Bisphosphonate Related Jaw Osteonecrosis

What is Bisphosphonate Related Jaw Osteonecrosis?

Bisphosphonate (BP) is a highly effective medication used for treating various health issues that trigger excessive activity in bone-eating cells, known as osteoclasts. These issues can include conditions related to cancer, osteoporosis, multiple myeloma, Paget disease, osteosclerosis, and fibrous dysplasia. With the growing use of BP, doctors have noticed a possible link between the drug and a condition called osteonecrosis or bone death in the jaw. Even though it’s rare, this jaw bone death is now identified as a potential side effect of BP use.

A specific type, called Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ), occurs when the use of BP leads to an exposed bone, or a bone that can be felt through a hole (or fistula) in the face and jaw area. This bone won’t heal within eight weeks, even though most surgical and infection sites would usually heal in that time. This timeline is considered, taking into account possible complications such as infection after surgery, chemotherapy, or systemic diseases. A key point to note is that these patients have not had any radiation therapy to their face and skull.

What Causes Bisphosphonate Related Jaw Osteonecrosis?

Bisphosphonates are a type of medication that works by stopping a type of bone cell known as an osteoclast from breaking down bone. They do this by causing these cells to self-destruct (a process called apoptosis), reducing their ability to break down bone, and stopping more osteoclasts from forming. This medication tends to build-up where these osteoclast cells are most active due to its strong attraction to bone minerals.

An issue occurs when bone resorption (breaking down of bone) and new bone formation stop because old bone is kept alive beyond its lifespan. This process also stops the maintenance of the capillary network, the tiny blood vessels in the bone, which can lead to a condition known as avascular necrosis of the jaw. This condition is characterized by the death of bone tissue due to a lack of blood supply.
On top of this, high-strength bisphosphonates may cause cell death due to their harmful effects on soft tissues and bone cells, and the complexity of these effects can be enhanced if an infection is present.

Another problem with bisphosphonates is that they can interfere with wound healing. For instance, if there is a cut in the mouth lining, it could take longer to heal, leading to long-term infection and causing the death of bone tissue, a condition known as osteonecrosis.

This side effect is particularly prominent in the jaw, as it regularly remodels itself more than other bones in the body. This makes it more susceptible to the effects of bisphosphonates.

Risk Factors and Frequency for Bisphosphonate Related Jaw Osteonecrosis

Osteonecrosis, or bone death, of the jaw is mostly reported with the use of strong, nitrogen-containing Biphosphonates (BPs) formed into drugs like pamidronate and zoledronic acid. Of the two, zoledronic acid is associated with a higher rate due to its stronger bone-dissolving capacity, which leads to decreased bone turnover.

Oral Biphosphonates, on the other hand, rarely cause osteonecrosis of the jaw. They are less harsh than intravenous BP, and the osteonecrosis caused by oral BP is more responsive to treatment. Oral BPs are less soluble in fat, which limits their absorption in the intestine, and results in less bone storage.

The frequency of osteonecrosis increases with a higher dosage of potent BPs and a longer duration of administration. The risk ranges from just over 1% at 12 months to 11% after four years of treatment. Using zoledronic acid alone can increase the risk of osteonecrosis to 21% after three years.

For those with bone conditions like osteoporosis, the risk of BP-induced osteonecrosis is very low, ranging from 0.15% to less than 0.001% per years of exposure. This rate is only slightly higher than in patients without osteoporosis. Cancer patients with bone metastasis have a much higher risk, due to higher exposure to bone-dissolving drugs and high-dose, intravenous BPs.

Osteonecrosis most frequently occurs in the mandible, or lower jawbone, than in the upper jawbone. It almost always starts in the alveolar bone, which is found in the roof of the mouth or sockets of teeth, due to its high rate of bone turnover. The condition often depends on bone remodeling because of biting and teeth-wearing pressure.

• The risk of BP-induced osteonecrosis of the jaw increases with more potent, nitrogen-containing intravenous BPs.
• The risk goes up with higher dosages and longer treatment durations.
• Cancer patients with bone metastasis also have a higher risk.
• Areas with a high bone turnover rate, like the alveolar bone of the lower jaw, are more prone to osteonecrosis.

Signs and Symptoms of Bisphosphonate Related Jaw Osteonecrosis

BRONJ, or Bisphosphonate-Related Osteonecrosis of the Jaw, usually occurs after a dental procedure that impacts the bone, but it can also occur on its own. The affected bone might not show any symptoms for a long time, or develop symptoms due to inflammation of the surrounding soft tissue.

If you’ve taken anti-resorptive (bone-strengthening) drugs and experience slow healing after oral surgery, infection, swelling, numbness, strange sensations, or exposed bone, it’s worth considering BRONJ. However, it’s important to know that sometimes BRONJ is discovered by accident during a medical examination.

Some people with BRONJ might experience unusual nerve sensations. This happens because the blood vessels and nerves in the area are compressed, leading to strange sensations or even numbness in the area affected by the trigeminal nerve, which supplies the face. Numbness or loss of sensation in the lower lip has been noted as an early sign of BRONJ.

Unfortunately, BRONJ can lead to complications, including skin ulcers, sinus tracts (channels) both inside and outside the mouth, and abnormal connections called fistulas. Chronic inflammation of the maxillary sinuses (sinusitis) in people with bone involvement in the upper jaw (maxilla), and fractures in toothless (edentulous) patients with dental implants have also been reported.

• No symptoms
• Pain
• Infection of the soft tissues causing inflammation, ulcers, and pus formation
• Development of sinus tracts and fistulas both inside and outside the mouth
• Strange sensations or numbness of an associated nerve
• Fracture
• Chronic inflammation of the sinus in the upper jaw
• X-ray findings can range from no changes to varied mix of radiolucent (dark areas) and radiopaque (bright areas)

Testing for Bisphosphonate Related Jaw Osteonecrosis

When your doctor suspects you may be dealing with bone diseases like osteonecrosis (decay of bone tissue due to reduced blood flow), they may order a blood test to check your C-terminal telopeptide (CTX) value. This test helps detect the fragments that get released when bone is broken down. The level of these fragments can tell your doctor about the number and stage of disease, and how quickly your bone is breaking down and rebuilding. If your CTX value is less than 100 pg/mL, it suggests a high risk of developing a disease with decreased ability of your bones to heal. CTX values of 100 to 150 pg/mL suggest moderate risk, and anything above 150 pg/mL suggests minimum or no risk.

In terms of imaging, doctors use X-rays to look at your bones and surroundings. These can range from regular bone appearance to seeing small dark or light spots – indicating the presence and stage of the bone disease. It can also detect changes in bone shape, new bone being formed around the diseased area, increase in bone density, or pieces of dead bone separated from healthy bone. One of the early signs of bone disease could be changes in the ligament space or thickness of the bone layer around the teeth.

Radiographs (X-ray images) are the first step in inspecting the bones as they help your doctor view the bones easily and at a lower cost. These images can show signs such as thickening of bone layer around the teeth, increased bone density, signs of slow healing after a tooth has been pulled, changes in ligament space and bone curvature, and formation of dead bone pieces. However, the images aren’t always clear enough to tell diseased bone from healthy bone, and early disease stages can sometimes be missed.

Cone Beam Computed Tomography (CBCT) is a type of three-dimensional X-ray that can help visualize both the outer and inner bone, identify areas of increased or reduced bone density, examine bone reactions around the area, and inspect other structures close to the area. Despite its advantages, early stages might not be detected and it is not as good in detailing the soft tissues due to low contrast resolution.

Magnetic Resonance Imaging (MRI) is often used to detect early changes in bone marrow and surrounding tissue. It provides similar bone information as a CT scan, but can also show decreased bone marrow signal intensity due to cell death and repair processes like swelling or edema. It does have some limitations in showing the full extent of bone damage and can sometimes give false positives.

Scintigraphy is another imaging method that uses a radioactive substance and a camera to create pictures of your bones. It is highly sensitive for diagnosing early disease and can locate the exact areas that are affected. However, it exposes patients to significant radiation, is time-consuming, has lower resolution, and it can sometimes be hard to tell apart healing and progressing bone lesions.

Overall, each of these methods has its own advantages and shortcomings. So, combining CBCT with scintigraphy, using MRI with contrast agents, repeated imaging, and manipulating image planes can all be helpful measures to diagnose the early or preclinical stages of bone diseases.

Treatment Options for Bisphosphonate Related Jaw Osteonecrosis

Your treatment depends upon a variety of factors, including your age, gender, how advanced your disease is, the size of the affected area, any other health conditions you might have, and the type of medication you’re on. Currently, there aren’t any specific guidelines for the treatment of BRONJ (bisphosphonate-related osteonecrosis of the jaw). The main aim of treatment is to reduce pain, control infection, and stop the progression of exposed bone.

Conservative Therapy: A primary aspect of care involves non-aggressive treatments that provide long-term relief. It revolves around two key factors:

1. Managing pain and ensuring good oral hygiene: Alongside at-home cleaning of teeth and gums, regular visits to your dentist is crucial.
2. Treating active infection and dental diseases: This could involve using oral antimicrobial rinses and antibiotic treatments. A typical medication could be penicillin, though we occasionally suggest using other alternatives like levofloxacin, doxycycline, or azithromycin depending on how your body reacts. If antibiotics provide little relief, adding metronidazole can be considered.

A medication called teriparatide may also be used to facilitate healing. However, this is not usually recommended in certain patients, such as cancer patients, those who have had radiation therapy on their bones, or those with active bone metastasis, since they have a higher risk of developing or advancing bone malignancies. If you use an oral prosthesis, or artificial dental part, it’s important to minimize its contact with the exposed bone.

Surgical Therapy: In cases that don’t show improvement with these treatments, meaning they have permanent bone defects, surgical intervention may be needed. This could involve removing the affected bone area and extending into the adjacent healthy bone. In more severe cases like the presence of pathological fractures or disease extending to the sinus or bottom part of the lower jaw, reconstruction procedures may need to be considered.

Experimental Therapy: Other therapeutic approaches are also being explored. These include the use of hyperbaric oxygen (a treatment that uses pure oxygen), bone marrow stem cell transplantation in the affected area, local application of growth factor that stimulates platelets (which play a crucial role in the body’s defence against infection), and low-level laser therapy. The influence of these therapies on the treatment outcome, however, still needs further investigation.

In summary, the treatment approach includes:

1. Conservative and supportive therapy for managing pain and infection.
2. Surgical therapy for treating permanent bone defects.
3. Experimental therapy involving hyperbaric oxygen, bone marrow stem cell transplantation, growth factor from platelets, and low-level laser therapy.

What else can Bisphosphonate Related Jaw Osteonecrosis be?

BRONJ (Bisphosphonate-related osteonecrosis of the jaw) is identified by the presence of exposed bone. If there is no exposed bone, it can be mistaken for other conditions, such as:

• Periodontal and periapical pathosis (problems related to gums and tooth roots)
• Sinusitis (sinus infection)
• Gingivitis or mucositis (gum or mouth inflammation)
• Temporomandibular disorders (issues with the jaw muscles and joints)
• Osteomyelitis (bone infection)
• Metastatic bone tumors (cancer that has spread to bone)
• Osteonecrosis induced by neuralgia (sudden nerve-related pain)
• Osteoradionecrosis (bone death caused by radiation therapy)

Certain conditions demonstrating exposed bone may not be associated with bisphosphonate use, including:

• Cement osseous dysplasia with secondary sequestration (a bone disorder seen commonly in middle-aged women)
• Trauma (an injury)
• Infectious osteomyelitis (an infection in the bone)
• Osteonecrosis following Herpes zoster infection (bone death following shingles infection)
• HIV-associated necrotizing ulcerative periodontitis (a serious gum infection occurring in some people with HIV)

Preventing Bisphosphonate Related Jaw Osteonecrosis

The best way to avoid getting BRONJ (a disease that affects the bone in the jaw causing severe damage) is through prevention and strong cooperation between your dentist, oral surgeon, physician, nurse practitioners, and cancer doctors (oncologists). This involves a well-thought-out plan to minimize the risk of developing this condition.

Before Starting a Medication Called Bisphosphonate:

If you’re going to be starting a drug known as bisphosphonate, there are several steps you should know about to minimize your risk of developing BRONJ. This is particularly important during the initial 4 to 6 month period, when it has the most impact on the bones in your jaws:

1. Have a detailed dental check-up and make sure to maintain good oral hygiene. Regular visits to your dentist are a must.
2. Learn about proper practices for taking care of your mouth and teeth at home.
3. Understand the risk of getting BRONJ while on bisphosphonate medication.
4. Together with your dentist, develop a treatment plan to address any issues and make sure your teeth are in the best possible condition. This helps reduce the need for invasive procedures after the medication has started.
5. If you have any teeth that are irreparable or badly damaged, it’s recommended to have them removed.

Certain complex dental procedures may be carried out once the medication has been started, but it’s generally not advisable to have dental implants or orthodontic treatment. That said, if you’re using bisphosphonate for osteoporosis, dental implant placement is not ruled out, but you should fully understand the risks and give your consent.

For Patients Undergoing Bisphosphonate Treatment:

Once you’ve started bisphosphonate therapy and after 4 to 6 doses, the medication will have a significant effect on your bones making healing unpredictable and risky. During this time:

1. Understand the risk of developing BRONJ while undergoing this therapy.
2. Learn about proper oral care and maintenance at home.
3. Avoid oral surgical procedures like tooth extractions, bone shaping, bone grafting and other periodontal or surgical procedures.
4. If possible, try to have endodontic treatment (root canal therapy) instead of extractions and surgeries around your teeth roots.
5. Prefer noninvasive restorative procedures like placing crowns, bridges, removable partial and complete dentures to prevent the need for future surgeries.
6. Orthodontic procedures are not recommended.
7. Elective procedures like extractions of asymptomatic teeth, implant placement, and reducing bony growths in your mouth are not advised.

In cases where a tooth can’t be saved, it should be treated with a root canal and its crown (top) removed. Loose teeth can be splinted (joined to surrounding teeth for support). Failed root canals should be redone. If tooth extraction is unavoidable, you should be informed about the risk of BRONJ and sign a consent form before the procedure. If you’re using bisphosphonate and need extensive invasive oral surgery, or have multiple risk factors like steroid treatment, immunity issues, or diabetes, risk assessment is needed. Dentists should not suggest stopping the bisphosphonate drugs for dental procedures since there’s no evidence that the risk of BRONJ reduces once you stop taking the drug.