Bisphosphonate Related Osteonecrosis of the Jaws

Bisphosphonates are a class of drugs that prevent the loss of bone mass.   They are given either intravenously (IV) or taken orally in pill form.

The Oral Bisphosphonates: Fosamax (alendronate), Actonel (risedronate), and Boniva (ibadronate) are most commonly used to treat Osteoporosis, but also Paget Disease and other conditions that lead to bone fragility.  Additionally, Osteoporosis is also being treated by a newer and more potent Intravenous form Reclast (zolendronic acid).

Bisphosphonates are also powerful allies in the fight against cancers that have metastasized (spread) into bone. When used with chemotherapy agents, bisphosphonates have prolonged and improved the lives of many patients taking these medications.

The High-Potency Intravenous Bisphosphonates: Zometa (zolendronate) and Aredia (pamidronate) have been shown to modify the progression of malignant bone disease in several forms of cancer, especially in Multiple Myeloma, Metastatic Breast Cancer, Metastatic Prostate Cancer, and Metastatic Lung Cancer.

The FDA has also recently approved a new class of “Anti-Resorptive Biologic Drugs” known Prolia or Xgeva (Denosumab) for the treatment of osteoporosis in postmenopausal women at high risk for fractures and to reduce bone weakening or loss in cancer patients.

Our bones have a certain cell type called “osteoclasts,” whose job is to actively dissolve bone as part of the body’s normal activities in order to permit new bone formation.  When taken orally or intravenously, bisphosphonates bind tightly to the surface of osteoclasts, stopping them from dissolving bone. As a result, bone production continues, bone loss decreases, bone density is improved and the risk of Spine/Back (Vertebral) and Hip (Femur) fracture is reduced.

What Jaw Problems or Complications Can Develop from these Medications?

A condition known as Bisphosphonate Induced Osteonecrosis of the Jaws (BIONJ)/ Bisphosphonate Related Osteonecrosis of the Jaws (BRONJ) is a potential condition that can occur in patients currently taking or that have bisphosphonate medications in the past.   If a patient is on or has taken Denosumab (Prolia or Xgeva), the same condition can develop, and it is known as Drug Induced Osteonecrosis of the Jaws (DIONJ)/Drug Related Osteonecrosis of the Jaws (DRONJ).   For the purposes of this pamphlet, BIONJ/BRONJ, DIONJ/DONJ will be referred to as Osteonecrosis or Osteonecrosis of the Jaws.

What is Osteonecrosis of the Jaws?

This is a condition that develops in an area of the jaw bone that actually has died and become exposed in the mouth for more than 8 weeks in a person who was taken a bisphosphonate or anti-resorptive medication.

Symptoms include:

  • Exposed bone
  • Non-healing gum tissues
  • Swelling of the gum tissues and inflammation
  • Loosening of previously stable teeth
  • Possible localized pain (usually associated with infection in the bone).

Osteonecrosis is usually identified by the appearance of exposed non-healing bone in the oral cavity.

Risk Factors for Developing Osteonecrosis of the Jaws

While the majority of patients on intravenous (IV) and oral bisphosphonates will not develop osteonecrosis, it is important to understand the risk factors for the disease. Osteonecrosis is most often seen in patients who have received bisphosphonates or anti-resorptive medications through IV therapy, but cases have been reported in patients who are taking oral medications.  Researchers believe that the best treatment for osteonecrosis is to prevent its occurrence. They have identified three categories of risk factors for the disease.

1. Use of bisphosphonates or anti-resorptive medications. Although this is a common reason for the development of osteonecrosis, it is the dosage and length of therapy that appear to be the determining factors. IV bisphosphonates used in cancer treatment are much more potent than the oral bisphosphonates used to manage osteoporosis, thus increasing the risk for osteonecrosis in these patients.

2. Duration or number of treatments with bisphosphonates or anti-resorptive medications. The risk of developing osteonecrosis appears to increase in relation to the number of treatments with an IV bisphosphonate or IV anti-resorptive medication.  The risks of developing osteonecrosis also increases if patients have been on or are presently on steroids or receiving chemotherapy.

3. Dental procedures. Patients undergoing routine dental surgical procedures, including tooth extraction, periodontal surgery or dental implant placement, while being treated with bisphosphonates or anti-resorptive medications make up about 85% of the osteonecrosis cases.

The Osteonecrosis  Staging System Helps Surgeons More Accurately Diagnose The Condition

Stage 1- Is characterized by exposed bone, that shows no indication of disease or inflammation of the soft tissue around the bone.

Stage 2- Is distinguished by painful areas of exposed bone accompanied by soft tissue or bone inflammation or infection.

Stage 3- Is the most advanced stage of osteonecrosis.  One of the most significant features is a fracture of the mandible (the lower jawbone) that has been weakened by the disease or involvement of the osteonecrotic bone all the way in to the maxillary sinus in the upper jaw. In addition, there is an extensive amount of exposed bone, soft-tissue inflammation and infection present.

What Can Be done To Prevent Osteonecrosis?

It is important to disclose to your dentist and to your oral surgeon whether or not you have been on any of these medications, for how long, and if you are currently still on these medications.  Depending on how long you have been on a bisphosphonate or anti-resorptive medication and if you were also treated at some point with other medications such as steroids, methotrexate, or chemotherapy for other conditions, this will help your dentist and oral surgeon identify any concerns.

Based on this information, your oral surgeon may order a simple blood test (or request your physician to prescribe the test through your medical insurance) to help further guide him or her in planning your up-coming dental surgery. The test is known as a CTX and it involves giving a few drops of blood at the lab.  It is a quick and painless test that is performed while fasting.

The results of the CTX test are usually faxed or mailed back to your oral surgeon within 2 weeks.  Based on the results, your oral surgeon may say it is safe to proceed with the planned elective oral surgery procedure or they may wish to delay your elective procedure for a period of 3-9 months.  There are some instances where your surgeon may recommend that you see an Endodontist (Root Canal Specialist) to have a root-canal treatment performed on the tooth rather than having it extracted (even if the tooth cannot be restored with a crown or bridge).

During that period, your oral surgeon would communicate with your prescribing physician and request that they temporarily hold or discontinue your bisphosphonate or anti-resorptive medication for a period of 3-9 months in what is known as a “Drug Holiday.”  It is important to note that the decision to temporarily refrain or to completely stop taking a prescription medication should only be made in consultation with your prescribing physician.  Your oral surgeon would be happy to help discuss this further with your physician.

The medical and surgical literature has shown that by holding the medications for 3-9 months (or even being able to stop taking them completely) poses no greater risk to patients in developing vertebral or hip fractures. The reason is that after a single dose of a bisphosphonate medication, 50% of that medication will still be active in your body 11 years later!

In fact, research now shows that patients are able to receive the same benefits from bisphosphonates by taking lower doses, less frequently, and for shorter/defined periods of time (2-5 years). By doing so, not only are patients still receiving the benefits of these medications but also decreasing their risk of developing osteonecrosis of the jaws.

With a little investigative work regarding your medical history, perhaps undergoing the simple blood test (CTX), communicating with your prescribing physician, communicating with your referring dentist, and timing your elective oral surgery procedure, the risks of developing Osteonecrosis of the Jaws can be minimized and even avoided.

How is Osteonecrosis Treated?

If you are diagnosed with Bisphosphonate or Drug Induced Osteonecrosis, it is very important that your treatment plan include regular and thorough communication between your physician, family dentist, and oral-maxillofacial surgeon.  There are a number of treatment options available to your surgeon, who will select the one most appropriate for you.

Treatment May Include:

  • Daily Irrigation and Antimicrobial Mouth Rinses
  • Short and Long-Term Antibiotics to Control Infection
  • Surgical Treatment to Remove Necrotic/Dead Bone in Advanced Cases

In some cases, a removable appliance may be prescribed to cover and protect the exposed bone.  A protective stent may be recommended for patients in whom exposed bone damages and irritates the surrounding soft-tissues or makes normal function difficult.

Well-fitting dentures can be worn if appropriate care is taken to minimize irritation to the soft-tissues. This is particularly important for patients who have received or are receiving IV bisphosphonate therapy.  Dentures should be removed and thoroughly cleaned each night.


Bisphosphonates and Anti-Resorptive Drugs are excellent medications for bone diseases like osteoporosis that have helped relieve bone pain and prevent fractures in the hip and back.  However, long-term use of these medications, particularly the IV forms for metastatic bone disease, may be associated with a small but real risk of developing osteonecrosis of the jaw. While this is a new and potentially serious condition, it is important to know that your oral and maxillofacial surgeon is experienced and knowledgeable in decreasing risks, prevention, diagnosis, and treatment of this disease.