The use of denosumab (Xgeva) as an alternative to the more commonly prescribed zoledronic acid (Zometa) to slow down the development of bone metastases in men with advanced prostate cancer is becoming more common. The most common concern for men taking Zometa and now Xgeva has been osteonecrosis of the jaw. Osteonecrosis of the jaw is basically severe bone disease which is associated with bisphosphonate therapy (Zometa and now Xgeva).
One of the more common questions asked by many people is if osteonecrosis of the jaw is more or less common in men taking Zometa or Xgeva? The answer is simple; overall 2% of cancer patients treated with denosumab do developed jaw necrosis, which did not significantly different from the 1.45% incidence with Zometa.
According to a retrospective analysis of multiple randomized trials(1) of patients taking Xgeva, patients infrequently developed osteonecrosis of the jaw; however the rate appeared to increase over time in certain subgroups. Specifically, patients with breast and prostate cancers taking Xgeva were twice as likely to develop osteonecrosis of the jaw as treated patients with other solid tumors or multiple myeloma!
Tim van den Wyngaert, MD, of Antwerp University Hospital in Belgium, and colleagues concluded in a poster presentation at the International Conference on Cancer-Induced Bone Disease the longer treatment duration could explain the higher rates in patients with breast and prostate cancer patients. He said, “Current data suggest that additional gains in prevention
An integrated analysis of all three trials showed overall superiority for denosumab (Ann Oncol 2010; 21: Abstract 1249P). Separate analyses demonstrated the superiority of denosumab among patients with breast or prostate cancer and noninferiority versus zoledronic acid in patients with other solid malignancies or myeloma (J Clin Oncol 2011; 28: 5132-5139, Lancet 2011; 377: 813-822, J Clin Oncol 2011; 29: 1125-1132).
Van den Wyngaert noted in the introduction to the data section of the poster that although jaw necrosis is an uncommon complication in cancer, patients who develop it have few effective treatment options, making avoidance a consideration in the use of anti-resorptive agents.
The investigators also concluded that there should be set up “International Prospective ONJ Registries of patients Treated with Bisphosphonates or Denosumab. They should be established to document exposure, risk factors, and treatment in order to increase our understanding of ONJ incidence, biology, and outcome.”
(1)The three large randomized trials of patients treated with either denosumab or zoledronic acid (Bone. 2011;48:S18). The three trials had a similar design and comprised 5,700 patients. The studies involved patients with bone metastases from solid tumors or myeloma and at least one lytic bone lesion. Patients were randomized to denosumab or zoledronic acid, and the primary endpoint was time to a first skeletal-related event (SRE). The three trials showed that patients treated with denosumab and those treated with Zometa had a similar rate of osteonecrosis of the jaw
Primary source: International Conference on Cancer-Induced Bone Disease
Van den Wyngaert T et al. “RANK ligand inhibition in bone metastatic cancer and risk of osteonecrosis of the jaw (ONJ): Updated results with extended phase III data” CIBD 2011; Abstract P106.
Joel T Nowak, M.A., M.S.W.
Before starting the treatment visit your dentist and have any required dental work performed. Once you start Zometa or Xgeva you must pay close attention to your dental care, brushing and flossing are of paramount importance. – Joel
If one is on an XGEVA treatment regime, and develops need for dental care (pulled tooth), does stopping the XGEVA treatment decrease problems….if so, how long should you go without XGEVA before proceeding with dental care?
Gena, This is a problem. I don’t believe that there has been any research on how long after stopping XGEVA is best. However, if work is needed try and find a dentist that has experience with working with survivors who have taken XGEVA or Zometa. Sometimes if you go to a comprehensive cancer center they will have a dentist with this type of experience. If the work can be accomplished with out any insult to the bone it should be done in this manner. – Good Luck, Joel
Joel, I wish I have had done some research on XGEVA before my treatment. I would have had an implant before my jaw going to death zone. Now that I have two major molars out and more will be out as they are all start getting loose. The Onco I had just tell me to see a dentist which I hate going to one. I lost one molar and have one at the end with no other teeth around. That tooth was alone there for over 20 years with no problem. After XGEVA for less than a year poss only 5 shots, my that lone tooth started to loose. I went to a dentist who dealt with patients with XGEVA to have this tooth stabled but he said it needed to come out. I asked if implant can be done afterward, he then told me that I have jaw osteonecrosis because of XGEVA. I could not believe my ears. In my 66 years, I only visit dentist less than 10 times. I have perfect teeth and tried to avoid dentist if I can. Each time I went in, they drilled a stain spot until my teeth all loose. I went overseas and saw a dentist and hold me I have a lot of stain but he did not drill one tooth at all. I was able to stay away from dentists for over 20 years. If not because of the loose tooth, I would have stayed away from dentist for years. Before the loose tooth being pulled out, I have no other teeth problem. After this loose tooth being pulled out, I now experience the one next to the two missing teeth being very sensitive and starts to loose a little. I hope this is a lesson to all who will start XGEVA, If you need an implant do it first before XGEVA. My upper teeth are all intact and with no pain or feel loose at all. I just hope I can keep my lower jaw and the 12 teeth on it for long time. I am scare of loosing them. Rebecca
Thank you for sharing your experience and your wisdom.
Joel, my father who is 91 with advanced prostate cancer has been on xgeva for some time. He was having problems with his jaw. His Dr. had no idea why. Sent him to a dentist who sent him to a periodontist who sent him to an endodontist for a root canal. After searching the internet, I found the side effects of xgeva. I am so disgusted with his drs. The last time he went for xgeva injection his urologist said “oh yeah” . He is now off xgeva. Will this jaw pain get better? I feel so helpless.
Laraine, I am sorry that your father as had to suffer. Your story reinforces the need for men with advanced prostate cancer to make sure that their doctors are specialists in treating people with this disease. Most general urologists are not adequately equipped with the experience to do this the expertise that is required. The doctors who should be treating him are medical oncologists who specialize in advanced prostate cancer. Can you change his doctors? – Joel
My cousin took xgeva for stage 4 prostate cancer for less than year. They took him off it as he had tooth pain. In 2 months he had 2 teeth extracted. A month later had to have another one extracted. Now he can barely eat due to the ouseing and bleeding and he has to go back on chemo treatments. The extractions are not healing. I told him to get to s nutritionist as he is losing weight. Will his jaw heal or get worst
I don’t understand why Rebecca thinks an implant before xgeva would help. My front teeth Implants are implanted into the bone with metal screws If I lose the bone, I will lose the screws, just like teeth. . I also have a bridge for my lower teeth that are attached to two root canaled and capped bicuspids on either end. If I lose them I will lose the bridge too. seems the entire implant would come out with ONJ. Is there an alternative type of implant I could look into before starting xgeva ? It sounds to me that I would have to have a complete jaw replacement/! Is there ANY other bone hardener alternative available for multiple myeloma??