Medication Related Osteonecrosis of the Jaw

What is osteonecrosis of the jaw?

‘Osteo’ means bone. ‘Necrosis’ means death of cells or tissue in the body. Osteonecrosis of the jaw (ONJ) is a serious bone disease where there is a loss of blood supply to the bones of the jaw. This blood supply is needed to keep cells and tissues healthy and alive.

The loss of blood supply leads to exposed (uncovered) bone of the maxilla (upper jawbone) or mandible (lower jawbone). These bones should be covered by gum tissue. With ONJ, the bone is exposed, either through an opening in the gum tissue or because the gum tissue is completely missing.

Symptoms of ONJ may be:

• Pain.
• Swelling.
• Infection of the gums.
• Loosening of the teeth.
• Exposed bone (often at the site where a tooth has been removed/extracted).
• Numbness or tingling in the jaw or a "heavy" feeling of the jaw.

ONJ may have no symptoms for weeks or months and may only be found by feeling or seeing exposed bone.

ONJ is sometimes confused with osteoradionecrosis of the jaw, which is caused by radiation therapy and is treated differently than ONJ. This article will discuss osteonecrosis of the jaw.

What causes ONJ?

The exact cause of ONJ is not known, but possible causes may be:

• Dental work.
• Infection.
• Inflammation.
• The slowdown of angiogenesis (making of new blood vessels).

At first, ONJ was thought to be caused by dental work while taking certain medications for cancer treatment. Further research found that this dental work was often done because of dental disease, such as inflammation of the gum tissue or infection. It is now thought that the medications themselves cause ONJ.

Who is at risk for ONJ?

Some cancers affect your bones more than others, such as multiple myeloma or cancers that have spread to the bone (called bone metastasis). Other health issues like diabetes can also put you at greater risk of ONJ. Ways that cancer can affect the bone are:

• Tumors that have grown into the bones (called invasion) can cause that bone to wear away. This leaves small holes in the bone, called osteolytic lesions. When the bone starts to break down and wear away, it is called resorption. Resorption leaves bones weak and fragile.
• Tumors can also cause changes to your bone formation. Bone can build up, called osteosclerotic lesions. These lesions can be painful and can easily break or collapse.

Medications can be used to treat osteolytic lesions and osteosclerotic lesions caused by cancer. In some cases, these medications can cause ONJ.

Which medications are linked with ONJ?

There are some medications that are used to treat cancer that can lead to ONJ such as bisphosphonates, denosumab, and anti-angiogenic medications.

Bisphosphonates

Bisphosphonates are a group of medications that slow the breakdown of bone that happens with bone metastases or multiple myeloma (cancer of plasma cells, which invade and destroy bone). Bisphosphonates slow down how quickly the bone wears away (called resorption) and decreases the build-up of unstable bone. These problems can lead to "skeletal related events.” These include:

• Fractures.
• A faster spread of bone metastases.
• Spinal cord compression (when the bone in the spine compresses the spinal cord).
• Hypercalcemia (high levels of calcium in the blood caused by bone breakdown).

Bisphosphonates are used to help improve bone strength in diseases that cause bone resorption, like some cancers and osteoporosis.

Currently approved bisphosphonates include:

• Alendronate (Fosamax®).
• Etidronate (Didronel®).
• Ibandronate (Boniva®) – currently used only for osteoporosis.
• Pamidronate (Aredia®).
• Risedronate (Actonel®).
• Tiludronate (Skelid®).
• Zoledronic acid (Zometa®).

Denosumab

Another medication used to slow or prevent bone breakdown and bone issues is denosumab (Xgeva®). Denosumab is a monoclonal antibody, which is a medicine that targets a specific protein or cell. Denosumab targes a protein called RANKL, which is needed for bone breakdown and too much is made in bone metastases. By targeting RANKL, denosumab blocks or slows down bone breakdown.

Anti-angiogenic medications

Anti-angiogenesis inhibitors work by affecting a tumor's blood supply. These medications are used in many cancer treatment regimens.

Prevention is the Key

What experts have learned is that most cases of ONJ were related to a dental event, and if these are avoided, ONJ may be as well. Before taking a medication that can cause ONJ, you should be seen by an oral maxillofacial surgeon or dental oncologist familiar with ONJ. If there are any dental concerns (needing dental surgeries, extractions, root canals, or removal of abscessed teeth), therapy with the medication should wait (if possible). You should not start the medication until the dental concerns are addressed and healed. Dental exams should include cleaning, examining of denture fit, and patient education regarding oral care while on these medications.

Patients receiving bisphosphonates should have regularly-scheduled dental appointments, even as often as every 3-4 months. They should have good oral hygiene and have routine dental cleanings (with care to avoid injury to tissues).

If invasive dental procedures are needed, you may have to stop taking your medication. However, there is no evidence that this helps prevent ONJ in oncology patients. These medications remain in the body for many months after the last dose, meaning you would need several months or more off the medication to make stopping the therapy worthwhile. These medications clearly benefit patients at high risk of bone complications and no other class of medications have this benefit. The patient and provider must weigh the patient's risk with the benefit when considering these medications. Research continues about ONJ.

How do we treat ONJ?

You should have panoramic and/or intra-oral x-rays done to rule out other dental problems (impacted teeth, cysts, bone changes). You should be seen by an oral maxillofacial surgeon or dental oncologist familiar with ONJ. Primary goals of treatment of ONJ are to reduce pain, treat or prevent infection, and slow down progression.

Oral rinses with chlorhexidine (Peridex®) should be used 3-4 times a day. Dentures can be worn but may need some resizing or cushioning to prevent more injury to the bone. An appliance can be used to cover and protect the exposed bone. Antibiotics may be given. The area may be tested to find what bacteria is present to decide which antibiotic to use.

Surgery on these bones may not heal well and may worsen the problem so you may want to avoid surgery. In more advanced cases, surgical removal of the involved bone can improve quality of life, reduce pain, prevent the area of necrosis from spreading, and help promote soft tissue healing. When used, surgery may include the surgical removal of foreign material and/or dead, damaged, or infected tissue or bone and in some cases, reconstruction of the bone.

ONJ is rare, but as patients with multiple myeloma and bone metastases are living longer and being treated with medications associated with ONJ for many years, it is important to be aware of ONJ. You should follow any directions for mouth care that you are given and report any signs or symptoms of ONJ to your provider right away.