As strange as it may sound, we in the dental community may be facing a potentially serious epidemic that stems from a side effect associated with the drugs used in the treatment of cancer patients. These are the IV biphosphonates pamidronate (Aredia; Novartis Pharmeceuticals, East Hanover, NJ) and zolendronate (Zometa; Novartis Pharmeceuticals) that are being used in the treatment of cancer patients with bone metastasis or the treatment of hypercalcemic states. These drugs have been implicated in the condition that is known as biphosphonate induced osteonecrosis. There are a number of published reports implicating these drugs in the avascular necrosis of the jaws.(1,2,3) There are various clinical entities that may be similar in presentation such as osteomyelitis and radiation induced osteoradionecrosis. I would like to describe each of these individually and explain why these drugs have been implicated in a condition that seems similar, but is different. We must take this condition seriously, otherwise we may inflict a great deal of harm on to our patients.

When you are faced with a patient with exposed painful non-healing bone the following conditions must be ruled out:

Osteomyelitis of the jaws may come in various forms that I will not go into in detail. However, it is important to understand that this is an infectious process. By definition it is the inflammation of the marrow space and there is a clear etiology associated with it such as an infected tooth or a sequestrum, i.e. a foreign body. The symptoms are consistent with pain, drainage, parasthesia, and possible swelling. The treatment is removal of the source, sequestrotomy, and long-term antibiotic therapy.

Radiation induced osteoradionecrosis is a result of hypoxia, hypocellular, and hypovascular bone induced by high levels of radiation therapy. These patients may develop exposed necrotic bone or delayed healing with bone exposure after the removal of a tooth or with any trauma resulting in bone exposure. The treatment is local debridment and in severe conditions the effected bone must be sectioned down to bleeding margins. The best course of treatment is preoperative antibiotic therapy with atraumatic extractions and in some conditions HBO therapy if applicable.

The osteonecrosis that occurs as a side effect of the drugs, has been dubbed biphosphonate-induced osteonecrosis. These drugs are used to treat hypercalcemia in some malignancies or in reducing osteolysis in bone metastasis.(4) They do this by inhibiting osteoclastic activity, (5) which is one of the cornerstones for bone remodeling. Therefore the bone in these patients does not have this capability and it functions as dead bone for a lack of a better word. This is why we must take every action to avoid bone exposure of any kind since the normal bone physiology that results in bone remodeling (repair) has been interrupted. Furthermore, these patients cannot stop taking these medications since there life depends on it. Even if they stopped taking them the effects will not reverse for a very long time.

Biphosphonates such as etidronate (Didronel; Proctor & Gamble, Mason, OH), residronate (Actonel; Proctor & Gamble), and tiludronate (Skelid; Sanofi Weinthrop (Sanofi-Sythe Labo Inc), New York, NY) are in common usage today and do not cause bone necrosis. However, these drugs are non-nitrogen containing biphosphonates and are rapidly metabolized. Pamidronate (Aredia) and Zoledronate (Zometa) are nitrogen containing biphosphonates, and are much more potent and are not metabolized. (6) Therefore, they accumulate in bone and have an ongoing affect that results in bone necrosis after surgical insult.

Since the bone is unable to repair itself, these patients are refractory to any treatment and the best line of action is avoiding such complications by not performing any surgical procedures. In the event a tooth needs to be removed, the best course of action is a coronectomy and root canal therapy, even if it turns out to be a simple extraction. With edentulous patients soft tissue liners can be used to avoid any bone exposure.

If a complication should arise, then the best treatment is no further surgical intervention and the following recommendations may be followed: long term or intermittent penicillin therapy, 0.12% chlorhexidine rinse, and periodic minor debridement of soft textured sequestrating bone and wound irrigation. (1) According to the preliminary reports aggressive therapy leads to more problems.

Taking note on the issue raised in this article can save you from facing a serious complication in your practice. Therefore, it is essential to obtain relevant history on patients that have had chemotherapy and make sure that they have not been administered these medications. We must avoid any type of surgery that will result in bone exposure at all cost in patients that have been exposed to these medications. If there is no other option available then the patient must be informed about the risks and complications involved and be prepared for the long term care that he or she may have to receive.