These drugs not only reduce the risk of fractures (a common complication) but may, in some cases, improve survival. That’s because they also have anti-cancer properties.
This article looks at the new drugs for bone metastases, how they work, and other possible treatments.
Prescriptions
Two primary classes of drugs are used to treat bone metastases. These include:
BisphosphonatesA monoclonal antibody
These bone-modifying agents can help people with cancer in several ways:
Strengthening bones affected by metastases, which reduces pain and fracture riskImproving progression-free survival and overall survivalReducing the risk of bone metastases from breast cancer and possibly prostate cancer by a thirdReducing the risk of osteoporosis, which is increased by many treatments for breast and prostate cancer
Bone-modifying agents are recommended for anyone with breast cancer that’s spread to the bone and are frequently used with other solid tumors (such as lung cancer). Other treatments (such as radiation therapy) are usually needed, as are medications to control pain.
Bisphosphonates
Bisphosphonates suppress the breakdown of bone, which improves bone density. They were first used to treat osteoporosis and later noted to help with bone metastases.
Bisphosphonates most commonly used for bone metastases are given intravenously (into a vein). They include:
Zometa (zoledronic acid): For bone metastases from many different cancersAredia (pamidronate): Approved for breast cancer and multiple myeloma
Side Effects
Zometa and Aredia can cause side effects, including:
A mild flu-like syndrome for the first few days after the infusion (most common)Kidney damageLow calcium levels (hypocalcemia)AnemiaMuscle, joint, and/or bone pain (which can arise at any time after treatment)Blurred visionInfertilityLow thyroid activity (hypothyroidism)Blood-cell deficienciesBlood pressure changesUnusual fractures of the femur (thigh bone) with prolonged useAtrial fibrillation (an irregular and often rapid heart rhythm)Difficulty swallowingHeartburnAbdominal painNausea and constipationHeadacheRash
Bisphosphonates may not be recommended for people with kidney disease.
Monoclonal Antibody
Denosumab is a monoclonal antibody (man-made antibody) that can reduce complications of bone metastases, including fractures. It’s sold under two brand names, Xgeva and Prolia.
Denosumab is given by injection every four weeks. It increases bone density by blocking the activity of osteoclasts, a type of cell that breaks down bones.
A 2016 review of studies looked at three clinical trials of denosumab as a treatment for:
Breast cancerProstate cancerMultiple myeloma or other solid tumors that weren’t from breast or prostate cancer
With breast cancer and prostate cancer, denosumab was better than Zometa in reducing the risk of fractures related to bone metastases. With multiple myeloma and other solid tumors, denosumab was about as effective as Zometa.
With lung cancer, a 2015 study found that compared with Zometa, denosumab reduced the risk of a fracture by 17%. It also appears to delay the development of bone metastases, reduce skeletal tumor growth, and improve survival time by a little over a month.
Denosumab was also found to reduce the risk of treatment-related osteoporosis in breast cancer and prostate cancer.
Side Effects
Long-term use of denosumab is more likely than bisphosphonates to cause a low calcium level. For this reason, experts often recommend taking calcium and vitamin D supplements during treatment.
Some denosumab side effects are delayed while others are likely to happen soon after taking it. The short-term side effects include:
FatigueAtrial fibrillationAngioedemaSwelling of the larynx (voice box)Chest pain (angina)Red patches on the skinLow blood pressureWheezingFeverFlushingMuscle pain (myalgia)ChillsVertigoAbdominal painRashItchingIntestinal gasHeadacheDiarrheaNausea and vomiting
Unlike bisphosphonates, denosumab is safe for people with impaired kidney function.
Complications
A rare but serious complication of bisphosphonates and denosumab is osteonecrosis of the jaw, a condition that makes part of the jaw bone break down. People assigned female at birth and treated with Zometa for early-stage breast cancer appear to have about a 2% risk of this.
While any bisphosphonates can cause osteonecrosis, 94% of cases are in people who’ve had it in high-dose IV form, not in doses given for osteoporosis.
Osteonecrosis of the jaw is more likely if you:
Smoke cigarettesHad recent dental procedures such as tooth extractionHave gum diseaseHave poor dental hygiene
Scheduling dental exams every three months and using preventive antibiotics for dental procedures may reduce the risk. Treatment options include a combination of surgery, rinses, antibiotics, and hyperbaric oxygen treatments.
Guidelines for Bone-Modifying Agents With Bone Metastases
For breast cancer, prostate cancer, and other solid tumors with bone metastases, the American Society of Clinical Oncology recommends these drugs and dosage schedules.
Chemotherapy Targeted therapies Immunotherapy drugs
Treatments that specifically address bone metastases are:
Radiation therapy: A local therapy that can significantly reduce both pain and the likelihood of a fracture. Radiopharmaceuticals: Injected drugs containing a particle of radiation; effective for multiple or widespread metastases. Examples include Strontium-89 and Radium-223. Surgery: May be needed to stabilize a fracture or stabilize damaged bones to prevent a fracture. Stereotactic body radiotherapy (SBRT) and proton beam therapy: Less common treatments that precisely deliver radiation (SBRT) or high-energy protons (proton beam therapy) to a single metastasis or small number of metastases.
Summary
Bone metastases can reduce your quality of life and lower your chance of survival. Bone-modifying agents are a relatively new approach and are now recommended early on after a diagnosis of bone metastases for many cancers.
The bisphosphonates Aredia and Zometa and the monoclonal antibody denosumab can reduce the risk of fractures. Both classes of medications carry a small risk of osteonecrosis of the jaw. A dental exam is recommended before starting these drugs.
In addition to reducing fracture risk, these medications can help correct bone loss due to hormonal therapies used for breast and prostate cancers. Both bisphosphonates and denosumab appear to have significant anti-cancer activity. Zometa is also recommended as an add-on treatment for early-stage breast cancer to reduce the chance of bone metastases.
A Word From Verywell
The addition of new drugs to the cancer-fighting arsenal is good news. They give you and your healthcare team more options and better odds of defeating these diseases.
Educating yourself about your cancer and the possible treatments for it can help you be an active participant in your care.
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