Osteonecrosis of the Jaws (ONJ)

Osteonecrosis of the Jaws (ONJ) is a condition where the bone in the jaw becomes devitalized (dead) and the bone becomes exposed to the oral cavity. ONJ is a rare condition that can occur in association with a variety of conditions, including cancer and its treatments. Depending on the stage, ONJ can occur without symptoms or it can be associated with infection and pain.

Why does ONJ occur?

Doctor auscultating the neck of a patient

Within bone tissue, there are specific cells that break down and re-build the bones to release minerals into the bloodstream and maintain bone strength. Patients whose cancers have spread to the bones are often treated with antiresorptive medications that are designed to block this destruction of the bone tissue and prevent complications. In this patient population, ONJ is thought to occur due to the inhibition of the bone destruction and rebuilding process associated with certain cancer treatments. Other treatments such as radiation can also lead to necrosis.

Who is at risk of developing ONJ?

Antiresorptive medications are most often used in a general population to treat weak bones, a condition commonly referred to as osteoporosis. Antiresorptive medications are also used in the management of cancers that have spread to or involve the bone. While almost any cancer can spread to the bone on occasion, some of the most common types of cancers that spread to the bone include prostate cancer, breast cancer, lung cancer, and kidney cancer. Multiple myeloma also usually has bone involvement.

Approximately half of patients with cancer that has spread to the bone experience skeletal complications such as fractures or the need for radiation or surgery. These patients may also develop pain or elevated levels of calcium in the bloodstream. In this group of cancer patients, antiresorptive drugs are often used to prevent these types of skeletal complications, as research has shown that the use of antiresorptive drugs can decrease the risk of developing bone complications by over 50%.

While these are important medications used to manage and control cancer, patients who are taking any of these medications should be aware that they are at risk of developing ONJ.

Some specific examples of ONJ-associated medications include intravenously (IV) administered medications such as zoledronic acid (Zometa) or pamidonate (Aredia) or the injectable medication denosumab (Xgeva).

Other medications, such as “antiangiogenic” cancer drugs, can less commonly be associated with ONJ. Antiangiogenic medications aim to prevent the growth of new blood vessels within tumors. This class of drugs includes bevacizumab (Avastin) and sunitinib (Sutent), amongst many others, which are medications used to treat kidney cancers such as renal cell carcinoma and gastrointestinal cancers. Antiresorptive medications in lower doses can often be given by mouth or by injection for the treatment of weak bones (osteoporosis and osteopenia), and ONJ is much less common at these lower doses.

Because ONJ can detrimentally affect quality of life and is associated with increased risk of death, it’s important to know the signs, symptoms and risk factors. ONJ is more common in the lower jaw (mandible) than the upper jaw (maxilla). Local risk factors for ONJ include oral surgical procedures such as tooth extraction, periodontal surgery or implant placement, and the presence of dental disease. Denture use is also associated with a risk of ONJ. Systemic factors such as steroid use, diabetes and tobacco use may also increase the risk of ONJ.

How do I prevent ONJ?

Early screening and appropriate dental care is recommended for all patients who will be receiving an antiresorptive or antiangiogenic medication as part of their cancer therapy. A consultation with a dental professional who is experienced in the management of cancer patients receiving these medications is recommended prior to starting therapy. Studies have shown a decrease in the incidence of ONJ in patients who are in optimum oral health.

During cancer care, it is important to maintain optimum oral health by practicing good oral hygiene, using fluoride to prevent tooth decay and seeing your oral healthcare team for preventive care when appropriate. Any sign of infection in the jaw such as pain or swelling should be addressed immediately by alerting your oncologist and the appropriate dental professional. If possible, oral surgical procedures should be avoided unless determined to be necessary by a dental professional who is experienced in the management of ONJ.

Should I stop taking antiresorptive or antiangiogenic medications to prevent ONJ?

No. These medications should never be stopped without the knowledge of your oncologist. The benefits of taking these medications often outweigh the low risk of developing ONJ which is approximately 1-2% (1-2 people out of 100). In addition, certain therapies, such as bisphosphonate medications, can remain present in bone for many years, meaning that stopping them is unlikely to reduce the risk of ONJ.

If ONJ occurs, how is it treated?

Treatment of established ONJ aims to eliminate pain, control infection and limit progression of the necrotic bone. Depending on the clinical stage of ONJ, treatment strategies can range from management with antibiotics and pain medications to surgical removal of areas of dead bone.

At Weill Cornell Medicine and NewYork-Presbyterian, we provide supportive, specialty oral care before, during and after cancer treatment. To learn more about the services we offer, click here. To make an appointment with a dentist at our center who specializes in treating cancer patients, please call Dr. Heidi Hansen at 212-746-5115.

Special thanks to Heidi Hansen, DMD, for her contributions to this article.


For additional information about oral care during cancer therapy, visit the below links:

American Association of Oral and Maxillofacial Surgeons

National Cancer Institute

American Dental Association

 

Antibodies and Small Molecules: Two Different Tools to Target PSMA

Prostate-specific membrane antigen (PSMA) is a molecular marker present on the surface of virtually all prostate cancer cells. It can be targeted by different molecular agents that bind to PSMA. This enables a targeted approach to find and image or treat prostate cancer cells wherever they are in the body, including the cells that have escaped (metastasized) to other organs.

The most commonly used agents to target PSMA fall into two categories: small molecules (also known as peptides, ligands, or inhibitors) or antibodies (also termed monoclonal antibodies).

Small molecule- and antibody-based molecules that bind to PSMA have different physical characteristics and these have implications on the way the molecules circulate through the body.

For example, peptides and other small molecules that target PSMA are much smaller than antibodies – approximately 100-fold smaller. As a result of their small size, peptides are able to quickly travel through blood vessels and disperse throughout all body tissues – both normal and tumor – and they are also rapidly excreted by the kidney into the urine and bladder.

Conversely, the larger antibodies tend to stay within the circulating blood and flow more selectively through the larger, abnormal blood vessels within tumors than the vessels in normal tissues. Their large size also prevents them from being excreted by the kidneys. Because of these properties, peptides can penetrate tumors, as well as normal tissues, rapidly and then disappear from the body quickly, in minutes to hours; antibodies take longer to travel and enter the tumor, but this is compensated for by the longer amount of time they spend in the body (days to weeks) and their decreased likelihood to penetrate into normal tissues.

Imaging

From a diagnostic imaging perspective, small molecules are typically better, as the rapid excretion of the radiolabeled peptide quickly minimizes the radioactive background “noise” seen on a scan. Additionally, using small molecules means that patients can be injected with imaging agents and then undergo scans quickly thereafter (on the same day within 1-3 hours). Physicians can see good contrast of the cancerous cells compared to other parts of the body with this method. In comparison, patients must return approximately 3-8 days after infusion with a monoclonal antibody for scans. Some of the benefit of using small molecules is offset by the fact that they are excreted via the urine and accumulate in the urinary bladder. This may lead to an intense signal in the urinary bladder area of the scan, adjacent to the prostate gland and lymph nodes in the pelvis, thereby possibly obscuring these potential sites of tumor. On the other hand, some antibodies are taken up by the liver, obscuring visualization of that organ. Antibody fragments such as so-called “mini-bodies” (derived from the whole antibody), are half the size of a normal antibody, but still large enough so as not to be excreted in the urine, and as such, they may provide improved imaging of the prostate and the pelvic area. This is currently under investigation at Weill Cornell Medicine and NewYork-Presbyterian Hospital.

The nuances of these molecular targeting agents aside, it is clear that both peptide-, antibody or mini-body-based agents provide significantly improved targeted molecular imaging of prostate cancer compared with conventional modalities such as bone, CT, and MR scans and also have some advantages over glucose (FDG), sodium fluoride (bone), choline, or fluciclovine (FACBC) PET scans.

Treatment

From a therapeutic perspective, there are theoretical advantages to the faster tumor penetration of the smaller molecule targeting agents, but this may be offset by their quick disappearance and their ability to impact normal tissue. The longer time antibodies spend circulating in the body theoretically provides for a greater amount of the treatment agent to get internalized into the cancer cells, allowing greater uptake of the payload agent (such as a radionuclide) that is being delivered to kill the cancer cells. Additionally, some antibodies may also be engineered to generate an immune response.

Does uptake in different body areas lead to side effects?

The different characteristics of small molecules and antibodies confer advantages and disadvantages when targeting PSMA on cancer cells within the body. Because of their small size, small molecules/peptides can penetrate through the depths of the tumor very quickly, but they also readily target normal tissues that express low levels of PSMA such as the salivary glands, small intestine, and kidneys. When using as a therapeutic delivery vehicle, this might lead to dry mouth, nausea, or delayed kidney damage. Luckily, no significant kidney damage has been seen in humans to date, but the number of patients treated on prospective clinical trials remains small and follow up is short. An antibody, on the other hand, does not target salivary glands or kidneys because its larger size leads to relatively restricted access to those normal sites. However, it circulates in the body for a longer period of time including high flow through the bone marrow. Antibodies tagged with radioactive particles may therefore contribute to non-specific side effects such as temporary decreased blood counts. This is a common (expected) toxicity related to the dose and schedule of the radiolabeled antibody.

Currently, it is not known whether peptide-based or antibody-based targeted PSMA prostate cancer treatments provide better results, but both approaches offer therapeutic benefit to patients. At Weill Cornell Medicine and NewYork-Presbyterian Hospital – where we have almost two decades of experience pioneering prostate cancer imaging and treatment with PSMA-targeted agents – we are the only center in the world currently able to offer both types of imaging and treatment modalities and plan to combine both within individual patients. We hypothesize that will be able to use the favorable properties of each targeting agent at slightly lower than maximal doses to deliver a higher amount of therapeutic payload to tumor with less to normal organs, further improving the tumor kill : side effect ratio and have initiated a clinical trial testing this approach.


References

Phase I Trial of 177lutetium-Labeled J591, a Monoclonal Antibody to Prostate-Specific Membrane Antigen, in Patients with Androgen-Independent Prostate Cancer

Phase II Study of Lutetium-177-Labeled Anti-Prostate-Specific Membrane Antigen Monoclonal Antibody J591 for Metastatic Castration-Resistant Prostate Cancer 

 

What Women Need to Know About Sex and Cancer Treatment

Amid the onslaught of questions and worries that can be prompted by a bladder or kidney cancer diagnosis, most women are not immediately concerned with how the disease and its treatment might affect their sex life. Though sex may not be as top-of-mind as issues like survival itself or caring for a family, it is still a significant aspect of quality of life that is worth preserving and nurturing.

Maintaining a healthy sex life while dealing with cancer requires open and honest discussion both between partners as well as with a cancer care provider, but it may be difficult to know exactly what to discuss. We spoke with Dr. Tanaka Dune, a urogynecologist within the Weill Cornell Medicine and NewYork-Presbyterian Hospital (WCM/NYP) Center for Female Pelvic Health, and our Genitourinary (GU) Oncology Program’s own Dr. Ana Molina to find out how to guide the conversation.


Recognize Changes

Fighting cancer can be physically and mentally exhausting, leaving many women without much energy or desire to engage in sexual activity. Additionally, the potential aesthetic changes to the body caused by treatment, such as scarring, hair loss and weight fluctuation may hamper confidence or lead to feelings of unattractiveness. Yet, if all parties are consenting and communicative, it is safe to have sex during and after cancer treatment.

Women should be aware, however, that certain types of chemotherapy can damage the ovaries and lead to vaginal dryness, irritation and/or atrophy (thinning and shrinking of vaginal tissue due to lack of estrogen), which may cause discomfort during sex and otherwise.

Dune“You should never be aware of your vagina,” says Dr. Dune. “If you become aware, that’s when you need to start talking about it.”

Ask Questions

Healthcare providers work with the best interest of the whole person in mind, so women do not need to be afraid to ask questions or feel embarrassed about how much they do or do not know about sexuality. Clinician assistance often leads to better patient health outcomes, faster. For example, it can be difficult for women to discern between pain in the vagina and pain in the pelvic floor, the network of muscles that supports the vagina and other pelvic organs, and a doctor can ask clarifying questions to determine the appropriate next steps to treat the issue and suppress the pain.

Evaluate Options

As with most elements of cancer care, there is no one-size-fits-all approach to navigating sex during and after treatment.

To combat chemo-induced vaginal dryness, for example, lubrication options are abundant, granting patients the ability to customize based on individual needs and preferences. Certain compounds found in lubricants can trigger yeast infection, irritate the vulva and/or dry out vaginal and anal tissues, so women should avoid using petroleum-based lubricants like mineral oil or Vaseline, as well as those that contain nonoxynol-9, glycerin, glycols or parabens. Instead, they can opt for silicone- or water-based lubricants, or natural oil lubricants like vegetable, olive, peanut, avocado or coconut oil. To reduce vaginal tightness, doctors may recommend use of pelvic floor physical therapists, who teach exercises that involve contracting and relaxing vaginal and pelvic floor muscles. This type of therapy can be achieved manually and/or with the use of vaginal dilators.

For issues of insecurity and anxiety that may disturb some women’s sex lives, possible remedies include psycho-social and/or psycho-sexual support services. The WCM/NYP Genitourinary Oncology Program connects patients and spouses/partners with support groups and counseling and can even offer hair-preserving cold cap therapy or a wig prescription to combat chemotherapy-induced hair loss that may contribute to a lack of confidence.

Molina“Addressing psycho-social issues together with your partner via counseling or support groups can have a positive impact on your life and intimate relationships,” says Dr. Ana Molina.


Since most forms of cancer treatment weaken the immune system, it is especially important that women use barrier protection during oral, anal and vaginal sex to prevent exchange of bodily fluids that can lead to sexually transmitted disease.

Patients should note that while the Internet is a fantastic tool for resources and self-education – often preferred because of the ability to search for information within the comfort of one’s own home – it is best to check with a healthcare team before acting on health advice found online.