Role and Precautions About to the Use of Bisphosphonate Drugs

Once a man with metastatic prostate cancer becomes castrate resistant (mCRPC) it is common to add a bisphosphonate like injectable zoledronic acid (Zometa) or denosumab (Xgeva) to his drug regimen.

As we age, our bones tend to get thinner (a decrease in our bone mineral density, aka BMD) and become weaker, leading to an increase in our fracture risk.  Oral bisphosphonates are used to prevent the loss of BMD leading to the weakening of the bones.

Injectable bisphosphonates, used in men with mCRPC have a different role than oral bisphosphonates that are used to maintain bone mineral density (BMD) (bone strength).  In different cancers, including in men with advanced prostate cancer that has become castrate resistant (mCRPC), infusions of bisphosphonates are the standard of care. Injectable bisphosphonates not only reduce the risk of declining BMD, but they also counter bone the development of complications and metastases, as well as controlling existing bone metastases.

Like all other drugs, bisphosphonates have unwanted side effects, some which can be mediated.  Towards this end, it is highly advisable that you:

·      Have a comprehensive oral examination and complete all recommended dental work before your first infusion.

·      Maintain excellent oral care.

If you have begun bisphosphonate treatment and need any dental work, before starting the dental treatment, you should consult with an oral surgeon who has experience with patients who are taking bisphosphonates.  Also, discuss the proposed treatment with your oncologists and stop bisphosphonate treatments as your medical staff directs. Do not restart the bisphosphonate treatment until advised by your medical team (see the ONJ recommendations below).

Stay well hydrated by drinking a lot of water before and during the infusion. 

Make sure that the infusion staff actively monitors your electrolytes during the infusion.

Ask your doctor to time your initial infusion at a rate that will last at least one hour, and then not less than 30 minutes for each subsequent infusion.

A small number of men experience incapacitating bone, joint and/or muscle pain from the infusion. If you do, let your doctor know and discuss discontinuing the bisphosphonate treatment.

You should consult with your medical team limiting your long-term use of bisphosphonates as explained in the Special Precautions part of this post.

Denosumab (Xgeva) v. Zoledronic Acid (Zometa)

Denosumab (Xgeva), approved by the FDA in November 2010, is the newest of the injectable bisphosphonate drugs.  Compared to the older Zometa, Xgeva has been shown to be superior in delaying the onset of bone problems, including the development of new bone metastases. It also has been shown to reduce pain and improve the quality of life

A Special Precaution About Long-Term Use Of Injectable Bisphosphonates

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


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.”  However, a cautionary finding also stated that long-term users were more likely to develop serious fractures in the thigh bone just below the hip (sub-trochanteric) and further down the straight part (femoral shaft) of the thigh bone—areas where fractures are not typically seen in people with osteoporosis.” You should speak with your doctor regarding this risk if you have been taking bisphosphonate drugs for five years or more.

Osteonecrosis of the Jaw (ONJ)

An additional adverse side effect of bisphosphonates is osteonecrosis of the Jaw (ONJ).  ONJ is a disfiguring and disabling condition where the jawbones suffer bone death, infection and rotting.  However, ONJ’s reputation far exceeds its actual impact, as only a small number of men develop ONJ.  Even though the risk of developing ONJ is small, there is nothing wrong about taking precautions to prevent the possibility of developing it.

Precautions should include having a comprehensive dental examination and completion of all needed dental work before starting any bisphosphonate treatment. 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 before any dental work does not lower your risk, as these drugs remain in your body for an exceedingly long time.

Injectable bisphosphonates are a powerful treatment for men with mCRPC.  However, like all other cancer treatments, it should not be taken without proper consideration of how it is administered as well as developing a plan of action to mitigate the possible adverse side effects.

Joel T. Nowak, MA, MSW wrote this Post.  Joel is the CEO/Executive Director of Cancer ABCs.  He is a Cancer Thriver diagnosed with five primary cancers - Thyroid, Metastatic Prostate, Renal, Melanoma, and the rare cancer Appendiceal cancer.