What are Bisphosphonate Drugs?

Bisphosphonates are a class of drugs that prevent the loss of bone mass. High-potency intravenous bisphosphonates have been shown to modify the progression of malignant bone disease in several forms of cancer, especially breast and frequently prostate cancer. Oral bisphosphonates are used to treat osteoporosis, osteitis deformans (Paget’s disease of the bone) and other conditions that lead to bone fragility.

After they are taken orally or intravenously, bisphosphonates bind tightly to the surface of the bone directly beneath the bone cells known as “osteoclasts,” which actively dissolve bone. The drugs then become incorporated into the osteoclasts, stopping them from dissolving bone. As a result, bone production continues, bone loss decreases, bone density is improved and the risk of fracture is reduced.

Bisphosphonates are allies in the fight against malignant bone disease. When used with chemotherapy agents, bisphosphonates have been shown to significantly reduce skeletal complications in patients with bone cancers.

The drugs have also proven effective when taken orally by patients with or at risk for osteoporosis. Treatment in these cases increases the density of the patient’s bones and reduces the risk of fracture. The benefits of bisphosphonate therapy for osteoporosis sufferers are still evident several years after treatment.

The FDA has recently approved a new class of drugs called monoclonal antibodies (Denosumab®) for the treatment of osteoporosis in postmenopausal women at high risk for fractures, and to reduce bone weakening or loss in cancer patients. Denosumab has been identified as just as high a risk factor for osteonecrosis as bisphosphonates.

What is BRONJ?

Bisphosphonate Related Osteonecrosis of the Jaw (BRONJ) can be described as an area of bone in the jaw that has died and been exposed in the mouth for more than 8 weeks in a person taking any bisphosphonate. Although the exact cause is unknown, BRONJ is considered to be a side effect of bisphosphonate therapy. BRONJ is usually identified by the appearance of exposed bone in the oral cavity.

Symptoms of BRONJ include:

  • exposed bone
  • localized pain
  • swelling of the gum tissues and inflammation
  • loosening of previously stable teeth

Risk Factors for BRONJ

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

1. Use of bisphosphonates. Although this is a common reason for the development of BRONJ, it is the dosage and length of therapy that are 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 BRONJ in these patients.

2. Duration or number of treatments with bisphosphonates. The risk of developing BRONJ appears to increase in relation to the number of treatments with an IV bisphosphonate.

3. Dental procedures. Patients undergoing routine dental surgical procedures, including tooth extraction, periodontal surgery or dental implant placement, while being treated with bisphosphonates comprise about 60% of BRONJ cases.

Three Stages of BRONJ

The BRONJ staging system helps surgeons more accurately diagnose the progress of the disease.

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 BRONJ. One of the most significant features is a fracture of bone that has been weakened by the disease. In addition, there is an extensive amount of exposed bone, soft-tissue inflammation and infection.

What Can be Done to Prevent BRONJ?

If you are about to begin monthly IV bisphosphonate therapy for the treatment of bone cancer, visit your family dentist for a thorough check up. Take care of all necessary procedures, including oral surgical procedures, before treatment starts. If you have removable dentures, make sure they fit well and are comfortable.

If you are currently being treated with either IV or oral bisphosphonates, be sure to tell your family dentist and oral and maxillofacial surgeon the reason for bisphosphonate treatment, the method of treatment (IV or oral), and the dosage level before you schedule a surgical procedure.

Oral hygiene is particularly important if you are being treated with bisphosphonates. It is also crucial that you schedule regular examinations with your family dentist so that any infections or problems can be identified and addressed early.

Perform a regular self-examination of your mouth for signs and symptoms of BRONJ, such as pain, swelling and exposed bone. Early detection allows your oral and maxillofacial surgeon to diagnose and treat the condition as quickly as possible.

Panoramic radiograph revealing a segment of detached necrotic bone in the lower left jaw of a patient receiving oral bisphosphonates for osteoporosis.

How is BRONJ Treated?

If you are diagnosed with BRONJ, it is very important that your treatment plan include regular and thorough communications between your physician, family dentist and oral and 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 rinses
  • Antibiotics to control infection
  • Surgical treatment to remove the necrotic bone may be advisable in more 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 the surrounding soft tissues or makes normal function difficult.

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


Bisphosphonates are excellent medications for bone diseases and osteoporosis that help relieve bone pain and prevent fractures. However, long-term use of bisphosphonates, particularly IV bisphosphonates for metastatic bone disease, may be associated with a small but real risk of developing osteonecrosis of the jaw. While BRONJ is a new and potentially serious condition, it is important to know that your oral and maxillofacial surgeon is experienced and knowledgeable in the prevention and treatment of this disease.

 © American Association of Oral and Maxillofacial Surgeons (AAOMS). All rights reserved.

Reprinted with permission from American Association of Oral and Maxillofacial Surgeons.

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