the following:

• Polyradiculoneuropathy (an inflammatory disorder affecting multiple types of nerves)
• A plasma cell disorder

Additionally, they must be diagnosed with at least one of the following:

• Sclerotic bone lesions
• High VEGF levels
• Castleman disease (a rare disorder involving overgrowth of cells in the lymph nodes)

Minor Criteria

Additionally, a person must have at least one of the following symptoms (described above) for a diagnosis of osteosclerotic myeloma:

• Enlarged organs
• Fluid buildup outside blood vessels
• Problems with hormone-producing endocrine glands
• Certain skin changes
• Swelling of the optic nerve
• High levels of platelets in the blood or polycythemia (an excess of red blood cells)

Diagnosing osteosclerotic myeloma requires a range of tests, starting with a detailed medical history and a thorough physical examination. Additional tests — including blood tests, biopsies, and imaging studies of the bones — help confirm the diagnosis and assess the extent of the condition.

Treatments for Osteosclerotic Myeloma

Osteosclerotic myeloma is treated based on the stage of the disease. Treatment for osteosclerotic myeloma is usually divided into two arms: treatment to kill myeloma and treatment to manage other symptoms.

It’s generally recommended to start treatment only after symptoms appear. There’s no proven benefit to initiating therapy in individuals with no symptoms.

Approved, effective treatments against multiple myeloma — such as bortezomib (Velcade), dexamethasone, and lenalidomide (Revlimid) — are also effective in targeting osteosclerotic myeloma cells. It can take months to years for treatment to achieve its full cancer-killing and symptom-improving effects.

For early-stage osteosclerotic myeloma, radiation therapy is used to target certain areas of the body. Radiation to osteosclerotic lesions helps improve progression-free survival and can be curative.

For more advanced disease, systemic therapy (treatment covering the whole body) is used. For eligible individuals, autologous bone marrow transplantation is part of an optimal treatment plan. This procedure involves:

• Removing and storing the person’s healthy blood cells
• Administering high-dose therapy to kill cancer cells
• Reinfusing the healthy cells to help restore normal blood cell production

How Does Osteosclerotic Myeloma Differ From Other Myelomas?

Osteosclerotic myeloma stands apart from other types of multiple myeloma and plasma cell disorders due to unique differences in its diagnosis, treatment approach, and overall outlook. Key differences include these aspects:

• Hormone problems are common in osteosclerotic myeloma, unlike traditional myeloma.
• High VEGF levels are common in osteosclerotic myeloma but not traditional myeloma.
• Sclerotic bone lesions are only seen in osteosclerotic myeloma.
• Individuals with osteosclerotic myeloma often have better overall survival compared to those with other forms of myeloma.

Outlook for Osteosclerotic Myeloma

People with osteosclerotic myeloma, especially when associated with POEMS syndrome, often have a better prognosis — living longer, experiencing less severe disease progression, and reporting a better quality of life compared to those with other types of myeloma. Pinpointing specific survival rates for osteosclerotic myeloma is difficult, however. This is because osteosclerotic myeloma is rare, so survival data is limited and often overlaps with findings from POEMS syndrome.

A long-term study of POEMS syndrome at Mayo Clinic reported a 10-year overall survival of 62 percent. This means that after 10 years, 62 percent of participants were still alive. Outcomes were significantly better for those who underwent autologous bone marrow transplantation and had a good response to treatment.

Some studies have reported five- and 10-year survival exceeding 90 percent for certain groups. For instance, younger age and higher albumin levels at diagnosis are linked to better outcomes.

Ongoing clinical trials are focused on improving the diagnosis, treatment, and overall outcomes for individuals living with osteosclerotic myeloma.

Talk With Others Who Understand

MyMyelomaTeam is the social network for people living with multiple myeloma and their loved ones. On MyMyelomaTeam, more than 27,000 members come together to ask questions, give advice, and share their stories with others who understand life with myeloma.

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