Bisphosphonates are drugs that prevent bone from breaking down or becoming reabsorbed. There are two FDA approved drugs in this class, zoledronic Acid (Zometa) and denosumab (Xgeva).

Zoledronic acid (Zometa) is the most commonly used bisphosphonate in men with advanced prostate cancer. Zometa not only reduces the risk of developing bone complications, it also controls existing bone metastases. Zometa is prescribed for men with castrate resistant prostate cancer after ADT fails.  This should not be confused with taking oral bisphosphonates to maintain bone mineral density (BMD).

Stay well hydrated while getting your infusion.

Zometa is administered by infusion (IV). Be sure that you are well hydrated by drinking a lot of water prior to the infusion (and during it).  Make sure that the infusion staff member monitors your electrolytes during the treatment course. A small number of men experience incapacitating bone, joint and/or muscle pain. If you do, discontinue the bisphosphonate treatment. In order to minimize potential side effects, ask your doctor to time your initial infusion rate to not less than one hour, and then not less than 30 minutes for each subsequent infusion.

Denosumab (Xgeva), approved by the FDA in November 2010, is the newest of the bisphosphonates, and is a human monoclonal antibody for the treatment of osteoporosis, treatment-induced bone loss (i.e. by ADT), and bone metastases in men with castrate resistant non-metastatic prostate cancer.

Compared to Zometa, Xgeva has been shown to delay the onset of bone problems, including bone metastases. It also has been shown to reduce pain and improve the a man’s quality of life ( ). It is delivered monthly via injection. (Citation: XGEVA Delays The Onset Of Bone Metastases In Men With NonMetastatic Castrate Resistant Prostate Cancer

According to a Johns Hopkins alert there is a growing body of evidence that has linked the extended use of bisphosphonate therapy to an increasing risk of an uncommon and very serious fracture in the thighbone (femur). (

Long-term bisphosphonate use creates a significant increase in the risk of dangerous and unusual fractures.

In a 2011 long-term study of bisphosphonate use published in the Journal of the American Medical Association (JAMA), “Researchers found that older women who had used bisphosphonates for at least five years had a 24 percent lower risk of developing fractures in the hip and spine than their counterparts on bisphosphonate therapy for less than five years.  It went on to caution that long-term users were more likely to develop fractures in the thigh bone just below the hip (subtrochanteric) and further down the straight part (femoral shaft) of the thigh bone—areas where fractures are not typically seen in people with osteoporosis.” Speak with your doctor regarding this risk.

Osteonecrosis of the Jaw (ONJ)

Osteonecrosis of the Jaw (ONJ) is a disfiguring and disabling condition where the jawbones suffer literal bone death through infection and rotting.  ONJ is a well-known side effect of all the bisphosphonates, both Zometa and Xgeva.  However, its reputation far exceeds its actual impact, as only a very small number of men ever develop ONJ.  However, there is nothing wrong about taking precautions to prevent the possibility of developing ONJ. These would include a comprehensive dental examination and completion of all needed dental work before starting any bisphosphonate treatment protocol. While receiving treatment, maintaining excellent oral hygiene is vital. Try to avoid all invasive dental procedures such as tooth removal, and make sure that your dental professionals know that you are taking bisphosphonates whenever you have any treatment.  Just stopping bisphosphonates prior to any dental work does not lower your risk, as these drugs remain in your body for an exceedingly long time.

The risks of developing ONJ are statistically the same whether you take Zometa or Xgeva. Overall, 2% of cancer patients treated with Xgeva developed jaw necrosis, not significantly different from the 1.45% incidence with Zometa.