May 21, 2007
- Bisphosphonates are an important treatment option that can help to strengthen bones in people with multiple myeloma.
- The two bisphosphonates used in the United States are pamidronate and zoledronic acid; talk with your doctor about the benefits and risks of each drug.
- Patients should receive bisphosphonate treatment every three to four weeks for no longer than two years because of the potential side effects.
- Before receiving bisphosphonate treatment, patients should schedule an examination with a dentist.
To help doctors give their patients the best possible care, the American Society of Clinical Oncology (ASCO) asks its medical experts to develop recommendations for specific areas of cancer care. In 2002, ASCO published a clinical practice guideline about bisphosphonate treatment for multiple myeloma. The scope of this guideline was expanded and updated in 2007. This guide for patients is based on ASCO's recommendations.
As you read this guide, please keep in mind that every person treated for cancer is different. These recommendations are not meant to replace your judgment or that of your doctor. The final decisions you and your doctors make will be based on your individual circumstances.
Myeloma is a cancer of the plasma cells in the bone marrow, the spongy tissue inside of bones. Plasma cells are a part of the body's immune system and help the body fight infections. If a plasma cell mutates (changes abnormally), it can grow uncontrollably and eventually form a tumor called a plasmacytoma. Solitary plasmacytoma is a mass of myeloma cells that is in only one site in the bone or other organs. Myeloma is often called multiple myeloma because more than 90% of people have cancer in multiple places in the bone marrow at the time it is diagnosed. Myeloma often causes structural bone damage resulting in painful fractures (broken bones).
Bones are continually shaped and maintained by bone cells called osteoclasts and osteoblasts. Osteoclasts destroy old bone, and osteoblasts build new bone. People with myeloma have abnormally high levels of osteoclasts, which mean that bone is destroyed faster than it can be replaced, potentially causing fractures, bone pain, osteoporosis (thinning of the bones), and hypercalcemia (high levels of calcium in the blood).
Bisphosphonates are medications that help strengthen the bone. Two bisphosphonates are approved by the U.S. Food and Drug Administration (FDA) for treating bone loss from multiple myeloma: pamidronate (Aredia) and zoledronic acid (Zometa). These drugs are given intravenously (IV) through a vein. The side effects may include flu-like symptoms, anemia, and joint and muscle pain. Uncommon but serious side effects have been identified in some patients, including:
- Kidney problems
- Acute kidney failure (when the kidneys suddenly stop working)
- Osteonecrosis (bone loss/weakening) of the jaw. Symptoms include pain, swelling, and infection of the jaw; loose teeth; drainage; and exposed bone.
ASCO recommends the following for the use of bisphosphonates for multiple myeloma:
- Patients with multiple myeloma who experience bone loss or fractures of the spine from osteopenia (lower bone density that leads to weaker bones) should receive either pamidronate or zoledronic acid every three to four weeks. Each treatment of pamidronate should be at least two hours, and each treatment of zoledronic acid should be at least 15 minutes.
- Bisphosphonate treatment should be given for two years. At two years, bisphosphonate treatment may be stopped if it is working. Treatment should begin again if the myeloma comes back and new bone problems develop.
- To learn whether a bisphosphonate is causing kidney problems, the level of creatinine (a measure of kidney function) should be checked before each dose of pamidronate or zoledronic acid, and patients should be monitored every three to six months for albuminuria (high levels of the protein, albumin, in the urine that might indicate damage to the kidneys). The drugs should be stopped for patients who develop kidney problems while receiving a bisphosphonate, but they may be resumed once the problem is identified and resolved.
- The dose of pamidronate should be lowered in patients with pre-existing mild to moderate kidney disease. The maker of zoledronic acid previously recommended lowering the treatment dose for these patients.
- For patients with existing severe kidney problems and extensive bone disease, a longer infusion (4 to 6 hours) of pamidronate is recommended instead of a two-hour infusion. Zoledronic acid is not recommended for these patients.
- Osteonecrosis of the jaw is an uncommon but potentially serious side effect of pamidronate and zoledronic acid. Before treatment, patients should receive a thorough dental examination, and any tooth or mouth infections should be treated. While receiving bisphosphonate treatment, patients should avoid having any invasive dental work done, such as dental surgery, and take good care of their teeth, mouth, and gums.
- Bisphosphonates may be used to treat pain from bone disease. For patients who are already experiencing bone pain, bisphosphonates may be used along with other standard methods to relieve pain, such as radiation therapy, pain medication, or surgery for bone fractures.
Bisphosphonates are not recommended for patients with the following conditions:
- Solitary plasmacytoma (one bone tumor)
- Smoldering (indolent) myeloma
- Conditions of abnormal plasma cells that are not myeloma but may eventually develop into myeloma, such as monoclonal gammopathy of undetermined significance (MGUS)
The use of biochemical markers to monitor bisphosphonate treatment is not recommended.
What This Means for Patients
Bisphosphonates help strengthen bones and are an important part of treatment for patients with multiple myeloma. The two bisphosphonates used in the United States to treat multiple myeloma-related bone loss are pamidronate and zoledronic acid. The two drugs have different infusion times and potentially different side effects. Talk with your doctor about the differences between the two bisphosphonates.
Before starting intravenous bisphosphonate treatment, schedule an examination with a dentist and tell the dentist about the upcoming treatment. Take care of your teeth, gums, and tongue with regular brushing and flossing and avoid having invasive dental procedures while receiving bisphosphonates.
Because additional risks of bisphosphonate treatment have been identified, ASCO recommends that most patients receive this treatment for no longer than two years. Talk with your doctor for more information about stopping and restarting bisphosphonate treatment.
Questions to Ask the Doctor
To learn more about bisphosphonates for multiple myeloma, consider asking your doctor the following questions:
- Should I receive bisphosphonate treatment?
- Which drug do you recommend?
- How long do I need to take this drug?
- How much time does the infusion take?
- What side effects can I expect from this treatment?
- What signs or symptoms should I look for?
- How will my treatment be monitored?
- What clinical trials are open to me?
Read the entire clinical practice guideline published in the June 20, 2007 issue of the Journal of Clinical Oncology  (JCO).
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