Multiple myeloma is caused by abnormal growth, division, and function of plasma cells (a kind of blood cell). Osteosclerotic myeloma is a type of multiple myeloma. Osteosclerotic myeloma is extremely rare, accounting for less than three percent of multiple myeloma cases.

What Causes Osteosclerotic Myeloma?

The exact cause of osteosclerotic myeloma is unknown. It is thought that genetics are the driving force behind the development of the disease. Genes that make cytokines (immune system signaling molecules) are often mutated in people living with osteosclerotic myeloma. The functions of these genes tend to be related to the production of vascular endothelial growth factor (VEGF), immunoglobulin, and other cytokines involved in cancer development. However, the specific genetic factors associated with disease development and progression are largely unknown.

The pathogenesis (disease progression) of osteosclerotic myeloma is not well understood. Risk factors for a worse disease outcome include:

• Low levels of serum albumin (an indication of decreased liver function)
• Older age at diagnosis
• Pleural effusion (fluid buildup around the lungs)
• Hypertension (high blood pressure) or diseased blood vessels affecting the lungs
• High levels of VEGF
• Kidney disease

Osteosclerotic Myeloma and POEMS Syndrome

Most cases of osteosclerotic myeloma are accompanied by a diagnosis of POEMS syndrome. POEMS syndrome is a rare disease that is a combination of several disorders. POEMS stands for:

• Polyneuropathy (nerve disease)
• Organomegaly (abnormally large organs)
• Endocrinopathy (hormone gland disease)
• Monoclonal gammopathy (abnormal proteins in the blood)
• Skin abnormalities

Only a handful of cases of osteosclerotic myeloma without the presence of POEMS syndrome have ever been reported. The terms "osteosclerotic myeloma," "Crow-Fukase syndrome," and "POEMS syndrome" may be used to describe the same disease because they are almost always found together.

Signs and Symptoms of Osteosclerotic Myeloma

Osteosclerotic myeloma is characterized by bone lesions that are much harder or denser than regular bone. Common signs and symptoms of osteosclerotic myeloma with POEMS syndrome include:

• Weakness in the arms and legs that worsens over time
• An abnormally large spleen (splenomegaly) or liver (hepatomegaly)
• Enlarged lymph nodes
• Irregular darkening of the skin (hyperpigmentation)
• Thickening of the skin
• Excessive hair growth (hypertrichosis)
• Optic nerve swelling (papilledema)
• Endocrine problems, such as failure of sexual organs to function properly
• Diabetes mellitus
• Excessive retention of fluids in the ankles, abdomen, or lungs
• Painless bone scars visible by X-ray (osteosclerosis)
• High blood platelet counts

Diagnosis of Osteosclerotic Myeloma

The signs and symptoms of osteosclerotic myeloma are quite variable and often similar to those of other diseases, which can lead to a misdiagnosis. Diagnosis can also be delayed because osteosclerotic myeloma is rare. Most people living with osteosclerotic myeloma report waiting 13 to 18 months from the time of symptom onset to diagnosis.

Diagnosis of osteosclerotic myeloma relies on at least three major criteria and one minor criterion. Mandatory major criteria include polyradiculoneuropathy (an inflammatory disorder affecting multiple types of nerves) and multiple myeloma.

Other major criteria (of which one is required for diagnosis) are:

• Sclerotic bone lesions (areas of hardened or especially dense bone)
• High levels of VEGF
• Presence of Castleman disease (in which there’s excessive proliferation of cells in the lymph nodes)

Minor criteria for the diagnosis of osteosclerotic myeloma include:

• Enlarged organs, such as the spleen and liver
• Diseases of the endocrine glands
• Certain skin changes
• Papilledema (swelling of the optic nerve)
• Thrombocytosis (a high platelet count)

Diagnostic Tests for Osteosclerotic Myeloma

A diagnosis of osteosclerotic myeloma relies on many tests. First, most doctors will ask for a thorough medical history and perform a physical exam. Other tests to diagnose osteosclerotic myeloma include blood tests, biopsies, and imaging tests.

Physical Exam

During a physical exam, doctors will typically look for irregular darkening or thickening of the skin and note any areas of excessive body hair. Doctors may test the responsiveness of nerves and estimate the size of the spleen and liver.

Blood Tests

A complete blood count (CBC) and other tests that report the levels of certain hormones in the blood are required for diagnosis. The CBC can identify thrombocytosis, if present. Other blood tests can determine liver and kidney function, measure levels of VEGF, and indicate the health of reproductive organs.

Biopsies

Bone marrow biopsies are used to diagnose and predict the outlook of myeloma. Bone marrow aspirations (which take a liquid sample) and biopsies (which take a solid sample) are usually done at the same time. A nerve biopsy can be used to diagnose neurologic abnormalities such as polyradiculoneuropathy and demyelinating polyneuropathy.

Imaging Tests

Imaging tests, such as CT or positon emission tomography scans, can be used to find osteosclerotic lesions or enlarged organs. X-ray images of the chest can show symptoms such as fluid buildup in the lungs.

Treatments for Osteosclerotic Myeloma

Osteosclerotic myeloma is treated based on the stage (extent) of the disease. Treatment for osteosclerotic myeloma is usually divided into two arms: treatment to kill myeloma and treatment to manage other symptoms. There is no reported benefit of starting therapy before symptoms appear.

Approved, effective treatments for multiple myeloma — such as bortezomib, dexamethasone, and lenalidomide — are used to kill 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, radiotherapy is used to target cancerous areas of the body. Radiation to osteosclerotic lesions helps improve progression-free survival and can be curative.

For disease that has metastasized to the bone marrow or other sites within the body, systemic therapy is used. For eligible individuals, autologous stem cell transplantation (a procedure that removes and stores a person’s healthy stem cells before treatment and replaces them after treatment) is part of an optimal treatment plan.

How Does Osteosclerotic Myeloma Differ From Other Types of Myeloma?

Osteosclerotic myeloma is different in diagnosis, treatment, and outlook from other plasma cell disorders and other types of multiple myeloma. Differences of osteosclerotic myeloma include:

• Commonly reported symptoms of neuropathy and disease of the endocrine glands
• Symptoms unrelated to bone pain, the presence of cancerous cells in the bone marrow, or kidney failure
• High VEGF levels
• High prevalence of sclerotic bone lesions
• Better overall survival
• High prevalence of a different type of cancerous myeloma cell, known as a lambda monoclonal plasma cell

Outlook for Osteosclerotic Myeloma

If treated incorrectly or not at all, osteosclerotic myeloma can cause disabilities. For example, peripheral neuropathy (weakness, numbness, or pain in nerves) caused by osteosclerotic myeloma can be permanent. The outlook is much better for individuals who are correctly treated. People living with osteosclerotic myeloma typically live longer, have less severe disease, and report a higher quality of life than people with other types of myeloma.

Specifically, people who undergo an autologous stem cell transplant (SCT) have significantly higher 10-year survival rates compared to people who were treated with radiation and chemotherapy alone. For people treated with autologous SCT, the reported five-year survival rate is 94 percent and the 10-year survival rate is 90 percent. Clinical trials are underway to continue to improve diagnosis, treatment, and outlook for people 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 11,500 members come together to ask questions, give advice, and share their stories with others who understand life with myeloma.

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