Beyond Bisphosphonates – A Closer Look at MRONJ and Cancer Therapy
In 2014, the American Academy of Oral and Maxillofacial Surgeons released a position paper about medication–related osteonecrosis of the jaw (MRONJ), formerly known as bisphosphonate-related osteonecrosis of the jaw (BRONJ). In addition to anitresorptive drugs, such as bisphosphonates and denosumab, which were previously the primary focus, other medications have now been added to the list for potential risks of developing osteonecrosis of the jaw. Both medical and dental professionals must be aware of the role that each of these medications plays in the treatment of certain cancers, along with the necessity for patient education and preventive oral care.
First, it is helpful to understand the role of antiresorptive drugs and why they may be used with cancer therapy. Despite a different mechanism of action for bisphosphonates and denosumab, both are typically used in the treatment of osteoporosis and osteopenia to slow or prevent bone loss. Certain cancers and their treatments can also leave the patient at increased risk for bone loss and conditions such as hypercalcemia, which is high levels of calcium in the bloodstream, and skeletal related events (SRE), such as bone pain, fractures and spinal compressions. Most commonly, these medications would be used for Multiple Myeloma and secondary cancers that have spread to the bone.
The additional medications listed in the AAOMS Position Paper are also used in cancer therapy. They are sunitinib (Sutent®), and bevacizumab (Avastin®). Sutent® is classified as a tyrosine kinase inhibitor (TKI). This type of medication can block the enzyme called tyrosine kinase, which plays a role in the process of cell division by sending signals to a cell to grow and divide. Blocking this enzyme can slow or stop cancer cells from growing, and in some cases, it can cause the cells to die. Sutent® can also block a process called angiogenesis, which is the growth of blood vessels that occurs in both healthy and diseased tissue. Blocking the formation of blood vessels to tumors can literally starve cancer cells. Sutent® is most often used with advanced kidney cancer, pancreatic cancer and Gastrointestinal Stromal Tumor (GIST).
Bevacizumab (Avastin®) is also an anti-angiogenic agent that blocks a protein called vascular endothelial growth factor, or VEGF. Blocking VEGF can prevent the growth of new blood vessels. This includes both normal blood vessels and blood vessels that feed tumors. Avastin® is currently approved for treating several types of cancer, including certain cancers of the colon, kidney, lung, ovaries, brain and cervix. According to the AAOMS, "Osteonecrosis is classically considered an interruption in vascular supply or avascular necrosis, and therefore, it is not surprising that inhibition of angiogenesis is a leading hypothesis in ONJ pathophysiology."
While the FDA has currently issued an ONJ advisory only for bevacizumab and sunitinib in addition to antiresoprtive drugs, there are several other medications within the same drug classes that have a similar mechanism of action and may prove to have similar risks. It is imperative that medical and dental professionals are aware of these potential dangers and treat accordingly.
You can learn more about MRONJ and updates on prevention, diagnosis, staging, and management strategies at Medication-Related Osteonecrosis of the Jaw 2014 Update