Bone-modifying agents for multiple myeloma
Fact-checked by Bone-modifying agents are a class of supportive care medications used to ease bone pain and prevent bone-related complications in people with multiple myeloma.
Myeloma is a blood cancer in which immune plasma cells become abnormal and grow out of control in the bone marrow, the spongy center of bones where blood cells are made.
Most people with myeloma experience bone problems, including weak and fracture-prone bones, damaged bones, and bone pain. When bones are damaged, they also release excess calcium into the bloodstream (hypercalcemia), which can lead to other health complications.
Bone-modifying agents do not treat the underlying cancer. Rather, they help strengthen bones and prevent their destruction in order to ease bone-related symptoms. These medications are commonly recommended for people with active myeloma, even before obvious bone damage occurs.
What are bone-modifying agents?
The maintenance of healthy bones requires a balance between the cells that break down old bone tissue (osteoclasts) and the cells that build new bone (osteoblasts).
Cancerous myeloma cells disrupt that balance. Overactive osteoclasts cause bones to break down more quickly than they should, and osteoblasts can’t rebuild bone as efficiently as they need to.
Bone-modifying agents work in different ways to inhibit osteoclast activity, preventing excessive bone breakdown. That helps ease symptoms like pain while also preventing the excess release of calcium into the bloodstream.
Bone-modifying agents for multiple myeloma
In general, experts recommend bone-modifying treatment for people being treated for active, symptomatic myeloma, even in the absence of obvious signs of bone damage.
They are usually continued for up to two years, after which a doctor may advise discontinuing the medication or reducing the dose frequency if a person’s myeloma is stable or in remission. They can be restarted later if disease activity returns.
There are three main bone-modifying agents used for people with myeloma in the U.S.:
Bisphosphonates
Aredia and Zometa are bisphosphonates. They bind to a mineral on the surface of bones and are taken up by osteoclasts, where they act as a poison, inducing cellular dysfunction and death.
They are administered by infusion into the bloodstream, usually once every three or four weeks. Zometa is a newer medication that’s designed to be more potent, requiring lower doses and shorter infusion times.
Generic versions of these medications are also available in the U.S.
Xgeva
Xgeva is an antibody therapy that binds to RANKL, a protein important for osteoclast growth and survival. This interaction prevents the protein from performing its usual functions, inhibiting osteoclast-mediated bone destruction. Xgeva is given via under-the-skin injections once a month, and is preferred for people who have kidney problems.
Biosimilars of Xgeva are available in the U.S. These medications have the same active ingredient and no clinically meaningful differences from the original brand-name product in terms of safety and efficacy.
Side effects
The specific side effects of bone-modifying agents for myeloma will depend on which medication is used, but could include:
- low blood levels of calcium and other minerals
- bone or joint pain
- fatigue
- nausea, diarrhea, or other digestive problems
A rare but serious side effect of these medications is osteonecrosis of the jaw, characterized by bone cell death in the jaw that can lead to exposed bone, loose teeth, pain, and other problems. Patients should have a dental exam before starting these medications, and shouldn’t have major dental work while using them.
Bisphosphonate medications may cause flu-like symptoms, especially with the first dose. These therapies can also affect kidney function, which requires careful monitoring.
Patients using bone-modifying medications are advised to take daily calcium and vitamin D supplements, because these medications can cause blood calcium levels to get too low.
These medications may also cause fetal harm and are not recommended for use during pregnancy.
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