New evidence suggests that osteonecrosis of the jaw is uncommon after treatment with bisphosphonates or denosumab (Xgeva), a lab-created protein used to prevent bone fractures in cancers that metastasized to the bone. Monitoring oral dental health may prevent or resolve osteonecrosis as a side effect, the study found.
Developing osteonecrosis of the jaw is a common fear for women treated with bisphosphonates, bone-building or bone-strengthening medicines. Osteonecrosis, the death of bone tissue, occurs when blood flow is restricted to an area of the body. It is a known side effect of some medicines used to treat breast cancer that has spread to the bones.
Background and Reason for Study
Since the early 2000s, osteonecrosis of the jaw has been reported in people with bone metastasis from several types of cancer. People with this side effect had received chemotherapy and bisphosphonates given by vein, and they had pain, swelling of soft tissues, infection, loosening of teeth and numbness in the jaw.
Many studies have tried to identify the risk factors that may cause osteonecrosis of the jaw, and whether treatment with bisphosphonates is involved.
Researchers combined data from three similarly structured clinical trials that compared the effectiveness of denosumab to zoledronic acid (Zometa), a bisphosphonate, in people with bone metastases. Participants had breast cancer, prostate cancer, other solid-tumor cancers and multiple myeloma.
In all studies, participants were treated every four weeks and had not been treated for metastatic disease with bisphosphonates before the trial. None had recent treatment for severe, invasive dental or jaw conditions.
Investigators reported any development or potential development of osteonecrosis of the jaw, in addition to comparing the effectiveness of the two medicines. Together, the three trials yielded 5,723 participants, of which 2,046, about 36 percent, were women with metastatic breast cancer.
The combined analysis found the reports of osteonecrosis were low overall, with 89 confirmed cases in total. Of those 89, 37 received zoledronic acid and 52 took denosumab. These account for only 1.3 percent and 1.8 percent of total participants, respectively. The percentages are so close that they are not considered statistically significant, meaning it’s possible the differences are by chance.
The researchers found these risk factors associated with developing osteonecrosis of the jaw while being treated for metastatic cancer:
- Corticosteroid use: a slightly greater proportion of participants who developed osteonecrosis were treated with corticosteroids.
- Having a tooth removed, or tooth extraction, during treatment.
- Use of antiangiogenic medicines, or medicines that slow or stop the growth of blood vessels that help tumors to grow.
However, the investigators noted that recent analyses show no association in the development of osteonecrosis of the jaw and the use of antiangiogenics in women with metastatic breast cancer.
Due to the close monitoring participants received, the researchers believe that the low incidence rate and high healing rate (36 percent of participants with osteonecrosis fully recovered) may have been influenced by a heightened focus on their oral and dental health. They recommend that people treated with bisphosphonates or denosumab take care of dental issues before beginning treatment and monitor their oral health regularly.
What This Means for You
Although this study involved people with many types of cancer, the significant percentage with metastatic breast cancer may reassure you that your chances of developing osteonecrosis of the jaw are low. Talk with your team about possible risk factors before and throughout treatment.
If you are concerned about the side effects of bone-targeting medicines, talk to your medical team about maintaining good oral health throughout treatment. Promptly report any pain, swelling, drainage, infection or numbness in your jaw to find out if these are early symptoms of osteonecrosis. The sooner you treat osteonecrosis, the more likely your team can resolve its impact on your life.
Saad, F., Brown, J.E. et a. Incidence, risk factors, and outcomes of osteonecrosis of the jaw: integrated analysis from three blinded active-controlled phase III trials in cancer patients with bone metastases. Ann Oncol. 23:5 (1341 - 47) 2012.