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Xgeva More Likely to Cause Osteonecrosis of the Jaw in Women Diagnosed With Advanced-Stage Breast Cancer

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Both Xgeva (chemical name: denosumab) and Zometa (chemical name: zoledronic acid) are approved by the U.S. Food and Drug Administration (FDA) to reduce the risk of bone problems (such as breaking a bone) and bone pain caused by advanced-stage cancer that has spread to the bones.

Xgeva is given as an injection under the skin every 4 weeks. Zometa is given intravenously every 4 weeks. Zometa is a bisphosphonate. Bisphosphonates limit the activity of certain bone cells, called osteoclasts, which help cause the bone weakening and breakdown that leads to osteoporosis. Xgeva is a targeted therapy. Studies have shown that that Xgeva is somewhat better than Zometa at reducing the risk of cancer-related bone problems (called skeletal-related events or SREs in the study).

One uncommon but very serious side effect of Xgeva and Zometa (and other bisphosphonates) is jaw bone breakdown, called osteonecrosis of the jaw. Right now, there aren't good treatment options when osteonecrosis of the jaw happens and the condition can be very disabling.

A study that analyzed results from three other studies on the benefits of Xgeva for people with advanced-stage cancer found that people diagnosed with advanced-stage breast or prostate cancer who got Xgeva were about twice as likely to develop osteonecrosis of the jaw compared to people with other advanced-stage cancers who got Xgeva.

The results were presented at the 2011 International Conference on Cancer-Induced Bone Disease.

Some targeted therapies, including Xgeva, are antibodies that work like the antibodies made naturally by the immune system. Xgeva targets a protein called RANK ligand (RANKL). RANKL affects the activity of osteoclasts. Osteoclasts help with normal bone breakdown activity to regulate calcium levels. Xgeva blocks RANKL activity and limits osteoclast activity.

In women diagnosed with breast cancer that has spread to the bones, osteoclasts tend to be overactive. These overactive osteoclasts can cause bone pain and bone destruction. By limiting osteoclast activity, Xgeva can lessen pain and reduce the risk of bone problems for these women.

Under the brand name Prolia, denosumab is approved by the FDA to treat postmenopausal women diagnosed with osteoporosis who are at high risk of breaking a bone or who can't take or haven't gotten any benefit from other osteoporosis treatments. Prolia treats osteoporosis by restoring the delicate balance of bone building and bone breakdown.

While Prolia and Xgeva are made of the same chemical components, each is used for a different purpose.

Some possible side effects of Xgeva and Prolia include back, arm, and leg pain; high cholesterol levels; and urinary infections. In addition to osteonecrosis of the jaw, more serious but much less common side effects include low blood calcium levels, rashes, and severe infections. Because of these risks, the FDA requires that anyone considering taking Xgeva or Prolia be carefully evaluated and educated to make sure that the medicines are used appropriately.

Some doctors think Xgeva is a good alternative to Zometa because it appears to work better than Zometa, and because it is given as an injection under the skin rather than as an intravenous infusion. Still, this study suggests that the risk of osteonecrosis of the jaw may be higher with Xgeva for people diagnosed with advanced-stage breast or prostate cancer.

Experts aren't sure why the risk may be higher for these people. More research is needed to fully understand if jaw osteonecrosis in people with advanced-stage breast and prostate cancer is a larger problem than when Xgeva was approved.

If you've been diagnosed with advanced-stage breast cancer that has spread to the bones, you and your doctor will develop a treatment plan to minimize any pain you have and to reduce your risk of bone problems. Zometa or Xgeva may be part of that plan. Be sure to talk to your doctor about the risks of these options, including the risk of osteonecrosis of the jaw. Together, you and your doctor can decide whether the benefits of treatment outweigh the risks as well as which option makes the most sense for you and your unique situation.

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