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Osteonecrosis of the Jawbone (ONJ and BRONJ)

Osteonecrosis of the jawbone (ONJ) is a disease resulting from the temporary or permanent loss of the blood supply to the bone.  Without a blood supply, the bone dies (the term "osteo" means "bone"; the term "necrosis" means "death").   When this happens, the dead bone becomes exposed to the oral environment.  Exposed necrotic bone is not an uncommon complication after extractions of teeth, even in healthy patients who have never had radiation therapy or bisphphonate drug therapy.  Simple cases involve only the bone immediately surrounding the extraction socket, and usually, the necrotic bone will heal over spontaneously with time. 

Serious ONJ is extremely rare in dentistry, and it tends to happen only to patients who have known predisposing factors such as radiation therapy for cancers of the head and neck, chemotherapy for cancers, especially therapy including large doses of corticosteroids (prednisone and other steroids), or IV bisphosphonate drug therapy for metastasizing cancers or osteoporosis.  Osteonecrosis of the jaw  generally happens in susceptible patients after a dental extraction or periodontal osseous surgery.  It may also happen after a fall or an auto accident in which the jawbone is broken.  It can even happen under an ill fitting denture.    The presence of exposed necrotic bone in the oral cavity may cause the patient pain, but surprisingly, it is often asymptomatic, possibly because the necrotic bone acts like a dressing over the vital bone and allows healing to take place underneath it. 

There is no specific treatment for osteonecrosis of the jaw other than treatments aimed at preventing infection and controlling pain if present.   More advanced cases may require conservative debridement of necrotic bone.  Many cases of osteonecrosis will heal over time.  Some (very few) never heal.

Other terms for osteonecrosis are avascular necrosis, aseptic necrosis and ischemic bone necrosis. There are two named types of osteonecrosis in dentistry: Osteoradio-necrosis (radiation associated bone death), and Bisphosphonate Related OsteoNecrosis of the Jaw (BRONJ). 

Osteoradio-necrosis is the name given to necrosis of a portion of the jawbone in a patient who has received extensive radiation therapy for the treatment of cancers in the head and neck.  Radiation affects rapidly growing cells, and the cells in the endothelial lining of blood vessels are especially vulnerable to damage from large amounts of radiation.  High doses of radiation result in a cumulative progressive endarteritis (inflammation of the inner lining of the arteries) which eventually leads to the destruction of the smaller arteries in the bone.  Dense bone, like that found in the lower jaw is not especially well vascularized to begin with, and therapeutic amounts of radiation (far in excess of the radiation used to take normal diagnostic dental x-rays) reduces the blood flow further making normal healing of the bone difficult.

Patients who have had extensive cancer related radiation therapy to their head or neck should be sure to tell their dentist about this and avoid having teeth extracted.  This often means doing root canals on teeth that are otherwise hopelessly decayed and non restorable.  Patients who have had this type of radiation therapy should be especially careful to avoid excessive sugar intake and be meticulous about their oral hygiene.  

Osteoradio-necrosis is NOT associated with diagnostic x-rays like the ones your dentist takes periodically to examine your teeth.

Bisphosphonate Related Osteonecrosis of the Jaw (BRONJ)

Bisphosphonates are therapeutic agents used to treat diseases that feature bone fragility. These diseases include osteoporosis, Paget's disease of bone, multiple myeloma and certain cancers in which metastases are a feature, especially breast cancer.  Bisphosphonates inhibit osteoclast activity thus inhibiting the resorption of bone.  This will make the bone more dense, but also less vascularized and less able to remodel after injuries. 

Necrotic bone exposed to the oral environment for at least eight weeks in a patient that has been treated with any of the bisphosphonates is called Bisphosphonate Related OsteoNecrosis of the Jaw, or BRONJ for short.  Some authorities refer to it as BON which stands for Bisphosphonate OsteoNecrosis.  BRONJ can be a complication after extractions, periodontal surgery involving bone recontouring  or facial trauma from any source.  It can also occur spontaneously in susceptible patients.  BRONJ can occur in the upper or lower jaw, however the incidence in the lower jaw is twice as high as in the upper.  BRONJ may also follow less traumatic injuries such as chronic denture sores. 

There is no specific treatment for Bisphosphonate Related OsteoNecrosis of the Jaw other than treatments aimed at preventing infection and controlling pain if present.  More advanced cases may require conservative debridement of necrotic bone.  I am unable to find any reference to patients actually dying as a direct result of BRONJ, although patients being treated with IV bisphosphonates for metastasizing cancers or multiple myeloma may die of an accumulation of the side effects of their treatment modalities which may include very serious BRONJ.  In patients taking low doses of oral bisphosphonates  for osteoporosis (such as Actonel, Boniva, or Fosamax), spontaneous healing is actually quite a frequent occurrence.

Oral bisphosphonates

Most people are familiar with the names of several of the oral drugs used to treat osteoporosis, since the companies that manufacture them do a lot of advertising.

Brand Name

Manufacturer

Generic Name
Actonel Procter & Gamble Pharmaceuticals risedronate
Boniva Roche Laboratories ibandronate
Fosamax Merck & Co. alendronate
Fosamax Plus D Merck & Co. alendronate
Skelid Sanofi Pharmaceuticals tiludronate
Didronel Procter & Gamble Pharmaceuticals etidronate

Patients taking oral bisphosphonates such as the ones listed above, have a very low risk of developing BRONJ.  These patients seem to have less severe manifestations of necrosis which respond more readily to stage specific treatment regimens.  Dentists should inform patients that they have a small chance of contracting osteonecrosis, however dentoalveolar surgery does not appear to be contraindicated in this group. The actual incidence of BRONJ in the total population of patients who take oral bisphosphonates is approximately 0.7 cases per 100,000 patients per year.  The risk of BRONJ is especially low if the patient has been taking the bisphosphonate for less than three years and has no other complicating factors.  These complicating factors include: 

  • Diabetes

  • Concurrent steroid use

  • Smoking

  • Poor oral hygiene, especially in patients with periodontal disease

  • Therapeutic head and neck radiation

  • The concurrent administration of other chemotherapeutic agents. 

Question: Does the risk for BRONJ decrease if the patient stops taking the oral bisphosphonate for several months before having their extraction?

Answer: There is no hard data proving that there is a benefit to halting oral bisphosphonate medication, even for several months prior to the surgical procedure.  Evidence suggests that the drug remains in the bony structure more or less permanently.  The half life of bisphosphonates in bone is about 10 years.  Even so, drug holidays are still recommended for patients who have been taking their drug for over three years. 

The rule of thumb seems to be that no delay in surgery is necessary for patients who have been taking oral bisphosphonates  for less than three years unless they have one or more of the above complicating factors.  If the patient has been taking bisphosphonates for more than three years or has complicating factors, a three month drug holiday is advised prior to surgery with the holiday extending until bony healing is complete (usually about three months post-op).  Click here for the reference.

Question: Does the length of time a patient has been taking an oral bisphosphonate affect the probability that the patient will contract BRONJ?

Answer: Yes!  The general consensus is that the probability of contracting bisphosphonate related osteonecrosis of the jaw as a result of dental osseous surgeries during the first three years of oral drug therapy is substantially less than for those patients who have been taking the drug for more than three years.  Patients and dentists should strive to produce a state of oral health during the first three years of bisphosphonate therapy to reduce the likelihood of BRONJ later.

Question: Is a patient taking oral bisphosphonates likely to develop BRONJ after implant placement?

Answer: Implants have been known to fail in patients taking oral bisphosphonates, however it is not altogether clear if the failure of the implants in question were a result of the oral bisphosphonate regimen, or were associated with some other patient or technique related factor.  Studies of patients on oral bisphosphonates receiving implants indicate a very low risk of either implant loss or BRONJ following implant placement.  The general consensus now is that oral bisphosphonates are NOT a contraindication for dental implants, even if the patient has been taking them for a very prolonged period.

IV bisphosphonates

While patients taking oral bisphosphonates show a very low risk of BRONJ, patients taking IV (injection) bisphosphonates are at significant risk of developing BRONJ after extractions or other surgical interventions involving the  manipulation of bone (incidence is 0.8-12%).  IV bisphosphonates are generally used as part of a chemotherapeutic regimen for the treatment of cancer.  The most commonly used IV bisphosphonates are:

Brand Name Manufacturer Generic Name
Aredia Novartis pamidronate
Zometa Novartis zolendronic acid
Bonefos Schering AG clodronate

Any patient who has been treated with IV bisphosphonates should follow these guidelines:

  • Avoid extractions unless the teeth are very mobile.

  • Choose root canals rather than extractions whenever possible.

  • Have extremely good oral hygiene and regular dental care.

  • Be especially careful to keep your dentures in good repair to avoid chronic sore spots.  Patients are advised to have relines every 2 years and get new dentures every five to seven years. (Click here to see why.)

  • Before the prescription of bisphosphonates for bone disease the patient should be made dentally fit so that the need for subsequent dental extractions is minimized.

Staging and treatment for ONJ patients Click here for the reference.

  • Stage 1: Exposed/necrotic bone in patients who are asymptomatic and have no evidence of infection.

    • Treatment of stage 1: These patients benefit from the use of oral antimicrobial rinses, such as chlorhexidine 0.12%. No surgical treatment is indicated. Patients who present with Stage 1 disease have done well with this type of conservative treatment.

  • Stage 2: Exposed/necrotic bone in patients with pain and clinical evidence of infection.

    • Treatment of stage 2: These patients benefit from the use of oral antimicrobial rinses (chlorhexidine) in combination with antibiotic therapy.  Penicillin is the drug of choice, with clindamycin used if the patient is allergic to penicillin.

  • Stage 3: Exposed/necrotic bone in patients with pain, infection, and one or more of the following: pathologic fracture, extra-oral fistula, or osteolysis extending to the inferior border.

    • Treatment of stage 3: These patients typically have pain that impacts the quality of life. Surgical debridement/resection in combination with antibacterial mouth rinses (chlorhexidine) and antibiotic therapy may offer long-term palliation with resolution of acute infection and pain.


       

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